English

ThisiscontentfromElsevier'sDrugInformation

Tetrabenazine

Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.

Feb.27.2017

Tetrabenazine

Indications/Dosage

Labeled

  • Huntington's Disease (Huntington's Chorea)

Off-Label

    † Off-label indication

    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.[34389]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • 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.

    Patients with Hepatic Impairment Dosing

    Tetrabenazine is contraindicated in patients with hepatic impairment.

    Patients with Renal Impairment Dosing

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

    † Off-label indication
    Revision Date: 02/27/2017, 02:10:22 PM

    References

    34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.

    How Supplied

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (60505-3882) (Apotex Corp) null

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (42291-0806) (AvKARE, Inc.) (off market)

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (68682-0421) (Bausch Health US, LLC) null

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (69452-0117) (Bionpharma Inc) null

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (31722-0821) (Camber Pharmaceuticals Inc) null

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (43598-0394) (Dr. Reddy's Laboratories, Inc.) nullTetrabenazine 12.5mg Tablet package photo

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (51407-0480) (Golden State Medical Supply, Inc.) null

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (00054-0468) (Hikma Pharmaceuticals USA Inc.) (off market)

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (68180-0408) (Lupin Pharmaceuticals, Inc.) (off market)

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (70436-0101) (Slate Run Pharmaceuticals, LLC) null

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (47335-0277) (Sun Pharmaceutical Industries, Inc.) null

    Tetrabenazine Oral tablet

    Tetrabenazine 12.5mg Tablet (51224-0425) (TAGI Pharma, Inc.) null

    Tetrabenazine Oral tablet

    Xenazine 12.5mg Tablet (67386-0421) (Lundbeck Inc. ) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (60505-3883) (Apotex Corp) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (42291-0807) (AvKARE, Inc.) (off market)

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (68682-0422) (Bausch Health US, LLC) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (69452-0118) (Bionpharma Inc) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (31722-0822) (Camber Pharmaceuticals Inc) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (43598-0395) (Dr. Reddy's Laboratories, Inc.) nullTetrabenazine 25mg Tablet package photo

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (51407-0481) (Golden State Medical Supply, Inc.) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (00054-0469) (Hikma Pharmaceuticals USA Inc.) (off market)

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (68180-0409) (Lupin Pharmaceuticals, Inc.) (off market)

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (70436-0102) (Slate Run Pharmaceuticals, LLC) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (47335-0179) (Sun Pharmaceutical Industries, Inc.) null

    Tetrabenazine Oral tablet

    Tetrabenazine 25mg Tablet (51224-0426) (TAGI Pharma, Inc.) null

    Tetrabenazine Oral tablet

    Xenazine 25mg Tablet (67386-0422) (Lundbeck Inc. ) null

    Description/Classification

    Description

    Tetrabenazine, a synthetic benzoquinolizine derivative, is a monoamine depleter and dopamine receptor blocker that improves the symptoms associated with Huntington's disease (HD), and is considered a first line treatment for HD associated chorea by the American Academy of Neurology.[52476] Tetrabenazine appears to have the best effect in HD but has shown improvement in other hyperkinetic movements disorders, such as tardive dyskinesia (TD), dystonia, Tourette's syndrome, and myoclonus.[34371][34372][34374] Tetrabenazine may also have synergistic effects when used in combination with the dopamine antagonist pimozide.[34370] One case report describes the successful use of tetrabenazine as part of combination therapy to treat refractory orofacial tardive dyskinesia.[34373] A randomized, double-blind, placebo-controlled study in patients with HD examined the efficacy of tetrabenazine in treating chorea. Patients were randomized to receive tetrabenazine (n = 54) or placebo (n = 30) for 12 weeks. The primary outcome was the change from baseline in the chorea score as measured by the Unified Huntington's Disease Rating Scale (UHDRS). After 12 weeks, the mean chorea score in the tetrabenazine group declined significantly compared to the placebo group (a reduction of 5 vs. 1.5 points, respectively). Tetrabenazine was superior to placebo as assessed by the clinical global improvement scale. However, more patients in the active treatment group (89%) experienced at least one adverse effect compared to the placebo group (70%). Tetrabenazine decreased the chorea of HD, but it also caused slight worsening in mood, cognition, rigidity, and functional capacity.[52494] Because tetrabenazine can increase the risk of depression and suicidal thoughts and behavior, the benefit of tetrabenazine should be weighed against the risks of treatment, particularly in those with a history of depression or suicidal attempts or ideation. In addition, HD patients may be predisposed to develop tardive dyskinesia with typical dopamine antagonists; however, tetrabenazine has never been reported to cause TD.[34374] Pseudoparkinsonism has been documented with tetrabenazine. Tetrabenazine is available in Europe and Australia as Xenazine and in Canada as Nitoman for the treatment of hyperkinetic movement disorders. Tetrabenazine has been granted orphan drug status by the FDA for chorea in people with Huntington's disease. A Specialty Pharmacy Network will send all Xenazine prescriptions directly to the physician office or patient. Tetrabenazine was approved for the treatment of chorea in people with Huntington's disease in August 2008.

    Classifications

    • Central Nervous System
      • Other CNS Agents
        • Monoamine Depletor
    Revision Date: 09/21/2013, 01:06:44 PM

    References

    34370 - McArthur AW, Pollock M, Smidt N, et al. Combined therapy with tetrabenazine and pimozide in Huntington's chorea. N Z Med J 1976;83:114-16.34371 - Jankovic J, Orman J. Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. Neurology 1988;38:391-4.34372 - Ondo WG, Hanna PA, Jankovic J. Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol. Am J Psychiatry 1999;156:1279-81.34373 - Koch HJ, Szecsey A, Vogel M, et al. Successful therapy of tardive dyskinesia in a 71-year-old woman with a combination of tetrabenazine, olanzapine and tiapride. Int J Clin Pract 2003;57:147-9.34374 - Ondo WG, Tintner R, Thomas M, et al. Tetrabenazine treatment for Huntington's disease-associated chorea. Clin Neuropharmacol 2002;25:300-2.52476 - Armstrong MJ, Miyasaki JM. Evidence-based guideline: Pharmacologic treatment of chorea in Huntington disease: Report of the guideline development subcommittee of the American Academy of Neurology. Neurology 2012;79:597-603.52494 - Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology 2006;66:366-372.

    Administration Information

    General Administration Information

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

     

    • 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.

    Route-Specific Administration

    Oral Administration

    • May be administered without regard to meals.

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 10/05/2015, 11:21:28 AM

      References

      Adverse Reactions

      Moderate

      • akathisia
      • confusion
      • depression
      • dysarthria
      • dysphagia
      • dyspnea
      • dystonic reaction
      • dysuria
      • hyperprolactinemia
      • hypertonia
      • orthostatic hypotension
      • pseudoparkinsonism
      • QT prolongation

      Mild

      • anorexia
      • anxiety
      • diarrhea
      • dizziness
      • drowsiness
      • ecchymosis
      • fatigue
      • headache
      • hyperhidrosis
      • hyperkinesis
      • infection
      • insomnia
      • irritability
      • nausea
      • rash
      • restlessness
      • syncope
      • tremor
      • vomiting
      • weakness

