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    Ester Local Anesthetics

    DEA CLASS

    Rx

    DESCRIPTION

    Short-acting ester-type local anesthetic
    Used for infiltration anesthesia and peripheral, sympathetic, epidural, caudal, subarachoid, and intravenous regional (Bier's method) blocks
    Not effective as a topical anesthetic

    COMMON BRAND NAMES

    CLOROTEKAL, Nesacaine, Nesacaine MPF

    HOW SUPPLIED

    Chloroprocaine/Chloroprocaine Hydrochloride/Nesacaine/Nesacaine MPF Epidural Inj Sol: 2%, 3%
    Chloroprocaine/Chloroprocaine Hydrochloride/Nesacaine/Nesacaine MPF Infiltration Inj Sol: 1%, 2%, 3%
    Chloroprocaine/Chloroprocaine Hydrochloride/Nesacaine/Nesacaine MPF Intracaudal Inj Sol: 2%, 3%
    CLOROTEKAL Intrathecal Inj Sol: 1mL, 10mg

    DOSAGE & INDICATIONS

    For regional anesthesia.
    NOTE: Doses listed below are those considered necessary to produce a successful block and should be regarded as guidelines. Individual variations in onset and duration may occur.
    For caudal anesthesia.
    Epidural dosage
    Adults

    15 to 25 mL of a 2% or 3% solution (300 to 750 mg) epidurally. Repeat doses may be given at 40 to 60 minute intervals.

    For epidural anesthesia.
    Epidural dosage for the cervical or thoracic region
    Adults

    1.5 to 2 mL of a 2% or 3% solution (30 to 60 mg) epidurally for each segment to be anesthetized.

    Epidural dosage for the lumbar and sacral region
    Adults

    2 to 2.5 mL of a 2% or 3% solution epidurally for each segment to be anesthetized. Repeat doses of 2 to 6 mL less than the original dose may be given at 40 to 50 minute intervals.

    For spinal anesthesia (Clorotekal).
    Intrathecal dosage
    Adults

    50 mg intrathecally once to obtain an effective block to the T10 level for an adult with average height and weight (approximately 70 kg). The safety and efficacy of doses above 50 mg have not been established.

    For local anesthesia via infiltration anesthesia or nerve block anesthesia.
    NOTE: Doses listed below are those considered necessary to produce a successful block and should be regarded as guidelines. Individual variations in onset and duration may occur.
    Brachial plexus block.
    Regional dosage
    Adults

    30 to 40 mL of a 2% solution (600 to 800 mg).

    Cervical nerve block.
    Regional dosage
    Adults

    3 to 4 mL of a 1% to 2% solution (30 to 80 mg) per segment.

    Occipital nerve block.
    Regional dosage
    Adults

    3 to 5 mL of a 1% to 2% solution (30 to 100 mg).

    Mandibular nerve block or maxillary nerve block for dental anesthesia.
    Regional dosage
    Adults

    2 to 3 mL of a 2% solution (40 to 60 mg).

    Ophthalmic anesthesia via infraorbital nerve block.
    Regional dosage
    Adults

    0.5 to 1 mL of a 2% solution (10 to 20 mg).

    Ulnar nerve block or paravertebral block.
    Regional dosage
    Adults

    3 to 5 mL of a 2% solution (60 to 100 mg).

    Intercostal nerve block.
    Regional dosage
    Adults

    3 mL of a 1% to 2% solution (30 to 60 mg).

    Sciatic nerve block.
    Regional dosage
    Adults

    10 to 15 mL of a 2% solution (200 to 300 mg).

    Stellate ganglion block.
    Regional dosage
    Adults

    5 to 10 mL of a 1% to 2% solution (50 to 200 mg).

    Lumbar sympathetic block.
    Regional dosage
    Adults

    15 to 20 mL of a 1% to 2% solution (150 to 400 mg).

    Interdigital block.
    Regional dosage
    Adults

    3 to 4 mL of a 1% solution without epinephrine (30 to 40 mg).

    For use in obstetric anesthesia.
    Pudendal nerve block.
    Regional dosage
    Adults

    10 mL of a 2% solution (200 mg) for each side.

