Xenazine

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Xenazine

Classes

Monoamine Depletor

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.

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
hypertonia / Delayed / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
dystonic reaction / Delayed / Incidence not known
confusion / Early / 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
anorexia / Delayed / 4.0-4.0
headache / Early / 4.0-4.0
dizziness / Early / 4.0-4.0
diarrhea / Early / 1.9-1.9
syncope / Early / Incidence not known
hyperkinesis / Delayed / Incidence not known
restlessness / Early / Incidence not known
weakness / Early / Incidence not known
tremor / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known
rash / Early / Incidence not known

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.

Common Brand Names

Xenazine

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

Dosage And 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.

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.

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; Aspirin; 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; 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; Caffeine; 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.
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; Pamabrom; 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.
Adagrasib: (Major) Concomitant use of adagrasib and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Amiodarone: (Major) Concomitant use of tetrabenazine and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of atomoxetine, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Avoid coadministration of amisulpride with tetrabenazine due to the potential for additive QT prolongation. Amisulpride causes dose- and concentration- dependent QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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; Celecoxib: (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; 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; Valsartan; 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.
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; 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) Exercise caution when using apomorphine with tetrabenazine due to an increased risk for QT prolongation and CNS depression. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Tetrabenazine causes a small increase in the corrected QT interval (QTc) and is associated with a possible risk for torsade de pointes (TdP). Sedation is the most common dose-limiting adverse reaction of tetrabenazine, and apomorphine also causes significant somnolence.
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; 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) Concomitant use of tetrabenazine and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with tetrabenazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Azithromycin: (Major) Concomitant use of tetrabenazine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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; 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.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with tetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with tetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking tetrabenazine, reduce initial dosage and titrate to clinical response. If tetrabenazine is initiated a patient taking an opioid agonist, use a lower initial dose of tetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
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) Concomitant use of tetrabenazine and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of tetrabenazine and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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.
Butalbital; Acetaminophen: (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.
Butalbital; Acetaminophen; 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.
Butalbital; Acetaminophen; 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.
Butalbital; Aspirin; 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.
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.
Cabergoline: (Moderate) Cabergoline should not be coadministered with tetrabenazine, if possible. The prolactin-lowering effect of cabergoline may be diminished by medications that increase prolactin levels such as tetrabenazine.
Cabotegravir; 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.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and tetrabenazine. CNS depressants can potentiate the effects of cannabidiol.
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.
Carbidopa; Levodopa: (Moderate) Monitor for a decrease in levodopa efficacy during concomitant tetrabenazine use. Levodopa and tetrabenazine may antagonize each other's effects: levodopa is metabolized to dopamine while tetrabenazine depletes dopamine stores and acts as a dopamine receptor blocker. While concomitant use is generally not recommended for this reason, combination therapy may be beneficial in the management of some levodopa-related dyskinesias.
Carbidopa; Levodopa; 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. (Moderate) Monitor for a decrease in levodopa efficacy during concomitant tetrabenazine use. Levodopa and tetrabenazine may antagonize each other's effects: levodopa is metabolized to dopamine while tetrabenazine depletes dopamine stores and acts as a dopamine receptor blocker. While concomitant use is generally not recommended for this reason, combination therapy may be beneficial in the management of some levodopa-related dyskinesias.
Celecoxib; 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.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and tetrabenazine. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Avoid coadministration of tetrabenazine with ceritinib due to the risk of QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concentration-dependent QT prolongation has been reported with ceritinib treatment.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with tetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with tetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
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) Avoid coadministration of chloroquine with tetrabenazine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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; 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.
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) Concomitant use of tetrabenazine and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) 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) Concomitant use of tetrabenazine and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Clofazimine: (Major) Concomitant use of clofazimine and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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; 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.
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) Avoid coadministration of crizotinib with tetrabenazine due to the risk of QT prolongation. Crizotinib has been associated with concentration-dependent QT prolongation. Tetrabenazine also causes a small increase in the corrected QT interval (QTc).
Dacomitinib: (Major) Do not exceed a maximum single dose of tetrabenazine of 25 mg and a daily dose of 50 mg when coadministered with dacomitinib. Additionally, monitor for adverse effects associated with tetrabenazine such as QT prolongation, excess sedation, and extrapyramidal symptoms. Coadministration may increase serum concentrations of tetrabenazine. The primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Dacomitinib is a strong CYP2D6 inhibitor. In drug interaction studies, coadministration of tetrabenazine with another strong 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 were increased to approximately 14 hours.
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.
Darunavir; Cobicistat; 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.
Dasatinib: (Major) Avoid coadministration of tetrabenazine and dasatinib due to the potential for QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Degarelix: (Major) Avoid concurrent use of tetrabenazine with degarelix due to the potential for additive QT prolongation; the efficacy of degarelix may also be reduced. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval. Additionally, tetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog.
