PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Anti-arrhythmics, Class I-A

    BOXED WARNING

    Apheresis, bradycardia, cardiomyopathy, celiac disease, females, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, mortality, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Quinidine has proarrhythmic properties and may induce or worsen cardiac arrhythmias. Quinidine is a Class IA antiarrhythmic agent, and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Discontinue quinidine if significant QT prolongation or TdP occur during therapy. Quinidine has been associated with increased mortality when used to treat various arrhythmias. Use quinidine with extreme caution in patients with QT prolongation or a history of TdP. Avoid quinidine whenever possible in patients with pre-existing QT prolongation, acquired or congenital long QT syndrome, or a history of TdP. Use quinidine with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, pyrexia or elevated body temperature, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral and oral class IA antiarrhythmic; used for atrial arrhythmias and ventricular tachycardia; also used for severe malaria.

    COMMON BRAND NAMES

    Quinaglute, Quinora

    HOW SUPPLIED

    Quinaglute/Quinidine/Quinidine Gluconate Oral Tab ER: 324mg
    Quinidine/Quinidine Gluconate Intramuscular Inj Sol: 1mL, 80mg
    Quinidine/Quinidine Gluconate Intravenous Inj Sol: 1mL, 80mg
    Quinidine/Quinidine Sulfate/Quinora Oral Tab: 200mg, 300mg

    DOSAGE & INDICATIONS

    For conversion to and/or maintenance of sinus rhythm in patients with atrial fibrillation, atrial flutter, or ventricular tachycardia; or for the treatment of paroxysmal supraventricular tachycardia (PSVT); or for paroxysmal supraventricular tachycardia (PSVT) prophylaxis in patients with reentrant tachycardias, including patients with Wolff-Parkinson-White (WPW) syndrome.
    NOTE: Most adult patients require 10 to 20 mg/kg/day, expressed as quinidine base. Adjust dosages to produce a serum quinidine concentration of 2 to 6 mcg/mL. Quinidine sulfate, quinidine gluconate, and quinidine polygalacturonate (no longer commercially available) contain 83%, 62%, and 80% quinidine base, respectively.
    Oral dosage (quinidine sulfate immediate-release tablets)
    Adults

    Initially, 200 to 300 mg PO every 6 to 8 hours. May be increased to 600 mg PO every 6 hours if needed, based on serum quinidine concentrations. Alternatively, a rapid loading dose can be given, usually 200 mg PO every 2 to 3 hours for 5 to 6 doses or until clinical response or toxicity occurs.

    Adolescents† and Children†

    20 to 60 mg/kg/day PO or 900 mg/m2/day PO, given in divided doses every 6 hours.

    Oral dosage (quinidine sulfate extended-release tablets)
    Adults

    300 to 600 mg PO every 8 to 12 hours.

    Oral dosage (quinidine gluconate extended-release tablets)
    Adults

    Initially, 324 mg to 648 mg PO every 8 to 12 hours. If needed, the dose may be cautiously increased. The total daily dose should be decreased if QRS complex widens to 130% of pre-treatment duration; the QTc interval widens to 130% of pre-treatment duration and is longer than 500 msec; P waves disappear; or if the patient develops significant tachycardia, symptomatic bradycardia, or hypotension.[47357] Guidelines recommend quinidine 324 to 648 mg PO every 8 hours as an option for the maintenance of sinus rhythm in patients with atrial fibrillation only when other antiarrhythmic drugs cannot be used.[56966]

    For the treatment of persistent singultus (hiccups)†.
    Oral dosage (quinidine sulfate)
    Adults

    200 mg PO 4 times daily. Quinidine clearance may be reduced in geriatric patients; dosage reduction may be required in individual patients.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Quinidine has a narrow therapeutic index (serum concentration range: 2—6 mcg/ml). Dosage is individualized based on patient weight, age, renal and hepatic function, clinical goals, patient response, and serum quinidine concentrations.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Quinidine is approximately 60—80% metabolized by hepatic enzymes. Dosage should be adjusted based on the degree of hepatic impairment and clinical response; no quantitative recommendations are available.

    Renal Impairment

    CrCl > 10 ml/min: no dosage adjustment needed.
    CrCl <= 10 ml/min: dosage adjustment may be needed.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Oral Administration

    Administer quinidine with a full glass of water 1 hour before or 2 hours after meals for faster absorption. Do not administer with grapefruit juice, which could significantly inhibit the metabolism of quinidine. If gastric irritation occurs, may administer with or immediately after meals.

    Oral Solid Formulations

    Extended-release tablets: Swallow whole; do not crush, chew, or break.

    STORAGE

    Generic:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Quinaglute:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Quinora:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    AV block, bundle-branch block, digitalis toxicity

    Quinidine should be used cautiously, if at all, in patients with incomplete AV nodal block because complete block could develop. Quinidine is contraindicated in patients with complete AV block, severe intraventricular conduction defects, left bundle-branch block, or ventricular ectopy. AV block may increase the risk of prolonging the QT interval when using quinidine. Quinidine is contraindicated in patients with digitalis-induced AV conduction disorders. Use with caution in patients with digitalis intoxication even in the absence of conduction disorders, because the drug can cause additive depression of conduction, aggravating digitalis toxicity.

    Heart failure

    Quinidine should be used cautiously in patients with congestive heart failure. The direct negative inotropic effects of the drug can exacerbate congestive heart failure. Additionally, heart failure may increase the risk of prolonging the QT interval when using quinidine.

    Apheresis, bradycardia, cardiomyopathy, celiac disease, females, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, mortality, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Quinidine has proarrhythmic properties and may induce or worsen cardiac arrhythmias. Quinidine is a Class IA antiarrhythmic agent, and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Discontinue quinidine if significant QT prolongation or TdP occur during therapy. Quinidine has been associated with increased mortality when used to treat various arrhythmias. Use quinidine with extreme caution in patients with QT prolongation or a history of TdP. Avoid quinidine whenever possible in patients with pre-existing QT prolongation, acquired or congenital long QT syndrome, or a history of TdP. Use quinidine with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, pyrexia or elevated body temperature, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Asthma, fever, mefloquine hypersensitivity, quinidine hypersensitivity, quinine hypersensitivity

    Quinidine should not be used in patients with a known mefloquine hypersensitivity, quinine hypersensitivity, or quinidine hypersensitivity. Use quinidine cautiously in patients with preexisting asthma because it can mask quinidine hypersensitivity. Use quinidine cautiously in patients with fever because it can both mask quinidine hypersensitivity and increase the risk of prolonging the QT interval. Repeat use of quinidine is contraindicated in patients who previously developed drug-induced thrombocytopenic purpura as a result of quinidine treatment.

    Myasthenia gravis

    Quinidine use is contraindicated in patients with myasthenia gravis because the drug's anticholinergic properties can increase muscle weakness. In addition, quinidine can interact with drugs used in the treatment of myasthenia (see Drug Interactions).

    Hepatic disease, renal failure, renal impairment

    Renal impairment or hepatic disease results in delayed elimination of quinidine, and these conditions can lead to quinidine toxicity if dosage is not appropriately reduced. Quinidine should be used with particular caution in patients with severe renal impairment or renal failure with a creatinine clearance less than 10 mL/minute.

    Labor, pregnancy

    Quinidine is classified as FDA pregnancy risk category C. Safe use of quinidine during pregnancy has not been established. There have been no adequate or well-controlled pregnancy studies performed in humans. Use of quinidine during pregnancy should be avoided unless the potential maternal benefit justifies the possible risk to the fetus. In one neonate whose mother received quinidine throughout her pregnancy, the serum level of quinidine was equal to that of the mother. The concentration of quinidine in the amniotic fluid was approximately 3 times higher than that of the serum. No adverse effects were noted in the neonate. The effect of quinidine on labor and delivery is unknown; however, quinidine is known to be oxytocic in humans.

    Breast-feeding

    Quinidine is excreted in human milk at concentrations slightly lower than those found in maternal serum. Nursing infants would be expected to develop serum quinidine concentrations at least an order of magnitude lower than those of the mother. However, the pharmacokinetics and pharmacodynamics of quinidine in human infants have not been adequately studied. The reduced protein binding of quinidine in neonates may increase their risk of toxicity at low total serum concentrations. Avoid quinidine use in breast-feeding women, if possible.[47357] However, previous American Academy of Pediatrics recommendations considered quinidine to be usually compatible with breast-feeding.[27500]

    Geriatric

    Quinidine renal and/or hepatic clearance may be reduced in some geriatric patients; the quinidine dosage should be individualized to attain clinical goals. Monitor for adverse effects of quinidine more closely in geriatric patients, including QT prolongation. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. The OBRA guidelines caution that antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.

    ADVERSE REACTIONS

    Severe

    arrhythmia exacerbation / Early / 3.0-3.0
    esophageal stricture / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    night blindness / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    optic neuritis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    uveitis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known

    Moderate

    esophagitis / Delayed / 22.0-22.0
    palpitations / Early / 7.0-7.0
    hepatitis / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    PR prolongation / Rapid / Incidence not known
    scotomata / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    photophobia / Early / Incidence not known
    pneumonitis / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    confusion / Early / Incidence not known
    delirium / Early / Incidence not known