    Paracervical block.
    Regional dosage
    Adults

    3 mL of a 1% solution (30 mg) for each of 4 sites up to 120 mg.

    MAXIMUM DOSAGE

    The dose of local anesthetics differs with the anesthetic procedure; the area to be anesthetized; the vascularity of the tissues; the number of neuronal segments to be blocked; the intensity of the block; the degree of muscle relaxation required; the duration of anesthesia desired; individual tolerance; and the physical condition of the patient.

    Adults

    50 mg/dose intrathecally. 11 mg/kg for other routes, not to exceed 800 mg/dose when given without epinephrine. With epinephrine (1:200,000), 14 mg/kg, not to exceed 1,000 mg.

    Geriatric

    50 mg/dose intrathecally. 11 mg/kg for other routes, not to exceed 800 mg/dose when given without epinephrine. With epinephrine (1:200,000), 14 mg/kg, not to exceed 1,000 mg.

    Adolescents

    11 mg/kg. Concentrations of 0.5% to 1% are suggested for infiltration, and 1% to 1.5% are recommended for nerve block. Safety and efficacy of intrathecal chloroprocaine have not been established.

    Children

    4 years and older: 11 mg/kg. Concentrations of 0.5% to 1% are suggested for infiltration, and 1% to 1.5% are recommended for nerve block. Safety and efficacy of intrathecal chloroprocaine have not been established.
    3 years and younger: 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

    Use with caution in patients with advanced hepatic disease. Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

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

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Specialized references should be consulted for specific procedures and administration techniques.
    Resuscitative equipment and drugs used in the management of adverse reactions should be immediately available while administering local anesthetics.
    Chloroprocaine is administered by infiltration or peripheral or sympathetic block techniques.

    Other Injectable Administration

    Peripheral or sympathetic block:
    A solution containing 1:200,000 epinephrine/chloroprocaine may be prepared by adding 0.1 mL of epinephrine 1 mg/mL injection to 20 mL of chloroprocaine injection that does not contain preservatives. Do not use solutions containing epinephrine for interdigital anesthesia.
    Inject slowly and with frequent aspirations to prevent intravascular injection.
     
    Epidural Administration
    This route of administration should only be used by specially trained healthcare professionals. Specialized references should be consulted for specific procedures and administration techniques.
    Resuscitative equipment and drugs used in the management of adverse reactions should be immediately available while administering local anesthetics.
    May be given as intermittent epidural or caudal injection, continuous epidural infusion, or as patient controlled epidural analgesia.
    Placement of epidural catheter and administration should be at a site near the dermatomes covering the field of pain to decrease dose requirements and increase specificity.
    A test dose of 3 mL of a 3% injection or 5 mL of a 2% injection should be administered 5 minutes before administering the total dose. If the patient is moved in such a way as to displace the catheter, the test dose should be repeated. Inadvertent subarachnoid injection is indicated by motor paralysis and extensive sensory anesthesia.
    Epidural or caudal block:
    Injections containing preservatives should not be used for epidural or caudal block. Discard any partially used injections that do not contain preservatives.
    Large single doses should be divided into fractional doses and injected slowly with frequent aspirations. Care should be taken to prevent intravascular or subarachnoid injection.
    Epidural infusion:
    A controlled-infusion device must be used. For highly concentrated injections, an implantable controlled-microinfusion device is used. Monitor patients for several days after implantation of the device.
    Injections containing preservatives should not be used for epidural infusion. Discard any partially used injections that do not contain preservatives.
    Preservative-free 0.9% Sodium Chloride Injection is recommended for dilution.
    Implantable infusion device: Filling of the infusion device reservoir should only be done by fully trained and qualified healthcare professionals. Strict aseptic technique must be used. Withdraw dose from the ampule through a 5-micrometer (or smaller pore diameter) microfilter to avoid contamination with glass or other particles. Then remove filter needle and replace with a clean needle prior to injecting the reservoir. Ensure proper placement of the needle when filling the reservoir to avoid accidental overdosage.
    To avoid exacerbation of severe pain and/or reflux of CSF into the reservoir, avoid depletion of the reservoir.
     