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: (Contraindicated) Concurrent use of deutetrabenazine and tetrabenazine is contraindicated. Both drugs are inhibitors of vesicular monoamine transporter 2 (VMAT2) and deplete monoamine stores. Deutetrabenazine may be started the day after tetrabenazine discontinuation.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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; Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include tetrabenazine.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
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; 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.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with tetrabenazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
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: (Major) Coadministration of dofetilide and tetrabenazine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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.
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: (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: (Contraindicated) 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 Disoproxil Fumarate: (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; Lamivudine; Tenofovir Disoproxil Fumarate: (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.
Elvitegravir; Cobicistat; 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.
Elvitegravir; Cobicistat; 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.
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; 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.
Encorafenib: (Major) Avoid coadministration of encorafenib and tetrabenazine due to the potential for additive QT prolongation. Encorafenib is associated with dose-dependent prolongation of the QT interval. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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.
Entrectinib: (Major) Avoid coadministration of entrectinib with tetrabenazine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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) Concomitant use of tetrabenazine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Major) Concomitant use of tetrabenazine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and tetrabenazine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Ethanol: (Major) Advise patients to avoid alcohol-containing beverages while taking tetrabenazine. Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression.
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.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and tetrabenazine. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of opiate agonists with tetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with tetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking tetrabenazine, use a lower initial dose of the opiate and titrate to clinical response. If tetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of tetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
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) Concomitant use of tetrabenazine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Major) Concomitant use of tetrabenazine and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of tetrabenazine and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
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.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Foscarnet: (Major) 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.
Fostemsavir: (Major) Avoid concurrent use of tetrabenazine with fostemsavir due to the potential for additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tetrabenazine and gabapentin. Concurrent use may result in additive CNS depression.
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.
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.
Gilteritinib: (Major) Avoid concomitant use of tetrabenazine with gilteritinib due to the potential for additive QT prolongation. Gilteritinib has been associated with QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Glasdegib: (Major) Avoid coadministration of glasdegib with tetrabenazine due to the potential for additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia.
Goserelin: (Major) Avoid coadministration of goserelin with tetrabenazine due to the risk of reduced efficacy of goserelin; QT prolongation may also occur. Tetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
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.
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.
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: (Major) Avoid coadministration of histrelin with tetrabenazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Tetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
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; 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.
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; 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) Concomitant use of tetrabenazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Avoid coadministration of hydroxyzine and tetrabenazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including tetrabenazine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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.
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.
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: (Contraindicated) 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.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with tetrabenazine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and tetrabenazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; 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.
Lapatinib: (Major) Avoid coadministration of tetrabenazine with lapatinib due to the risk of QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tetrabenazine. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) Avoid coadministration of lefamulin with tetrabenazine as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tetrabenazine. Dosage adjustments of lemborexant and tetrabenazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with tetrabenazine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Tetrabenazine also causes a small increase in the corrected QT interval (QTc).
Leuprolide: (Major) Avoid coadministration of leuprolide with tetrabenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Tetrabenazine can cause leuprolide, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with tetrabenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Tetrabenazine can cause leuprolide, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levamlodipine: (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.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with tetrabenazine should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levodopa: (Moderate) Monitor for a decrease in levodopa efficacy during concomitant tetrabenazine use. Levodopa and tetrabenazine may antagonize each other's effects: levodopa is metabolized to dopamine while tetrabenazine depletes dopamine stores and acts as a dopamine receptor blocker. While concomitant use is generally not recommended for this reason, combination therapy may be beneficial in the management of some levodopa-related dyskinesias.
Levofloxacin: (Major) Concomitant use of tetrabenazine and levofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and tetrabenazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
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.
Lisinopril; 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.
Lithium: (Major) Concomitant use of tetrabenazine and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Avoid coadministration of lofexidine with tetrabenazine due to the potential for additive QT prolongation. Monitor ECG if coadministration cannot be avoided. Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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) Avoid coadministration of lopinavir with tetrabenazine due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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.
Lumateperone: (Moderate) Tetrabenazine is a reversible, dopamine depleting drug and lumateperone is a dopamine antagonist. The risk for pseudoparkinsonism, neuroleptic malignant syndrome, or akathisia may be increased with concomitant administration. Concurrent use of tetrabenazine and drugs that cause CNS depression, such as lumateperone, may have additive effects and worsen drowsiness or sedation.
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.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as tetrabenazine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Tetrabenazine also causes a small increase in the QTc.
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.
Mecamylamine: (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.
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.
