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  • CLASSES

    Monoamine Depletor

    BOXED WARNING

    Depression, suicidal ideation

    Deutetrabenazine is contraindicated in patients with Huntington's disease with active suicidal ideation or who have untreated or inadequately treated depression. Use deutetrabenazine with caution in patients with a history of depression or suicidal thoughts or behavior; weigh the risk of suicidality against the need for chorea treatment. Patients with Huntington's disease are at increased risk for depression and suicidal ideation or behaviors (suicidality). Deutetrabenazine use may increase the risk for suicidality in patients with Huntington's disease. Report unusual changes in mood, behaviors, or actions promptly to the treating health care professional. If depression or suicidality does not resolve, consider discontinuing treatment with deutetrabenazine. Periodically reevaluate the clinical need for deutetrabenazine.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, vesicular monoamine transporter 2 (VMAT 2) inhibitor
    Used for treatment of tardive dyskinesia and chorea associated with Huntington's disease
    May increase risk for suicidality

    COMMON BRAND NAMES

    Austedo

    HOW SUPPLIED

    Austedo Oral Tab: 6mg, 9mg, 12mg

    DOSAGE & INDICATIONS

    For the treatment of chorea associated with Huntington's Disease (Huntington's Chorea).
    Oral dosage in treatment-naive patients (i.e., patients not switching from tetrabenazine)
    Adults

    Initially, 6 mg PO twice daily. TITRATION: Increase the dosage based on reduction of chorea and tolerability at weekly intervals by increments of 6 mg/day. Administer total daily dosages of 12 mg or more in 2 divided doses. Max: 48 mg/day. Do not exceed 18 mg/dose or 36 mg/day in patients who are poor CYP2D6 metabolizers. INTERACTIONS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. INTERRUPTION OF TREATMENT: After a treatment interruption of more than 1 week, retitrate therapy when resumed. For an interruption of less than 1 week, resume treatment at the previous maintenance dose without titration. DISCONTINUATION: Discontinue treatment without tapering.

    Oral dosage in patients switching from tetrabenazine
    Adults

    Discontinue tetrabenazine and start deutetrabenazine the next day. Use 6 mg PO once daily for patients taking tetrabenazine 12.5 mg/day; 6 mg PO twice daily for patients taking tetrabenazine 25 mg/day; 9 mg PO twice daily for patients taking tetrabenazine 37.5 mg/day; 12 mg PO twice daily for patients taking tetrabenazine 50 mg/day; 15 mg PO twice daily for patients taking tetrabenazine 62.5 mg/day; 18 mg PO twice daily for patients taking tetrabenazine 75 mg/day; 21 mg PO twice daily for patients taking tetrabenazine 87.5 mg/day; and 24 mg PO twice daily for patients taking tetrabenazine 100 mg/day. TITRATION: Increase the dosage based on reduction of chorea and tolerability at weekly intervals by increments of 6 mg/day. Administer total daily dosages of 12 mg or more in 2 divided doses. Max: 48 mg/day. Do not exceed 18 mg/dose or 36 mg/day in patients who are poor CYP2D6 metabolizers. INTERACTIONS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. INTERRUPTION OF TREATMENT: After a treatment interruption of more than 1 week, retitrate therapy when resumed. For an interruption of less than 1 week, resume treatment at the previous maintenance dose without titration. DISCONTINUATION: Discontinue treatment without tapering.

    For the treatment of tardive dyskinesia.
    Oral dosage in treatment-naive patients (i.e., patients not switching from tetrabenazine)
    Adults

    Initially, 6 mg PO twice daily. TITRATION: Increase the dosage based on reduction of tardive dyskinesia and tolerability at weekly intervals by increments of 6 mg/day. Administer total daily dosages of 12 mg or more in 2 divided doses. Max: 48 mg/day. Do not exceed 18 mg/dose or 36 mg/day in patients who are poor CYP2D6 metabolizers. INTERACTIONS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. INTERRUPTION OF TREATMENT: After a treatment interruption of more than 1 week, retitrate therapy when resumed. For an interruption of less than 1 week, resume treatment at the previous maintenance dose without titration. DISCONTINUATION: Discontinue treatment without tapering.

    Oral dosage in patients switching from tetrabenazine
    Adults

    Discontinue tetrabenazine and start deutetrabenazine the next day. 6 mg PO once daily for patients taking tetrabenazine 12.5 mg/day; 6 mg PO twice daily for patients taking tetrabenazine 25 mg/day; 9 mg PO twice daily for patients taking tetrabenazine 37.5 mg/day; 12 mg PO twice daily for patients taking tetrabenazine 50 mg/day; 15 mg PO twice daily for patients taking tetrabenazine 62.5 mg/day; 18 mg PO twice daily for patients taking tetrabenazine 75 mg/day; 21 mg PO twice daily for patients taking tetrabenazine 87.5 mg/day; and 24 mg PO twice daily for patients taking tetrabenazine 100 mg/day. TITRATION: Increase the dosage based on reduction of tardive dyskinesia and tolerability at weekly intervals by increments of 6 mg/day. Administer total daily dosages of 12 mg or more in 2 divided doses. Max: 48 mg/day. Do not exceed 18 mg/dose or 36 mg/day in patients who are poor CYP2D6 metabolizers. INTERACTIONS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. INTERRUPTION OF TREATMENT: After a treatment interruption of more than 1 week, retitrate therapy when resumed. For an interruption of less than 1 week, resume treatment at the previous maintenance dose without titration. DISCONTINUATION: Discontinue treatment without tapering.

    MAXIMUM DOSAGE

    Adults

    48 mg/day PO; 18 mg/dose PO and 36 mg/day PO in poor CYP2D6 metabolizers.

    Geriatric

    48 mg/day PO; 18 mg/dose PO and 36 mg/day PO in poor CYP2D6 metabolizers.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Deutetrabenazine is contraindicated in patients with hepatic impairment.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Administer with food.
    Swallow tablets whole. Do not chew, crush, or break the tablets.