      Severe

      • neuroleptic malignant syndrome
      • suicidal ideation

      Serotonin and noradrenaline depletion are likely mechanisms of tetrabenazine-induced depression, which has been reported to occur in roughly 19% to 35% of patients treated with the drug. In a 12 week randomized, placebo-controlled trial, 19% of patients with Huntington's disease associated chorea who received tetrabenazine 100 mg daily (n = 54) experienced depression or worsening depression, compared to 0% of placebo recipients (n = 30). During 2 open-label studies, depression occurred in 35% of tetrabenazine recipients. In a retrospective chart review involving the use of tetrabenazine in movement disorders, 272 patients (52.5 %) had a documented history of depression and/or prior treatment with antidepressant therapy. During tetrabenazine treatment, 50 patients (18.4%) had an exacerbation of their depression or required a change in antidepressant (15.4%) and 28 patients (11.4%) experienced depression for the first time. A total of 16 patients (3.1%) discontinued treatment due to an adverse event of depression. The percentage of patients who discontinued treatment was not statistically different in patients with a prior history of depression (3.3%) and those with no prior history of depression (2.8%). Tetrabenazine increases the risk of suicidal ideation and behavior. Across all clinical studies of Huntington's disease chorea (n = 187), 1 patient committed suicide, 1 attempted suicide, and 6 had suicidal ideation. Because tetrabenazine can increase the risk of depression and suicidal ideation or behavior, and patients with Huntington's disease are at increased risk for depression or suicidal ideation/behaviors due to their natural disease, extreme caution is necessary when administering the drug. Instruct patients, as well as their caregivers and families, to promptly report the occurrence of depression, worsening depression, or suicidal intentions to their healthcare providers.[34389]

      Sedation and somnolence (or drowsiness) as well as insomnia are 2 frequently reported adverse reactions to tetrabenazine. Drowsiness was observed with tetrabenazine in 31% of Huntington's disease patients with chorea (n = 54) during a randomized, placebo-controlled trial, compared to 3% in the placebo group (n = 30); incidence rates up to 57% were observed during open-label experience. Drowsiness appears to be dose related, as decreases in doses yielded less drowsiness. Insomnia was noted in 22% of patients. Tetrabenazine may cause pseudoparkinsonism; symptoms suggestive of pseudoparkinsonism (e.g., hypertonia, rigidity, or bradykinesia) were noted in up to 15% of patients during clinical trials. As rigidity may develop as part of the natural disease process in Huntington's disease, tetrabenazine-induced pseudoparkinsonism may be difficult to diagnose; consider dose reduction or discontinuation in patients who develop symptoms of parkinsonism. Akathisia was observed in 19% to 20% of tetrabenazine recipients during randomized, placebo-controlled and open-label trials for chorea; restlessness and agitation may be indicators of akathisia development. Overall, 33% of patients experienced some type of extrapyramidal event during a placebo-controlled trial, defined as akathisia, hyperkinesis, restlessness, bradykinesia, pseudoparkinsonism, hypertonia, or other extrapyramidal disorders.[34389] Other CNS effects include anxiety (15%), irritability (9%), anorexia (4%), obsessive reactions (4%), balance difficulty (9%), drooling, and subjective weakness.[34374] [34389] Dizziness, dysarthria, gait unsteadiness, and headache occurred in 4% of tetrabenazine recipients. Postural dizziness was observed in healthy volunteers who received single doses of tetrabenazine 25 or 50 mg; syncope and orthostatic hypotension occurred. Tremor, confusion, and worsening aggression have been reported during post-marketing experience. Neuroleptic malignant syndrome (NMS) and acute dystonic reaction have also been observed. Symptoms of NMS may include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (e.g., irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac arrhythmias). Myoglobinuria, rhabdomyolysis, and acute renal failure may also occur. If NMS is diagnosed, tetrabenazine should be discontinued immediately, and appropriate supportive treatment given. NMS recurrence among tetrabenazine recipients has been observed. If treatment is needed following NMS recovery, monitor for signs of recurrence. Many adverse events with tetrabenazine appear to be dose-related and may improve following a reduction in dosage. Long-term studies have not shown the development of tolerance to the beneficial effects of the drug.[34389]

      During a 12-week placebo-controlled clinical trial of Huntington's disease associated chorea, dysphagia occurred in 4% of tetrabenazine recipients compared to 3% of those who received placebo. In 48-week and 80-week open-label studies, dysphagia occurred in 10% and 8% of treated patients, respectively. Dysphagia may occur as part of the underlying disease process of Huntington's disease; however, dysphagia has been observed with the use of drugs that reduce dopaminergic transmission such as tetrabenazine. Aspiration pneumonia did occur with dysphagia in some cases. Other gastrointestinal side effects of tetrabenazine reported by patients in clinical trials include nausea (13%), vomiting (6%), and diarrhea (1.9%). During an open-label trial, diarrhea began during tetrabenazine titration and normalized during maintenance dosing.[34389] [52505]

      Tetrabenazine may cause prolongation of the QT interval; a small increase of approximately 8 msec has been observed. As QT prolongation may lead to serious cardiac effects such as torsade de pointes, avoid the use of tetrabenazine in patients whose cardiac condition or history may predispose them to the development of dangerous arrhythmias. Tetrabenazine should also not be used in combination with other drugs known to prolong the QT interval.[34389]

      Elevated prolactin concentrations may occur with tetrabenazine treatment, leading to potential symptoms associated with hyperprolactinemia. In healthy volunteers, administration of tetrabenazine 25 mg increased peak plasma prolactin concentrations 4- to 5-fold. It is unknown if chronic elevations of prolactin occur with treatment. Patient conditions that may be prolactin-dependent (e.g., breast cancer, amenorrhea, galactorrhea, gynecomastia, and impotence) may develop or worsen; use caution and weigh the risk and benefits of tetrabenazine treatment. If hyperprolactinemia is suspected, laboratory assessments should occur and discontinuation of tetrabenazine should be considered.[34389]

      For the body as a whole, fatigue was commonly reported, occurring in 22% of tetrabenazine recipients (n = 54) compared to 13% of those who took placebo (n = 30) during a randomized trial. Ecchymosis occurred in 6% of patients given tetrabenazine. Falls and head lacerations were reported in 15% and 6% of patients, respectively. Hyperhidrosis and rash (unspecified) have been reported during post-marketing experience.[34389]

      Dysuria was observed in 4% of patients with Huntington's disease associated chorea given tetrabenazine during a randomized, controlled trial.[34389]

      Respiratory adverse reactions reported during tetrabenazine treatment in a randomized, placebo-controlled trial include upper respiratory tract infection (11%), dyspnea (4%), and bronchitis (4%). Pneumonia has been observed during post-marketing surveillance.[34389]

      Revision Date: 02/21/2018, 01:29:13 PM

      References

      34374 - Ondo WG, Tintner R, Thomas M, et al. Tetrabenazine treatment for Huntington's disease-associated chorea. Clin Neuropharmacol 2002;25:300-2.34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.52505 - Frank S. Tetrabenazine as anti-chorea therapy in Huntington Diseae: an open-label continuation study. BMC Neurol 2009;9:62.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • hepatic disease
      • MAOI therapy
      • suicidal ideation
      • alcoholism
      • apheresis
      • AV block
      • bradycardia
      • breast cancer
      • breast-feeding
      • cardiac arrhythmias
      • cardiomyopathy
      • celiac disease
      • children
      • CNS depression
      • coma
      • dehydration
      • depression
      • driving or operating machinery
      • dysphagia
      • females
      • fever
      • geriatric
      • heart failure
      • human immunodeficiency virus (HIV) infection
      • hyperparathyroidism
      • hyperprolactinemia
      • hypocalcemia
      • hypokalemia
      • hypomagnesemia
      • hypothermia
      • hypothyroidism
      • hypovolemia
      • infertility
      • long QT syndrome
      • myocardial infarction
      • neurological disease
      • orthostatic hypotension
      • Parkinson's disease
      • pheochromocytoma
      • pregnancy
      • QT prolongation
      • renal disease
      • renal failure
      • renal impairment
      • rheumatoid arthritis
      • sickle cell disease
      • sleep deprivation
      • stroke
      • surgery
      • systemic lupus erythematosus (SLE)

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

      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.[34389]

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

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

      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.[34389] 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.[48533] 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.[28307] [33492] [42938] 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.[34389]

      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.[34389] 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.[27500]

