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  • CLASSES

    Monoamine Depletor

    BOXED WARNING

    Depression, suicidal ideation

    Tetrabenazine is contraindicated in those with active suicidal ideation or who have untreated or inadequately treated depression. The drug should be used with caution in patients with a history of depression or suicidal thoughts or behavior. Patients with Huntington's disease (HD) are at increased risk for depression and suicidal ideation or behaviors (suicidality). Tetrabenazine use increases the risk for suicidality in patients with HD. Unusual changes in mood, behaviors, or actions should be reported promptly to the treating physician. If depression or suicidality does not resolve, consider discontinuing treatment with tetrabenazine. Tetrabenazine should be prescribed in the smallest quantity consistent with good management in order to reduce the risk of overdose.

    DEA CLASS

    Rx

    DESCRIPTION

    Monoamine depleter and dopamine receptor blocker
    Used for treating chorea associated with Huntington's disease
    May be useful for tardive dyskinesia, dystonia, Tourette's syndrome, and myoclonus

    COMMON BRAND NAMES

    Xenazine

    HOW SUPPLIED

    Tetrabenazine/Xenazine Oral Tab: 12.5mg, 25mg

    DOSAGE & INDICATIONS

    For the treatment of chorea associated with Huntington's Disease (Huntington's Chorea).
    NOTE: The FDA has designated tetrabenazine an orphan drug for this indication.
    Oral dosage
    Adults

    Initially, 12.5 mg PO each morning. After one week, increase to 12.5 mg PO twice daily. The dose may be increased by 12.5 mg each week. Dosage must be individualized. Patients who require doses more than 50 mg per day should be genotyped for CYP2D6 expression. In patients who do not express CYP2D6 (i.e., poor metabolizers of CYP2D6) and require a daily dose of 37.5 mg to 50 mg, administer in 3 divided doses. The maximum recommended single dose is 25 mg with a maximum daily dose of 50 mg. In patients who do express CYP2D6 (i.e., intermediate or extensive metabolizers of CYP2D6) and require a daily dose of at least 50 mg, administer in 3 divided doses. The maximum recommended single dose is 37.5 mg with a maximum daily dose of 100 mg. For patients receiving concomitant strong CYP2D6 inhibitors, the maximum single dose should not exceed 25 mg and the daily dose should not exceed 50 mg. If adverse events such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety, or intolerable sedation occur, reduce the dose. If the adverse event does not resolve, consider discontinuing tetrabenazine or initiating treatment for the adverse effect (e.g., antidepressant). Tetrabenazine may be abruptly discontinued, but chorea may occur 12 to 18 hours after the last dose. If tetrabenazine therapy is interrupted for 5 or more days, retitration of the dose is advised.

    MAXIMUM DOSAGE

    Adults

    100 mg/day PO in patients who express CYP2D6; 50 mg/day PO in patients who do not express CYP2D6.

    Elderly

    100 mg/day PO in patients who express CYP2D6; 50 mg/day PO in patients who do not express CYP2D6.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Tetrabenazine is contraindicated in patients with hepatic impairment.

    Renal Impairment

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

    ADMINISTRATION

     
    Instructions for obtaining tetrabenazine: The physician and patient must complete and sign the Xenazine Treatment Form. This form serves as the patient's prescription and should be faxed to the Xenazine Information Center at 1-888-882-6013 upon completion. The Xenazine Information Center then confirms the patient's insurance or potential eligibility for financial assistance. Thereafter, the prescription is sent by the Xenazine Information Center to a Specialty Pharmacy that coordinates all prescription activities including collecting the co-payment, filling and sending the initial supply and refills, and providing drug information about tetrabenazine. The Specialty Pharmacy will send the filled prescriptions to the physician's office or to the patient as requested.
    Prior to initiating treatment with tetrabenazine, the physician should review the following materials with the patient: Xenazine Medication Guide, Patient/Caregiver Counseling Guide, and Initial Dosing Plan. These documents may be obtained through the sales representative, manufacturer's website, or by calling the Xenazine Information Center at 1-888-882-6013.
    A MedGuide will be provided by the Specialty Pharmacy with each new prescription and refill. The provider should instruct patients to review this guide with each new prescription and refill.
    A Step-By-Step Patient Kit is available through the manufacturer which provides patients and caregivers with education and support materials for understanding tetrabenazine therapy. This kit may be obtained by calling the Xenazine Information Center at 888-882-6013.

    Oral Administration

    May be administered without regard to meals.

    STORAGE

    Xenazine:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Tetrabenazine should be avoided in patients with a previous hypersensitivity to tetrabenazine or any other component of the commercial product.

    Depression, suicidal ideation

    Tetrabenazine is contraindicated in those with active suicidal ideation or who have untreated or inadequately treated depression. The drug should be used with caution in patients with a history of depression or suicidal thoughts or behavior. Patients with Huntington's disease (HD) are at increased risk for depression and suicidal ideation or behaviors (suicidality). Tetrabenazine use increases the risk for suicidality in patients with HD. Unusual changes in mood, behaviors, or actions should be reported promptly to the treating physician. If depression or suicidality does not resolve, consider discontinuing treatment with tetrabenazine. Tetrabenazine should be prescribed in the smallest quantity consistent with good management in order to reduce the risk of overdose.

    CNS depression, coma, neurological disease

    Tetrabenazine may induce a variety of CNS effects and should be used cautiously in those with preexisting forms of neurological disease. Because tetrabenazine may cause CNS depression, it is not recommended for use in coma or other forms of severe CNS depression.

    Alcoholism, driving or operating machinery

    Tetrabenazine has the potential to impair cognitive and motor skills. Sedation is the most common dose-limiting side effect of tetrabenazine. Patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness, until they know how tetrabenazine affects them. Alcohol consumption may exacerbate sedation associated with the drug. Extreme caution is advisable in patients with alcoholism.