    STORAGE

    Austedo:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Hepatic disease

    Deutetrabenazine is contraindicated for use in patients with hepatic impairment or hepatic disease because of the possibility for increased drug exposure and a greater risk of serious adverse reactions. The effect of hepatic impairment on the pharmacokinetics of deutetrabenazine and its primary metabolites has not been studied. In a clinical study of tetrabenazine, a closely related VMAT2 inhibitor, there was a large increase in exposure to tetrabenazine and its active metabolites in patients with hepatic impairment.

    MAOI therapy

    Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. Deutetrabenazine is a reversible, monoamine-depleting drug that works by inhibiting the vesicular monoamine transporter 2 (VMAT2). Deutetrabenazine is contraindicated in patients who are receiving or have received reserpine within the past 20 days. Reserpine irreversibly binds to VMAT2, and the effect of reserpine lasts several days. Allow at least 20 days for chorea to reemerge before initiating deutetrabenazine to help reduce the risk of major depletion of serotonin and norepinephrine within the CNS. Deutetrabenazine is also contraindicated in patients taking tetrabenazine.

    Depression, suicidal ideation

    Deutetrabenazine is contraindicated in patients with Huntington's disease with active suicidal ideation or who have untreated or inadequately treated depression. Use deutetrabenazine with caution in patients with a history of depression or suicidal thoughts or behavior; weigh the risk of suicidality against the need for chorea treatment. Patients with Huntington's disease are at increased risk for depression and suicidal ideation or behaviors (suicidality). Deutetrabenazine use may increase the risk for suicidality in patients with Huntington's disease. Report unusual changes in mood, behaviors, or actions promptly to the treating health care professional. If depression or suicidality does not resolve, consider discontinuing treatment with deutetrabenazine. Periodically reevaluate the clinical need for deutetrabenazine.

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

    Avoid using deutetrabenazine in patients with congenital long QT syndrome or a history of cardiac arrhythmias. Use deutetrabenazine 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, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, 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. 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.

    Driving or operating machinery

    Deutetrabenazine has the potential to impair cognitive and motor skills. Sedation is a common dose-limiting side effect of deutetrabenazine. Advise patients to use caution when driving or operating machinery, or performing other tasks that require mental alertness, until they know how deutetrabenazine affects them. Alcohol consumption may exacerbate sedation associated with the drug.

    Breast cancer, hyperprolactinemia

    The effect of deutetrabenazine on serum prolactin concentrations has not been evaluated, but it is possible the drug may induce hyperprolactinemia. Tetrabenazine, a closely related VMAT2 inhibitor, can cause hyperprolactinemia. Some human breast cancers may be prolactin-dependent. Therefore, use deutetrabenazine cautiously in those who have a history of breast cancer.[61845]

    Pregnancy

    There are no adequate data on the developmental risk associated with deutetrabenazine use during pregnancy. Deutetrabenazine (5, 10, or 30 mg/kg/day) produced no clear adverse effects on embryofetal development when given to rats during the period of organogenesis. However, administration of tetrabenazine, a closely related VMAT2 inhibitor, to rats from organogenesis through lactation resulted in an increase in stillbirths and postnatal mortality.

    Breast-feeding

    Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for deutetrabenazine and any potential adverse effects on the breast-feeding infant from the drug or the mother's underlying condition. There are no data on the presence of deutetrabenazine or its metabolites in human breast milk, the effects on the breast-fed infant, or the effects of the drug on milk production.

    ADVERSE REACTIONS

    Severe

    suicidal ideation / Delayed / 2.0-2.0
    neuroleptic malignant syndrome / Delayed / Incidence not known

    Moderate

    cystitis / Delayed / 7.0-7.0
    depression / Delayed / 2.0-4.0
    akathisia / Delayed / 2.0-4.0
    constipation / Delayed / 4.0-4.0
    pseudoparkinsonism / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known