      Tetrabenazine may cause an increase in the corrected QTc interval in some patients. Other drugs that prolong the QT interval have been associated with torsade de pointes (TdP), a life-threatening arrhythmia; existent QT prolongation increases the risk of TdP. Tetrabenazine should be avoided in those with QT prolongation associated with congenital long QT syndrome or those with a history of cardiac arrhythmias. Tetrabenazine should not be used in combination with medications known to prolong the QT interval, because the risk for TdP may be increased. Use tetrabenazine with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, pyrexia or elevated body temperature, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. It should be noted that patients with recent myocardial infarction or unstable heart disease were excluded from clinical trials; therefore, the effects of the drug in patients with these conditions are generally unknown. Postural dizziness, syncope, and orthostatic hypotension have been reported. Hypotension caused by hypovolemia, antihypertensive drugs, or dehydration may be potentiated. The pharmacokinetics of tetrabenazine have not been formally studied in geriatric patients. Caution is advisable in the elderly since this patient population may be more susceptible to the cardiac effects of the drug.[28432] [28457] [34389] [56592] [65180]

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

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

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

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

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

      Neuroleptic malignant syndrome has been reported in association with the use of tetrabenazine. In the presence of high fever, the possibility of this complication should be considered. Additionally, fever may increase the risk of prolonging the QT interval when using tetrabenazine.[28432] [28457] [34389] [56592] [65180]

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

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

      Tetrabenazine is contraindicated in patients who are receiving MAOI therapy or reserpine.

      Revision Date: 08/24/2020, 12:28:42 PM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.28307 - Haldol (haloperidol) injection for immediate release package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Feb.28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.33492 - Haldol Decanoate (haloperidol decanoate) for intramuscular injection package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Nov.34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.42938 - Haloperidol tablets package insert. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2020 Jul.48533 - Lubbe WF, Walker EB. Chorea gravidarum associated with circulating lupus anticoagulant: successful outcome of pregnancy with prednisone and aspirin therapy. Case report. Br J Obstet Gynaecol 1983;90:487-90.56592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/

      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.

      Revision Date: 02/07/2009, 04:10:17 AM

      References

      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.[34389]

       

      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.[34389]

      Route-Specific Pharmacokinetics

      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.[34389]

      Special Populations

      Hepatic Impairment

      Pharmacokinetic evaluations in a limited number of subjects indicated that those with mild to moderate hepatic impairment experienced a 7—190-fold higher maximum blood concentration of tetrabenazine than healthy subjects. The elimination half-life of tetrabenazine was approximately 17.5 hours, and the elimination half-lives of alpha-HTBZ and beta-HTBZ were 10 and 8 hours, respectively. The safety and efficacy of increased exposure to tetrabenazine and its metabolites in those with hepatic impairment is unknown; therefore, the drug is contraindicated in patients with any degree of hepatic dysfunction.

      Revision Date: 03/04/2014, 03:36:41 PM

      References

      34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.

      Pregnancy/Breast-feeding

      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.[34389] 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.[48533] 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.[28307] [33492] [42938] 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.[34389]

      breast-feeding

      There are no data on the presence of tetrabenazine or its metabolites in human breast milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tetrabenazine and any potential adverse effects on the breast-fed infant from the drug or the mother's underlying condition. Tetrabenazine elevates serum prolactin concentrations in humans, and thus, interference with proper lactation is possible.[34389] 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.[27500]

      Revision Date: 10/03/2017, 04:23:32 PM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.28307 - Haldol (haloperidol) injection for immediate release package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Feb.33492 - Haldol Decanoate (haloperidol decanoate) for intramuscular injection package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Nov.34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.42938 - Haloperidol tablets package insert. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2020 Jul.48533 - Lubbe WF, Walker EB. Chorea gravidarum associated with circulating lupus anticoagulant: successful outcome of pregnancy with prednisone and aspirin therapy. Case report. Br J Obstet Gynaecol 1983;90:487-90.

      Interactions

      Level 1 (Severe)

      • Cisapride
      • Deutetrabenazine
      • Dextromethorphan; Quinidine
      • Dronedarone
      • Isocarboxazid
      • Ketoconazole
      • Levoketoconazole
      • Monoamine oxidase inhibitors
      • Phenelzine
      • Pimozide
      • Quinidine
      • Rasagiline
      • Safinamide
      • Selegiline
      • Thioridazine
      • Tranylcypromine
      • Valbenazine

      Level 2 (Major)

      • Adagrasib
      • Alfuzosin
      • Amiodarone
      • Amisulpride
      • Amoxicillin; Clarithromycin; Omeprazole
      • Anagrelide
      • Apomorphine
      • Aripiprazole
      • Arsenic Trioxide
      • Artemether; Lumefantrine
      • Asenapine
      • Atomoxetine
      • Azithromycin
      • Bedaquiline
      • Benzhydrocodone; Acetaminophen
      • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Brexpiprazole
      • Buprenorphine
      • Buprenorphine; Naloxone
      • Cabotegravir; Rilpivirine
      • Ceritinib
      • Chloroquine
      • Chlorpromazine
      • Ciprofloxacin
      • Citalopram
      • Clarithromycin
      • Clofazimine
      • Clozapine
      • Codeine; Phenylephrine; Promethazine
      • Codeine; Promethazine
      • Crizotinib
      • Dacomitinib
      • Dasatinib
      • Degarelix
      • Desflurane
      • Desvenlafaxine
      • Dexmedetomidine
      • Disopyramide
      • Dofetilide
      • Dolasetron
      • Dolutegravir; Rilpivirine
      • Donepezil
      • Donepezil; Memantine
      • Droperidol
      • Efavirenz
      • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Eliglustat
      • Emtricitabine; Rilpivirine; Tenofovir alafenamide
      • Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate
      • Encorafenib
      • Entrectinib
      • Eribulin
      • Erythromycin
      • Escitalopram
      • Ethanol
      • Etrasimod
      • Fentanyl
      • Fexinidazole
      • Fingolimod
      • Flecainide
      • Fluconazole
      • Fluoxetine
      • Fluphenazine
      • Fluvoxamine
      • food
      • Foscarnet
      • Fostemsavir
      • Gemifloxacin
      • Gemtuzumab Ozogamicin
      • Gilteritinib
      • Glasdegib
      • Goserelin
      • Granisetron
      • Halogenated Anesthetics
      • Haloperidol
      • Histrelin
      • Hydroxychloroquine
      • Hydroxyzine
      • Ibutilide
      • Iloperidone
      • Inotuzumab Ozogamicin
      • Isoflurane
      • Itraconazole
      • Ivosidenib
      • Lansoprazole; Amoxicillin; Clarithromycin
      • Lapatinib
      • Lefamulin
      • Lenvatinib
      • Leuprolide
      • Leuprolide; Norethindrone
      • Levofloxacin
      • Lithium
      • Lofexidine
      • Loperamide
      • Loperamide; Simethicone
      • Lopinavir; Ritonavir
      • Loxapine
      • Lurasidone
      • Macimorelin
      • Maprotiline
      • Mefloquine
      • Methadone
      • Metoclopramide
      • Metronidazole
      • Midostaurin
      • Mifepristone
      • Mirtazapine
      • Mobocertinib
      • Molindone
      • Morphine
      • Morphine; Naltrexone
      • Moxifloxacin
      • Nilotinib
      • Ofloxacin
      • Olanzapine
      • Olanzapine; Fluoxetine
      • Olanzapine; Samidorphan
      • Ondansetron
      • Osilodrostat
      • Osimertinib
      • Oxaliplatin
      • Ozanimod
      • Pacritinib
      • Paliperidone
      • Panobinostat
      • Paroxetine
      • Pasireotide
      • Pazopanib
      • Pentamidine
      • Perphenazine
      • Perphenazine; Amitriptyline
      • Pimavanserin
      • Pitolisant
      • Ponesimod
      • Posaconazole
      • Primaquine
      • Procainamide
      • Prochlorperazine
      • Promethazine
      • Promethazine; Dextromethorphan
      • Promethazine; Phenylephrine
      • Propafenone
      • Quetiapine
      • Quinine
      • Quizartinib
      • Ranolazine
      • Relugolix
      • Relugolix; Estradiol; Norethindrone acetate
      • Ribociclib
      • Ribociclib; Letrozole
      • Rilpivirine
      • Risperidone
      • Rolapitant
      • Romidepsin
      • Saquinavir
      • Selpercatinib
      • Sertraline
      • Sevoflurane
      • Siponimod
      • Sodium Stibogluconate
      • Solifenacin
      • Sorafenib
      • Sotalol
      • Sunitinib
      • Tacrolimus
      • Tamoxifen
      • Telavancin
      • Thiothixene
      • Tipranavir
      • Tolterodine
      • Toremifene
      • Trazodone
      • Triclabendazole
      • Trifluoperazine
      • Triptorelin
      • Vandetanib
      • Vardenafil
      • Vemurafenib
      • Venlafaxine
      • Voclosporin
      • Vonoprazan; Amoxicillin; Clarithromycin
      • Voriconazole
      • Vorinostat
      • Ziprasidone
      • Zuranolone