    Mild

    diarrhea / Early / 24.0-35.0
    pyrosis (heartburn) / Early / 22.0-22.0
    headache / Early / 3.0-7.0
    fatigue / Early / 7.0-7.0
    rash / Early / 5.0-6.0
    fever / Early / 6.0-6.0
    weakness / Early / 5.0-5.0
    vomiting / Early / 3.0-3.0
    nausea / Early / 3.0-3.0
    dizziness / Early / 3.0-3.0
    tremor / Early / 2.0-2.0
    asthenia / Delayed / 2.0-2.0
    syncope / Early / Incidence not known
    mydriasis / Early / Incidence not known
    diplopia / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    photosensitivity / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    arthralgia / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    vertigo / Early / Incidence not known
    tinnitus / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Contraindicated) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as Class IA antiarrhythmics.
    Acebutolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like acebutololl. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with quinidine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinidine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinidine is a strong inhibitor of CYP2D6.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Acetaminophen; Diphenhydramine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Acetaminophen; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Acetaminophen; Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like quinidine.
    Acetazolamide: (Major) Acetazolamide can decrease excretion of quinidine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of quinidine can be prolonged or enhanced.
    Aclidinium; Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as quinidine, may decrease adefovir elimination by competing for common renal tubular transport systems, therefore increasing serum concentrations of either adefovir and/or these coadministered drugs.
    Afatinib: (Moderate) If the concomitant use of quinidine and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of quinidine. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
    Albuterol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aldesleukin, IL-2: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with CYP3A4 inhibitors such as aldesleukin, IL-2 may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
    Alfuzosin: (Major) Alfuzosin should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
    Aliskiren; Amlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Alkalinizing Agents: (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
    Alvimopan: (Moderate) Alvimopan is a substrate of P-glycoprotein (P-gp). Although the concomitant use of mild to moderate inhibitors of P-gp did not influence the pharmacokinetics of alvimopan, the concomitant use of strong P-gp inhibitors, such as quinidine, has not been studied. Coadministration of quinidine and alvimopan may result in elevated concentrations of alvimopan. If these drugs are coadministered, patients should be monitored for increased toxicity as well as increased therapeutic effect of alvimopan.
    Amantadine: (Minor) Concomitant administration of quinidine with amantadine has been shown to decrease the renal clearance of amantadine. An in vivo study demonstrated that quinidine, a known organic cation transporter inhibitor, reduced amantadine clearance by approximately 33% in humans. The proposed mechanism is inhibition of the renal tubular secretion of amantadine, but the mechanism appears to be independent of OCT2 or other known renal drug transporters. The clinical significance is not known. Monitor for possible side effects of amantadine, including dizziness, confusion, nausea/vomiting, xerostomia, and anticholinergic effects.
    Ambenonium Chloride: (Moderate) The anticholinergic properties of certain antiarrhythmic treatments may lessen the effectiveness of cholinomimetic agent treatment, such as therapy with ambenonium. Quinidine has some anticholinergic properties and should be used cautiously in patients with myasthenia gravis.
    Amiloride: (Contraindicated) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
    Amiloride; Hydrochlorothiazide, HCTZ: (Contraindicated) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
    Amiodarone: (Major) Amiodarone coadministration increases quinidine concentrations by about 33% after 2 days, by decreasing its renal clearance or by inhibiting its hepatic metabolism. Quinidine may also be displaced from tissue and protein binding sites. Prolongation of the QT interval is well documented with quinidine, and the addition of amiodarone may increase this effect, placing the patient at an increased risk for the development of torsade de pointes. Careful clinical observation of the patient as well as close monitoring of the ECG and serum quinidine concentrations are essential with adjustment of the quinidine dosing regimen performed as necessary to avoid enhanced toxicity or pharmacodynamic effects. An empiric reduction of the quinidine dose by 33-50% is suggested within 2 days following initiation of amiodarone therapy, with consideration given to immediately discontinuing of quinidine once amiodarone therapy is begun. Combination antiarrhythmic therapy is reserved for patients with refractory life-threatening arrhythmias. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Amisulpride causes dose- and concentration- dependent QT prolongation.
    Amitriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Amlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Atorvastatin: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Benazepril: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Celecoxib: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Olmesartan: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Valsartan: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Amobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Amoxapine: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as quinidine. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased. Anti-arrhythmics that are less potent inhibitors of CYP2D6, such as propafenone, may similarly interact with amoxapine. CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
    Amphetamines: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of quinidine, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
    Amprenavir: (Major) Amprenavir can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is responsible for the metabolism of quinidine. The concurrent use of quinidine and amprenavir should be avoided or approached with great caution due to the potential for serious toxicity. Quinidine doses may require adjustment if amprenavir is added or discontinued during quinidine therapy.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include quinidine.
    Angiotensin II receptor antagonists: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Angiotensin-converting enzyme inhibitors: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Antacids: (Major) Alkalinizing agents such as antacids can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Apalutamide: (Moderate) Closely monitor quinidine concentrations if apalutamide is added to existing quinidine therapy. No special precautions appear necessary if apalutamide is started several weeks before quinidine, but quinidine doses may require adjustment if apalutamide is added or discontinued during quinidine therapy. Quinidine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the half-life and corresponding AUC of quinidine by 50% to 60%.
    Apomorphine: (Major) Use apomorphine and quinidine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Quinidine administration is associated with QT prolongation and torsades de pointes.
    Aprepitant, Fosaprepitant: (Major) Use caution if quinidine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in quinidine-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. Quinidine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of quinidine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Arformoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aripiprazole: (Contraindicated) Avoid use of aripiprazole with quinidine unless the benefit outweighs the risk. Quinidine is generally contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as aripiprazole, as the effects on the QT interval may be increased. Manufacturer recommendations for this combination have varied. Do not use the combination product of dextromethorphan; quinidine with aripiprazole. The manufacturers of aripiprazole products do not contraindicate use of quinidine, but recommend dosage adjustments of aripiprazole when used with potent CYP2D6 inhibitors, such as quinidine. For example, the oral aripiprazole dose should be reduced by 50%. Injectable forms of aripiprazole require dose adjustment when the potent CYP2D6 inhibitor will be used for more than 14 days. See the manufacturer prescribing information for detailed recommendations. Both aripiprazole and quinidine are associated with QT prolongation. Increased aripiprazole exposure is likely when a potent CYP2D6 inhibitor like quinidine is used concurrently. In one evaluation, concurrent use of quinidine and oral aripiprazole resulted in an increase in the AUC of aripiprazole of 112% and a decrease in the AUC of its active metabolite by 35%.
    Arsenic Trioxide: (Major) If possible, quinidine should be discontinued prior to initiating arsenic trioxide therapy. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
    Articaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
    Asenapine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with quinidine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinidine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinidine is a strong inhibitor of CYP2D6.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Aspirin, ASA; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Atazanavir: (Major) Caution is advised when administering quinidine with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of quinidine is contraindicated. Use of all 3 drugs together may significantly increase quinidine concentrations and increase the risk for QT prolongation and serious or life-threatening cardiac arrhythmias. Atazanavir and ritonavir are CYP3A4 inhibitors; quinidine is metabolized by this enzyme.
    Atazanavir; Cobicistat: (Major) Caution is advised when administering quinidine with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of quinidine is contraindicated. Use of all 3 drugs together may significantly increase quinidine concentrations and increase the risk for QT prolongation and serious or life-threatening cardiac arrhythmias. Atazanavir and ritonavir are CYP3A4 inhibitors; quinidine is metabolized by this enzyme. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Atenolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like atenolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
    Atenolol; Chlorthalidone: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like atenolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
    Atomoxetine: (Major) If possible, quinidine should be avoided in patients receiving atomoxetine. Coadministration of quinidine with atomoxetine may result in additive QT prolongation and increased exposure to atomoxetine. When administered as quinidine; dextromethorphan, coadministration with atomoxetine is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Atomoxetine is a CYP2D6 substrate. In children and adolescents up to 70 kg receiving quinidine, atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving quinidine, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Atropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Difenoxin: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Atropine; Edrophonium: (Major) Disopyramide possesses anticholinergic properties. It is unclear if disopyramide can interfere with the cholinomimetic activity of edrophonium. Procainamide and quinidine also have anticholinergic properties, albeit somewhat less than disopyramide. Edrophonium may not terminate paroxysmal supraventricular tachycardias in patients receiving quinidine, disopyramide or procainamide, although data are limited. These antiarrhythmics should be used cautiously in patients with myasthenia gravis. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Azithromycin: (Major) Avoid coadministration of azithromycin with quinidine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Quinidine administration is associated with QT prolongation and TdP.
    Barbiturates: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with quinidine or quinidine-containing products, such as dextromethorphan; quinidine. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Bendroflumethiazide; Nadolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like nadolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Benztropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Bepridil: (Contraindicated) Bepridil is contraindicated for use with drugs that prolong the QT interval, including class 1A antiarrhythmic agents, due to the risk of torsade de pointes (TdP). Bepridil has Class I antiarrhythmic properties and is associated with a well-established risk of QT prolongation and TdP. Patients receiving other drugs which have the potential for QT prolongation, such as class 1A antiarrhythmics, have an increased risk of developing proarrhythmias during bepridil therapy.
    Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking quinidine. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Additionally, monitor ECG and for quinidine-related adverse reactions as concurrent use may result in increased plasma concentrations of quinidine. Berotralstat is a P-gp substrate and moderate CYP3A4 inhibitor; quinidine is a CYP3A4 substrate and P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
    Betaxolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like betaxolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Ophthalmic betaxolol is not as likely to interact; however, bradycardia and heart block have been reported, and additive effects on conduction may be considered.
    Bethanechol: (Moderate) Drugs that possess antimuscarinic properties, such as quinidine, are pharmacologic opposites of bethanechol. These agents should not be used with bethanechol except when the specific intent is to counteract excessive actions of one or the other.
    Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving quinidine. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving quinidine. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; quinidine inhibits P-gp.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bisoprolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as quinidine. The dose of the concomitant drug may need to be adjusted.
    Boceprevir: (Major) Close clinical monitoring is advised when administering quinidine with boceprevir due to an increased potential for serious and/or life-threatening quinidine-related adverse events. If quinidine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and boceprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Additionally, both quinidine and boceprevir are substrates and inhibitors of P-glycoprotein (PGP) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated.
    Bosentan: (Moderate) Bosentan is an inducer of cytochrome P450 enzymes, specifically the CYP2C9 and CYP3A4 isoenzymes, and may decrease concentrations of drugs metabolized by these enzymes, including quinidine.
    Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving a strong CYP2D6 inhibitor and one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Quinidine is a strong inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. It should be noted that no dosage adjustment is needed in patients taking a strong CYP2D6 inhibitor who are receiving brexpiprazole as adjunct treatment for major depressive disorder because CYP2D6 considerations are already factored into general dosing recommendations.
    Brigatinib: (Moderate) Monitor for an increase in quinine-related adverse reactions if coadministration with brigatinib is necessary. Quinidine is a substrate of P-glycoprotein (P-gp). Brigatinib inhibits P-gp in vitro and may have the potential to increase concentrations of P-gp substrates.
    Brimonidine; Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Budesonide; Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Bupivacaine; Lidocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
    Buprenorphine: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Butabarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Butalbital; Acetaminophen: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Butalbital; Acetaminophen; Caffeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Cabotegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Cabozantinib: (Minor) Monitor for an increase in quinidine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of quinidine may be necessary. Quinidine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
    Calcium Carbonate: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Calcium Carbonate; Magnesium Hydroxide: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Calcium Carbonate; Risedronate: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Calcium Carbonate; Simethicone: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Canakinumab: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with canakinumab is necessary. Inhibition of IL-1 signaling by canakinumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when canakinumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping canakinumab. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug.
    Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Quinidine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Carbamazepine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Quinidine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely if quinidine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Cardiac glycosides: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a substrate for P-glycoprotein (P-gp). Quinidine inhibits P-gp, an energy-dependent cellular drug efflux pump. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
    Carteolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like carteololl. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure, Reduce the beta-blocker dosage if necessary. Carteolol is not as likely to interact as it is a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA); however, additive effects on conduction may be considered, even with ophthalmic use.
    Carvedilol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with carvedilol, a beta-blocker. Altered concentrations of quinidine and/or carvedilol may occur during coadministration. Quinidine is a CYP2D6 inhibitor and P-glycoprotein (P-gp) inhibitor and substrate. Carvedilol is a P-gp inhibitor and substrate and a substrate of CYP2D6. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Central-acting adrenergic agents: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Ceritinib: (Major) Avoid coadministration of ceritinib with quinidine if possible due to the risk of QT prolongation; plasma concentrations of quinidine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Quinidine is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
    Cevimeline: (Moderate) Cevimeline is metabolized by cytochrome P450 3A4 and CYP2D6. Concurrent administration of inhibitors of these enzymes, such as quinidine, may lead to increased cevimeline plasma concentrations.
    Chlordiazepoxide; Amitriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Chlordiazepoxide; Clidinium: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics. Anticholinergic agents administered concurrently with quinidine may produce additive antivagal effects on AV nodal conduction.
    Chloroquine: (Major) Avoid coadministration of chloroquine with quinidine due to the increased risk of QT prolongation or other drug toxicities. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Quinidine administration is also associated with QT prolongation and TdP.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with quinidine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinidine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinidine is a strong inhibitor of CYP2D6.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with quinidine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinidine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinidine is a strong inhibitor of CYP2D6.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Chlorpromazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include chlorpromazine.
    Cimetidine: (Major) Quinidine concentrations should be monitored closely after cimetidine is added; choose an alternate acid-reducing therapy if possible. Quinidine is eliminated primarily by the CYP3A4 isoenzyme. Cimetidine can inhibit quinidine metabolism and produce quinidine toxicity.
    Ciprofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering quinidine with ciprofloxacin. Quinidine is associated with QT prolongation and TdP. The manufacturer of dextromethorphan; quinidine recommends an ECG in patients taking it in combination with other drugs known to prolong the QTc, such as ciprofloxacin.
    Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Administration of Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) is associated with QT prolongation and TdP. Because of the potential for TdP, concurrent use of Class IA antiarrhythmics and cisapride is contraindicated.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Citalopram: (Major) Because citalopram and quinidine are associated with QT prolongation, these combinations should be used cautiously and with close monitoring. The manufacturers of quinidine and citalopram recommend an ECG in patients taking either of these drugs in combination with other drugs known to cause QT prolongation.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
    Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and quinidine, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients receiving clofazimine in combination with QT prolonging medications.
    Clomipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Clozapine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include clozapine.
    Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Cobimetinib: (Minor) If concurrent use of cobimetinib and quinidine is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and quinidine is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
    Codeine: (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Codeine; Phenylephrine; Promethazine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Codeine; Promethazine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
    Colchicine: (Major) Coadministration of colchicine and quinidine should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and quinidine is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of antiarrhythmics if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
    Conivaptan: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with conivaptan is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
    Crizotinib: (Major) Avoid coadministration of crizotinib with quinidine due to the risk of QT prolongation; exposure to quinidine may also increase. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Quinidine administration is also associated with QT prolongation and torsade de pointes (TdP).
    Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with quinidine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like quinidine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with quinidine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of quinidine 200 mg every 2 hours up to a total dose of 1000 mg and dabigatran administered over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing, resulted in an increase in dabigatran AUC and Cmax of 53% and 56%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
    Daclatasvir: (Major) Systemic exposure of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of quinidine; monitor patients for potential adverse effects.
    Dalfopristin; Quinupristin: (Moderate) Coadministration of quinidine with dalfopristin; quinupristin may result in elevated quinidine plasma concentrations. If these drugs are used together, closely monitor for signs of quinidine-related adverse events. Quinidine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
    Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates including quinidine.
    Darifenacin: (Moderate) Clinicians should monitor patients for increased anticholinergic effects when CYP2D6 inhibitors, such as quinidine, are coadministered with darifenacin; the dosage of darifenacin should be adjusted, if necessary.
    Darunavir: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended.
    Darunavir; Cobicistat: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) The manufacturer of ombitasvir; paritaprevir; ritonavir recommends caution and therapeutic drug monitoring (when available) if administered concurrently with quinidine. However, since one of the components of the 3-drug combination is ritonavir, use of these drugs together is contraindicated. Both ritonavir and quinidine are associated with QT prolongation; concomitant use increases the risk for developing Torsade de Pointes (TdP). In addition, ritonavir is a potent CYP3A4 inhibitor, an enzyme partially responsible for the metabolism of quinidine. If administered together, serum concentration of quinidine may increase. (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use.
    Dasatinib: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and quinidine is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Quinidine administration is associated with QT prolongation and TdP.
    Degarelix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as class IA antiarrhythmics. Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
    Delavirdine: (Major) Delavirdine is a potent inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. Increased quinidine concentrations may be associated with severe cardiovascular adverse reactions. Quinidine doses may require adjustment if delavirdine is added or discontinued during quinidine therapy.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Desipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine and dextromethorphan; quinidine are contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Deutetrabenazine: (Contraindicated) Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Quinidine is a strong CYP2D6 inhibitor, and the metabolites of deutetrabenazine, alpha- and beta-HTBZ, are CYP2D6 substrates. The systemic exposure of alpha- and beta-HTBZ may be increased resulting in an increase in deutetrabenazine-related adverse reactions.
    Dexamethasone: (Moderate) Quinidine is a substrate of the CYP3A4 isoenzyme. Inducers of CYP3A4 such as dexamethasone may increase hepatic elimination of quinidine with the potential for reduced efficacy of quinidine.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diazoxide: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as quinidine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Digitoxin: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a substrate for P-glycoprotein (P-gp). Quinidine inhibits P-gp, an energy-dependent cellular drug efflux pump. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
    Digoxin: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a substrate for P-glycoprotein (P-gp). Quinidine inhibits P-gp, an energy-dependent cellular drug efflux pump. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with quinidine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinidine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinidine is a strong inhibitor of CYP2D6.
    Diltiazem: (Major) Diltiazem significantly decreases the clearance and increases the half-life of quinidine. Quinidine does not alter the kinetics of diltiazem. Concurrent use of diltiazem and quinidine in some patients may cause additive hypotension. Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction. Medications that possess negative inotropic effects and/or slow AV conduction, such as quinidine, should be administered with caution to patients receiving concomitant therapy with diltiazem due to the risk of additive effects. Diltiazem may increase serum quinidine concentrations (AUC increases by 51%) by reducing the oral clearance of quinidine by 33%. During diltiazem coadministration, monitor quinidine serum concentrations and therapeutic response; adjust quinidine dosage if needed.
    Diphenhydramine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme. (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Diphenhydramine; Ibuprofen: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diphenhydramine; Naproxen: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
    Diphenoxylate; Atropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Disopyramide: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided.
    Dofetilide: (Contraindicated) Coadministration of dofetilide and quinidine is contraindicated as concurrent use may increase the risk QT prolongation and torsades de pointes (TdP). Class I antiarrhythmic agents, such as quinidine, should be withheld for at least 3 half-lives prior to initiating dofetilide therapy. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinidine administration is associated with QT prolongation and TdP.
    Dolasetron: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include dolasetron.
    Dolutegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Donepezil: (Contraindicated) Quinidine and combination products containing quinidine (e.g., dextromethorphan; quinidine) are contraindicated for use with medications that both prolong the QT interval and are CYP2D6 substrates, such as donepezil. Quinidine has QT prolonging actions and has been shown in vitro to inhibit the metabolism of donepezil by CYP2D6 inhibition; therefore, the effects on the QT interval may be increased during concurrent use of these agents. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and the drug is considered a drug with a known risk of TdP.
    Donepezil; Memantine: (Contraindicated) Quinidine and combination products containing quinidine (e.g., dextromethorphan; quinidine) are contraindicated for use with medications that both prolong the QT interval and are CYP2D6 substrates, such as donepezil. Quinidine has QT prolonging actions and has been shown in vitro to inhibit the metabolism of donepezil by CYP2D6 inhibition; therefore, the effects on the QT interval may be increased during concurrent use of these agents. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and the drug is considered a drug with a known risk of TdP. (Major) Cationic drugs that are eliminated by renal tubular secretion, such as quinidine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or quinidine is recommended to assess for needed dosage adjustments. In selected individuals, quinidine serum concentration monitoring may be appropriate.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Dorzolamide; Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Doxazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Doxepin: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Doxorubicin: (Major) Avoid coadministration of quinidine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Quinidine is a potent CYP2D6 inhibitor and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP2D6 and P-gp. Concurrent use of CYP2D6 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
    Dronedarone: (Contraindicated) Concurrent use of dronedarone and quinidine is contraindicated. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
    Duloxetine: (Moderate) Monitor for increased duloxetine-related adverse effects if coadministered with quinidine. Concurrent use may result in increased duloxetine exposure resulting in excessive serotonin activity. Quinidine is a strong CYP2D6 inhibitor; duloxetine is a CYP2D6 substrate. Coadministration with another strong CYP2D6 inhibitor increased the duloxetine AUC by about 60%.
    Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Edoxaban: (Major) Reduce the dose of edoxaban to 30 mg/day PO in patients being treated for deep venous thrombosis (DVT) or pulmonary embolism and receiving concomitant therapy with quinidine. No dosage adjustment is required in patients with atrial fibrillation. Edoxaban is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of quinidine; monitor for increased adverse effects of edoxaban. Similar interactions may occur with dextromethorphan; quinidine.
    Edrophonium: (Major) Disopyramide possesses anticholinergic properties. It is unclear if disopyramide can interfere with the cholinomimetic activity of edrophonium. Procainamide and quinidine also have anticholinergic properties, albeit somewhat less than disopyramide. Edrophonium may not terminate paroxysmal supraventricular tachycardias in patients receiving quinidine, disopyramide or procainamide, although data are limited. These antiarrhythmics should be used cautiously in patients with myasthenia gravis.
    Efavirenz: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Elbasvir; Grazoprevir: (Moderate) Administering quinidine with elbasvir; grazoprevir may result in elevated quinidine plasma concentrations. Quinidine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: (Contraindicated) Coadministration of quinidine (including dextromethorphan; quinidine) and eliglustat is contraindicated. Quinidine is a P-glycoprotein (P-gp) substrate and strong CYP2D6 inhibitor associated with a well-established risk of QT prolongation and torsades de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6. Eliglustat is a CYP2D6 substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinidine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emapalumab: (Moderate) Monitor for decreased efficacy of quinidine and adjust the dose as needed during coadministration with emapalumab. Quinidine is a CYP3A4 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Enalapril; Felodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Encorafenib: (Major) Avoid coadministration of encorafenib and quinidine due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
    Enflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Entecavir: (Major) Both entecavir and quinidine are secreted by active tubular secretion. In theory, coadministration of entecavir with quinidine may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Entrectinib: (Major) Avoid coadministration of entrectinib with quinidine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