    Pregnancy

    There are no adequate data on the developmental risk associated with tetrabenazine use during pregnancy. In rat studies, administration of tetrabenazine from the beginning of organogenesis through the lactation period was associated with an increase in stillbirths and offspring postnatal mortality at doses of 15 and 30 mg/kg/day (3 times the maximum recommended human dose of 100 mg/day on a mg/m2 basis); delayed pup maturation was observed at doses of 5 to 30 mg/kg/day. However, no clear effects of tetrabenazine on embryofetal development have been observed during animal studies. When 9-desmethyl-beta-DHTBZ, a major metabolite of tetrabenazine, was administered to pregnant rats during organogenesis, increases in embryofetal mortality were observed at doses of 15 and 40 mg/kg/day, and decreased fetal body weights were observed at a dose of 40 mg/kg/day. Increases in gestation duration, stillbirths, and offspring postnatal mortality (40 mg/kg/day); decreases in pup weight (40 mg/kg/day); and neurobehavioral (increased activity, learning and memory deficits) and reproductive (decreased litter size) impairment (15 and 40 mg/kg/day) were observed with 9-desmethyl-beta-DHTBZ administration to pregnant rats throughout organogenesis and lactation. The 9-desmethyl-beta-DHTBZ no-effect dose for developmental toxicity of 8 mg/kg/day in rats was associated with an AUC lower than that in humans at the maximum recommended human dose. In a case report, tetrabenazine treatment (75 mg/day) was initiated late in the second trimester in a woman with chorea gravidarum. Although the infant was born with a small ventricular septal defect, an association to the tetrabenazine therapy was thought to be unlikely since fusion of the intraventricular septum is normally complete by 8 weeks gestation. Extrapyramidal and withdrawal symptoms including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported after delivery in neonates exposed to dopamine antagonists (e.g., antipsychotics) during the third trimester. These effects have varied in severity ranging from self-limited to requiring intensive care unit stays and prolonged hospitalization. As a central dopamine depletor, tetrabenazine has the potential to cause similar effects. It is not clear if tetrabenazine, through its effect on prolactin, would affect labor or delivery.

    Breast-feeding

    There are no data on the presence of tetrabenazine or its metabolites in human breast 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 tetrabenazine and any potential adverse effects on the breast-fed infant from the drug or the mother's underlying condition. Tetrabenazine elevates serum prolactin concentrations in humans, and thus, interference with proper lactation is possible. Previous American Academy of Pediatrics (AAP) did not make specific recommendations regarding tetrabenazine use during breast-feeding, but the AAP cautioned that psychotropic medications affect neurotransmitter function in the developing central nervous system, and therefore, the accurate prediction of long-term adverse effects may not be possible.

    Bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, dehydration, diabetes mellitus, females, geriatric, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, hypovolemia, long QT syndrome, malnutrition, myocardial infarction, orthostatic hypotension, QT prolongation, thyroid disease

    Tetrabenazine may cause an increase in the corrected QTc interval in some patients. Other drugs that prolong the QT interval have been associated with torsade de pointes (TdP), a life-threatening arrhythmia. Existent QT prolongation increases the risk of TdP. Therefore, tetrabenazine should be avoided in those with QT prolongation associated with congenital long QT syndrome or those with a history of cardiac arrhythmias. Tetrabenazine should not be used in combination with other drugs known to prolong QTc because the risk for TdP may be increased. Use tetrabenazine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation. It should be noted that patients with recent myocardial infarction or unstable heart disease were excluded from clinical trials; therefore, the effects of the drug in patients with these conditions are generally unknown. Postural dizziness, syncope, and orthostatic hypotension have been reported. Hypotension caused by hypovolemia, antihypertensive drugs, or dehydration may be potentiated. The pharmacokinetics of tetrabenazine have not been formally studied in geriatric patients. Caution is advisable in the elderly since this patient population may be more susceptible to the cardiac effects of the drug.

    Parkinson's disease

    Tetrabenazine should be used with caution in those patients with Parkinson's disease because of possible aggravation of EPS due to dopamine-receptor blockade.

    Children

    Safety and efficacy of tetrabenazine use in children has not been established. Routine cardiovascular monitoring has been suggested for children receiving psychotropic medications due to the potential of these agents to produce adverse cardiac effects.

    Renal disease, renal failure, renal impairment

    The safe use of tetrabenazine in renal disease has not been fully evaluated. Caution is recommended when tetrabenazine is prescribed to patients with renal failure or any degree of renal impairment.

    Hepatic disease

    Tetrabenazine is contraindicated in patients with any degree of hepatic impairment or hepatic disease. Pharmacokinetic evaluations indicate that patients with hepatic impairment experience a 7- to 190-fold higher maximum blood concentration of tetrabenazine than healthy subjects. In addition, the half-lives of tetrabenazine and its metabolites are prolonged. The safety and efficacy of increased exposure to tetrabenazine and its metabolites in those with hepatic impairment is unknown.

    Surgery

    Caution is advised for patients on tetrabenazine who will receive general anesthesia, due to the potential for CNS effects. Check with the anesthesiologist regarding the continuation of tetrabenazine in a patient who is scheduled for surgery.

    Fever

    Neuroleptic malignant syndrome has been reported in association with the use of tetrabenazine. In the presence of high fever, the possibility of this complication should be considered.

    Breast cancer, hyperprolactinemia, infertility

    Tetrabenazine can cause hyperprolactinemia, likely due to central D2 antagonism. Elevations in prolactin may induce infertility in either men or women, or may induce other endocrine abnormalities (see Adverse Reactions). Some human breast cancers may be prolactin-dependent and therefore tetrabenazine should be used cautiously in those who have a history of breast cancer.

    Dysphagia

    Tetrabenazine should be used cautiously in patients with dysphagia or other conditions causing difficulty swallowing. Esophageal dysmotility and aspiration have been associated with the use of other anti-dopaminergic drugs.

    MAOI therapy

    Tetrabenazine is contraindicated in patients who are receiving MAOI therapy or reserpine (see Drug Interactions).