      Level 3 (Moderate)

      • Acebutolol
      • Acetaminophen; Aspirin; Diphenhydramine
      • Acetaminophen; Caffeine; Dihydrocodeine
      • Acetaminophen; Caffeine; Pyrilamine
      • Acetaminophen; Codeine
      • Acetaminophen; Dextromethorphan; Doxylamine
      • Acetaminophen; Dichloralphenazone; Isometheptene
      • Acetaminophen; Diphenhydramine
      • Acetaminophen; Hydrocodone
      • Acetaminophen; Oxycodone
      • Acetaminophen; Pamabrom; Pyrilamine
      • Alfentanil
      • Aliskiren; Hydrochlorothiazide, HCTZ
      • Alprazolam
      • Amiloride
      • Amiloride; Hydrochlorothiazide, HCTZ
      • Amitriptyline
      • Amlodipine
      • Amlodipine; Atorvastatin
      • Amlodipine; Benazepril
      • Amlodipine; Celecoxib
      • Amlodipine; Olmesartan
      • Amlodipine; Valsartan
      • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
      • Amobarbital
      • Angiotensin-converting enzyme inhibitors
      • Anxiolytics; Sedatives; and Hypnotics
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Carisoprodol; Codeine
      • Aspirin, ASA; Oxycodone
      • Atazanavir; Cobicistat
      • Atenolol
      • Atenolol; Chlorthalidone
      • Atropine; Difenoxin
      • Azilsartan; Chlorthalidone
      • Belladonna; Opium
      • Benazepril
      • Benazepril; Hydrochlorothiazide, HCTZ
      • Benzodiazepines
      • Beta-adrenergic blockers
      • Betaxolol
      • Bisoprolol
      • Bisoprolol; Hydrochlorothiazide, HCTZ
      • Brimonidine; Timolol
      • Buspirone
      • Butalbital; Acetaminophen
      • Butalbital; Acetaminophen; Caffeine
      • Butalbital; Acetaminophen; Caffeine; Codeine
      • Butalbital; Aspirin; Caffeine; Codeine
      • Butorphanol
      • Cabergoline
      • Candesartan; Hydrochlorothiazide, HCTZ
      • Cannabidiol
      • Captopril
      • Captopril; Hydrochlorothiazide, HCTZ
      • Carbidopa; Levodopa
      • Carbidopa; Levodopa; Entacapone
      • Carteolol
      • Carvedilol
      • Celecoxib; Tramadol
      • Cenobamate
      • Cetirizine
      • Cetirizine; Pseudoephedrine
      • Cetrorelix
      • Chlordiazepoxide
      • Chlordiazepoxide; Amitriptyline
      • Chlordiazepoxide; Clidinium
      • Chlorothiazide
      • Chlorpheniramine; Codeine
      • Chlorpheniramine; Hydrocodone
      • Chlorthalidone
      • Clevidipine
      • Clomipramine
      • Clonazepam
      • Clonidine
      • Clorazepate
      • Cobicistat
      • Codeine
      • Codeine; Guaifenesin
      • Codeine; Guaifenesin; Pseudoephedrine
      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Desipramine
      • Dextromethorphan; Diphenhydramine; Phenylephrine
      • Diazepam
      • Difelikefalin
      • Diltiazem
      • Diphenhydramine
      • Diphenhydramine; Ibuprofen
      • Diphenhydramine; Naproxen
      • Diphenhydramine; Phenylephrine
      • Diphenoxylate; Atropine
      • Dorzolamide; Timolol
      • Doxazosin
      • Doxepin
      • Doxylamine
      • Doxylamine; Pyridoxine
      • Dronabinol
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Enalapril, Enalaprilat
      • Enalapril; Hydrochlorothiazide, HCTZ
      • Entacapone
      • Eplerenone
      • Eprosartan; Hydrochlorothiazide, HCTZ
      • Esketamine
      • Esmolol
      • Estazolam
      • Eszopiclone
      • Felodipine
      • Fenfluramine
      • Flurazepam
      • Fosinopril
      • Fosinopril; Hydrochlorothiazide, HCTZ
      • Gabapentin
      • Ganirelix
      • Guaifenesin; Hydrocodone
      • Guanfacine
      • Homatropine; Hydrocodone
      • Hydrochlorothiazide, HCTZ
      • Hydrochlorothiazide, HCTZ; Moexipril
      • Hydrocodone
      • Hydrocodone; Ibuprofen
      • Hydrocodone; Pseudoephedrine
      • Hydromorphone
      • Ibuprofen; Oxycodone
      • Iloprost
      • Imipramine
      • Irbesartan; Hydrochlorothiazide, HCTZ
      • Isradipine
      • Labetalol
      • Lasmiditan
      • Lemborexant
      • Levamlodipine
      • Levobunolol
      • Levocetirizine
      • Levodopa
      • Levorphanol
      • Lisinopril
      • Lisinopril; Hydrochlorothiazide, HCTZ
      • Lorazepam
      • Losartan; Hydrochlorothiazide, HCTZ
      • Lumateperone
      • Mecamylamine
      • Meperidine
      • Meprobamate
      • Methyldopa
      • Metolazone
      • Metoprolol
      • Metoprolol; Hydrochlorothiazide, HCTZ
      • Midazolam
      • Mirabegron
      • Moexipril
      • Nabilone
      • Nadolol
      • Nafarelin
      • Nalbuphine
      • Nebivolol
      • Nebivolol; Valsartan
      • Nifedipine
      • Nimodipine
      • Nisoldipine
      • Nortriptyline
      • Oliceridine
      • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
      • Olmesartan; Hydrochlorothiazide, HCTZ
      • Opicapone
      • Oritavancin
      • Oxazepam
      • Oxycodone
      • Oxymorphone
      • Peginterferon Alfa-2b
      • Pentazocine
      • Pentazocine; Naloxone
      • Pentobarbital
      • Perindopril
      • Perindopril; Amlodipine
      • Phenobarbital
      • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
      • Phenoxybenzamine
      • Phentolamine
      • Pindolol
      • Potassium-sparing diuretics
      • Prazosin
      • Pregabalin
      • Propranolol
      • Protriptyline
      • Quazepam
      • Quinapril
      • Quinapril; Hydrochlorothiazide, HCTZ
      • Ramipril
      • Remifentanil
      • Remimazolam
      • Spironolactone
      • Spironolactone; Hydrochlorothiazide, HCTZ
      • Stiripentol
      • Sufentanil
      • Telmisartan; Amlodipine
      • Telmisartan; Hydrochlorothiazide, HCTZ
      • Temazepam
      • Terazosin
      • Thiazide diuretics
      • Timolol
      • Tolcapone
      • Tramadol
      • Tramadol; Acetaminophen
      • Trandolapril
      • Trandolapril; Verapamil
      • Treprostinil
      • Triamterene
      • Triamterene; Hydrochlorothiazide, HCTZ
      • Triazolam
      • Tricyclic antidepressants
      • Trimipramine
      • Valsartan; Hydrochlorothiazide, HCTZ
      • Verapamil
      • Zaleplon
      • Zolpidem
      Acebutolol: (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. [34389] 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. [11246] 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. [11246] 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. [11246] 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. [11246] 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. [11246] 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. [11246] 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. [11246] 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. [34389] 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. [34389] 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. [11246] 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. [34389] [68325] 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. [11246] 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. [11246] [28261] Aliskiren; 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. [34389] Alprazolam: (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. [11246] Amiloride: (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. [11246] Amiloride; 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. [11246] (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. [34389] Amiodarone: (Major) Concomitant use of amiodarone 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. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation. [28224] [28432] [28457] [34389] 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). [34389] [65068] Amitriptyline: (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. [11246] [28225] [28416] 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. [34389] 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. [34389] 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. [11246] (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. [34389] 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. [34389] 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. [34389] 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. [34389] 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. [34389] 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. [11246] 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. [11246] [28225] [28238] 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. [11246] [30163] 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. [11246] 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. [11246] 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. [28661] [34389] [59321] 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. [34389] [42845] 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. [11246] [28226] [28432] [28457] 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. [11246] [34389] [35401] 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). [34389] [36343] 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. [11246] 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. [11246] 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. [34389] 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. [11246] [58000] Atenolol: (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. [34389] Atenolol; Chlorthalidone: (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. [34389] 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. [28405] [34389] [59321] Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with tetrabenazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. [11246] [30269] Azilsartan; Chlorthalidone: (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. [34389] 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. [28855] [34389] [43974] [65157] [65170] 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). [11246] [52746] 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. [11246] 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. [11246] 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. [11246] (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. [34389] 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. [61143] [62889] 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. [11246] 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. [34389] Betaxolol: (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. [34389] 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. [34389] [36894] 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. [34389] [36894] Bisoprolol: (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. [34389] Bisoprolol; 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. [34389] 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. [11246] Brimonidine; Timolol: (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. [34389] 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. [34389] [41235] [59321] 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. [34389] [41235] [59321] 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. [11246] 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. [11246] 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. [11246] 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. [11246] (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. [11246] 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. [11246] (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. [11246] 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. [34389] 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. [27964] [34389] 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. [11246] [44376] Candesartan; 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. [34389] Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and tetrabenazine. CNS depressants can potentiate the effects of cannabidiol. [34389] [63309] 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. [11246] 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. [11246] (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. [34389] 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. [48681] [68784] 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. [11246] (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. [48681] [68784] Carteolol: (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. [34389] Carvedilol: (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. [34389] 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. [34389] Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and tetrabenazine. Concurrent use may result in additive CNS depression. [34389] [64768] 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. [34389] [57094] 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. [33350] [40967] 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. [33350] [40967] 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. [11246] Chlordiazepoxide: (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. [11246] Chlordiazepoxide; Amitriptyline: (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. [11246] (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. [11246] [28225] [28416] Chlordiazepoxide; Clidinium: (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. [11246] 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). [28229] [28230] [28231] [29758] [34389] [65157] [65170] Chlorothiazide: (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. [34389] 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. [11246] 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. [34389] 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. [28415] [28416] [34389] [43065] Chlorthalidone: (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. [34389] 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. [11246] [43411] 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. [11246] [28978] [47221] 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. [11246] [28269] 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. [11246] [28225] [28238] 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. [11246] 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. [34389] [63936] Clomipramine: (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. [11246] [28225] [28416] Clonazepam: (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. [11246] 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. [11246] Clorazepate: (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. [11246] 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. [28262] 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. [11246] [58000] 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. [11246] 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. [11246] 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. [11246] 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. [28225] [34389] [55578] (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. [11246] 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. [28225] [34389] [55578] (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. [11246] 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). [34389] [45458] 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. [34389] [63584] 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. [11246] [58000] 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. [11246] [58000] 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). [34389] [60087] 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. [34389] [45411] [46869] Desflurane: (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. [11246] [28457] [28458] [28754] [28755] [28756] Desipramine: (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. [11246] [28225] [28416] 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. [34940] 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. [61845] 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. [34389] [67509] 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. [11246] 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. [11246] [42280] [47357] Diazepam: (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. [11246] 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. [66926] 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. [11246] 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. [11246] 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. [11246] 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. [11246] 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. [11246] Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with tetrabenazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. [11246] [30269] 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). [11246] [28228] 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). [11246] [28221] [28432] [28457] 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. [34389] [42844] 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. [11246] [44376] 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. [34389] [59321] [59322] 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. [34389] [59321] [59322] Dorzolamide; Timolol: (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. [34389] 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. [34389] Doxepin: (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. [11246] [28225] [28416] 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. [11246] 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. [11246] 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. [34389] 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. [11246] [36101] 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. [11246] [28235] [28236] [28237] [28737] [51289] [5187] 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. [28442] [34389] 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. [28442] [34389] 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. [28442] [34389] 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. [34389] [57803] 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. [11246] [58000] 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. [11246] [58000] 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. [11246] [44376] 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. [11246] [44376] 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. [11246] 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. [11246] (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. [34389] 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). [34389] [63317] 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. [11246] 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). [34389] [64567] 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. [11246] Eprosartan; 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. [34389] 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. [11246] [42449] 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. [11246] [43258] 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. [28270] [34389] 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. [34389] [63989] Esmolol: (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. [34389] Estazolam: (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. [11246] Eszopiclone: (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. [11246] 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. [34389] Etrasimod: (Major) Concomitant use of etrasimod 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. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval. [34389] [69114] 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. [11246] Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and tetrabenazine. Concurrent use may result in additive CNS depression. [34389] [65634] 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. [34389] [61143] Fexinidazole: (Major) Concomitant use of fexinidazole 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. [34389] [66812] 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. [11246] 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. [11246] [23774] 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. [11246] [28674] 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. [32127] [34389] 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. [34389] Flurazepam: (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. [11246] 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. [34389] [50507] 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. [67473] 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. [28377] [34389] 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. [11246] 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. [11246] (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. [34389] 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. [34389] [65666] Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tetrabenazine and gabapentin. Concurrent use may result in additive CNS depression. [27986] [34389] [64848] 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. [11246] 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. [11246] [28419] [28420] [28424] 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. [34389] [62292] 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). [34389] [63787] 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. [34389] [63777] 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. [28592] [34389] [45411] 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. [11246] [31723] 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. [34389] 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. [11246] 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. [11246] [28457] [28458] [28754] [28755] [28756] 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. [11246] [23500] [23779] [28225] [28307] [28415] [28416] 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. [30369] [34389] [45411] 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. [34389] 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. [34389] 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. [11246] (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. [34389] 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. [34389] 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. [34389] 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. [34389] 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. [11246] 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. [34389] [41806] [65157] [65170] 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). [11246] [47129] 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. [34389] 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. [11246] [41830] 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). [34389] [36146] 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. [11246] Imipramine: (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. [11246] [28225] [28416] 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). [34389] [62245] Irbesartan; 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. [34389] 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. [34389] Isoflurane: (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. [11246] [28457] [28458] [28754] [28755] [28756] 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. [11246] 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. [11246] [40233] [57441] 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). [34389] [63368] Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and tetrabenazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [34389] [67231] Labetalol: (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. [34389] 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. [11246] [28225] [28238] 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. [33192] [34389] Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tetrabenazine. Concurrent use may result in additive CNS depression. [34389] [64685] 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). [34389] [64576] 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. [34389] [64870] 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). [34389] [58782] 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. [34389] [43800] [45411] 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. [34389] [43800] [45411] 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. [34389] Levobunolol: (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. [34389] 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. [33350] [40967] 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. [48681] [68784] 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. [11246] [28421] Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and tetrabenazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [34389] [67231] 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. [11246] 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. [11246] 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. [11246] (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. [34389] 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. [34389] [59809] [59810] [59811] 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). [34389] [63161] 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. [34389] [60864] 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. [34389] [60864] 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). [28341] [34389] [65157] [65170] Lorazepam: (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. [11246] Losartan; 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. [34389] 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. [11246] 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. [34389] [64885] 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. [34389] 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. [34389] [62723] 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. [11246] 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. [11246] 