    Mild

    drowsiness / Early / 11.0-11.0
    fatigue / Early / 9.0-9.0
    xerostomia / Early / 9.0-9.0
    diarrhea / Early / 9.0-9.0
    insomnia / Early / 4.0-7.0
    restlessness / Early / 2.0-4.0
    agitation / Early / 2.0-4.0
    dizziness / Early / 4.0-4.0
    anxiety / Delayed / 4.0-4.0
    pharyngitis / Delayed / 4.0-4.0
    tremor / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Acetaminophen; Chlorpheniramine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Codeine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as doxylamine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Diphenhydramine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Acetaminophen; Hydrocodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Acetaminophen; Oxycodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If extended-release oxycodone or oxycodone; naloxone is initiated in a patient taking a barbiturate, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of immediate-release oxycodone, oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet every 12 hours. If a barbitruate is prescribed for a patient taking an opioid agonist, use a lower initial dose of the barbitruate and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Pentazocine: (Major) Concomitant use of mixed opiate agonists/antagonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Alfentanil: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Alfuzosin: (Moderate) Use caution during coadministration of alfuzosin and deutetrabenazine due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. 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.
    Alprazolam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as alprazolam, may have additive effects and worsen drowsiness or sedation.
    Amiodarone: (Major) Avoid coadministration of amiodarone and drugs known to prolong the QT interval, if possible. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. 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.
    Amisulpride: (Major) Monitor the ECG in patients taking amisulpride with deutetrabenazine due to the risk of additive QT prolongation. Amisulpride causes dose- and concentration-dependent QT prolongation. 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.
    Amitriptyline: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Amobarbital: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Amoxapine: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and amoxapine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Also, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as amoxapine, may have additive effects and worsen drowsiness or sedation.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with deutetrabenazine. Clarithromycin is associated with an established risk for 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.
    Anagrelide: (Major) Do not use anagrelide with other drugs that may prolong the QT interval. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. 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.
    Apomorphine: (Moderate) Use apomorphine and deutetrabenazine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. 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. Also, monitor for excessive sedation and somnolence during coadministration of apomorphine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Aripiprazole: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and aripiprazole. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and aripiprazole is a partial dopamine agonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of aripiprazole and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide and deutetrabenazine due to the potential for QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. 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.
    Artemether; Lumefantrine: (Major) Avoid coadministration of artemether; lumefantrine with deutetrabenazine due to the potential for additive QT prolongation. Consider ECG monitoring if deutetrabenazine must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. 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. (Major) Avoid coadministration of artemether; lumefantrine with deutetrabenazine due to the potential for additive QT prolongation. Consider ECG monitoring if deutetrabenazine must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. 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. Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if concurrent use of deutetrabenazine with artemether; lumefantrine is necessary. Lumefantrine 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, like QT prolongation and drowsiness.
    Asenapine: (Major) Avoid using asenapine in combination with deutetrabenazine due to the potential for QT prolongation. Asenapine has been associated with QT prolongation. 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. Also, deutetrabenazine is a reversible, dopamine depleting drug and asenapine is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use may also result in additive CNS depression.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as orphenadrine, may have additive effects and worsen drowsiness or sedation.
    Aspirin, ASA; Carisoprodol: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as carisoprodol, may have additive effects and worsen drowsiness or sedation.
    Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as carisoprodol, may have additive effects and worsen drowsiness or sedation.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If extended-release oxycodone or oxycodone; naloxone is initiated in a patient taking a barbiturate, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of immediate-release oxycodone, oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet every 12 hours. If a barbitruate is prescribed for a patient taking an opioid agonist, use a lower initial dose of the barbitruate and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Atomoxetine: (Minor) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and atomoxetine. 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. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Azelastine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as azelastine, may have additive effects and worsen drowsiness or sedation.
    Azelastine; Fluticasone: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as azelastine, may have additive effects and worsen drowsiness or sedation.
    Azithromycin: (Major) Avoid coadministration of azithromycin with deutetrabenazine 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. 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.
    Baclofen: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as baclofen, may have additive effects and worsen drowsiness or sedation.
    Barbiturates: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Bedaquiline: (Major) Monitor ECGs if bedaquiline is coadministered with deutetrabenazine. Discontinue bedaquiline if evidence of significant ventricular arrhythmia or QTcF interval greater than 500 msec. Bedaquiline prolongs the QT interval. 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.
    Belladonna; Opium: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as belladonna, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking deutetrabenazine, reduce initial dosage and titrate to clinical response. If deutetrabenazine is prescribed in a patient taking an opioid agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and deutetrabenazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and deutetrabenazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Brexpiprazole: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as brexpiprazole, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Brompheniramine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as brompheniramine, may have additive effects and worsen drowsiness or sedation.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as brompheniramine, may have additive effects and worsen drowsiness or sedation.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as brompheniramine, may have additive effects and worsen drowsiness or sedation.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as brompheniramine, may have additive effects and worsen drowsiness or sedation.
    Brompheniramine; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as brompheniramine, may have additive effects and worsen drowsiness or sedation.
    Brompheniramine; Pseudoephedrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as brompheniramine, may have additive effects and worsen drowsiness or sedation.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as brompheniramine, may have additive effects and worsen drowsiness or sedation.
    Buprenorphine: (Major) Avoid coadministration of buprenorphine with deutetrabenazine. Buprenorphine has been associated with QT prolongation and has a possible risk of 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. Concomitant use of buprenorphine with deutetrabenazine may cause excessive sedation and somnolence. Limit the use of buprenorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Buprenorphine; Naloxone: (Major) Avoid coadministration of buprenorphine with deutetrabenazine. Buprenorphine has been associated with QT prolongation and has a possible risk of 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. Concomitant use of buprenorphine with deutetrabenazine may cause excessive sedation and somnolence. Limit the use of buprenorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Bupropion: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Bupropion 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, like QT prolongation and drowsiness.
    Bupropion; Naltrexone: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Bupropion 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, like QT prolongation and drowsiness.
    Butabarbital: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Butalbital; Acetaminophen: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Butorphanol: (Major) Concomitant use of mixed opiate agonists/antagonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cabergoline: (Moderate) Cabergoline should not be coadministered with deutetrabenazine, if possible. The prolactin-lowering effect of cabergoline may be diminished by medications that increase prolactin levels such as deutetrabenazine.
    Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with deutetrabenazine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. 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.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as sodium oxybate, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and deutetrabenazine. CNS depressants can potentiate the effects of cannabidiol.
    Capsaicin; Metaxalone: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as metaxalone, may have additive effects and worsen drowsiness or sedation.
    Carbetapentane; Chlorpheniramine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as entacapone, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Cariprazine: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as cariprazine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Carisoprodol: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as carisoprodol, may have additive effects and worsen drowsiness or sedation.
    Celecoxib; Tramadol: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Ceritinib: (Major) Avoid coadministration of ceritinib with deutetrabenazine if possible due to the risk of QT prolongation. 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. Ceritinib causes concentration-dependent QT prolongation. 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.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with deutetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with deutetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Chlordiazepoxide: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlordiazepoxide, may have additive effects and worsen drowsiness or sedation.
    Chlordiazepoxide; Amitriptyline: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlordiazepoxide, may have additive effects and worsen drowsiness or sedation. (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Chlordiazepoxide; Clidinium: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlordiazepoxide, may have additive effects and worsen drowsiness or sedation.
    Chloroquine: (Major) Avoid coadministration of chloroquine with deutetrabenazine 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. 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. 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.
    Chlorpheniramine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Codeine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Dextromethorphan: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpheniramine, may have additive effects and worsen drowsiness or sedation.
    Chlorpromazine: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and chlorpromazine. 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. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and chlorpromazine is a dopamine antagonist. Monitor for excessive sedation and somnolence during coadministration of chlorpromazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Chlorthalidone; Clonidine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clonidine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Chlorzoxazone: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorzoxazone, may have additive effects and worsen drowsiness or sedation.
    Ciprofloxacin: (Moderate) Use ciprofloxacin with caution in patients receiving other drugs that prolong the QT interval. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. 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.
    Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of deutetrabenazine with cisapride is contraindicated. QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. 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.
    Citalopram: (Major) Avoid citalopram use in combination with deutetrabenazine due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. 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.
    Clarithromycin: (Major) Avoid coadministration of clarithromycin with deutetrabenazine. Clarithromycin is associated with an established risk for 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.
    Clemastine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clemastine, may have additive effects and worsen drowsiness or sedation.
    Clobazam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clobazam, may have additive effects and worsen drowsiness or sedation.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with deutetrabenazine. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. 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.
    Clomipramine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Clonazepam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clonazepam, may have additive effects and worsen drowsiness or sedation.
    Clonidine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clonidine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Clorazepate: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clorazepate, may have additive effects and worsen drowsiness or sedation.
    Clozapine: (Major) Use clozapine with caution in combination with deutetrabenazine. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and clozapine is a dopamine antagonist. Additionally, monitor for excessive sedation and somnolence during coadministration of clozapine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Codeine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Codeine; Guaifenesin: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and promethazine. 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and promethazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of promethazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Codeine; Promethazine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine. (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and promethazine. 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and promethazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of promethazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Crizotinib: (Major) Avoid coadministration of crizotinib with deutetrabenazine due to the risk of QT prolongation. 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 can cause concentration-dependent QT prolongation. 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.
    Cyclobenzaprine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as cyclobenzaprine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Cyproheptadine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as cyproheptadine, may have additive effects and worsen drowsiness or sedation.
    Dacomitinib: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if used concurrently with dacomitinib. Dacomitinib 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, like QT prolongation and drowsiness.
    Dantrolene: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as dantrolene, may have additive effects and worsen drowsiness or sedation.
    Dasatinib: (Moderate) Use dasatinib with caution in combination with deutetrabenazine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. 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.
    Degarelix: (Major) Avoid coadministration of degarelix with deutetrabenazine due to the risk of reduced efficacy of degarelix. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; degarelix is a GnRH analog. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval. 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.
    Desflurane: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and halogenated anesthetics. 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. Halogenated anesthetics can prolong the QT interval.
    Desipramine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Dexmedetomidine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as dexmedetomidine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Dextromethorphan; Bupropion: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Bupropion 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, like QT prolongation and drowsiness.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Dextromethorphan; Quinidine: (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.
    Diazepam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diazepam, may have additive effects and worsen drowsiness or sedation.
    Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
    Dimenhydrinate: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as dimenhydrinate, may have additive effects and worsen drowsiness or sedation.
    Diphenhydramine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Diphenhydramine; Ibuprofen: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Diphenhydramine; Naproxen: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Diphenhydramine; Phenylephrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, may have additive effects and worsen drowsiness or sedation.
    Disopyramide: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and disopyramide. 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. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
    Dofetilide: (Major) Coadministration of dofetilide and deutetrabenazine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of 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.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with deutetrabenazine due to risk of additive QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. 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.
    Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with deutetrabenazine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. 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.
    Donepezil: (Moderate) Use donepezil with caution in combination with deutetrabenazine due to the risk for additive QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. 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.
    Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with deutetrabenazine due to the risk for additive QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. 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.
    Doxepin: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Doxylamine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as doxylamine, may have additive effects and worsen drowsiness or sedation.
    Doxylamine; Pyridoxine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as doxylamine, may have additive effects and worsen drowsiness or sedation.
    Dronedarone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of deutetrabenazine with dronedarone is contraindicated. 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 1,600 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. 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.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as deutetrabenazine. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and droperidol is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of droperidol and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with deutetrabenazine due to the risk for additive QT prolongation. QTc prolongation has been observed with the use of efavirenz. 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.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with deutetrabenazine due to the risk for additive QT prolongation. QTc prolongation has been observed with the use of efavirenz. 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.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with deutetrabenazine due to the risk for additive QT prolongation. QTc prolongation has been observed with the use of efavirenz. 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.
    Eliglustat: (Minor) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and eliglustat. 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. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with deutetrabenazine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. 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.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering rilpivirine with deutetrabenazine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. 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.
    Encorafenib: (Major) Avoid coadministration of encorafenib and deutetrabenazine due to an increased risk of QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. 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.
    Entacapone: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as entacapone, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Entrectinib: (Major) Avoid coadministration of entrectinib with deutetrabenazine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. 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.
    Eribulin: (Major) ECG monitoring is recommended if eribulin is administered with deutetrabenazine. The risk of QT prolongation may be increased with coadministration of deutetrabenazine and eribulin. 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. Eribulin has been associated with QT prolongation.
    Erythromycin: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and erythromycin. 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. Erythromycin is associated with QT prolongation and torsade de pointes (TdP).
    Escitalopram: (Moderate) Use escitalopram with caution in combination with deutetrabenazine. The risk of QT prolongation may be increased with coadministration of deutetrabenazine and escitalopram. 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. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP).
    Esketamine: (Moderate) Closely monitor patients receiving esketamine and deutetrabenazine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Estazolam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as estazolam, may have additive effects and worsen drowsiness or sedation.
    Eszopiclone: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as eszopiclone, may have additive effects and worsen drowsiness or sedation.
    Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Fentanyl: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Fingolimod: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and fingolimod. 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. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of torsade de pointes (TdP) in patients with bradycardia.
    Flecainide: (Major) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. 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.
    Flibanserin: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as flibanserin, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Fluconazole: (Moderate) Use fluconazole with caution in combination with deutetrabenazine. Fluconazole has been associated with QT prolongation and rare cases of 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.
    Fluoxetine: (Moderate) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor, such as fluoxetine. Fluoxetine 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, like QT prolongation and drowsiness. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine. 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.
    Fluphenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and fluphenazine. 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. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and fluphenazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of fluphenazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Flurazepam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as flurazepam, may have additive effects and worsen drowsiness or sedation.
    Fluvoxamine: (Minor) Use fluvoxamine with caution in combination with deutetrabenazine. QT prolongation and torsade de pointes (TdP) have been reported during fluvoxamine postmarketing use. 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.
    Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
    Foscarnet: (Major) Avoid coadministration of foscarnet with deutetrabenazine due to the potential for QT prolongation. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet. 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.
    Fostemsavir: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and fostemsavir. 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. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of deutetrabenazine and gabapentin. Concurrent use may result in additive CNS depression.
    Gemifloxacin: (Moderate) Gemifloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of TdP, such as deutetrabenazine. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 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. 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.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and deutetrabenazine 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. 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.
    Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and deutetrabenazine is necessary. Gilteritinib has been associated with QT prolongation. 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.
    Glasdegib: (Major) Avoid coadministration of glasdegib with deutetrabenazine 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. 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.