    ADVERSE REACTIONS

    Severe

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

    Moderate

    depression / Delayed / 19.0-35.0
    akathisia / Delayed / 19.0-20.0
    pseudoparkinsonism / Delayed / 3.0-15.0
    dysphagia / Delayed / 4.0-10.0
    dysarthria / Delayed / 4.0-4.0
    dysuria / Early / 4.0-4.0
    dyspnea / Early / 4.0-4.0
    orthostatic hypotension / Delayed / Incidence not known
    hypertonia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    dystonic reaction / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known

    Mild

    drowsiness / Early / 17.0-57.0
    insomnia / Early / 22.0-22.0
    fatigue / Early / 22.0-22.0
    anxiety / Delayed / 15.0-15.0
    nausea / Early / 13.0-13.0
    infection / Delayed / 0-11.0
    irritability / Delayed / 9.0-9.0
    vomiting / Early / 6.0-6.0
    ecchymosis / Delayed / 6.0-6.0
    headache / Early / 4.0-4.0
    anorexia / Delayed / 4.0-4.0
    dizziness / Early / 4.0-4.0
    diarrhea / Early / 1.9-1.9
    hyperkinesis / Delayed / Incidence not known
    syncope / Early / Incidence not known
    weakness / Early / Incidence not known
    restlessness / Early / Incidence not known
    tremor / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Use caution during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including abarelix. In addition, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (abarelix) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Acetaminophen; Butalbital: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as butalbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as butalbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension. (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as butalbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Codeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as doxylamine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as dichloralphenazone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Diphenhydramine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Hydrocodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Oxycodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Pentazocine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression, like pentazocine. Concurrent use of tetrabenazine and pentazocine can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Propoxyphene: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Acetaminophen; Tramadol: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as tramadol, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Albuterol: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Albuterol; Ipratropium: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Alfentanil: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Alfuzosin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as alfuzosin. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg.
    Aliskiren; Amlodipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amiodarone: (Major) The concomitant use of amiodarone and tetrabenazine should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amlodipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Atorvastatin: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Benazepril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly. (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Olmesartan: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Telmisartan: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Valsartan: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Amobarbital: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as amobarbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Concurrent use of tetrabenazine and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc), while clarithromycin is associated with an established risk for QT prolongation and TdP.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of tetrabenazine and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc), while clarithromycin is associated with an established risk for QT prolongation and TdP.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include tetrabenazine.
    Angiotensin-converting enzyme inhibitors: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Anxiolytics; Sedatives; and Hypnotics: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as anxiolytics, sedatives, and hypnotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Apomorphine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, including apomorphine. Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2-10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended.
    Arformoterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aripiprazole: (Major) Both tetrabenazine and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP). If possible, concurrent use of aripiprazole and tetrabenazine should be avoided since the risk of adverse effects such as QT prolongation, drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Arsenic Trioxide: (Major) f possible, drugs that are known to prolong the QT interval, such as tetrabenazine, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Artemether; Lumefantrine: (Major) Artemether; lumefantrine is an inhibitor and tetrabenazine is a substrate of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased tetrabenazine concentrations. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval such as tetrabenazine should be avoided. Consider ECG monitoring if tetrabenazine must be used with or after artemether; lumefantrine treatment.
    Asenapine: (Major) Coadministration of asenapine and tetrabenazine should be avoided. Asenapine has been associated with QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as butalbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension. (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as butalbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Aspirin, ASA; Oxycodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Atazanavir; Cobicistat: (Moderate) The plasma concentrations of tetrabenazine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while tetrabenazine is a CYP2D6 substrate.
    Atomoxetine: (Major) Avoid coadministration of tetrabenazine and atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concurrent use may result in additive effects on the QT interval.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with tetrabenazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Diphenoxylate: (Moderate) Concurrent administration of diphenoxylate/difenoxin with tetrabenazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as phenobarbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Azithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering tetrabenazine with azithromycin. Tetrabenazine causes a small increase in the corrected QT interval (QTc), and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin.
    Bedaquiline: (Major) Concurrent use of tetrabenazine and bedaquiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as phenobarbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Belladonna; Opium: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Benazepril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Benzodiazepines: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as benzodiazepines, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Beta-adrenergic blockers: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Avoid coadministration of tetrabenazine and metronidazole due to the potential for QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Potential QT prolongation has also been reported in limited case reports with metronidazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Avoid coadministration of tetrabenazine and metronidazole due to the potential for QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Potential QT prolongation has also been reported in limited case reports with metronidazole.
    Brexpiprazole: (Major) Both brexpiprazole and tetrabenazine antagonize the effects of dopamine. If possible, concurrent use of brexpiprazole and tetrabenazine should be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Budesonide; Formoterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, coadministration of tetrabenazine and buprenorphine should be avoided. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Tetrabenazine also has a possible risk for QT prolongation and TdP. Some buprenorphine labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of tetrabenazine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, coadministration of tetrabenazine and buprenorphine should be avoided. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Tetrabenazine also has a possible risk for QT prolongation and TdP. Some buprenorphine labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of tetrabenazine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buspirone: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as buspirone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Butabarbital: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as butabarbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Butorphanol: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression, like butorphanol. Concurrent use of tetrabenazine and butorphanol can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Captopril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as pyrilamine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Carbetapentane; Pyrilamine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as pyrilamine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Carbidopa; Levodopa: (Severe) Coadministration of carbidopa; levodopa with tetrabenazine is not recommended. Tetrabenazine can deplete dopamine stores in the brain, thereby antagonizing the effects of levodopa.
    Carbidopa; Levodopa; Entacapone: (Severe) Coadministration of carbidopa; levodopa with tetrabenazine is not recommended. Tetrabenazine can deplete dopamine stores in the brain, thereby antagonizing the effects of levodopa. (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as entacapone, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how tetrabenazine affects them.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Ceritinib: (Major) The manufacturer of tetrabenazine recommends avoiding coadministration with other drugs known to prolong the QTc interval, such as ceritinib. If coadministration is unavoidable, periodically monitor electrolytes and ECGs; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Tetrabenazine causes a small increase in the corrected QT interval (QTc), and ceritinib has been associated with concentration-dependent QT prolongation.
    Cetrorelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (cetrorelix) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Chloroquine: (Major) The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QT, such as chloroquine. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses.