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. [11246] [28301] 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. [11246] Meprobamate: (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. [11246] 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. [11246] [28319] [28320] [28321] [28322] [33136] [5109] 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. [11246] 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. [11246] [28953] Metolazone: (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. [34389] Metoprolol: (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. [34389] Metoprolol; 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. [34389] 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. [34389] [36894] Midazolam: (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. [11246] 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. [34389] [61906] 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. [34389] [48697] 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. [34389] [51111] 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. [34389] [40942] 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. [34389] [66990] 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. [11246] 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. [34389] 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. [34389] 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. [34389] 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. [34389] 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. [11246] [28423] 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. [11246] Nadolol: (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. [34389] 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. [11246] 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. [34389] Nebivolol: (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. [34389] Nebivolol; 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. [34389] 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. [11246] 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. [34389] [58766] 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. [11246] 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. [11246] Nortriptyline: (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. [11246] [28225] [28416] 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. [11246] [30738] 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. [11246] [28785] [32732] [32734] [32745] [32746] 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. [32127] [34389] (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. [11246] [28785] [32732] [32734] [32745] [32746] 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. [11246] [28785] [32732] [32734] [32745] [32746] 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. [34389] [65809] 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. [34389] Olmesartan; 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. [34389] 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. [31266] [32722] [34389] 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. [34389] [65338] 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. [11246] [57741] 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. [34389] [65098] 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. [34389] [60297] 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. [34389] [41958] Oxazepam: (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. [11246] 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. [34389] 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. [11246] 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). [34389] [65159] 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. [34389] [67427] 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. [40936] 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%). [11246] [58821] 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. [28260] [34389] [59321] 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. [11246] [52611] 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. [11246] [37098] 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. [29627] [34389] [43887] 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. [11246] [23620] [23778] [28419] [28879] 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. [34389] 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. [34389] 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. [11246] 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. [11246] 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. [11246] (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. [34389] 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. [28415] [34389] 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. [28415] [34389] (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. [11246] [28225] [28416] 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. [34389] 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. [11246] 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. [11246] 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. [11246] 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. [11246] 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. [34389] [60748] 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. [28225] [34389] [43463] Pindolol: (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. [34389] 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). [34389] [64562] 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). [34389] [66527] 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. [11246] [32723] 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. [11246] 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. [11246] Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tetrabenazine and pregabalin. Concurrent use may result in additive CNS depression. [31493] [34389] [64848] 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. [34389] [41984] 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). [11246] [28250] 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. [28225] [28415] [34389] 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. [28225] [34389] [55578] 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. [28225] [34389] [55578] 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. [28225] [34389] [55578] 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. [11246] [28287] Propranolol: (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. [34389] Protriptyline: (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. [11246] [28225] [28416] Quazepam: (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. [11246] 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. [29118] [33068] [33072] [33074] [34389] 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. [11246] 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. [11246] (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. [34389] 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. [11246] [42280] [47357] 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. [11246] [31403] 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. [34389] [69220] 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. [11246] 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. [11246] [31938] 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. [34389] 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. [34389] [66183] 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. [34389] [66183] 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. [11246] Remimazolam: (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. [11246] 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. [34389] [61816] 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. [34389] [61816] 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. [11246] [44376] Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as risperidone. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased. [11246] [28225] [28414] [28416] 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. [34389] [60142] 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. [11246] [37292] 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. [34389] 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. [11246] [28995] [39156] 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. [34389] 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. [34389] [65387] 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. [28343] [34389] [64391] [64392] [64394] [64395] [64396] Sevoflurane: (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. [11246] [28457] [28458] [28754] [28755] [28756] 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). [34389] [64031] 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. [34389] [64608] 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). [11246] [30515] 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. [31832] [34389] 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. [11246] [28234] Spironolactone: (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. [11246] Spironolactone; 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. [11246] (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. [34389] Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tetrabenazine. CNS depressants can potentiate the effects of stiripentol. [63456] 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. [11246] 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). [31970] [34389] 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. [11246] [27353] [27354] [28225] 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. [34389] [61870] [61871] [61872] [63589] 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. [11246] [36615] 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. [34389] Telmisartan; 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. [34389] Temazepam: (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. [11246] 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. [11246] 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. [34389] 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. [34389] [43069] 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. [11246] Timolol: (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. [34389] 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. [34389] 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. [11246] 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). [11246] [31112] 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. [28822] [34389] 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. [34389] 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. [34389] 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. [11246] 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. [11246] 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. [34389] 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. [34389] [38831] 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. [11246] Triamterene: (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. [11246] Triamterene; 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. [11246] (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. [34389] Triazolam: (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. [11246] 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. [34389] [63962] 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. [11246] [28225] [28416] 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. [28415] [34389] Trimipramine: (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. [11246] [28225] [28416] 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. [34389] [45411] Valbenazine: (Contraindicated) Concurrent use of tetrabenazine and valbenazine is contraindicated. Both drugs are inhibitors of vesicular monoamine transporter 2 (VMAT2) and deplete monoamine stores. [34389] [61873] 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. [34389] 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). [34389] [43901] 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. [11246] [28216] 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. [11246] [45335] 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. [33715] [34389] 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. [11246] 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. [34389] [66336] 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. [11246] [28225] [28238] 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). [11246] [28158] 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. [11246] [32789] Zaleplon: (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. [11246] 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. [28233] [34389] Zolpidem: (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. [11246] Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm. [69264]
      Revision Date: 02/02/2024, 02:07:00 AM