    Intrathecal Administration (Clorotekal ONLY)
    Clorotekal is only for intrathecal administration. Do not administer by any other parenteral route. The safety of administration via continuous spinal catheters has not been established.
    Use only during surgical procedures suitable for the short duration of action of chloroprocaine.
    Clorotekal is intended for single use only. Use a filter needle to draw up the product. Administer immediately after opening.
    Do not mix or dilute with other products. Do not substitute the product with a different chloroprocaine product.
    Storage: Discard any unused product. Protect from light. Do not freeze, heat, or autoclave.

    STORAGE

    CLOROTEKAL:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not autoclave
    - Do not freeze
    - Do not refrigerate
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in carton until time of use
    Nesacaine:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not autoclave
    - Protect from freezing
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nesacaine MPF:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not autoclave
    - Protect from freezing
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Local anesthetics should only be administered by a clinician trained in the diagnosis and management of drug-related toxicity and other acute emergencies that might arise from the administration of a regional anesthetic block. The immediate availability of oxygen, cardiopulmonary resuscitative equipment and drugs and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured. Any delay in appropriate management may lead to the development of acidosis, cardiac arrest and possibly death.

    Ester local anesthetic hypersensitivity, para-aminobenzoic acid, PABA hypersensitivity, paraben hypersensitivity

    Chloroprocaine is contraindicated in patients with known ester local anesthetic hypersensitivity or para-aminobenzoic acid, PABA hypersensitivity. Chloroprocaine is more likely to cause hypersensitivity reactions than are amide-type local anesthetics. Some formulations contain methylparaben and may be inappropriate for patients with paraben hypersensitivity. Also, formulations with methylparaben should not be used for lumbar or caudal epidural anesthesia because safety of this antimicrobial preservative has not been established in regard to inadvertent or intended intrathecal injection.

    Epidural administration, intraarterial administration, intrathecal administration, intravenous administration, requires an experienced clinician

    The use of chloroprocaine requires an experienced clinician knowledgeable in anesthetic technique and the management of dose-related toxicities. Intravenous administration or intraarterial administration of chloroprocaine should be avoided. Only the Clorotekal formulation of chloroprocaine is intended for intrathecal administration; other chloroprocaine products must not be given intrathecally. Clorotekal is contraindicated for use in intravenous regional anesthesia, and epidural administration should be avoided. Unintended intravenous or intraarterial administration may result in cardiac arrest and may require prolonged resuscitation. To avoid intravascular administration of chloroprocaine during local anesthetic procedures, aspiration should be performed before the local anesthetic is injected and after repositioning of the needle. During epidural administration, a test dose should be administered initially and the patient should be monitored for CNS and cardiovascular toxicity, as well as signs of inadvertent intrathecal administration. Syringe aspiration should also be performed before and during each supplemental injection in continuous catheter techniques. Clinicians should be aware that the absence of blood return does not guarantee that intravascular injection has been avoided.

    Head and neck anesthesia

    During head and neck anesthesia, including dental and ophthalmic anesthesia, small doses of local anesthetics may produce adverse reactions similar to the systemic toxicity seen with unintentional intravascular injections of larger doses. Patients receiving local head and neck anesthesia are at increased risk of CNS toxicity due to potential intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should have their ventilatory and circulatory systems monitored closely. Recommended doses should not be exceeded in these patients.

    Ocular surgery

    When local anesthetics are used for retrobulbar block during ocular surgery, lack of corneal sensation should not be relied upon to determine whether or not the patient is ready for surgery. Lack of corneal sensation usually precedes clinically acceptable external ocular muscle akinesia.

    Coagulopathy, hypertension, infection, neurological disease, sepsis

    Intrathecal chloroprocaine is contraindicated in patients with coagulopathy, local infection at the injection site, or sepsis. Use lumbar and caudal epidural anesthesia with extreme caution in patients with neurological disease, spinal deformities, sepsis, or severe hypertension.