    Chlorpheniramine; Codeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Chlorpheniramine; Hydrocodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Chlorpromazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as chlorpromazine. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. In addition, concurrent use of these medications and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Chlorthalidone; Clonidine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Ciprofloxacin: (Major) Concurrent use of tetrabenazine and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc), and ciprofloxacin has been associated with a possible risk for QT prolongation and TdP.
    Cisapride: (Severe) Tetrabenazine causes a small increase in the corrected QT interval (QTc). QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of tetrabenazine with cisapride is contraindicated.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. Tetrabenazine is associated with a possible risk for QT prolongation and torsade de pointes. According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Clarithromycin: (Major) Concurrent use of tetrabenazine and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc), while clarithromycin is associated with an established risk for QT prolongation and TdP.
    Clevidipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Clobazam: (Moderate) A dosage reduction of CYP2D6 substrates may be necessary during co-administration of clobazam. The active metabolite of tetrabenazine is a substrate of CYP2D6 and limited in vivo data suggest that clobazam is an inhibitor of CYP2D6. If these agents are used in combination, it is advisable to monitor the patient for tetrabenazine-related adverse reactions.
    Clonidine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Clozapine: (Major) Concurrent use of tetrabenazine and clozapine should be avoided if possible. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer of tetrabenazine recommends against concurrent use of tetrabenazine with other drugs known to prolong QTc. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and clozapine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Cobicistat: (Moderate) The plasma concentrations of tetrabenazine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while tetrabenazine is a CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of tetrabenazine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while tetrabenazine is a CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of tetrabenazine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while tetrabenazine is a CYP2D6 substrate.
    Codeine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Codeine; Guaifenesin: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Codeine; Phenylephrine; Promethazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and promethazine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased. (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Codeine; Promethazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and promethazine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased. (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Crizotinib: (Major) According to the manufacturer of tetrabenazine, coadministration with other drugs known to prolong the QTc interval, such as crizotinib, should be avoided. If coadministration cannot be avoided, monitor ECGs and electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Crizotinib has been associated with concentration-dependent QT prolongation.
    Cyclobenzaprine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Cyclobenzaprine is associated with a possible risk of QT prolongation and torsade de pointes, particularly in the event of acute overdose. The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Darunavir; Cobicistat: (Moderate) The plasma concentrations of tetrabenazine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while tetrabenazine is a CYP2D6 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include tetrabenazine.
    Dasatinib: (Major) In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Daunorubicin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). Therefore, it should be used cautiously with daunorubicin or doxorubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Degarelix: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including degarelix. In addition, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (degarelix) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Desvenlafaxine: (Major) Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer recommends that primary substrates of CYP2D6, such as tetrabenazine, be dosed at the original level when co-administered with desvenlafaxine 100 mg or lower or when desvenlafaxine is discontinued. The dose of these CYP2D6 substrates should be reduced by up to one-half if co-administered with desvenlafaxine 400 mg/day.
    Deutetrabenazine: (Severe) Concurrent use of deutetrabenazine and tetrabenazine is contraindicated. Both drugs are inhibitors of vesicular monoamine transporter 2 (VMAT2) and deplete monoamine stores. Deutetrabenazine may be started the day after tetrabenazine discontinuation.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Dextromethorphan; Promethazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and promethazine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Dextromethorphan; Quinidine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include tetrabenazine.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Diltiazem: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Diphenhydramine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension. (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Diphenhydramine; Naproxen: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as diphenhydramine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Disopyramide: (Major) The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
    Dofetilide: (Severe) Tetrabenazine causes a small increase in the corrected QT interval (QTc). Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Because of the potential for TdP, use of dofetilide with tetrabenazine is contraindicated.
    Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of dolasetron and tetrabenazine should be avoided. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Dolutegravir; Rilpivirine: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as rilpivirine.
    Donepezil: (Major) Avoid coadministration of tetrabenazine and donepezil due to the potential for QT prolongation. Both tetrabenazine and donepezil have been associated with a risk of QT prolongation; torsade de pointes (TdP) can occur during donepezil therapy. Concurrent use may result in additive effects on the QT interval.
    Donepezil; Memantine: (Major) Avoid coadministration of tetrabenazine and donepezil due to the potential for QT prolongation. Both tetrabenazine and donepezil have been associated with a risk of QT prolongation; torsade de pointes (TdP) can occur during donepezil therapy. Concurrent use may result in additive effects on the QT interval.
    Doxazosin: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Doxorubicin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). Therefore, it should be used cautiously with daunorubicin or doxorubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Doxylamine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as doxylamine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Doxylamine; Pyridoxine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as doxylamine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Dronabinol, THC: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as dronabinol, THC, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Dronedarone: (Severe) Concomitant use of dronedarone and tetrabenazine is contraindicated. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as droperidol. In addition, concurrent use of droperidol and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Efavirenz: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as efavirenz.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as efavirenz.
    Eliglustat: (Major) Coadministration of tetrabenazine and eliglustat may result in increased concentrations of the primary metabolites of tetrabenazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of tetrabenazine. Although specific guidance is not available, FDA-approved labeling for tetrabenazine recommends a maximum of 25 mg/dose or 50 mg/day in patients taking a concurrent CYP2D6 inhibitor (e.g., quinidine, fluoxetine, paroxetine). Tetrabenazine is a CYP2D6 substrate associated with a small increase in the corrected QT interval (QTc). Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as rilpivirine.
    Enalapril, Enalaprilat: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Enalapril; Felodipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Entacapone: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as entacapone, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how tetrabenazine affects them.
    Epirubicin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tetrabenazine with epirubicin. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Acute cardiotoxicity can also occur during administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eplerenone: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Eribulin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with tetrabenazine include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as erythromycin.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as erythromycin.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as tetrabenazine, should be done with caution and close monitoring.
    Ester local anesthetics: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including local anesthetics.
    Ethanol: (Major) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as ethanol, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Ezogabine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with tetrabenazine include ezogabine.
    Felodipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Fentanyl: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Fingolimod: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. If coadministration is necessary, after the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Fluconazole: (Major) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Fluoxetine: (Major) The primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Based upon limited data from coadministration with the potent CYP2D6 inhibitor paroxetine, the daily dose of tetrabenazine should be halved when fluoxetine is added to an existing tetrabenazine regimen. In addition, tetrabenazine causes a small increase in the corrected QT interval (QTc). Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval.