      References

      5109 - Methadone Hydrochloride Injection package insert. Wilmington, NC: AAI Pharma; 2004 Feb.5187 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.11246 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.23500 - Wilt JL, Minnema AM, Johnson RF, et al. Torsade de pointes associated with the use of intravenous haloperidol. Ann Intern Med 1993;119:391-4.23620 - Green PT, Reents S, Harman E, et al. Pentamidine-induced torsades de pointes in a renal tranplant recipient with Pneumocystis carinii pneumonia. S Med J 1990;83:481-4.23774 - Lui HK, Lee G, Dietrich P, et al. Flecainide-induced QT prolongation and ventricular tachycardia. Am Heart J 1982;103:567-9.23778 - Wharton JM, Demopulos PA, Goldschlager N. Torsade de pointes during administration of pentamidine isethionate. Am J Med 1987;83:571-6.23779 - Kriwisky M, Perry GY, Tarchitsky D, et al. Haloperidol-induced torsades de pointes. Chest 1990;98:482-3.27353 - Hodak SP, Moubarak JB, Rodriguez I, et al. QT Prolongation and near fatal cardiac arrhythmia after intravenous tacrolimus administration: a case report. Transplantation 1998;66:535-7.27354 - Johnson MC, So S, Marsh JW, et al. QT prolongation and Torsades de Pointes after administration of FK506. Transplantation 1992;53:929-30.27964 - Dostinex (cabergoline) package insert. Kalamazoo, MI: Pharmacia and Upjohn Company; 2019 Dec.27982 - Ketoconazole tablets package insert. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2017 Sept.27986 - Neurontin (gabapentin) package insert. New York, NY: Pfizer; 2020 Dec.28158 - VFEND (voriconazole) tablets, suspension, and injection package insert. New York, NY: Pfizer Inc; 2022 Oct.28216 - Levitra (vardenafil) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; 2023 Mar.28221 - Tikosyn (dofetilide) package insert. New York, NY: Pfizer Labs; 2019 Aug.28224 - Pacerone (amiodarone) tablets package insert. Maple Grove, MN: Upsher-Smith Laboratories, LLC.; 2018 Nov.28225 - CredibleMeds. Drugs to avoid in congenital long QT. Available on the World Wide Web at http://www.crediblemeds.org.28226 - Trisenox (arsenic trioxide) package insert. Frazer, PA: Cephalon, Inc; 2010 Jun.28228 - Norpace and Norpace CR (disopyramide) package insert. Chicago, IL: G.D. Searle LLC division of Pfizer Inc; 2016 Aug.28229 - Demaziere J, Fourcade JM, Busseuil CT, et al. The hazards of chloroquine self prescription in west Africa. J Toxicol Clin Toxicol 1995;33:369-70.28230 - Mansfield RJ, Thomas RD. Recurrent syncope. Drug induced long QT syndrome. Postgrad Med J 2001;77:344, 352-3.28231 - Pinski SL, Eguia LE, Trohman RG. What is the minimal pacing rate that prevents torsades de pointes? Insights from patients with permanent pacemakers. Pacing Clin Electrophysiol 2002;25:1612-5.28233 - Geodon (ziprasidone) package insert. New York, NY: Pfizer: 2021 May.28234 - Betapace (sotalol) package insert. Wayne, NJ: Berlex Laboratories; 2011 Aug.28235 - Richards JR, Schneir AB. Droperidol in the emergency department: is it safe? J Emerg Med 2003;24:441-7.28236 - Kao LW, Kirk MA, Evers SJ, et al. Droperidol, QT prolongation, and sudden death: what is the evidence? Ann Emerg Med 2003;41:546-58.28237 - Food and Drug Administration Press Office. FDA strengthens warnings for droperidol. FDA Talk Paper. December 5, 2001. Accessed: April 16, 2004. Available on the World Wide Web at: http://www.fda.gov/bbs/topics/answers/2001/ans01123.html28238 - Biaxin (clarithromycin) package insert. North Chicago, IL: AbbVie, Inc.; 2019 Sep.28250 - Procanbid (procainamide) package insert. Bristol, TN: Monarch Pharmaceuticals; 2002 Jan.28260 - Paxil (paroxetine) tablet package insert. Weston, FL: Apotex Corp.; 2023 Aug.28261 - Uroxatral (alfuzosin extended-release tablets) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, INC.; 2015 May.28262 - Clozaril (clozapine) tablets package insert. Rosemont, PA: HLS Therapeutics (USA), Inc.; 2023 May.28269 - Celexa (citalopram) tablets package insert. Madison, NJ: Allergan USA, Inc.; 2023 Aug.28270 - Lexapro (escitalopram) package insert. North Chicago, IL: Abbvie, Inc.; 2023 Aug.28287 - Rythmol SR (propafenone hydrochloride) capsule extended release package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Nov.28301 - Mefloquine hydrochloride package insert. North Wales PA: Teva Pharmaceuticals USA Inc.; 2019 Mar.28307 - Haldol (haloperidol) injection for immediate release package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Feb.28319 - Krantz MJ, Kutinsky IB, Robertson AD, et al. Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Pharmacotherapy 2003;23:802-5.28320 - Walker PW, Klein D, Kasza L. High dose methadone and ventricular arrhythmias: a report of three cases. Pain 2003;103:321-4.28321 - Kornick CA, Kilborn MJ, Santiago-Palma J, et al. QTc interval prolongation associated with intravenous methadone. Pain 2003;105:499-506.28322 - Gil M, Sala M, Anguera I, et al. QT prolongation and Torsades de Pointes in patients infected with human immunodeficiency virus and treated with methadone. Am J Cardiol 2003;92:995-7.28341 - Kaletra (lopinavir; ritonavir) tablet and solution package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.28343 - Zoloft (sertraline) package insert. Morgantown, WV: Viatris Specialty LLC; 2023 Aug.28377 - Foscavir (foscarnet) package insert. Lake Forest, IL: Hospira, Inc.; 2020 Oct.28405 - Strattera (atomoxetine) package insert. Indianapolis, IN: Eli Lilly and Company; 2022 Jan.28414 - Risperdal (risperidone tablets, oral solution, and orally disintegrating tablets) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Aug.28415 - Nora Goldschlager, Andrew E Epstein, Blair P Grubb, et al. Etiologic considerations in the patient with syncope and an apparently normal heart. Arch Intern Med 2003;163:151-62.28416 - Hansten PD, Horn JR. Drug Interactions with Drugs that Increase QTc Intervals. In: The Top 100 Drug Interactions - A Guide to Patient Management. 2007 Edition. Freeland, WA: H&H Publications; 2007:144-8.28419 - Owens RC Jr. Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes. Pharmacotherapy 2001;21:301-19.28420 - Iannini PB. Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval. Expert Opin Drug Saf 2002;1:121-8.28421 - Levaquin (levofloxacin) tablet package insert. Titusville, NJ: Janssen Pharmaceutical, Inc.; 2020 Jun.28423 - Avelox (moxifloxacin) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2020 May.28424 - Factive (gemifloxacin mesylate) package insert. Toronto, ON: Merus Labs International, Inc.; 2019 May.28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28442 - Sustiva (efavirenz) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2023 Nov.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.28458 - Schmeling WT, Warltier DC, McDonald DJ, et al. Prolongation of the QT interval by enflurane, isoflurane, and halothane in humans. Anesth Analg 1991;72:137-44.28592 - Zoladex (goserelin acetate 3.6 mg implant) package insert. Lake Forest, IL: TerSera Therapeutics LLC; 2023 March28661 - Apokyn and Apokyn Pen (apomorphine) injection package insert. Rockville, MD: MMD US Operations, LLC; 2022 Jun28674 - Diflucan oral tablet and suspension (fluconazole) package insert. New York, NY: Pfizer; 2024 Feb.28737 - Inapsine (Droperidol) Injection package insert. Lake Forest, IL: Akorn, Inc.; 2011 Oct.28754 - Loeckinger A, Kleinsasser A, Maier S, et al. Sustained prolongation of the QTc interval after anesthesia with sevoflurane in infants during the first 6 months of life. Anesthesiology 2003;98:639-42.28755 - Kleinsasser A, Loeckinger A, Lindner KH, et al. Reversing sevoflurane-associated Q-Tc prolongation by changing to propofol. Anaesthesia 2001;56:248-50.28756 - Kuenszberg E, Loeckinger A, Kleinsasser A, et al. Sevoflurane progressively prolongs the QT interval in unpremedicated female adults. Eur J Anaesthesiol 2000;17:662-4.28785 - Zyprexa (olanzapine, all oral formulations and injectable solution) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Apr.28822 - Fareston (toremifene citrate) tablets package insert. Bedminster, NJ: Kyowa Kirin