    AV block, cardiac disease, dehydration, hypotension, hypovolemia, myasthenia gravis, shock

    Intrathecal chloroprocaine is specifically contraindicated for use in patients with decompensated cardiac insufficiency, hypovolemic shock, and other serious problems with cardiac conduction. Local anesthetics should be used with caution in patients with hypotension, hypovolemia or dehydration, myasthenia gravis, shock, or cardiac disease. Patients with impaired cardiac function, particularly AV block, may be less able to compensate for functional changes associated with prolonged A-V conduction (i.e., PR or QT prolongation) caused by local anesthetics.

    Geriatric

    Geriatric patients, especially those receiving treatment for hypertension, may be at increased risk for the hypotensive effects of local anesthetics. Monitor blood pressure carefully.

    Pseudocholinesterase deficiency

    Ester-type local anesthetics should be used cautiously, if at all, in patients with low plasma concentrations of pseudocholinesterase (e.g., pseudocholinesterase deficiency). Ester-type local anesthetics are metabolized by hydrolysis by pseudocholinesterase.

    Hepatic disease

    Use chloroprocaine with caution in patients with advanced hepatic disease. Ester-type anesthetics are hydrolyzed by plasma cholinesterase produced by the liver, and the risk of toxic effects may be greater in patients with advanced hepatic disease.

    Renal failure, renal impairment

    Chloroprocaine and its metabolites undergo substantial renal elimination, and the risk of toxic effects may be greater in patients with renal impairment or renal failure.

    Eclampsia, fetal distress, fetal prematurity, labor, obstetric delivery, paracervical nerve block, pregnancy, pudendal nerve block

    The limited data with chloroprocaine use in pregnancy are insufficient to inform a drug associated risk of adverse developmental outcomes. Placental transfer of local anesthetics is dependent upon the degree of plasma protein binding, ionization, and lipid solubility of each agent. No intact chloroprocaine and only trace amounts of its byproduct have been found in umbilical cord arterial or venous plasma after properly administered paracervical blocks. Local anesthetics used as epidural, paracervical, caudal, or pudendal nerve block anesthesia for obstetric delivery can cause maternal, fetal, or neonatal toxicity. The incidence and severity of toxicity depend upon the procedure performed, the type and amount of drug used, and drug administration technique. Proper positioning of the patient will help to decrease maternal hypotension occurring secondary to anesthetic-induced vasodilation. Injection of the local anesthetic should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Epidural, caudal, paracervical, or pudendal nerve block may alter the forces of parturition. The use of obstetrical anesthesia may alter the duration of various phases of labor and increase the need for forceps assistance. Paracervical nerve block may be associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation. Epidural or spinal anesthesia may prolong the second stage of labor by removing the reflex urge to bear down or by interfering with motor function. Fetal bradycardia has occurred during use of paracervical block anesthesia in about 5% to 10% of cases where initial total doses of 120 to 400 mg of chloroprocaine were administered. Fetal heart rate should always be monitored during paracervical anesthesia. Use of obstetrical paracervical block with chloroprocaine in the presence of eclampsia, fetal distress, or fetal prematurity is not recommended. In general, local anesthetics should be used with extreme caution in patients with pregnancies complicated by fetal prematurity, eclampsia, fetal distress, or maternal or fetal sepsis. Electronic fetal monitoring for signs of fetal distress is highly recommended. Use of paracervical block in early pregnancy (i.e., anesthesia for elective abortion) may result in rapid systemic absorption and can result in maternal seizures or cardiovascular collapse. Injections should be administered slowly with frequent aspirations. Allow a 5-minute interval between chloroprocaine administration to each side. When used during labor and delivery, some local anesthetics have been associated with diminished muscle strength and tone in the newborn for the first day or 2 of life.

    Breast-feeding

    There are no data describing the presence of chloroprocaine in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for chloroprocaine and any potential adverse effects on the breast-fed infant from chloroprocaine or the underlying maternal condition. Other local anesthetics, such as lidocaine and bupivacaine, are minimally excreted into breast milk; however, the potential for adverse effects in the nursing infant is low due to poor oral absorption. Although chloroprocaine was not evaluated by the American Academy of Pediatrics (AAP), previous AAP recommendations considered lidocaine to be usually compatible with breast-feeding.