    Enzalutamide: (Moderate) Closely monitor quinidine concentrations if enzalutamide is added to existing quinidine therapy. No special precautions appear necessary if enzalutamide is started several weeks before quinidine, but quinidine doses may require adjustment if enzalutamide is added or discontinued during quinidine therapy. Quinidine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the half-life and corresponding AUC of quinidine by 50% to 60%.
    Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and quinidine; quinidine antagonizes the pressor effect of ephedrine.
    Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and quinidine; quinidine antagonizes the pressor effect of ephedrine.
    Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
    Eplerenone: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Epoprostenol: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Eribulin: (Major) Eribulin has been associated with QT prolongation. Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with quinidine. Concurrent use of erythromycin with procainamide should be avoided. In addition, erythromycin may theoretically increase plasma concentrations of quinidine via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with quinidine. Concurrent use of erythromycin with procainamide should be avoided. In addition, erythromycin may theoretically increase plasma concentrations of quinidine via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as quinidine, should be done with caution and close monitoring.
    Esmolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like esmolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Etravirine: (Major) Etravirine is an inducer of CYP3A4; quinidine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor quinidine concentrations when possible.
    Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with quinidine is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
    Ezogabine: (Major) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with ezogabine include class IA antiarrhythmics (disopyramide, procainamide, quinidine).
    Felodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Fenoldopam: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Fentanyl: (Moderate) Quinidine increases fentanyl serum concentrations by inhibiting intestinal P-glycoprotein (P-gp). Receipt of fentanyl 2.5 mcg/kg orally 1 hour after a single dose of immediate-release quinidine 600 mg led to a fentanyl mean area under the plasma concentration-time curve (AUC) of 2.34 +/- 0.63 ng x hour/mL as compared with 0.9 +/- 0.47 ng x hour/mL with placebo. Elevated fentanyl serum concentrations can result in an increase in the pharmacologic effects of fentanyl, such as CNS or respiratory depression.
    Fingolimod: (Contraindicated) Concurrent use of fingolimod with class Ia antiarrhythmics such as disopyramide, quinidine, and procainamide is contraindicated. Fingolimod initiation results in decreased heart rate, and class IA antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.
    Flavoxate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Flecainide: (Contraindicated) Class IC antiarrhythmic agents, such as flecainide, have proarrhythmic properties, and may have additive electrophysiologic effects with other Class I agents such as quinidine. In addition, quinidine should be considered contraindicated with flecainide. Quinidine and flecainide are associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; therefore, the effects on the QT interval may be increased during concurrent use of quinidine with flecainide or propafenone.
    Fluconazole: (Contraindicated) The concomitant administration of fluconazole and quinidine is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as quinidine. Coadministration of fluconazole with quinidine may result in elevated plasma concentrations of quinidine, causing an increased risk for adverse events, such as QT prolongation.
    Fluoxetine: (Contraindicated) Concurrent use of either quinidine or dextromethorphan; quinidine and fluoxetine is considered a contraindication. Quinidine and dextromethorphan; quinidine are contraindicated for use in patients taking drugs that prolong the QT interval and are metabolized by CYP2D6. Fluoxetine is a primary substrate of CYP2D6, and is associated with a risk of QT prolongation and torsade de pointes (TdP).
    Fluphenazine: (Minor) Fluphenazine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Fluticasone; Salmeterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Vilanterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation, torsade de pointes (TdP), or elevated plasma concentrations of either quinidine or fluvoxamine during coadministration. Quinidine administration is associated with QT prolongation and TdP. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. In addition, fluvoxamine is a moderate CYP3A4 inhibitor and the metabolism of CYP3A4 substrates such as quinidine may be reduced. In a small open-label study (n = 6), fluvoxamine 100 mg/day decreased the total oral clearance of quinidine by 29%. Conversely, quinidine is a CYP2D6 inhibitor and CYP2D6 is partially responsible for fluvoxamine metabolism, which may lead to elevated fluvoxamine concentrations.
    Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Formoterol; Mometasone: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fosamprenavir: (Major) Fosamprenavir can inhibit CYP3A4, an isoenzyme that is responsible for the metabolism of quinidine. Concurrent use should be avoided or approached with great caution due to the potential for serious toxicity. Quinidine doses may require adjustment if fosamprenavir is added or discontinued during quinidine therapy.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as quinidine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Quinidine administration is also associated with QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fostamatinib: (Moderate) Monitor for quinidine toxicities that may require quinidine dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a CYP3A4 or P-gp substrate may increase the concentration of the CYP3A4 or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a CYP3A4 inhibitor; quinidine is a CYP3A4 and P-gp substrate. Coadministration of fostamatinib with a sensitive CYP3A4 substrate increased the substrate AUC by 64% and Cmax by 113%. Coadministration of fostamatinib with another P-gp substrate increased the P-gp substrate AUC by 37% and Cmax by 70%.
    Fostemsavir: (Major) Avoid coadministration of quinidine with fostemsavir as concomitant use may increase the risk of QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with quinidine is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and quinidine is strong CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
    Gemifloxacin: (Major) According to the manufacturer, gemifloxacin should be avoided in patients receiving Class IA antiarrhythmics (such as disopyramide, quinidine and procainamide). Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and quinidine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Quinidine administration is also associated with QT prolongation and TdP.
    Gilteritinib: (Major) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and quinidine is necessary. Gilteritinib has been associated with QT prolongation. Quinidine is associated with QT prolongation and torsade de pointes (TdP).
    Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Glasdegib: (Major) Avoid coadministration of glasdegib with quinidine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and quinidine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and quinidine are substrates and inhibitors of P-glycoprotein (P-gp).
    Glycerol Phenylbutyrate: (Moderate) Concomitant use of glycerol phenylbutyrate and quinidine may result in decreased exposure of quinidine. Quinidine is a CYP3A substrate; glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of quinidine during coadministration.
    Glycopyrrolate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Glycopyrrolate; Formoterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Granisetron: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
    Grapefruit juice: (Major) Grapefruit juice contains an unknown compound that inhibits cytochrome P-450 3A4 isozymes in the gut wall. Coadministration of quinidine with grapefruit juice to healthy volunteers delayed quinidine absorption and inhibited the conversion of quinidine to the major metabolite. Although the clinical significance of the interaction is unknown, concomitant administration with grapefruit juice should be avoided.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Halofantrine: (Contraindicated) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes. Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation; these drugs include class IA antiarrhythmics.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Haloperidol: (Contraindicated) Quinidine should be considered contraindicated with haloperidol. QT prolongation and torsade de pointes (TdP) have been observed during both haloperidol and quinidine treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval; however, quinidine is contraindicated for use with drugs that are CYP2D6 substrates that prolong the QT interval. Pretreatment with quinidine caused peak haloperidol serum concentrations and haloperidol AUC to increase.
    Halothane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Hydantoins: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4, such as fosphenytoin or phenytoin, may increase hepatic elimination of quinidine and decrease its serum concentrations. Quinidine concentrations should be monitored closely after the anticonvulsant is added to the treatment regimen. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Hydralazine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
    Hydroxychloroquine: (Major) Avoid coadministration of quinidine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
    Hydroxyzine: (Major) Caution is recommended if hydroxyzine is administered with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Quinidine administration is associated with QT prolongation and TdP.
    Hyoscyamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Ibuprofen; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Ibutilide: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
    Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinidine, a CYP3A substrate, as quinidine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include iloperidone.
    Imatinib: (Major) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may inhibit quinidine metabolism leading to increased concentrations and risk of adverse reactions.
    Imipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Indacaterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Indacaterol; Glycopyrrolate: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Indinavir: (Moderate) Concurrent administration of indinavir and quinidine caused indinavir AUC to increase by about 10%. There were no effects on quinidine pharmacokinetics.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Quinidine administration is also associated with QT prolongation and TdP.
    Ipratropium; Albuterol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Irinotecan Liposomal: (Moderate) Monitor for an increase in irinotecan-related adverse reactions if coadministration with quinidine is necessary. Irinotecan is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Concomitant use may increase irinotecan exposure.
    Irinotecan: (Moderate) Monitor for an increase in irinotecan-related adverse reactions if coadministration with quinidine is necessary. Irinotecan is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Concomitant use may increase irinotecan exposure.
    Isavuconazonium: (Moderate) Caution and therapeutic drug concentration monitoring, if available, are recommended during coadministration of quinidine with isavuconazonium. Quinidine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Concurrent use may result in elevated quinidine plasma concentrations.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Isoniazid, INH; Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Isradipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Istradefylline: (Moderate) Monitor for quinidine-related adverse reactions if coadministration of istradefylline 40 mg daily is necessary. Quinidine is a CYP3A4 substrate; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
    Itraconazole: (Contraindicated) Quinidine is contraindicated for use during and for 2 weeks after itraconazole therapy. Serious cardiovascular events including EKG changes (i.e., QT prolongation) and cardiac arrhythmias, including ventricular arrhythmias and torsade de pointes, cardiac arrest, and/or sudden death have occurred when these drugs were administered together. Reports have documented cases in which substantial elevations in serum quinidine concentrations occurred after the addition of itraconazole. Quinidine is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. Transient or permanent hearing loss has also been reported in elderly patients receiving quinidine in combination with itraconazole.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with quinidine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
    Ixabepilone: (Minor) Quinidine is an inhibitor of and substrate for P-glycoprotein (Pgp). Ixabepilone is a mild inhibitor of and substrate for Pgp. Concomitant use of these agents may cause an increase in ixabepilone concentrations and/or an increase in quinidine concentrations. Caution is recommended if ixabepilone is coadministered with a Pgp inhibitor.
    Ketoconazole: (Contraindicated) Ketoconazole inhibits the hepatic CYP3A4 isoenzyme; quinidine is metabolized by this isoenzyme. Coadministration results in increased quinidine serum concentrations, with potential to result in proarrhythmias. A single case report has documented substantial elevations in serum quinidine concentrations after the addition of ketoconazole. The patient was receiving other drugs concomitantly and it is unclear if drug-induced arrhythmias occurred. Until more data are available, ketoconazole should be considered contraindicated in patients receiving quinidine.
    Labetalol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like labetalol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Lamotrigine: (Moderate) Obtain an ECG before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
    Lanreotide: (Major) Monitor ECGs for QT prolongation and watch for an increase in quinidine-related adverse reactions if coadministration with lanreotide is necessary. Quinidine is a CYP3A4 substrate with a narrow therapeutic range. Limited published data available indicate that somatostatin analogs may decrease the metabolic clearance of CYP3A4 substrates, which may be due to the suppression of growth hormone; it cannot be excluded that lanreotide has this effect.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
    Lanthanum Carbonate: (Major) The manufacturer recommends that oral compounds known to interact with antacids should not be taken within 2 hours of dosing with lanthanum carbonate, including quinidine. If these agents are used concomitantly, space the dosing intervals appropriately; monitoring of serum concentrations and clinical condition may be prudent.
    Lapatinib: (Major) Monitor for an increase in treatment-related adverse reactions if coadministration of lapatinib with quinidine is necessary; also monitor ECGs for QT prolongation and monitor electrolytes. Correct any electrolyte abnormalities prior to treatment. Lapatinib is a P-glycoprotein (P-gp) substrate/inhibitor that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Quinidine is also a P-gp substrate/inhibitor that is also associated with QT prolongation and TdP. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors.
    Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of quinidine and ledipasvir; sofosbuvir. Both ledipasvir and quinidine are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
    Lefamulin: (Major) Avoid coadministration of lefamulin with quinidine as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. If coadministration cannot be avoided, monitor ECG during treatment; additionally, monitor for lefamulin-related adverse effects if oral lefamulin is administered. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with quinidine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Quinidine administration is also associated with QT prolongation as well as torsade de pointes (TdP).
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) Closely monitor for quinidine-related adverse events including arrhythmias, if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. A clinically relevant increase in the plasma concentration of quinidine, a CYP3A4 substrate, may occur during concurrent administration with letermovir, a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Levalbuterol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Levamlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Levobunolol: (Moderate) The concomitant use of ophthalmic beta-blockers, like levobunolol, in patients receiving antiarrhythmics which slow AV conduction (quinidine) may result in additive negative dromotropic effects, especially in patients with pre-existing cardiac disease or left ventricular dysfunction. Since ophthalmic levobunolol may be systemically absorbed, there is potential for enhanced hypotensive effects when it is given with beta-blockers.