    Goserelin: (Major) Avoid coadministration of goserelin with deutetrabenazine due to the risk of reduced efficacy of goserelin. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval. 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.
    Granisetron: (Moderate) Use granisetron with caution in combination with deutetrabenazine. Granisetron has been associated with QT prolongation. 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.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Halogenated Anesthetics: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and halogenated anesthetics. 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. Halogenated anesthetics can prolong the QT interval.
    Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently with deutetrabenazine. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and haloperidol is a dopamine antagonist. Monitor for excessive sedation and somnolence during coadministration of haloperidol and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Histrelin: (Major) Avoid coadministration of histrelin with deutetrabenazine due to the risk of reduced efficacy of histrelin. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. 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.
    Homatropine; Hydrocodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as methyldopa, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Hydrocodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If acetaminophen; hydrocodone or hydrocodone; ibuprofen are initiated in a patient taking deutetrabenazine, reduced initial doses are recommended. If a decision is made to start treatment with hydrocodone extended-release tabIets or capsules, initiate hydrocodone at 20% to 30% of the usual dosage. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking deutetrabenazine.
    Hydromorphone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If hydromorphone is initiated in a patient taking deutetrabenazine, use an initial dose of hydromorphone at 1/3 to 1/2 the usual dosage and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydroxychloroquine: (Major) Avoid coadministration of deutetrabenazine and hydroxychloroquine due to the risk of increased 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. 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.
    Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with deutetrabenazine. Postmarketing data indicate that hydroxyzine causes 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. Also, monitor for excessive sedation and somnolence during coadministration of hydroxyzine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Ibuprofen; Oxycodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If extended-release oxycodone or oxycodone; naloxone is initiated in a patient taking a barbiturate, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of immediate-release oxycodone, oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet every 12 hours. If a barbitruate is prescribed for a patient taking an opioid agonist, use a lower initial dose of the barbitruate and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. 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.
    Iloperidone: (Major) Avoid iloperidone in combination with other drugs known to prolong the QT interval. Iloperidone has been associated with QT prolongation. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and iloperidone is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of iloperidone and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Imipramine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with deutetrabenazine due to the potential for additive QT interval prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of inotuzumab treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. 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.
    Isocarboxazid: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Isoflurane: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and halogenated anesthetics. 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. Halogenated anesthetics can prolong the QT interval.
    Itraconazole: (Moderate) Use itraconazole with caution in combination with deutetrabenazine. Itraconazole has been associated with prolongation of the QT interval. 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.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with deutetrabenazine if possible 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. 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.
    Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and deutetrabenazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with deutetrabenazine. Clarithromycin is associated with an established risk for 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.
    Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with deutetrabenazine. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. 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.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Lefamulin: (Major) Avoid coadministration of lefamulin with deutetrabenazine as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended during treatment. Lefamulin 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. 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.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and deutetrabenazine. Dosage adjustments of lemborexant and deutetrabenazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with deutetrabenazine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. 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.
    Leuprolide: (Major) Avoid coadministration of leuprolide with deutetrabenazine due to the risk of reduced efficacy of leuprolide. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. 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.
    Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with deutetrabenazine due to the risk of reduced efficacy of leuprolide. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. 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.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with deutetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Levofloxacin: (Moderate) Use levofloxacin with caution in patients receiving other drugs that prolong the QT interval. Levofloxacin has been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin. 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.
    Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and deutetrabenazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Levorphanol: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If levorphanol is initiated in a patient taking deutetrabenazine, reduce the initial dose of levorphanol by approximately 50% or more. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Lithium: (Moderate) Use lithium with caution in combination with deutetrabenazine. Lithium has been associated with QT prolongation. 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.
    Lofexidine: (Major) ECG monitoring is recommended if lofexidine is coadministered with deutetrabenazine due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. 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. Also, monitor for excessive sedation and somnolence during coadministration of lofexidine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Loperamide: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and loperamide. 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. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
    Loperamide; Simethicone: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and loperamide. 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. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with deutetrabenazine due to the risk of 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. 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. Lopinavir is associated with QT prolongation.
    Lorazepam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as lorazepam, may have additive effects and worsen drowsiness or sedation.
    Loxapine: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and loxapine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as loxapine, may have additive effects and worsen drowsiness or sedation.
    Lumateperone: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation during coadministration of lumateperone and deutetrabenazine. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and lumateperone is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of deutetrabenazine and lumateperone. Concurrent use may result in additive CNS depression.
    Lurasidone: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and lurasidone is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as lurasidone, may have additive effects and worsen drowsiness or sedation.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as deutetrabenazine. 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. 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.
    Maprotiline: (Moderate) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is 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 maprotiline in combination with other QT-prolonging drugs. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and neuroleptic malignant-like syndrome has been reported with maprotiline. Monitor for excessive sedation and somnolence during coadministration of maprotiline and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Meclizine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as meclizine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Mefloquine: (Minor) Use mefloquine with caution in patients receiving deutetrabenazine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. 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.
    Melatonin: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as melatonin, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Meperidine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Meperidine; Promethazine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and promethazine. 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and promethazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of promethazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Meprobamate: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as meprobamate, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Metaxalone: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as metaxalone, may have additive effects and worsen drowsiness or sedation.
    Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. 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. Concomitant use of opioid agonists with deutetrabenazine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Methocarbamol: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as methocarbamol, may have additive effects and worsen drowsiness or sedation.
    Methohexital: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Methyldopa: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as methyldopa, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Metoclopramide: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and metoclopramide is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as metoclopramide, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Metronidazole: (Moderate) Concomitant use of metronidazole and deutetrabenazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Midazolam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as midazolam, may have additive effects and worsen drowsiness or sedation.
    Midostaurin: (Major) Consider interval assessments of QT by ECG if midostaurin is taken concurrently with deutetrabenazine. QT prolongation was reported in patients who received midostaurin in clinical trials. 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.
    Mifepristone: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. 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.
    Mirtazapine: (Moderate) Use caution when using mirtazipine in combination with deutetrabenazine. Mirtazipine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported postmarketing with mirtazipine, primarily in overdose or in patients with other risk factors for QT prolongation. 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. Monitor for excessive sedation and somnolence during coadministration of mirtazapine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Mobocertinib: (Major) Concomitant use of mobocertinib and deutetrabenazine 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. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Molindone: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and molindone is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as molindone, may have additive effects and worsen drowsiness or sedation.
    Monoamine oxidase inhibitors: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Morphine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking deutetrabenazine, reduced initial dosages are recommended. For extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Use an initial morphine; naltrexone dose of 20 mg/0.8 mg every 24 hours. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Morphine; Naltrexone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking deutetrabenazine, reduced initial dosages are recommended. For extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Use an initial morphine; naltrexone dose of 20 mg/0.8 mg every 24 hours. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Moxifloxacin: (Major) Avoid coadministration of moxifloxacin with deutetrabenazine as concurrent use may increase the risk of QT prolongation and torsade de pointes (TdP). Quinolones have been associated with a risk of QT prolongation. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. 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.