    G6PD deficiency, infants, methemoglobinemia, neonates, pulmonary disease

    Methemoglobinemia has been reported with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), preexisting (congenital or idiopathic) methemoglobinemia, cardiac or pulmonary compromise (cardiac disease or pulmonary disease), neonates and infants younger than 6 months, and those with concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing methemoglobinemia. Monitor such patients closely for signs and symptoms of methemoglobinemia if a local anesthetic must be used. Signs of methemoglobinemia may occur immediately or may be delayed hours after exposure. Immediately discontinue the local anesthetic to avoid serious central nervous system and cardiovascular adverse events, as methemoglobin concentrations may continue to rise. Patients may require supportive care such as oxygen therapy and hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / 0-1.0
    muscle paralysis / Delayed / Incidence not known
    coma / Early / Incidence not known
    respiratory arrest / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    AV block / Early / Incidence not known
    visual impairment / Early / Incidence not known
    atrial fibrillation / Early / Incidence not known
    apnea / Delayed / Incidence not known
    arachnoiditis / Early / Incidence not known
    neonatal depression / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    chondrolysis / Delayed / Incidence not known
    methemoglobinemia / Early / Incidence not known

    Moderate

    hypotension / Rapid / 4.9-4.9
    hyperglycemia / Delayed / 0-2.0
    dyspnea / Early / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known
    myoclonia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    akathisia / Delayed / Incidence not known
    PR prolongation / Rapid / Incidence not known
    angina / Early / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    palpitations / Early / Incidence not known
    urinary incontinence / Early / Incidence not known
    hot flashes / Early / Incidence not known
    fetal bradycardia / Delayed / Incidence not known
    fetal acidosis / Delayed / Incidence not known
    hypotonia / Delayed / Incidence not known
    erythema / Early / Incidence not known
    blurred vision / Early / Incidence not known
    photophobia / Early / Incidence not known