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) Concomitant use of tetrabenazine and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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: (Major) Concomitant use of tetrabenazine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tetrabenazine may be increased when 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) Concomitant use of tetrabenazine and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mobocertinib: (Major) Concomitant use of mobocertinib and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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: (Contraindicated) 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.
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 and tetrabenazine; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have occurred in patients who received nilotinib therapy. Tetrabenazine causes a small increase in the corrected QT interval.
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.
Ofloxacin: (Major) Concomitant use of tetrabenazine and ofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Olanzapine; Fluoxetine: (Major) Concomitant use of tetrabenazine and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (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.
Olanzapine; Samidorphan: (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.
Oliceridine: (Moderate) Concomitant use of oliceridine with tetrabenazine may cause excessive sedation and somnolence. Limit the use of oliceridine with tetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Olmesartan; 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.
Ondansetron: (Major) Concomitant use of tetrabenazine and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Opicapone: (Moderate) Opicapone should be given cautiously with other agents that cause CNS depression, including tetrabenazine, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
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.
Osilodrostat: (Major) Avoid coadministration of osilodrostat with tetrabenazine due to the potential for additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Osilodrostat is associated with dose-dependent QT prolongation.
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.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking tetrabenazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Pacritinib: (Major) Concomitant use of pacritinib and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. 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, pseudoparkinsonism, neuroleptic malignant syndrome, akathisia, or orthostasis. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, 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: (Contraindicated) 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.
Phenobarbital; Hyoscyamine; Atropine; 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.
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.
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: (Contraindicated) 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.
Pitolisant: (Major) Avoid coadministration of pitolisant with tetrabenazine as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking tetrabenazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
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.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tetrabenazine and pregabalin. Concurrent use may result in additive CNS depression.
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.
Promethazine; Dextromethorphan: (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.
Promethazine; Phenylephrine: (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) Concomitant use of tetrabenazine and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Quetiapine: (Major) Concomitant use of tetrabenazine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Quinapril; 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.
Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include tetrabenazine.
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.
Quizartinib: (Major) Concomitant use of quizartinib and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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: (Contraindicated) 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.
Relugolix: (Major) Avoid concurrent use of tetrabenazine with relugolix due to the potential for additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concurrent use of tetrabenazine with relugolix due to the potential for additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
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.
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 e xtrapyramidal symptoms may be increased.
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 is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
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: (Contraindicated) 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.
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: (Contraindicated) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy, such as selegiline, within the past 14 days. The major metabolites of 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.
Selpercatinib: (Major) Avoid concurrent use of tetrabenazine with selpercatinib due to the potential for additive QT prolongation. Monitor ECGs more frequently for QT prolongation if coadministration is necessary. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
Sertraline: (Major) Concomitant use of tetrabenazine and sertraline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Siponimod: (Major) Avoid coadministration of siponimod and tetrabenazine due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Avoid coadministration of tetrabenazine with sorafenib due to the risk of QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Sorafenib has also been associated with QT prolongation.
Sotalol: (Major) Concomitant use of tetrabenazine and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tetrabenazine. CNS depressants can potentiate the effects of stiripentol.
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.
Sunitinib: (Major) Avoid coadministration of tetrabenazine with other drugs known to prolong the corrected QT interval (QTc), such as sunitinib. Tetrabenazine causes a small increase in the QTc. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
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) Concomitant use of tetrabenazine and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Telmisartan; 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.
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.
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: (Contraindicated) 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.
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.
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) Avoid coadministration of tetrabenazine with toremifene due to the risk of additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Toremifene has also 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.
Tramadol; Acetaminophen: (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: (Contraindicated) 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) Concomitant use of trazodone and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Triclabendazole: (Major) Concomitant use of triclabendazole and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Avoid coadministration of triptorelin with tetrabenazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Tetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Valbenazine: (Contraindicated) Concurrent use of tetrabenazine and valbenazine is contraindicated. Both drugs are inhibitors of vesicular monoamine transporter 2 (VMAT2) and deplete monoamine stores.
Vandetanib: (Major) Avoid coadministration of vandetanib with tetrabenazine 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).
Vardenafil: (Major) Concomitant use of vardenafil and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Concomitant use of venlafaxine and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Voclosporin: (Major) Avoid concomitant use of tetrabenazine and voclosporin due to the risk of additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; 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.
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: (Major) Concomitant use of ziprasidone and tetrabenazine should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. 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.

How Supplied

Tetrabenazine/Xenazine Oral Tab: 12.5mg, 25mg

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.

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.

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.