    Levofloxacin: (Major) Levofloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Levomethadyl: (Contraindicated) Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval, such as Class IA antiarrhythmics.
    Lidocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
    Lidocaine; Prilocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
    Lithium: (Major) Lithium should be used cautiously and with close monitoring with quinidine. Lithium has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP).
    Lofexidine: (Contraindicated) Concomitant use of lofexidine and quinidine is contraindicated due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine is a CYP2D6 substrate that prolongs the QT interval. In addition, there are postmarketing reports of TdP. Quinidine is a CYP2D6 inhibitor and is associated with QT prolongation and TdP.
    Lonafarnib: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with lonafarnib is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
    Long-acting beta-agonists: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Loop diuretics: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Loperamide: (Major) Concurrent administration of loperamide and quinidine may increase the risk for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS events. Quinidine and high doses of loperamide are associated with QT prolongation and torsades de pointes (TdP). Additionally, loperamide is a substrate for CYP2D6 and the drug transporter P-glycoprotein (P-gp); quinidine is an inhibitor of both CYP2D6 and P-gp. Although the exact mechanism has not been determined, it is postulated that the P-glycoprotein (P-gp) pump acts to limit the oral absorption of drugs from the gastrointestinal tract as well as limit the concentration of drug in the central nervous system (CNS). In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and quinidine or ritonavir (600 mg), known P-gp inhibitors, lead to a 2 to 3 fold increase in loperamide plasma concentrations. Also, in the presence of a P-gp inhibitor, elevated CNS concentrations of loperamide lead to subsequent respiratory depression. The mechanism appears to be an effect on P-gp efflux transport across the blood-brain-barrier. Normally loperamide is efficiently removed from the CNS, however coadministration of a P-gp inhibitor hinders its transport out of the CNS. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered.
    Loperamide; Simethicone: (Major) Concurrent administration of loperamide and quinidine may increase the risk for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS events. Quinidine and high doses of loperamide are associated with QT prolongation and torsades de pointes (TdP). Additionally, loperamide is a substrate for CYP2D6 and the drug transporter P-glycoprotein (P-gp); quinidine is an inhibitor of both CYP2D6 and P-gp. Although the exact mechanism has not been determined, it is postulated that the P-glycoprotein (P-gp) pump acts to limit the oral absorption of drugs from the gastrointestinal tract as well as limit the concentration of drug in the central nervous system (CNS). In-vivo, single dose pharmacokinetic studies suggest that oral coadministration of loperamide (16 mg) and quinidine or ritonavir (600 mg), known P-gp inhibitors, lead to a 2 to 3 fold increase in loperamide plasma concentrations. Also, in the presence of a P-gp inhibitor, elevated CNS concentrations of loperamide lead to subsequent respiratory depression. The mechanism appears to be an effect on P-gp efflux transport across the blood-brain-barrier. Normally loperamide is efficiently removed from the CNS, however coadministration of a P-gp inhibitor hinders its transport out of the CNS. Monitor for depressed respiratory ventilation and adverse cardiac effects if these drugs are to be coadministered.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with quinidine due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may alter the therapeutic effects of quinidine. Use these agents together with caution; monitor quinidine concentrations and adjust the dosage as needed to attain antiarrhythmic efficacy endpoints. Quinidine is a substrate of CYP3A and the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of quinidine metabolism through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased antiarrhythmic efficacy or increased or prolonged therapeutic effects and adverse events.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as quinidine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
    Maprotiline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include maprotiline.
    Maraviroc: (Moderate) Use caution and careful monitoring with the coadministration of maraviroc and quinidine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); quinidine is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Mecamylamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Mefloquine: (Contraindicated) The use of mefloquine is contraindicated in patients receiving quinidine or quinidine containing drugs, including dextromethorphan; quinidine. Quinidine is a Class IA antiarrhythmic agent and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP); using these drugs together could increase the risk of TdP.
    Memantine: (Major) Cationic drugs that are eliminated by renal tubular secretion, such as quinidine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or quinidine is recommended to assess for needed dosage adjustments. In selected individuals, quinidine serum concentration monitoring may be appropriate.
    Mepenzolate: (Moderate) The reduction in GI motility produced by mepenzolate may increase the absorption of some drugs, including quinidine. Increased monitoring is advised in patients receiving this combination.
    Meperidine; Promethazine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Mephobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Mesoridazine: (Contraindicated) Mesoridazine has been associated with orthostatic hypotension and a risk of QT prolongation and/or torsades de pointes, particularly at higher doses and is generally contraindicated in combination with other agents that prolong the QT interval including class IA antiarrhythmics.
    Metaproterenol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Methadone: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include methadone.
    Methazolamide: (Major) Methazolamide can decrease the urinary excretion and enhance the clinical effects of quinidine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption into the systemic circulation.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
    Methohexital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Methscopolamine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Metoclopramide: (Major) Dose reductions of oral metoclopramide are recommended when administered in combination with quinidine due to likely increased metoclopramide exposure and an increased risk of extrapyramidal adverse reactions. In patients with diabetic gastroparesis, avoid coadministration of metoclopramide with quinidine. If coadministration cannot be avoided, the recommended dose of metoclopramide is 5 mg PO four times daily times daily. In patients with gastroesophageal reflux, the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily when coadministered with quinidine. Metoclopramide is a substrate of CYP2D6 and quinidine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased the metoclopramide Cmax and AUC by 40% and 90%, respectively.
    Metoprolol: (Major) Patients receiving combined therapy with quinidine and metoprolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used with metoprolol. Quinidine is also a known inhibitor of CYP2D6 and metoprolol is a CYP2D6 substrate. In healthy subjects with CYP2D6 extensive metabolizer (normal metabolizer) phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. This interaction may be more pronounced in poor CYP2D6 metabolizers. Patients should be monitored for excess beta-blockade.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Patients receiving combined therapy with quinidine and metoprolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used with metoprolol. Quinidine is also a known inhibitor of CYP2D6 and metoprolol is a CYP2D6 substrate. In healthy subjects with CYP2D6 extensive metabolizer (normal metabolizer) phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. This interaction may be more pronounced in poor CYP2D6 metabolizers. Patients should be monitored for excess beta-blockade.
    Metreleptin: (Moderate) Upon initiation or discontinuation of metreleptin in a patient receiving quinidine, drug concentration monitoring should be performed and the quinidine dosage adjusted as needed. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with a narrow therapeutic index, such as quinidine.
    Metronidazole: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Mexiletine: (Moderate) Quinidine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinidine with other CYP2D6 substrates, such as mexiletine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
    Midodrine: (Minor) Although the exact mechanism is uncertain, midodrine may be excreted by the same base-secreting pathway of the kidneys responsible for secretion of other basic drugs like quinidine. By this pathway, midodrine may potentially interact with quinidine; however, no drug interactions of this kind have been reported.
    Midostaurin: (Major) The concomitant use of midostaurin and quinidine may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Quinidine is a Class IA antiarrhythmic agent; it is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinidine should be discontinued if significant QT prolongation or TdP occur during therapy.
    Mifepristone: (Contraindicated) Use of quinidine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase quinidine concentrations and adverse effects, since quinidine is a CYP3A4 substrate with a narrow therapeutic index. Increased quinidine concentrations are likely to cause proarrythmia and ECG changes, as well as symptoms of cinchonism. Both quinidine and mifepristone have been associated with QT prolongation and a risk for torsade de pointes (TdP). Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Minoxidil: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and quinidine. Coadminister with caution. Quinidine administration is associated with QT prolongation and TdP. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mitotane: (Major) Use caution if mitotane and quinidine are used concomitantly, and monitor for decreased efficacy of quinidine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and quinidine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of quinidine. Quinidine concentrations should be monitored closely after mitotane is added to the treatment regimen.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Mobocertinib: (Major) Concomitant use of mobocertinib and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moricizine: (Contraindicated) The effects of concomitant administration of Class IC antiarrhythmic agents with other antiarrhythmics can be synergistic, additive, or antagonistic, and adverse cardiac effects can be additive. Based on Class IC drug pharmacology, moricizine may have additive sodium channel blockade effects with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Additive Class I electrophysiologic effects can increase the risk for proarrhythmias. Although moricizine primarily is associated with Class IB and IC actions, it also is associated with quinidine-like (i.e, Class IA) features.
    Morphine: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects.
    Morphine; Naltrexone: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects.
    Moxifloxacin: (Major) Moxifloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, quinidine, and procainamide). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Nadolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like nadolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Nebivolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with nebivolol, a beta-blocker. Quinidine is a known inhibitor of CYP2D6 and nebivolol is metabolized by CYP2D6. Quinidine could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Nebivolol; Valsartan: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with nebivolol, a beta-blocker. Quinidine is a known inhibitor of CYP2D6 and nebivolol is metabolized by CYP2D6. Quinidine could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Nefazodone: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with moderate CYP3A4 inhibitors, such as nefazodone, may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
    Nelfinavir: (Contraindicated) Coadministration of quinidine and nelfinavir is contraindicated. Nelfinavir inhibits the CYP3A4 metabolism of quinidine; concurrent use increases the potential for serious and/or life-threatening cardiac arrhythmias.
    Netupitant, Fosnetupitant; Palonosetron: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Nevirapine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as quinidine, may require dosage adjustments as the concentration may be decreased.
    Nicardipine: (Moderate) Quinidine concentrations decrease by 20 to 40% when nicardipine is added and rise after nicardipine is withdrawn. Although this appears to be an idiosyncratic reaction, quinidine doses may need to be adjusted when nicardipine is added or withdrawn. Careful monitoring of serum quinidine concentrations is prudent following the addition or discontinuation of nicardipine.
    Nifedipine: (Moderate) Nifedipine has been reported to rarely decrease quinidine serum concentrations. Quinidine concentrations may decrease by 20% to 40% when nifedipine is added, and potentially increase after nifedipine is withdrawn. There have also been reports of no significant change in quinidine concentrations or effect. In addition, both drugs can cause hypotension, and these effects can be additive. Careful monitoring of serum quinidine concentrations is prudent following the addition or discontinuation of nifedipine, with dose adjustment as clinically warranted. Monitor heart rate, blood pressure, and cardiac response.
    Nilotinib: (Major) Avoid coadministration of nilotinib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Nilotinib is a moderate CYP3A4 inhibitor. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Quinidine is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP).
    Nisoldipine: (Moderate) Quinidine may decrease the bioavailability of nisoldipine by 26% without affecting the peak concentration. Monitoring serum quinidine concentrations is prudent following the addition or discontinuation of nisoldipine.
    Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as quinidine.Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with quinidine.
    Nitroprusside: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Norfloxacin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with norfloxacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, torsade de pointes has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nortriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Octreotide: (Major) Limited data indicate that somatostatin analogs may inhibit the clearance of drugs metabolized by CYP isoenzymes; this may be due to the suppression of growth hormones. Coadminister octreotide cautiously with drugs that have a narrow therapeutic index and are metabolized by CYP3A4, such as quinidine, as octreotide may inhibit drug metabolism. In addition, until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval, such as quinidine. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) should be used cautiously and with close monitoring with ofloxacin. Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) are associated with QT prolongation and torsades de pointes (TdP). Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP).
    Olanzapine: (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together.
    Olanzapine; Fluoxetine: (Contraindicated) Concurrent use of either quinidine or dextromethorphan; quinidine and fluoxetine is considered a contraindication. Quinidine and dextromethorphan; quinidine are contraindicated for use in patients taking drugs that prolong the QT interval and are metabolized by CYP2D6. Fluoxetine is a primary substrate of CYP2D6, and is associated with a risk of QT prolongation and torsade de pointes (TdP). (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together.
    Olanzapine; Samidorphan: (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together.
    Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and quinidine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and quinidine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If quinidine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Olodaterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) The manufacturer of ombitasvir; paritaprevir; ritonavir recommends caution and therapeutic drug monitoring (when available) if administered concurrently with quinidine. However, since one of the components of the 3-drug combination is ritonavir, use of these drugs together is contraindicated. Both ritonavir and quinidine are associated with QT prolongation; concomitant use increases the risk for developing Torsade de Pointes (TdP). In addition, ritonavir is a potent CYP3A4 inhibitor, an enzyme partially responsible for the metabolism of quinidine. If administered together, serum concentration of quinidine may increase. (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Rifabutin is an inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinidine.
    Ondansetron: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include ondansetron.
    Oritavancin: (Moderate) Quinidine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of quinidine may be reduced if these drugs are administered concurrently. Quinidine concentrations should be monitored closely after oritavancin is added to the treatment regimen. No special precautions appear necessary if oritavancin is begun several weeks before quinidine is added but quinidine doses may require adjustment if oritavancin is added or discontinued during quinidine therapy.
    Osilodrostat: (Major) Use osilodrostat and quinidine together with caution and consider more frequent ECG monitoring due to the risk of additive QT prolongation. Osilodrostat is associated with dose-dependent QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP.
    Osimertinib: (Major) Avoid coadministration of quinidine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in quinidine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Quinidine administration is associated with both QT prolongation and TdP. Additionally, quinidine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of quinidine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Oxybutynin: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking quinidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinidine administration is associated with QT prolongation and TdP.
    Paliperidone: (Major) Coadministration of paliperidone and quinidine should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinidine, a CYP2D6 inhibitor, is associated with QT prolongation and torsades de pointes (TdP). According to the manufacturer of paliperidone, the drug should be avoided in combination with other agents also known to have this effect. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. While in vitro studies indicate that CYP2D6 is minimally involved in paliperidone metabolism, in vivo studies do not show decreased elimination by CYP2D6 and it contributes to only a small fraction of total body clearance of paliperidone. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Palonosetron: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Panobinostat: (Contraindicated) Because of the potential for torsade de pointes, avoid the use of quinidine or dextromethorphan; quinidine with panobinostat. Panobinostat is a CYP2D6 inhibitor and quinidine is a CYP2D6 substrate. When a single 60-mg dose of dextromethorphan was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
    Paroxetine: (Moderate) Quinidine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinidine with CYP2D6 substrates, including paroxetine.
    Pasireotide: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and quinidine (including dextromethorphan; quinidine have been reported to prolong the QT interval. If pazopanib and quinidine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (P-gp). Quinidine is a substrate for CYP3A4 and an inhibitor of P-gp. Concurrent administration of quinidine and pazopanib may result in increased pazopanib and/or quinidine concentrations. Use caution when concurrent administration is necessary.
    Penbutolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like penbutolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
    Pentamidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include systemic pentamidine.
    Pentobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Perindopril; Amlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Perphenazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include perphenazine.
    Perphenazine; Amitriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6. (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include perphenazine.
    Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with quinidine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Phenobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs. (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics. (Moderate) The reduction in GI motility produced by scopolamine may increase the absorption of some drugs, including quinidine, resulting in increased anticholinergic effects. Increased monitoring is advised in patients receiving this combination.
    Phenoxybenzamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Phentolamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP).
    Pimozide: (Contraindicated) Coadministration of pimozide and quinidine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide exposure may also be increased; elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. Quinidine is a strong CYP2D6 inhibitor that has been associated with QT prolongation and rare cases of TdP. Pimozide is a CYP2D6 substrate that is associated with a well-established risk of QT prolongation and TdP. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
    Pindolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
    Pirbuterol: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Pitolisant: (Major) Avoid coadministration of pitolisant and quinidine as concurrent use may increase the risk of QT prolongation. When administered as quinidine; dextromethorphan, coadministration with pitolisant is contraindicated. If concurrent use is unavoidable, initiate pitolisant at 8.9 mg once daily in patients taking quinidine; increase pitolisant after 7 days to a maximum dosage of 17.8 mg once daily. If quinidine is initiated in a patient on a stable dose of pitolisant, reduce the pitolisant dose by half. Pitolisant is a CYP2D6 substrate that prolongs the QT interval; quinidine is a strong CYP2D6 inhibitor that has been associated with QT prolongation and torsade de pointes. Coadministration of strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold.
    Polymyxins: (Moderate) Quinidine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking quinidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinidine administration is associated with QT prolongation and TdP.
    Posaconazole: (Contraindicated) The concurrent use of posaconazole and quinidine (or products containing quinidine such as dextromethorphan; quinidine) is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinidine. Further, both posaconazole and quinidine are inhibitors and substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of either drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinidine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quinidine.
    Potassium Bicarbonate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Potassium Chloride: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Potassium Citrate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Potassium Citrate; Citric Acid: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
    Prazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Prilocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include quinidine.
    Primidone: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Probenecid; Colchicine: (Major) Coadministration of colchicine and quinidine should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and quinidine is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Procainamide: (Major) According to the manufacturer of procainamide, use with other Class 1A agents, such as quinidine, is contraindicated; however, the manufacturer also states such use may be reserved for patients with serious arrhythmias unresponsive to a single drug if under close observation. Quinidine should only be used with extreme caution with procainamide, due to the potential for QT prolongation and similar effects on the cardiac action potential. Coadministration of quinidine may increase serum concentrations of procainamide, possibly by competing for pathways of renal clearance.
    Prochlorperazine: (Minor) Prochlorperazine is associated with a possible risk for QT prolongation.] Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with prochlorperazine include: quinidine (including dextromethorphan; quinidine),
    Promethazine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Promethazine; Dextromethorphan: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Promethazine; Phenylephrine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
    Propafenone: (Contraindicated) Class IA antiarrhythmics are associated with QT prolongation and ventricular arrhythmias including torsades de pointes (TdP), and concurrent use with propafenone is not recommended by the manufacturer. Before switching from another antiarrhythmic drug to propafenone therapy, Class IA antiarrhythmics and Class III antiarrhythmics generally should be withheld for at least five half-lives prior to initiating propafenone. Quinidine is a CYP2D6 inhibitor with potential to inhibit propafenone metabolism, and coadministration is contraindicated. Small doses of quinidine completely inhibit the CYP2D6 hydroxylation metabolic pathway, with the result that extensive metabolizers become poor metabolizers. Coadministration with quinidine markedly decreases propafenone clearance in extensive metabolizers, and increases plasma propafenone concentrations by 2 to 3-fold at steady-state. Steady-state plasma concentrations increased more than 2-fold for propafenone, and decreased 50% for 5-OH-propafenone.
    Propantheline: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like quinidine.
    Propranolol: (Major) Patients receiving combined therapy with quinidine and propranolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, such as propranolol. Quinidine is a known inhibitor of CYP2D6, and may additionally impair the hepatic clearance of propanolol (CYP2D6 substrate); patients should be monitored for excess beta-blockade.
    Propranolol; Hydrochlorothiazide, HCTZ: (Major) Patients receiving combined therapy with quinidine and propranolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, such as propranolol. Quinidine is a known inhibitor of CYP2D6, and may additionally impair the hepatic clearance of propanolol (CYP2D6 substrate); patients should be monitored for excess beta-blockade.
    Protriptyline: (Major) TCAs should be used cautiously and with close monitoring with cardiac drugs known to prolong the QT interval such as quinidine. The need to coadminister TCAs with protriptyline should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA. The dosage of protriptyline may need to be reduced if these drugs are coadministered. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Certain cardiac drugs prolong repolarization at therapeutic or elevated plasma concentrations, and the addition of other drugs may increase the risk of QT prolongation and torsades de pointes via pharmacokinetic or pharmacodynamic interactions.
    Pyridostigmine: (Moderate) Quinidine can potentiate the effects of depolarizing and nondepolarizing neuromuscular blockers. Recurrent paralysis may occur if quinidine injection is administered during recovery from use of nondepolarizing muscle relaxants. Consider the possible effect from quinidine when administering anticholinesterase agents such as pyridostigmine to antagonize neuromuscular blockade induced by nondepolarizing muscle relaxants
    Quetiapine: (Major) Quetiapine should be used cautiously and with close monitoring with quinidine. Quinidine is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Quinine: (Contraindicated) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP3A4. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4 substrates, such as quinidine. Coadministration may result in an elevated quinidine plasma concentration, causing an increased risk for adverse events, such as QT prolongation. Further, both quinine and quinidine are cinchona alkaloids; the possibility of cinchonism is increased if these drugs are administered concomitantly
    Ranolazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include ranolazine.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Relugolix: (Major) Avoid concomitant use of relugolix and oral quinidine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer quinidine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
    Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral quinidine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer quinidine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
    Reserpine: (Moderate) Reserpine-induced arrhythmias are more likely to occur during concomitant administration of quinidine. Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Ribociclib: (Major) Avoid coadministration of ribociclib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Quinidine is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP). Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Quinidine is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP). Concomitant use may increase the risk for QT prolongation.
    Rifabutin: (Moderate) Rifabutin is an inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinidine.
    Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
    Rifapentine: (Moderate) Monitor for decreased efficacy of quinidine if coadministration with rifapentine is necessary. Concomitant use may result in decreased plasma concentrations of quinidine. Quinidine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
    Rifaximin: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and quinidine, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
    Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
    Riluzole: (Major) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and quinidine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
    Rimegepant: (Major) Avoid coadministration of rimegepant with quinidine; concurrent use may increase rimegepant exposure. Rimegepant is a substrate of P-gp and quinidine is a P-gp inhibitor.
    Risperidone: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include risperidone.
    Ritonavir: (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use.
    Rivaroxaban: (Minor) Coadministration of rivaroxaban and quinidine may result in increases in rivaroxaban exposure and may increase bleeding risk. Quinidine is an inhibitor of P-glycoprotein (P-gp), and rivaroxaban is a substrate of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rolapitant: (Moderate) Use caution if quinidine and rolapitant are used concurrently, and monitor for quinidine-related adverse effects, including QT prolongation. Quinidine is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
    Romidepsin: (Major) Romidepsin is a substrate for P-glycoprotein (P-gp). Quinidine is an inhibitor of P-gp. Concurrent administration of romidepsin with an inhibitor of P-gp may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary. In addition, romidepsin has been reported to prolong the QT interval. Quinidine also prolongs the QT interval. If romidepsin and quinidine must be coadministered, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as quinidine, may occur during concurrent use with rufinamide.
    Salmeterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Saquinavir: (Contraindicated) Concurrent use of quinidine or quinidine-containing products (e.g., dextromethorphan; quinidine) and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening cardiac arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of quinidine. Concurrent administration may result in large increases in quinidine serum concentrations, which could cause fatal cardiac arrhythmias. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such quinidine.
    Sarilumab: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug.
    Scopolamine: (Moderate) The reduction in GI motility produced by scopolamine may increase the absorption of some drugs, including quinidine, resulting in increased anticholinergic effects. Increased monitoring is advised in patients receiving this combination.
    Secobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Secukinumab: (Moderate) If secukinumab is initiated or discontinued in a patient taking quinidine, monitor for altered patient response to quinidine; quinidine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as quinidine.
    Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with quinidine is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
    Sertraline: (Major) Use quinidine with caution in combination with sertraline as concurrent use may increase the risk of QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). QTc prolongation and TdP have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
    Short-acting beta-agonists: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Sildenafil: (Moderate) Sildenafil is metabolized principally by the hepatic isoenzymes CYP3A4 and CYP2C9. Inhibitors of these isoenzymes, such as quinidine, may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects.