    Fluoxetine; Olanzapine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, concurrent use of olanzapine and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased. (Major) The primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Based upon limited data from coadministration with the potent CYP2D6 inhibitor paroxetine, the daily dose of tetrabenazine should be halved when fluoxetine is added to an existing tetrabenazine regimen. In addition, tetrabenazine causes a small increase in the corrected QT interval (QTc). Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval.
    Fluphenazine: (Major) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as fluphenazine. In addition, concurrent use of fluphenazine and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Fluticasone; Salmeterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Vilanterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and tetrabenazine. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Because tetrabenazine causes a small increase in the corrected QT interval (QTc), the manufacturer recommends avoiding use of tetrabenazine with other drugs known to prolong QTc.
    Formoterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Formoterol; Mometasone: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as tetrabenazine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc). If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosinopril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Ganirelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (ganirelix) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Gefitinib: (Moderate) Monitor for an increased incidence of tetrabenazine-related adverse effects if gefitinib and tetrabenazine are used concomitantly. At high concentrations, gefitinib is an inhibitor of CYP2D6, which is the primary isoenzyme responsible for the metabolism of tetrabenazine. In patients with solid tumors, exposure to metoprolol, another CYP2D6 substrate, was increased by 30% when given on day 15 of gefitinib dosing (500 mg daily); however, the effect of gefitinib on CYP2D6-dependent drugs is only likely to be clinically relevant when given with CYP2D6 substrates with a narrow therapeutic index or that are individually dose titrated.
    Gemifloxacin: (Major) Concurrent use of tetrabenazine and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval. Gemifloxacin may also prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with tetrabenazine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin.Tetrabenazine causes a small increase in the corrected QT interval.
    Glycopyrrolate; Formoterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Goserelin: (Major) Tetrabenazine should be used cautiously and with close monitoring with goserelin. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. In addition, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Granisetron: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, the use of granisetron in patients concurrently treated with drugs known to prolong the QT interval (e.g., tetrabenazine) and/or are arrhythmogenic, may result in clinical consequences. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Guaifenesin; Hydrocodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Guanabenz: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Guanfacine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Halofantrine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as halofantrine.
    Halogenated Anesthetics: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc including halogenated anesthetics.
    Haloperidol: (Major) Concurrent use of tetrabenazine and haloperidol should be avoided if possible. Tetrabenazine causes a small increase in the corrected QT interval (QTc). QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. The manufacturer of tetrabenazine recommends against concurrent use of tetrabenazine with other drugs known to prolong QTc. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and haloperidol is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Histrelin: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (histrelin) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Homatropine; Hydrocodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Hydrocodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydrocodone; Ibuprofen: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydrocodone; Phenylephrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydrocodone; Pseudoephedrine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydrocodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydromorphone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and tetrabenazine. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include tetrabenazine. In addition, concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydroxyzine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Ibuprofen; Oxycodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Ibutilide: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as ibutilide. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
    Idarubicin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). Therefore, it should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as tetrabenazine. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Iloprost: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Indacaterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Indacaterol; Glycopyrrolate: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with tetrabenazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Isocarboxazid: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Isradipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include tetrabenazine.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include tetrabenazine.
    Lapatinib: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc including lapatinib.
    Lenvatinib: (Major) Tetrabenazine should be used cautiously and with close monitoring with lenvatinib. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Leuprolide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval, such as tetrabenazine. In addition, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (leuprolide) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Leuprolide; Norethindrone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval, such as tetrabenazine. In addition, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (leuprolide) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Levalbuterol: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Levodopa: (Severe) Coadministration of carbidopa; levodopa with tetrabenazine is not recommended. Tetrabenazine can deplete dopamine stores in the brain, thereby antagonizing the effects of levodopa.
    Levofloxacin: (Major) Concurrent use of tetrabenazine and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Tetrabenazine causes a small increase in the corrected QT interval.
    Levorphanol: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Lisinopril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Lithium: (Major) Lithium should be used cautiously and with close monitoring with tetrabenazine. Lithium has been associated with QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Long-acting beta-agonists: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Tetrabenazine also has been associated with an increase in QT interval. The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong the QTc interval.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Tetrabenazine also has been associated with an increase in QT interval. The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong the QTc interval.
    Lopinavir; Ritonavir: (Major) QT prolongation in patients taking lopinavir; ritonavir has been reported. Coadministration of lopinavir; ritonavir with other drugs that prolong the QT interval, such as tetrabenazine, may result in additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include tetrabenazine.
    Loxapine: (Major) Concurrent use of loxapine and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Lurasidone: (Major) Tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and lurasidone is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Maprotiline: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as maprotiline, particularly when given in excessive doses or overdosage. Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, concurrent use should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, or orthostatic hypotension may be increased.
    Mefloquine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including mefloquine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
    Meperidine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Meperidine; Promethazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and promethazine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased. (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Mephobarbital: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as mephobarbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Mesoridazine: (Severe) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to cause QT prolongation. Mesoridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Mesoridazine is generally considered contraindicated for use along with agents that may cause QT prolongation or TdP such as tetrabenazine. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and mesoridazine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Metaproterenol: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Methadone: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as methadone. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. In addition, concurrent use of methadone and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, or orthostatic hypotension may be increased.
    Methyldopa: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Metoclopramide: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Tetrabenazine is a centrally-acting dopamine depleting drug. Pseudoparkinsonism (6 to12%) and akathisia (9%) were among the most frequently reported side effects during clinical trials with tetrabenazine. Neuroleptic malignant syndrome and acute dystonic reactions have also been noted rarely. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and tetrabenazine; however, concurrent use should be avoided if possible.
    Metronidazole: (Major) Avoid coadministration of tetrabenazine and metronidazole due to the potential for QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Potential QT prolongation has also been reported in limited case reports with metronidazole.
    Midostaurin: (Major) Avoid the concomitant use of midostaurin and tetrabenazine; both drugs have been reported to increase the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin.