    Nabilone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of nabilone and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Nalbuphine: (Major) Concomitant use of mixed opiate agonists/antagonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Nefazodone: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as nefazodone, may have additive effects and worsen drowsiness or sedation.
    Nilotinib: (Major) Avoid administration of nilotinib with other drugs with a known potential to prolong the QT interval. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. 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.
    Nortriptyline: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Octreotide: (Minor) Use octreotide with caution in combination with deutetrabenazine. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (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. 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.
    Ofloxacin: (Moderate) Use ofloxacin with caution in patients receiving other drugs that prolong the QT interval. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. 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.
    Olanzapine: (Moderate) Caution is advised when administering olanzapine with deutetrabenazine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and olanzapine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of olanzapine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Olanzapine; Fluoxetine: (Moderate) Caution is advised when administering olanzapine with deutetrabenazine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and olanzapine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of olanzapine and deutetrabenazine. Concurrent use may result in additive CNS depression. (Moderate) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor, such as fluoxetine. Fluoxetine 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, like QT prolongation and drowsiness. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine. 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.
    Olanzapine; Samidorphan: (Moderate) Caution is advised when administering olanzapine with deutetrabenazine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and olanzapine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of olanzapine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Oliceridine: (Moderate) Concomitant use of oliceridine with deutetrabenazine may cause excessive sedation and somnolence. Limit the use of oliceridine with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Ondansetron: (Major) If ondansetron and deutetrabenazine must be coadministered, ECG monitoring is recommended. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of 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.
    Opicapone: (Moderate) Opicapone should be given cautiously with other agents that cause CNS depression, including deutetrabenazine, due to the possibility of additive sedation. COMT inhibitors, such as opicapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Orphenadrine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as orphenadrine, may have additive effects and worsen drowsiness or sedation.
    Osilodrostat: (Moderate) Use osilodrostat and deutetrabenazine 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. 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.
    Osimertinib: (Major) Avoid coadministration of deutetrabenazine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, 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. 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.
    Oxaliplatin: (Major) Monitor ECG and electrolytes in patients receiving oxaliplatin concomitantly with deutetrabenazine; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. 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.
    Oxazepam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as oxazepam, may have additive effects and worsen drowsiness or sedation.
    Oxycodone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If extended-release oxycodone or oxycodone; naloxone is initiated in a patient taking a barbiturate, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of immediate-release oxycodone, oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet every 12 hours. If a barbitruate is prescribed for a patient taking an opioid agonist, use a lower initial dose of the barbitruate and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxymorphone: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxymorphone is initiated in a patient taking deutetrabenazine, use an initial dose of oxymorphone at 1/3 to 1/2 the usual dosage and titrate to clinical response. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, it is recommended to use an initial dosage of 5 mg PO every 12 hours. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking deutetrabenazine 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. 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.
    Pacritinib: (Major) Concomitant use of pacritinib and deutetrabenazine 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. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Paliperidone: (Major) Avoid coadministration of paliperidone with deutetrabenazine due to the potential for additive QT prolongation. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. 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. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and paliperidone is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of paliperidone and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Panobinostat: (Major) Use of panobinostat with deutetrabenazine is not recommended. QT prolongation has been reported with panobinostat. 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.
    Paroxetine: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Paroxetine 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, like QT prolongation and drowsiness. After 8 days of paroxetine 20 mg PO daily, systemic exposure (AUC) of alpha- and beta-HTBZ increased 1.9-fold and 6.5-fold, respectively, following a single 22.5 mg dose of deutetrabenazine. The clearance of alpha- and beta-HTBZ was reduced, with corresponding increases in mean half-life of 1.5-fold and 2.7-fold, respectively. The Cmax of alpha- and beta-HTBZ increased 1.2-fold and 2.2-fold, respectively.
    Pasireotide: (Moderate) Use caution when using pasireotide in combination with other drugs that prolong the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supratherapeutic doses. 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.
    Pazopanib: (Major) Avoid coadministration of deutetrabenazine with pazopanib due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib has been associated with QT prolongation. 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.
    Pentamidine: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and pentamidine. 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. Systemic pentamidine has been associated with QT prolongation.
    Pentazocine: (Major) Concomitant use of mixed opiate agonists/antagonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Pentazocine; Naloxone: (Major) Concomitant use of mixed opiate agonists/antagonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Pentobarbital: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Perampanel: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as perampanel, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Perphenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and perphenazine. 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. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and perphenazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of perphenazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Perphenazine; Amitriptyline: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and perphenazine. 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. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and perphenazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of perphenazine and deutetrabenazine. Concurrent use may result in additive CNS depression. (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Phenelzine: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Phenobarbital: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation. (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as scopolamine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Pimavanserin: (Major) Avoid coadministration of pimavanserin with deutetrabenazine due to additive QT effects and increased risk of cardiac arrhythmia. Pimavanserin prolongs the QT interval. 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. Monitor for excessive sedation and somnolence during coadministration of pimavanserin and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Pimozide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of deutetrabenazine with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and 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. Also, deutetrabenazine is a reversible, dopamine depleting drug and pimozide is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additive CNS depression may occur during coadministration of pimozide and deutetrabenazine.
    Pitolisant: (Major) Avoid coadministration of pitolisant with deutetrabenazine as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. 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.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking deutetrabenazine 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. 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.
    Posaconazole: (Moderate) Use posaconazole with caution in combination with deutetrabenazine. Posaconazole has been associated with QT prolongation as well as rare cases of 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.
    Pramipexole: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as pramipexole, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of deutetrabenazine and pregabalin. Concurrent use may result in additive CNS depression.
    Primaquine: (Moderate) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. 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.
    Primidone: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Procainamide: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and procainamide. 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. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Prochlorperazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and prochlorperazine. 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. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and prochlorperazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of prochlorperazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Promethazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and promethazine. 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and promethazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of promethazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Promethazine; Dextromethorphan: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and promethazine. 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and promethazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of promethazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Promethazine; Phenylephrine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and promethazine. 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and promethazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, monitor for excessive sedation and somnolence during coadministration of promethazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Propafenone: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and propafenone. 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. Propafenone is a Class IC antiarrhythmic that increases the QT interval, but largely due to prolongation of the QRS interval.
    Propantheline: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as propantheline, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Protriptyline: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Quazepam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as quazepam, may have additive effects and worsen drowsiness or sedation.
    Quetiapine: (Major) Avoid use of quetiapine in combination with deutetrabenazine due to the potential for additive QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. 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. Also, deutetrabenazine is a reversible, dopamine depleting drug and quetiapine is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as quetiapine, may have additive effects and worsen drowsiness or sedation.
    Quinidine: (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.
    Quinine: (Major) Avoid concurrent use of quinine with deutetrabenazine. Quinine has been associated with QT prolongation and rare cases of 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.
    Ramelteon: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as ramelteon, may have additive effects and worsen drowsiness or sedation.
    Ranolazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and ranolazine. 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. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