    Siltuximab: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with siltuximab is necessary. Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when siltuximab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping siltuximab. In vitro, siltuximab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug.
    Simeprevir: (Moderate) Use of orally administered quinidine with simeprevir, an intestinal CYP3A4 inhibitor, may result in mild increases in quinidine plasma concentrations. If these drugs are administered together, monitoring of quinidine plasma concentrations (if available) is recommended.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving quinidine due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Quinidine administration is associated with QT prolongation and torsade de pointes.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
    Solifenacin: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval.Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
    Sorafenib: (Major) Avoid coadministration of sorafenib with quinidine due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Sorafenib is associated with QTc prolongation.
    Sotalol: (Major) Sotalol administration is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Drugs that prolong the QT interval should be used with extreme caution in combination with sotalol. Ventricular tachycardia, including torsade de pointes and monomorphic ventricular tachycardia can occur with excessive prolongation of the QT interval. Examples of agents that may prolong the QT interval include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Before initiating sotalol, the previous Class I antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives for the discontinued drug.
    Spironolactone: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    St. John's Wort, Hypericum perforatum: (Major) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system, including CYP3A4. Coadministration of St. John's wort could decrease the efficacy of some medications metabolized by this enzyme, such as quinidine. Clinicians should observe patients closely if St. John's wort is used.
    Streptogramins: (Moderate) Coadministration of quinidine with dalfopristin; quinupristin may result in elevated quinidine plasma concentrations. If these drugs are used together, closely monitor for signs of quinidine-related adverse events. Quinidine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
    Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of quinidine with sunitinib is necessary. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Tacrolimus: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). As the risk of TdP is increased with greater QT prolongation, avoid use of quinidine with another drug that prolongs the QT interval such as tacrolimus. It should be noted that the manufacturer of tacrolimus recommends reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation when coadministrating tacrolimus with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval such as quinidine. Tacrolimus and quinidine are both metabolized by cytochrome P450 3A4.
    Tadalafil: (Moderate) Tadalafil is metabolized predominantly by the hepatic isoenzyme CYP3A4. Inhibitors of CYP3A4, such as quinidine, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in an increase in tadalafil-induced adverse effects, including hypotension.
    Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinidine is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Tamoxifen: (Major) Coadministration of quinidine with tamoxifen may result in additive QT prolongation and decreased efficacy of tamoxifen. When administered as quinidine; dextromethorphan, coadministration with tamoxifen is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Tamoxifen is a CYP2D6 substrate that has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
    Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Teduglutide: (Moderate) Teduglutide may increase absorption of quinidine because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of quinidine is recommended.
    Telaprevir: (Major) Close clinical monitoring is advised when administering quinidine with telaprevir due to an increased potential for serious and/or life-threatening quinidine-related adverse events. If quinidine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and telaprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Additionally, both quinidine and telaprevir are substrates and inhibitors of P-glycoprotein (P-gp) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated.
    Telavancin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with telavancin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and telavancin has been associated with QT prolongation.
    Telithromycin: (Major) Concurrent use of quinidine and/or quinidine-containing products (e.g., dextromethorphan; quinidinne) with telithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). The manufacturer of dextromethorphan; quinidine recommends an initial ECG evaluation (baseline and 3 to 4 hours post-dose) in patients taking dextromethorphan; quinidine in combination with moderate or strong CYP3A4 inhibitors such as telithromycin. The quinidine component of dextromethorphan; quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of dextromethorphan; quinidine with moderate or strong CYP3A4 inhibitors may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects. In addition, telithromycin has the potential to prolong the QTc interval in some patients.
    Telmisartan; Amlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Temsirolimus: (Moderate) Monitor for an increase in temsirolimus- and quinidine-related adverse reactions if coadministration is necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Concomitant use is likely to lead to increased concentrations of both temsirolimus and quinidine.
    Tenofovir, PMPA: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Terazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Terbutaline: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Terfenadine: (Contraindicated) Use together is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Terfenadine has a well-established risk for QT prolongation and torsade de pointes (TdP). Other drugs that have also been independently associated with prolonged QT syndrome and/or TdP, such as quinidine, should not be used concomitantly with terfenadine.
    Tetrabenazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include tetrabenazine.
    Thiazide diuretics: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Thiopental: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
    Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of quinidine and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Ticagrelor: (Moderate) Coadministration of ticagrelor and quinidine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
    Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
    Tiotropium; Olodaterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Tipranavir: (Contraindicated) Concurrent use of quinidine and tipranavir is contraindicated due to the potential for serious and/or life-threatening cardiac arrhythmias. Tipranavir inhibits the CYP3A4 metabolism of quinidine, resulting in elevated quinidine serum concentrations.
    Tocilizumab: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with tocilizumab is necessary. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when tocilizumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug.
    Tolterodine: (Major) Use tolterodine and quinidine concomitantly with caution and close monitoring. Quinidine can inhibit the hepatic CYP2D6 isoenzyme, which may decrease the metabolism of tolterodine. It is not known if dosage adjustments in tolterodine would be needed as the result of this interaction. In addition, tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6, and quinidine (including dextromethorphan; quinidine) is associated with an established risk of QT prolongation. In addition, the anticholinergic effects of quinidine may be significant and may be enhanced when combined with tolterodine. Anticholinergic agents administered concurrently with quinidine may produce additive antivagal effects on AV nodal conduction.
    Topotecan: (Major) Avoid coadministration of quinidine with oral topotecan due to increased topotecan exposure; quinidine may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and quinidine is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
    Toremifene: (Major) Avoid coadministration of quinidine with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Quinidine administration is also associated with QT prolongation and torsade de pointes (TdP).
    Tramadol: (Moderate) As quinidine is a potent inhibitor of CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Tramadol; Acetaminophen: (Moderate) As quinidine is a potent inhibitor of CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Trandolapril; Verapamil: (Major) Pharmacokinetic and pharmacodynamic interactions exist between quinidine and verapamil. Oral verapamil has been shown to reduce the clearance and metabolism of oral quinidine. Quinidine half-life increased and plasma concentrations were higher after verapamil. No changes in quinidine protein binding were observed. In addition to the pharmacokinetic interaction which may potentiate quinidine's clinical effects, both quinidine and verapamil can cause hypotension. When quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral (alpha)-blockade is sometimes reported. Concurrent use of verapamil and quinidine in patients with hypertrophic cardiomyopathy or arrhythmias can cause significant hypotension. It is recommended to avoid combined therapy with verapamil and quinidine in patients with hypertrophic cardiomyopathy. Quinidine and verapamil may also have additive negative inotropic effects. Concurrent use of verapamil and quinidine should be monitored carefully for electrophysiologic and hemodynamic effects.
    Trazodone: (Major) Avoid coadministration of quinidine and trazodone if possible due to a potential increase in risk of QT prolongation and torsade de pointes (TdP). Quinidine administration is associated with QT prolongation and TdP. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of TdP for trazodone. Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Treprostinil: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Triamterene: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Triclabendazole: (Major) Monitor ECGs in patients receiving triclabendazole with quinidine. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. Quinidine administration is associated with QT prolongation and torsade de pointes.
    Trifluoperazine: (Minor) Trifluoperazine and quinidine should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Quinidine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Trihexyphenidyl: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Trimipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
    Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Trospium: (Major) Trospium is eliminated by active tubular secretion and has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion, such as quinidine. In theory, coadministration of trospium with quinidine may increase the serum concentrations of trospium or quinidine due to competition for the drug elimination pathway.
    Tubocurarine: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Tucatinib: (Moderate) Monitor for quinidine-related adverse reactions if coadministration with tucatinib is necessary. Concurrent use may increase quinidine exposure. Quinidine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
    Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with quinidine. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; quinidine is a P-gp inhibitor.
    Ulipristal: (Minor) In vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as quinidine may increase quinidine concentrations; use caution. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
    Umeclidinium; Vilanterol: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Valbenazine: (Major) Consider reducing the dose of valbenazine, based on tolerability, during co-administration with a strong CYP2D6 inhibitor, such as quinidine. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, concentrations of the active metabolite of valbenazine may be higher in patients taking a strong CYP2D6 inhibitor and QT prolongation may become clinically significant.
    Vandetanib: (Major) Avoid coadministration of vandetanib with quinidine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Quinidine administration is also associated with QT prolongation and TdP.
    Vardenafil: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
    Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). If vemurafenib and quinidine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, quinidine is also a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate/inhibitor. Vemurafenib is a CYP3A4 substrate/inducer, and a P-gp substrate/inhibitor. Quinidine concentrations may be increased or decreased and vemurafenib concentrations may be increased during concurrent use.
    Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with quinidine due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of quinidine. Venetoclax is a P-glycoprotein (P-gp) substrate; quinidine is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
    Venlafaxine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine includes venlafaxine.
    Verapamil: (Major) Pharmacokinetic and pharmacodynamic interactions exist between quinidine and verapamil. Oral verapamil has been shown to reduce the clearance and metabolism of oral quinidine. Quinidine half-life increased and plasma concentrations were higher after verapamil. No changes in quinidine protein binding were observed. In addition to the pharmacokinetic interaction which may potentiate quinidine's clinical effects, both quinidine and verapamil can cause hypotension. When quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral (alpha)-blockade is sometimes reported. Concurrent use of verapamil and quinidine in patients with hypertrophic cardiomyopathy or arrhythmias can cause significant hypotension. It is recommended to avoid combined therapy with verapamil and quinidine in patients with hypertrophic cardiomyopathy. Quinidine and verapamil may also have additive negative inotropic effects. Concurrent use of verapamil and quinidine should be monitored carefully for electrophysiologic and hemodynamic effects.
    Vincristine Liposomal: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vincristine: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Voclosporin: (Major) Use caution if quinidine is coadministered with voclosporin due to the risk of additive QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
    Voriconazole: (Contraindicated) Quinidine (including dextromethorphan; quinidine) use is contraindicated with voriconazole according to recommendations made by the manufacturer of voriconazole. Voriconazole inhibits the CYP3A4 enzyme that is responsible for quinidine metabolism; elevated and toxic levels of quinidine may occur potentiating the risk for QT prolongation and cardiac arrhythmias (e.g., torsade de pointes).
    Vorinostat: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with quinidine.
    Vortioxetine: (Major) The primary isoenzyme involved in the metabolim of vortioxetine is CYP2D6; therefore, the manufacturer recommends a reduction in the vortioxetine dose by one-half during co-administration with strong inhibitors of CYP2D6 such as quinidine. The vortioxetine dose should be increased to the original level when the CYP2D6 inhibitor is discontinued.
    Warfarin: (Moderate) Quinidine may potentiate the anticoagulation effects of warfarin; bleeding has been reported. This interaction is probably due to additive hypoprothrombinemia associated with concomitant administration of warfarin and quinine or quinidine. Close monitoring of the INR is required when either of these agents is added to warfarin therapy.
    Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as quinidine.
    Zileuton: (Moderate) Zileuton is metabolized by the hepatic isoenzyme CYP3A4 and may inhibit CYP3A4 isoenzymes. Zileuton could potentially compete with other CYP3A4 substrates, including quinidine.
    Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and class 1A antiarrhythmics, such as quinidine, is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Class 1A antiarrhythmics are associated with a well-established risk of QT prolongation and TdP.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and quinidine is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Quinidine is excreted in human milk at concentrations slightly lower than those found in maternal serum. Nursing infants would be expected to develop serum quinidine concentrations at least an order of magnitude lower than those of the mother. However, the pharmacokinetics and pharmacodynamics of quinidine in human infants have not been adequately studied. The reduced protein binding of quinidine in neonates may increase their risk of toxicity at low total serum concentrations. Avoid quinidine use in breast-feeding women, if possible.[47357] However, previous American Academy of Pediatrics recommendations considered quinidine to be usually compatible with breast-feeding.[27500]