    Mifepristone, RU-486: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of mifepristone and tetrabenazine should be avoided if possible. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tetrabenazine may be increased when co-administered with mirabegron. Two of the primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and tetrabenazine. Because tetrabenazine causes a small increase in the corrected QT interval (QTc), the manufacturer recommends avoiding use of tetrabenazine with other drugs known to prolong QTc. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Moexipril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Molindone: (Major) Concurrent use of molindone and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Monoamine oxidase inhibitors: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Morphine: (Major) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Morphine; Naltrexone: (Major) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Moxifloxacin: (Major) Concurrent use of tetrabenazine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc). Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Nabilone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as nabilone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Nafarelin: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (nafarelin) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Nalbuphine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression, such as nalbuphine. Concurrent use of tetrabenazine and nalbuphine can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Nicardipine: (Major) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypretensive agents such as nicardipine. Additionally, nicardipine is a strong inhibitor of CYP2D6. The primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Increased alpha-HTBZ and beta-HTBZ serum concentrations may occur during coadministration with nicardipine, leading to an increased risk of tetrabenazine-related adverse reactions. When tetrabenazine is given with a strong inhibitor of CYP2D6, the maximum single dose of tetrabenazine should not exceed 25 mg and the daily dose should not exceed 50 mg.
    Nifedipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval. Tetrabenazine causes a small increase in the corrected QT interval. Additionally, nilotinib is a CYP2D6 inhibitor and tetrabenazine is a substrate of CYP2D6; administering these drugs together may result in increased tetrabenazine levels. If the use of tetrabenazine is necessary, hold nilotinib therapy. Use caution and monitor patients for toxicity (e.g., QT interval prolongation) if these drugs are used together.
    Nimodipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Nisoldipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Norfloxacin: (Major) Concurrent use of tetrabenazine and norfloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc). Quinolones have also been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Octreotide: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc including octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Concurrent use of tetrabenazine and ofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc). Some quinolones, including ofloxacin, have also been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, concurrent use of olanzapine and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Olodaterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include tetrabenazine.
    Ondansetron: (Major) Avoid coadministration of tetrabenazine and ondansetron. If coadministration cannot be avoided, monitor ECG for evidence of QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP).
    Oritavancin: (Moderate) The active metabolites of tetrabenazine are metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. The efficacy of tetrabenazine may be reduced if these drugs are administered concurrently.
    Osimertinib: (Major) Avoid coadministration of tetrabenazine with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib.
    Oxaliplatin: (Major) Avoid coadministration of tetrabenazine with oxaliplatin due to the risk of additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Oxycodone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Oxymorphone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as tetrabenazine. Tetrabenazine causes a small increase in the corrected QT interval (QTc). In addition, coadministration may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased. If coadministration is considered necessary by the practitioner, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential.
    Panobinostat: (Major) The co-administration of panobinostat with tetrabenazine is not recommended; QT prolongation has been reported with both agents. If concomitant use cannot be avoided, closely monitor patients for signs and symptoms of tetrabenazine toxicity, including QT prolongation and cardiac arrhythmias. Panobinostat is a CYP2D6 inhibitor and tetrabenazine is a CYP2D6 substrate. When a single-dose of a CYP2D6-sensitive substrate was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
    Paroxetine: (Major) The primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Coadministration of 50 mg of tetrabenazine following 10 days of 20 mg of paroxetine, a potent CYP2D6 inhibitor, resulted in an increase in Cmax of approximately 30% and a 3-fold increase in AUC for alpha-HTBZ. The Cmax and AUC for beta-HTBZ increased 2.4-fold and 9-fold, respectively. The elimination half-life of alpha-HTBZ and beta-HTBZ was approximately 14 hours when tetrabenazine was given with paroxetine. When tetrabenazine is given with a strong inhibitor of CYP2D6 such as paroxetine, the maximum single dose of tetrabenazine should not exceed 25 mg and the daily dose should not exceed 50 mg. In addition, because tetrabenazine is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. During use of this combination, monitor for adverse effects associated with tetrabenazine such as QT prolongation, excess sedation, and extrapyramidal symptoms.
    Pasireotide: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc) and should be used cautiously and with close monitoring with pasireotide as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tetrabenazine, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and tetrabenazine must be continued, closely monitor the patient for QT interval prolongation.
    Peginterferon Alfa-2b: (Moderate) Peginterferon alfa-2b is a CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as tetrabenazine may be increased when co-administered with peginterferon alfa-2b. Two of the primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Therefore, appropriate monitoring may be necessary.
    Pentamidine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as pentamidine.
    Pentazocine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression, like pentazocine. Concurrent use of tetrabenazine and pentazocine can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Pentazocine; Naloxone: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression, like pentazocine. Concurrent use of tetrabenazine and pentazocine can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Pentobarbital: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as pentobarbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Perindopril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Perindopril; Amlodipine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly. (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Perphenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as perphenazine. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, concurrent use of these medications and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Perphenazine; Amitriptyline: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as perphenazine. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, concurrent use of these medications and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Phenelzine: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Phenobarbital: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as phenobarbital, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Phenoxybenzamine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Phentolamine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Phenylephrine; Promethazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and promethazine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as tetrabenazine. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Coadministration may increase the risk for QT prolongation.
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of tetrabenazine with pimozide is contraindicated.
    Pirbuterol: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Posaconazole: (Major) Posaconazole has been associated with QT prolongation and in rare cases, torsade de pointes. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc inlcuding posaconazole.
    Potassium-sparing diuretics: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Prazosin: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include tetrabenazine.
    Procainamide: (Major) The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Prochlorperazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as prochlorperazine. Phenothiazines have been reported to prolong the QT interval. In addition, concurrent use of prochlorperazine and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Promethazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and promethazine is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Propafenone: (Major) Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as propafenone.
    Propoxyphene: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Quetiapine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, concurrent use of quetiapine and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Quinapril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Quinidine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include tetrabenazine.
    Quinine: (Major) Concurrent use of quinine and tetrabenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Tetrabenazine causes a small increase in the corrected QT interval (QTc). In addition, concentrations of tetrabenazine may be increased with concomitant use of quinine. Tetrabenazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Ramipril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, such as tetrabenazine, coadministration of such drugs may result in additive QT prolongation. The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. In addition, ranolazine and/or metabolites are moderate inhibitors of CYP2D6 isoenzymes and tetrabenazine is a substrate. Based on drug interaction studies with metoprolol, a CYP2D6 substrate, ranolazine may theoretically increase plasma concentrations of CYP2D6 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. The manufacturer for ranolazine suggests that lower doses of CYP2D6 substrates may be required during ranolazine treatment.