    Rasagiline: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Relugolix: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and relugolix. 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. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and relugolix. 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. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Remifentanil: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Reserpine: (Contraindicated) Concurrent use of deutetrabenazine and reserpine is contraindicated. At least 20 days should elapse after stopping reserpine before initiating treatment with deutetrabenazine; wait for chorea or dyskinesia to reemerge before administering deutetrabenazine to reduce the risk of overdosage and major depletion of serotonin and norepinephrine in the CNS. Reserpine binds irreversibly to vesicular monoamine transporter 2 (VMAT2), and the duration of its effect is several days. Deutetrabenazine is a selective, reversible, monoamine depleting drug that works by inhibiting VMAT2.
    Ribociclib: (Major) Ribociclib should be avoided in patients receiving medications known to prolong the QT interval. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. The ribociclib ECG changes occurred within the first 4 weeks of treatment and were reversible with dose interruption. 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.
    Ribociclib; Letrozole: (Major) Ribociclib should be avoided in patients receiving medications known to prolong the QT interval. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. The ribociclib ECG changes occurred within the first 4 weeks of treatment and were reversible with dose interruption. 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.
    Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with deutetrabenazine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. 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.
    Risperidone: (Moderate) Use risperidone and deutetrabenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. 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. Monitor for excessive sedation and somnolence during coadministration of risperidone and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with deutetrabenazine. Romidepsin has been reported to prolong the QT interval. 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.
    Ropinirole: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as ropinirole, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Rotigotine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as rotigotine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Rufinamide: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as rufinamide, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Safinamide: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Saquinavir: (Major) Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as 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.
    Scopolamine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as scopolamine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Secobarbital: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as barbiturates, may have additive effects and worsen drowsiness or sedation.
    Selegiline: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy, such as selegiline, within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Selpercatinib: (Major) Monitor ECGs for QT prolongation if coadministration of deutetrabenazine with selpercatinib is necessary. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. 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.
    Sertraline: (Moderate) Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, 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). If use of sertraline and deutetrabenazine together is necessary, use caution and monitor patients for QT prolongation. 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.
    Sevoflurane: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and halogenated anesthetics. 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. Halogenated anesthetics can prolong the QT interval.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving deutetrabenazine 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. 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.
    Sodium Oxybate: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as sodium oxybate, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Solifenacin: (Moderate) Consider the potential for additive QT prolongation if solifenacin is administered with deutetrabenazine. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. 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.
    Sorafenib: (Major) Avoid coadministration of sorafenib with deutetrabenazine due to the potential risk of 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. Sorafenib is associated with QTc prolongation. 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.
    Sotalol: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and sotalol. 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. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Sufentanil: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinub is administered with deutetrabenazine. Sunitinib can prolong the QT interval. 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.
    Suvorexant: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as suvorexant, may have additive effects and worsen drowsiness or sedation.
    Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with deutetrabenazine. Tacrolimus may prolong the QT interval and cause 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.
    Tamoxifen: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tamoxifen. 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. Tamoxifen has 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.
    Tapentadol: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If tapentadol is initiated in a patient taking deutetrabenazine, a reduced initial dosage of tapentadol is recommended. If the extended-release tapentadol tablets are used concurrently with deutetrabenazine, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tasimelteon: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as tasimelteon, may have additive effects and worsen drowsiness or sedation.
    Telavancin: (Moderate) Use caution if telavancin is administered with deutetrabenazine. Telavancin has been associated with QT prolongation. 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. Telavancin has been associated with QT prolongation.
    Telithromycin: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and telithromycin. 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. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Temazepam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as temazepam, may have additive effects and worsen drowsiness or sedation.
    Tetrabenazine: (Contraindicated) Concurrent use of deutetrabenazine and tetrabenazine is contraindicated. Both drugs are inhibitors of vesicular monoamine transporter 2 (VMAT2) and deplete monoamine stores. Deutetrabenazine may be started the day after tetrabenazine discontinuation.
    Thalidomide: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as thalidomide, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of deutetrabenazine with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and 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. Also, deutetrabenazine is a reversible, dopamine depleting drug and thioridazine is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as thioridazine, may have additive effects and worsen drowsiness or sedation.
    Thiothixene: (Major) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and thiothixene is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as thiothixene, may have additive effects and worsen drowsiness or sedation.
    Tipranavir: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Tipranavir 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, like QT prolongation and drowsiness.
    Tizanidine: (Moderate) Use tizanidine and deutetrabenazine together with caution due to additive CNS depression. Monitor patients for symptoms of excess sedation.
    Tolcapone: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as tolcapone, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Tolterodine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tolterodine. 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. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
    Toremifene: (Major) Avoid coadministration of deutetrabenazine with toremifene 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 also been shown to prolong the QTc interval in a dose- and concentration-related manner. 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.
    Tramadol: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tramadol; Acetaminophen: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tranylcypromine: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Trazodone: (Major) Avoid coadministration of trazodone with deutetrabenazine due to the potential for additive QT prolongation. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of 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. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as trazodone, may have additive effects and worsen drowsiness or sedation.
    Triazolam: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as triazolam, may have additive effects and worsen drowsiness or sedation.
    Triclabendazole: (Moderate) Concomitant use of triclabendazole and deutetrabenazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Tricyclic antidepressants: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Trifluoperazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and trifluoperazine. 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. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and trifluoperazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of trifluoperazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Trimipramine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and tricyclic antidepressants (TCAs). 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. 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). Monitor for excessive sedation and somnolence during coadministration of TCAs and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Triptorelin: (Major) Avoid coadministration of triptorelin with deutetrabenazine due to the risk of reduced efficacy of triptorelin. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. 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.
    Valbenazine: (Contraindicated) Concurrent use of deutetrabenazine and valbenazine is contraindicated. Both drugs are inhibitors of vesicular monoamine transporter 2 (VMAT2) and deplete monoamine stores.
    Valerian, Valeriana officinalis: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as valerian, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Valproic Acid, Divalproex Sodium: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as valproic acid, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Vandetanib: (Major) Avoid coadministration of vandetanib with deutetrabenazine 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 hypokalemia 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. 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.
    Vardenafil: (Moderate) Consider the potential for additive QT effects if vardenafil is administered with deutetrabenazine. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. 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.
    Vemurafenib: (Major) Avoid vemurafenib in patients receiving medications known to prolong the QT interval such as deutetrabenazine. Vemurafenib has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. 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.
    Venlafaxine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and venlafaxine. 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. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has been reported with postmarketing use.
    Vigabatrin: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as vigabatrin, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Voclosporin: (Moderate) Concomitant use of voclosporin and deutetrabenazine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. 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.
    Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with deutetrabenazine. Clarithromycin is associated with an established risk for 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.
    Voriconazole: (Moderate) Use voriconazole with caution in combination with deutetrabenazine due to additive QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of 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.
    Vorinostat: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and vorinostat. 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. Vorinostat therapy is associated with a risk of QT prolongation.
    Zaleplon: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as zaleplon, may have additive effects and worsen drowsiness or sedation.
    Ziprasidone: (Major) Concomitant use of ziprasidone and deutetrabenazine should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. 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. Additionally, deutetrabenazine is a reversible, dopamine-depleting drug, and ziprasidone is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as ziprasidone, may have additive effects and worsen drowsiness or sedation.
    Zolpidem: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as zolpidem, may have additive effects and worsen drowsiness or sedation.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate data on the developmental risk associated with deutetrabenazine use during pregnancy. Deutetrabenazine (5, 10, or 30 mg/kg/day) produced no clear adverse effects on embryofetal development when given to rats during the period of organogenesis. However, administration of tetrabenazine, a closely related VMAT2 inhibitor, to rats from organogenesis through lactation resulted in an increase in stillbirths and postnatal mortality.

    Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for deutetrabenazine and any potential adverse effects on the breast-feeding infant from the drug or the mother's underlying condition. There are no data on the presence of deutetrabenazine or its metabolites in human breast milk, the effects on the breast-fed infant, or the effects of the drug on milk production.

    MECHANISM OF ACTION

    The exact mechanism by which deutetrabenazine exerts its anti-chorea effects is unknown. Deutetrabenazine is a reversible depletor of monoamines (e.g., dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

    PHARMACOKINETICS

    Deutetrabenazine is administered orally. Protein binding of the major metabolites, alpha-dihydrotetrabenazine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), ranges from 60% to 68% and 59% to 63%, respectively. Deutetrabenazine is extensively metabolized to alpha-HTBZ and beta-HTBZ, primarily by carbonyl reductase. Alpha-HTBZ and beta-HTBZ are subsequently metabolized by CYP2D6 to form several minor metabolites, with minor contributions from CYP1A2 and CYP3A4/5. The metabolites are primarily renally eliminated. Approximately 75% to 86% and 8% to 11% of a dose is eliminated in the urine and feces, respectively. The half-life of total alpha-HTBZ and beta-HTBZ from deutetrabenazine is approximately 9 to 10 hours.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6
    In vitro studies indicate that alpha-HTBZ and beta-HTBZ metabolites of deutetrabenazine are substrates for CYP2D6.

    Oral Route

    After oral administration of deutetrabenazine, the extent of absorption is at least 80%. Plasma concentrations of deutetrabenazine are generally below detectable limits due to extensive and rapid hepatic metabolism. Peak plasma concentrations of the active metabolites, alpha-HTBZ and beta-HTBZ, are reached within 3 to 4 hours after a dose. Food has no effect on the AUC of alpha-HTBZ and beta-HTBZ; however, Cmax is increased by approximately 50% in the presence of food.