    Mild

    injection site reaction / Rapid / 3.7-3.7
    nausea / Early / 0-2.0
    headache / Early / 0-2.0
    shivering / Rapid / Incidence not known
    dysesthesia / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    vomiting / Early / Incidence not known
    weakness / Early / Incidence not known
    drowsiness / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    restlessness / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    tremor / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    back pain / Delayed / Incidence not known
    malaise / Early / Incidence not known
    rash / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    sneezing / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    syncope / Early / Incidence not known
    fever / Early / Incidence not known
    diplopia / Early / Incidence not known
    tinnitus / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Acetaminophen: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Caffeine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Codeine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Acetaminophen; Dextromethorphan: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Diphenhydramine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Hydrocodone: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Acetaminophen; Oxycodone: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Pentazocine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Propoxyphene: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Acetaminophen; Pseudoephedrine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Alfentanil: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Alfuzosin: (Major) Alfuzosin has a slight effect to prolong the QT interval, and should be used cautiously in combination with other medications known to prolong the QT interval, such as local anesthetics.
    Aliskiren; Amlodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Ambenonium Chloride: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Amiloride: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as aminosalicylic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Amlodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Amlodipine; Atorvastatin: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Amlodipine; Benazepril: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Amlodipine; Celecoxib: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Amlodipine; Olmesartan: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Amlodipine; Valsartan: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Angiotensin II receptor antagonists: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Angiotensin-converting enzyme inhibitors: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Articaine; Epinephrine: (Moderate) Use articaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Aspirin, ASA; Oxycodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Atenolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Atenolol; Chlorthalidone: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Atropine; Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug. (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Belladonna; Opium: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Bendroflumethiazide; Nadolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Benzalkonium Chloride; Benzocaine: (Moderate) Use chloroprocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Benzhydrocodone; Acetaminophen: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Benzocaine: (Moderate) Use chloroprocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Benzocaine; Butamben; Tetracaine: (Moderate) Use chloroprocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Beta-adrenergic blockers: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Betaxolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Bisoprolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Brimonidine; Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Brompheniramine; Guaifenesin; Hydrocodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Bupivacaine Liposomal: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use chloroprocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use chloroprocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine; Epinephrine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use chloroprocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine; Lidocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use chloroprocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Use lidocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine; Meloxicam: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use chloroprocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Butalbital; Acetaminophen: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Calcium-channel blockers: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Carteolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Carvedilol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Central-acting adrenergic agents: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chloroquine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as chloroquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Chlorpheniramine; Codeine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Chlorpheniramine; Hydrocodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Cholinesterase inhibitors: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Clevidipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Codeine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Codeine; Guaifenesin: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Codeine; Guaifenesin; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Codeine; Phenylephrine; Promethazine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Codeine; Promethazine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Cyclophosphamide: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as cyclophosphamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Dapsone: (Moderate) Coadministration of dapsone with chloroprocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
    Daratumumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Dihydroergotamine: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Diltiazem: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Donepezil: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Donepezil; Memantine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Dorzolamide; Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Enalapril; Felodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Enflurane: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Eplerenone: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Ergoloid Mesylates: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Ergonovine: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Ergot alkaloids: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Ergotamine: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Ergotamine; Caffeine: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Erythromycin; Sulfisoxazole: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Esmolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Etomidate: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Felodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Fentanyl: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics 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. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Flutamide: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Fosphenytoin: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as fosphenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Fospropofol: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Galantamine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    General anesthetics: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Guaifenesin; Hydrocodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Halothane: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Homatropine; Hydrocodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Hydrocodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hydrocodone; Ibuprofen: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hydrocodone; Phenylephrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hydrocodone; Potassium Guaiacolsulfonate: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hydrocodone; Pseudoephedrine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hydromorphone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Hydroxyurea: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as hydroxyurea, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Ibuprofen; Oxycodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Ifosfamide: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as ifosfamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Iloprost: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Isoflurane: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Isradipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Ketamine: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Labetalol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as chloroprocaine. Concomitant use of chloroprocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
    Levamlodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Levobetaxolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Levobunolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Levorphanol: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Lidocaine: (Moderate) Use lidocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Lidocaine; Epinephrine: (Moderate) Use lidocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Lidocaine; Prilocaine: (Moderate) Use lidocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Use prilocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Loop diuretics: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Mecamylamine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Meperidine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Meperidine; Promethazine: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Mepivacaine: (Moderate) Use mepivacaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Mepivacaine; Levonordefrin: (Moderate) Use mepivacaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Methohexital: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Methylergonovine: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Methysergide: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Metoclopramide: (Moderate) Coadministration of chloroprocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Metoprolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Minocycline: (Moderate) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Monoamine oxidase inhibitors: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Nadolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nebivolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nebivolol; Valsartan: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Neostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Nicardipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nifedipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nimodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nisoldipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nitrates: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Nitrofurantoin: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as nitrofurantoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Oxycodone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Oxymorphone: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Penbutolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Pergolide: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
    Perindopril; Amlodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Pertuzumab; Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Phenobarbital: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Phenytoin: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as phenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Physostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Pindolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Potassium-sparing diuretics: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Prilocaine: (Moderate) Use prilocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Prilocaine; Epinephrine: (Moderate) Use prilocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Primaquine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as primaquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Primidone: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as primidone, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Procarbazine: (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
    Propofol: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Propoxyphene: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Propranolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Pyridostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Pyrimethamine; Sulfadoxine: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Quinine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rasburicase: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Remifentanil: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Reserpine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Rituximab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Rivastigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Ropivacaine: (Moderate) Use ropivacaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sevoflurane: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Spironolactone: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Sufentanil: (Minor) Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Sulfadiazine: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfasalazine: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfisoxazole: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfonamides: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Tacrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Telmisartan; Amlodipine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Tetracaine: (Moderate) Use tetracaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Thiazide diuretics: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Thiopental: (Major) If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Tramadol; Acetaminophen: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Trandolapril; Verapamil: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Treprostinil: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Triamterene: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Tubocurarine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Valproic Acid, Divalproex Sodium: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as valproic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Vasodilators: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Verapamil: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.