    Rasagiline: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received a monoamine oxidase inhibitor, such as rasagiline, within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Regadenoson: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously with tetrabenazine include regadenoson.
    Remifentanil: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Reserpine: (Severe) Reserpine binds irreversibly to vesicular monoamine transporter 2 (VMAT2) and the duration of its effect on serotonin and norepinephrine in the CNS is several days. Tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug that works by inhibiting vesicular monoamine transporter 2 (VMAT2). Therefore, concurrently use of tetrabenazine and reserpine is contraindicated. At least 20 days should elapse after stopping reserpine before initiating treatment with tetrabenazine.
    Ribociclib: (Major) Avoid coadministration of ribociclib with tetrabenazine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with tetrabenazine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer of tetrabenazine recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as rilpivirine.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as risperidone. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include tetrabenazine.
    Rolapitant: (Major) Use caution if tetrabenazine and rolapitant are used concurrently, and monitor for tetrabenazine-related adverse effects. Tetrabenazine is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant lasts for at least 7 days, and may last longer after single dose administration. The Cmax and AUC of another CYP2D6 substrate, dextromethorphan, were increased by 120% and 160%, respectively, on day 1 with rolapitant, and by 180% and 230%, respectively, on day 8 after rolapitant administration.
    Romidepsin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as romidepsin. If romidepsin and tetrabenazine must be coadministered, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Safinamide: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received a monoamine oxidase inhibitor, such as safinamide, within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Salmeterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Saquinavir: (Major) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as tetrabenazine. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
    Selegiline: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Sertraline: (Major) Avoid coadministration of tetrabenazine and sertraline due to increased risk for QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc). There have been post-marketing reports of QT prolongation and TdP during treatment with sertraline.
    Short-acting beta-agonists: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Solifenacin: (Major) Concurrent use of tetrabenazine and solifenacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Tetrabenazine also causes a small increase in the corrected QT interval (QTc).
    Sorafenib: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as sorafenib. If sorafenib and tetrabenazine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Sotalol: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Sparfloxacin: (Severe) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as sparfloxacin.
    Sufentanil: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include tetrabenazine.
    Sunitinib: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including sunitinib.
    Tacrolimus: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including tacrolimus.
    Tamoxifen: (Major) Avoid coadministration of tamoxifen with tetrabenazine due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Telavancin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as telavancin.
    Telithromycin: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc including telithromycin.
    Terazosin: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Terbutaline: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Thiazide diuretics: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Thioridazine: (Severe) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Because of the potential for TdP, use of tetrabenazine with thioridazine is contraindicated.
    Thiothixene: (Major) Concurrent use of thiothixene and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Tiotropium; Olodaterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Tipranavir: (Major) The primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Increased alpha-HTBZ and beta-HTBZ serum concentrations may occur during coadministration with tipranavir, leading to an increased risk of tetrabenazine-related adverse reactions. When tetrabenazine is given with a strong inhibitor of CYP2D6, such as tipranavir, the maximum single dose of tetrabenazine should not exceed 25 mg and the daily dose should not exceed 50 mg.
    Tizanidine: (Major) Avoid coadministration of tizanidine and tetrabenazine. Tizanidine administration may result in QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
    Tolcapone: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as tolcapone, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how tetrabenazine affects them.
    Tolterodine: (Major) Concurrent use of tetrabenazine and tolterodine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Tetrabenazine also causes a small increase in the corrected QT interval (QTc).
    Toremifene: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner.
    Tramadol: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as tramadol, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Trandolapril: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Trandolapril; Verapamil: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Tranylcypromine: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Trazodone: (Major) Avoid coadministration of trazodone and tetrabenazine. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval. In addition, additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as trazodone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Treprostinil: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Tricyclic antidepressants: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, concurrent use of tricyclics and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, or orthostatic hypotension may be increased.
    Trifluoperazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as trifluoperazine. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, concurrent use of these medications and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Triptorelin: (Major) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with triptorelin include tetrabenazine. In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (cetrorelix, ganirelix, leuprolide, or triptorelin) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Umeclidinium; Vilanterol: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Valbenazine: (Severe) Concurrent use of tetrabenazine and valbenazine is contraindicated. Both drugs are inhibitors of vesicular monoamine transporter 2 (VMAT2) and deplete monoamine stores.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib. Tetrabenazine causes a small increase in the corrected QT interval (QTc). If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including vardenafil. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). When vardenafil (10 mg) was given with gatifloxacin (400 mg), an additive effect on the QT interval was observed. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. If vemurafenib and tetrabenazine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, the active metabolites for tetrabenazine are substrates for CYP1A2 and 2D6, while vemurafenib is an inhibitor of both enzymes. Therefore increased concentrations of the tetrabenazine metabolites may occur with concomitant use. Monitor patients for increased side effect.
    Venlafaxine: (Major) etrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as venlafaxine. Venlafaxine administration is associated with a possible risk of QT prolongation; torsades de pointes (TdP) has reported with post-marketing use.
    Verapamil: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Voriconazole: (Major) Concurrent use of tetrabenazine and voriconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Vorinostat: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with tetrabenazine.
    Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including tetrabenazine.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate data on the developmental risk associated with tetrabenazine use during pregnancy. In rat studies, administration of tetrabenazine from the beginning of organogenesis through the lactation period was associated with an increase in stillbirths and offspring postnatal mortality at doses of 15 and 30 mg/kg/day (3 times the maximum recommended human dose of 100 mg/day on a mg/m2 basis); delayed pup maturation was observed at doses of 5 to 30 mg/kg/day. However, no clear effects of tetrabenazine on embryofetal development have been observed during animal studies. When 9-desmethyl-beta-DHTBZ, a major metabolite of tetrabenazine, was administered to pregnant rats during organogenesis, increases in embryofetal mortality were observed at doses of 15 and 40 mg/kg/day, and decreased fetal body weights were observed at a dose of 40 mg/kg/day. Increases in gestation duration, stillbirths, and offspring postnatal mortality (40 mg/kg/day); decreases in pup weight (40 mg/kg/day); and neurobehavioral (increased activity, learning and memory deficits) and reproductive (decreased litter size) impairment (15 and 40 mg/kg/day) were observed with 9-desmethyl-beta-DHTBZ administration to pregnant rats throughout organogenesis and lactation. The 9-desmethyl-beta-DHTBZ no-effect dose for developmental toxicity of 8 mg/kg/day in rats was associated with an AUC lower than that in humans at the maximum recommended human dose. In a case report, tetrabenazine treatment (75 mg/day) was initiated late in the second trimester in a woman with chorea gravidarum. Although the infant was born with a small ventricular septal defect, an association to the tetrabenazine therapy was thought to be unlikely since fusion of the intraventricular septum is normally complete by 8 weeks gestation. Extrapyramidal and withdrawal symptoms including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported after delivery in neonates exposed to dopamine antagonists (e.g., antipsychotics) during the third trimester. These effects have varied in severity ranging from self-limited to requiring intensive care unit stays and prolonged hospitalization. As a central dopamine depletor, tetrabenazine has the potential to cause similar effects. It is not clear if tetrabenazine, through its effect on prolactin, would affect labor or delivery.