    MECHANISM OF ACTION

    Mechanism of Action: Quinidine has properties similar to those of other class Ia antiarrhythmics (disopyramide and procainamide). These drugs decrease myocardial conduction velocity, excitability, and contractility by inhibiting the influx of sodium through "fast" channels of the myocardial cell membrane, thereby increasing the recovery period after repolarization. Quinidine suppresses atrial flutter or fibrillation by increasing the effective refractory period and the action potential duration in the atria, ventricles, and His-Purkinje system. The effective refractory period is increased more than the action potential duration, so the myocardium remains refractory even after the resting membrane potential has been restored. Quinidine decreases automaticity in the His-Purkinje system and decreases conduction velocity in the atria and ventricles. Quinidine prolongs the QRS and QT intervals in both normal sinus rhythm and atrial arrhythmias, and measurement of these intervals can be used to monitor therapy.Quinidine also exhibits anticholinergic properties that may modify its myocardial effects. When using quinidine to treat atrial flutter or fibrillation, ventricular rate can accelerate due to vagolytic effects on the AV node.

    PHARMACOKINETICS

    All quinidine salts can be administered orally. Only quinidine gluconate can be administered intravenously. Quinidine is commercially available as quinidine sulfate or quinidine gluconate, which contain 83% or 62% of anhydrous quinidine alkaloid, respectively. Quinidine distributes rapidly into all tissues except the brain, concentrating mainly in the heart, skeletal muscle, liver, and kidneys. The therapeutic range for quinidine serum concentrations ranges from 2—6 mcg/ml. The drug is 80—90% plasma protein-bound, with alpha-1-acid glycoprotein accounting for the majority of binding. 
     
    Quinidine is metabolized by a series of hydroxylations in the liver to form two active derivatives. Approximately 60—80% of a dose is metabolized via the cytochrome P450 enzyme system in the liver. Quinidine is primarily metabolized by the CYP3A4 enzyme and drugs that affect this enzyme may theoretically alter its' metabolism. Quinidine is an inhibitor of CYP2D6. There are several different hydroxylated metabolites, including some with antiarrhythmic activity. The most important active metabolite is 3-hydroxy-quinidine (3HQ). As measured by antiarrhythmic effects in animals, by QTc prolongation in human volunteers, or by various in vitro techniques, 3HQ has at least half the antiarrhythmic activity of the parent compound, so it may be responsible for a substantial fraction of the therapeutic response. Serum concentrations of 3HQ can approach those of quinidine in patients receiving conventional doses of oral quinidine. The volume of distribution of 3HQ appears to be larger than that of quinidine, and the elimination half-life of 3HQ is about 12 hours. 
     
    The elimination half-life of quinidine is 6—8 hours in adults. Roughly 10% is excreted unchanged in the urine, and 5% is excreted in the feces within 24 hours. Alkalinization of the urine can decrease renal elimination, while acidification will enhance excretion. 
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4, P-gp
    Quinidine is an inhibitor but not a substrate of the CYP2D6 cytochrome P450 enzyme and theoretically may interact with drugs that are metabolized by this enzyme. It also inhibits P-glycoprotein (P-gp) transport and is a substrate for P-gp. Quinidine is primarily metabolized by the CYP3A4 enzyme and drugs that affect this enzyme may theoretically alter the metabolism of quinidine.

    Oral Route

    Quinidine is readily absorbed from the GI tract, but interpatient variation in bioavailability, distribution, and elimination of the drug causes serum levels to differ greatly among individuals. The absolute bioavailability of the drug ranges 45—100%. Peak plasma concentrations and peak therapeutic effects are reached within 1—3 hours for quinidine sulfate regular-release capsules and tablets. Elimination half-life for quinidine averages 6.3—7.3 hours, although this varies considerably. Therapeutic effects usually last 6—8 hours. Quinidine sulfate regular-release capsules and tablets require three to four doses per day. Absorption of the extended-release quinidine sulfate or quinidine gluconate tablets is slower and more prolonged, and the duration of action for these formulations is about 12 hours. The presence of food in the stomach can decrease the absorption rate of regular-release quinidine sulfate capsules and tablets but not of extended-release preparations. Food does not affect the extent of absorption of these oral dosage forms. Administration with grapefruit juice delays the absorption of quinidine and inhibits CYP3A4 metabolism of quinidine to 3-hydroxyquinidine. The absorption of oral quinidine preparations can be decreased if antacids (except aluminum hydroxide gel) or antidiarrheals are administered concomitantly.