    PREGNANCY AND LACTATION

    Pregnancy

    The limited data with chloroprocaine use in pregnancy are insufficient to inform a drug associated risk of adverse developmental outcomes. Placental transfer of local anesthetics is dependent upon the degree of plasma protein binding, ionization, and lipid solubility of each agent. No intact chloroprocaine and only trace amounts of its byproduct have been found in umbilical cord arterial or venous plasma after properly administered paracervical blocks. Local anesthetics used as epidural, paracervical, caudal, or pudendal nerve block anesthesia for obstetric delivery can cause maternal, fetal, or neonatal toxicity. The incidence and severity of toxicity depend upon the procedure performed, the type and amount of drug used, and drug administration technique. Proper positioning of the patient will help to decrease maternal hypotension occurring secondary to anesthetic-induced vasodilation. Injection of the local anesthetic should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Epidural, caudal, paracervical, or pudendal nerve block may alter the forces of parturition. The use of obstetrical anesthesia may alter the duration of various phases of labor and increase the need for forceps assistance. Paracervical nerve block may be associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation. Epidural or spinal anesthesia may prolong the second stage of labor by removing the reflex urge to bear down or by interfering with motor function. Fetal bradycardia has occurred during use of paracervical block anesthesia in about 5% to 10% of cases where initial total doses of 120 to 400 mg of chloroprocaine were administered. Fetal heart rate should always be monitored during paracervical anesthesia. Use of obstetrical paracervical block with chloroprocaine in the presence of eclampsia, fetal distress, or fetal prematurity is not recommended. In general, local anesthetics should be used with extreme caution in patients with pregnancies complicated by fetal prematurity, eclampsia, fetal distress, or maternal or fetal sepsis. Electronic fetal monitoring for signs of fetal distress is highly recommended. Use of paracervical block in early pregnancy (i.e., anesthesia for elective abortion) may result in rapid systemic absorption and can result in maternal seizures or cardiovascular collapse. Injections should be administered slowly with frequent aspirations. Allow a 5-minute interval between chloroprocaine administration to each side. When used during labor and delivery, some local anesthetics have been associated with diminished muscle strength and tone in the newborn for the first day or 2 of life.

    MECHANISM OF ACTION

    Like all local anesthetics, chloroprocaine causes a reversible nerve-conduction blockade by decreasing nerve membrane permeability to sodium. This decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade affects all nerve fibers in the following sequence: autonomic, sensory, and motor, with effects diminishing in reverse order. Loss of nerve function clinically is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by injecting the local anesthetic solution subcutaneously, intradermally, or submucosally around the nerve trunks or ganglia supplying the area to be anesthetized.
     
    Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance have been reported. Toxic blood concentrations depress cardiac conduction and excitability, which may lead to AV block, ventricular arrhythmia, and cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Local anesthetics can produce central nervous system stimulation, depression, or both following systemic absorption. CNS stimulation is usually manifested as restlessness, tremors, and shivering progressing to convulsions, followed by depression and coma, progressing ultimately to respiratory arrest. However, local anesthetics have a primary depressant effect on the medulla and higher centers. The depressed stage may occur without the prior excitatory stage.

    PHARMACOKINETICS

    Chloroprocaine is administered parenterally via infiltration or nerve block, epidurally, or intrathecally. Chloroprocaine is distributed to all body tissues, with a high concentration in well-perfused organs such as the liver, lungs, heart, and brain. Chloroprocaine is hydrolyzed by plasma pseudocholinesterases. It is renally excreted and has an in vitro plasma half-life of 19 to 26 seconds in adults. The apparent half-life in vivo was 3.1 +/- 1.6 minutes (range 1.5 to 6.4 minutes) in maternal plasma following intrapartum epidural anesthesia.

    Other Route(s)

    Epidural and Regional Routes
    The absorption of chloroprocaine depends on the dose, concentration, route of administration, tissue vascularity, and degree of vasodilation. A vasoconstrictor, such as epinephrine, may be necessary to counteract the vasodilation produced by chloroprocaine. Epinephrine will slow the rate of absorption, prolong the duration of action, and maintain hemostasis. Anesthesia is obtained within 6 to 12 minutes and lasts approximately 30 to 60 minutes (60 to 90 minutes if epinephrine 1:200,000 is used).