    There are no data on the presence of tetrabenazine or its metabolites in human breast 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 tetrabenazine and any potential adverse effects on the breast-fed infant from the drug or the mother's underlying condition. Tetrabenazine elevates serum prolactin concentrations in humans, and thus, interference with proper lactation is possible. Previous American Academy of Pediatrics (AAP) did not make specific recommendations regarding tetrabenazine use during breast-feeding, but the AAP cautioned that psychotropic medications affect neurotransmitter function in the developing central nervous system, and therefore, the accurate prediction of long-term adverse effects may not be possible.

    MECHANISM OF ACTION

    Mechanism of Action: Tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug that works by inhibiting vesicular monoamine transporter 2 (VMAT2). Tetrabenazine depletes presynaptic dopamine, norepinephrine, and serotonin storage and antagonizes postsynaptic dopamine receptors. In vitro data indicate that tetrabenazine exhibits a weak binding affinity at the dopamine-2 receptor. Clinically, tetrabenazine improves the symptoms associated with hyperkinetic movement disorders such as Huntington's disease.

    PHARMACOKINETICS

    Tetrabenazine is administered orally. The protein binding of tetrabenazine and its metabolites is less than 90%. Although 19 metabolites have been identified, the major metabolites are alpha-HTBZ, beta-HTBZ, and 9-desmethyl-beta-DHTBZ. The activity of 9-desmethyl-beta-DHTBZ relative to tetrabenazine is unknown. The alpha-HTBZ and beta-HTBZ metabolites are formed primarily by carbonyl reductase in the liver. Subsequently, alpha-HTBZ is O-dealkylated to 9-desmethyl-alpha-DHTBZ principally by CYP2D6, and CYP1A2 to a lesser extent while beta-HTBZ is O-dealkylated principally by CYP2D6 to form 9-desmethyl-beta-DHTBZ. The half-lives of alpha-HTBZ, beta-HTBZ, and 9-desmethyl-beta-DHTBZ are 7 hours, 5 hours, and 12 hours, respectively. Approximately 75% and 7—16% of a dose is eliminated in the urine and feces, respectively. Sulfate and glucuronide conjugates of HTBZ metabolites account for the majority of renally eliminated metabolites, with less than 10% of a dose found in the urine as alpha-HTBZ and beta-HTBZ.
     
    Affected cytochrome P450 isoenzymes and drug transporters:  none
    In vitro data suggest that tetrabenazine, alpha-HTBZ, and beta-HTBZ are not likely to be clinically significant inhibitors of CYP2D6, CYP1A2, CYP2C8, CYP2C9, CYPC19, CYP2E1, CYP3A, or P-glycoprotein (P-gp). In vitro data also suggest that tetrabenazine, alpha-HTBZ, and beta-HTBZ are not likely to be clinically significant inducers of CYP1A2, CYP3A4, CYP2B6, CYP2C8, CYP2C9, or CYP2C19. According to the manufacturer, in vitro data indicate that clinically significant interactions with CYP inhibitors other than 2D6 are unlikely. It should be noted that the potential of the 9-desmethyl-beta-DHTBZ metabolite to interact with other drugs, including any possible involvement of the CYP450 system, has not been studied.

    Oral Route

    Absorption following oral administration is at least 75% of the dose. Plasma concentrations of tetrabenazine will likely be below detectable levels after single doses up to 50 mg due to extensive and rapid hepatic metabolism. Peak plasma concentrations of the active metabolites alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ) are reached within 1—1.5 hours following a dose. The major metabolite 9-desmethyl-beta-DHTBZ, which is formed from beta-HTBZ, reaches peak plasma concentrations approximately 2 hours post-dose. Food has no effect on the pharmacokinetics of the drug; therefore, it may be given without regard to meals.