Inc.; 2017 May.28855 - Zithromax (azithromycin 250 mg and 500 mg tablets and azithromycin oral suspension) package insert. New York, NY: Pfizer Inc.; 2021 Nov.28879 - Pentamidine isethionate injection package insert. East Brunswick, NJ: Avet Pharmaceuticals Inc.; 2021 Jan.28953 - Metoclopramide hydrochloride oral solution package insert. Baudette, MN: Ani Pharmaceuticals, Inc.; 2019 Nov.28978 - Michalets EL, Williams CR. Drug interactions with cisapride: clinical implications. Clin Pharmacokinet 2000;39:49-75.28995 - Invirase (saquinavir) package insert. South San Francisco, CA: Genentech Inc.; 2020 Sept.29118 - Seroquel (quetiapine fumarate) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 Jan.29627 - PegIntron (peginterferon alfa-2b) package insert. Whitehouse Station, NJ: Merck and Co., Inc.; 2019 Jan.29758 - Aralen (chloroquine) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC.; 2018 Oct.30163 - Agrylin (anagrelide) capsules package insert. Lexington, MA: Takeda Pharmaceuticals USA, Inc.; 2021 Oct.30269 - Lomotil (diphenoxylate hydrochloride and atropine sulfate) tablets package insert. New York, NY: Pfizer Inc.; 2018 Feb.30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2022 Feb.30515 - Vesicare (solifenacin) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2012 Jul.30738 - Ofloxacin tablets package insert. Sacramento, CA: Nivagen Pharmaceuticals, Inc.; 2019 Feb.31112 - Detrol (tolterodine tartrate) package insert. New York, NY: Pharmacia and Upjohn Co., division of Pfizer; 2016 Nov.31266 - Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.31403 - Qualaquin (quinine sulfate) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019 Jun.31493 - Lyrica (pregabalin) package insert. Morgantown, WV: Viatris Specialty LLC; 2023 Dec.31723 - Kytril injection (granisetron) package insert. Nutley, NJ: Roche Pharmaceuticals; 2011 Nov.31832 - Nexavar (sorafenib) package insert. Wayne, NJ; Bayer HealthCare Pharmaceuticals Inc.; 2020 July.31938 - Ranexa (ranolazine extended-release tablets) package insert. Foster City, CA: Gilead Sciences, Inc. 2019 Oct.31970 - Sunitinib (Sutent) package insert. New York, NY: Pfizer Labs; 2020 Aug.32127 - Prozac (fluoxetine) capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2023 Aug.32722 - Charbit B, Albaladejo P, Funck-Brentano C, et al. Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 2005;102:1094-100.32723 - Noxafil (posaconazole) package insert. Whitehouse Station, NJ: Merck & Co. Inc.: 2022 Jan.32732 - Stollberger C, Huber JO, Finsterer J. Antipsychotic drugs and QT prolongation. Int Clin Psychopharmacol 2005;20:243-51.32734 - Su KP, Lane HY, Chuang CL, et al. Olanzapine-induced QTc prolongation in a patient with wolff-parkinson-white syndrome. Schizophrenia Research 2004;66:191-2.32745 - Dineen S, Withrow K, Voronovitch L, et al. QTc prolongation and high-dose olanzapine. Psychosomatics 2003;44:174-5.32746 - Gurovich, I. QTc prolongation: chlorpromazine and high-dosage olanzapine. Can J Psychiatry 2003;48:348.32789 - Zolinza (vorinostat) capsules package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2018 Dec.33068 - Gajwani P, Pozuelo L, Tesar G, et al. QT interval prolongation associated with quetiapine (seroquel) overdose. Psychosomatics 2000;41:63-5.33072 - Beelen AP, Yeo KTJ, Lewis LD. Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone. Hum Exp Toxicol 2001;20:215-9.33074 - Furst BA, Champion KM, Pierre JM, et al. Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin. Biol Psychiatry 2002;51:264-5.33136 - Methadone hydrochloride tablets package insert. Webster Groves, MO: SpecGx LLC; 2024 Jan.33192 - Tykerb (lapatinib) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2022 March.33350 - Xyzal (levocetirizine) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2019 April.33715 - Effexor XR (venlafaxine extended-release capsules) package insert. Morgatown, WV: Viatris Specialty LLC; 2023 Aug.34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.34940 - Pristiq (desvenlafaxine) extended-release tablets package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2023 Aug.35401 - Coartem (artemether; lumefantrine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Aug.36101 - Multaq (dronedarone) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2023 Oct.36146 - Fanapt (iloperidone) package insert. Rockville, MD: Vanda Pharmaceuticals, Inc.; 2017 Mar.36343 - Saphris (asenapine) sublingual tablet package insert. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2017 Mar.36615 - Vibativ (telavancin) package insert. Nashville, TN: Cumberland Pharmaceuticals Inc.; 2020 July.36894 - Metronidazole injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2021 Dec.37098 - Votrient (pazopanib) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2011 Oct.37292 - Istodax (romidepsin) injection package insert. Summit, NJ: Celgene Corporation; 2021 July.38831 - Oleptro (trazodone hydrochloride) extended-release tablets package insert. Dublin, Ireland: Labopharm Europe Limited; 2014 Jul.39156 - Food and Drug Administration MedWatch. Invirase (saquinavir): ongoing safety review of clinical trial data. Retrieved Feb. 24, 2010. Available on the World Wide Web at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm201563.htm.40233 - Sporanox (itraconazole) oral solution package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2024 Feb.40936 - Invega Sustenna (paliperidone palmitate injectable suspension) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Jul.40942 - Remeron and Remeron SolTabs (mirtazapine tablets and ODT tablets) package insert. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2021 Nov.40967 - Zyrtec (cetirizine hydrochloride chewable tablet) package insert. Fort Washington, PA: Johnson & Johnson Consumer Inc.; 2023 March.41235 - Butrans (buprenorphine transdermal system) package insert. Stamford, CT: Purdue Pharma L.P.; 2023 Dec.41806 - Plaquenil (hydroxychloroquine) package insert. Dublin, Ireland: Amdipharm Limited; 2023 Dec.41830 - Corvert (ibutilide) package insert. New York, NY: Pharmacia and Upjohn Company; 2016 Aug.41958 - Eloxatin (oxaliplatin) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2023 June.41984 - Primaquine phosphate package insert. Bridgewater, NJ: Sanofi-aventis; 2017 Jun.42280 - Nuedexta (dextromethorphan hydrobromide; quinidine sulfate capsule) package insert. Aliso Viejo, CA: Avanir Pharmaceuticals, Inc.; 2019 Jun.42449 - Halaven (eribulin mesylate) injection package insert. Woodcliffe Lake, NJ: Eisai Inc.; 2022 Sept.42844 - FDA Drug Safety Communication: Abnormal heart rhythms associated with use of Anzemet (dolasetron mesylate). Retrieved December 17, 2010. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm237081.htm.42845 - Abilify (aripiprazole) tablets, discmelt orally-disintegrating tablets, oral solution, and intramuscular injection package insert. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2022 Nov.43065 - Chlorpromazine package insert. Princeton, NJ: Sandoz Inc; 2019 Dec.43069 - Thioridazine package insert. Philadelphia, PA:Mutual Pharmaceutical Company, Inc;2010 Sept.43258 - Eryped (erythromycin ethylsuccinate) package insert. Atlanta, GA: Arbor Pharmaceuticals, INC.; 2018 Apr.43411 - Cipro (ciprofloxacin tablet; suspension) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 Nov.43463 - Pimozide tablets package insert. Chestnut Ridge, NY: Par Pharmaceuticals; 2017 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2023 Jan.43887 - Sylatron (peginterferon alfa-2b) package insert. Whitehouse Station, NJ: Merck & Co, Inc; 2018 Dec.43901 - Caprelsa (vandetanib) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 March.43974 - Zithromax (azithromycin injection) package insert. New York, NY: Pfizer Inc.; 2021 Nov.44376 - Edurant (rilpivirine) package insert. Titusville, NJ: Janssen Therapeutics; 2022 Oct.45335 - Zelboraf (vemurafenib) tablet package insert. South San Francisco, CA: Genentech USA, Inc.; 2020 May.45411 - Trelstar (triptorelin pamoate for injectable suspension) package insert. Ewing, NJ: Verity Pharmaceuticals, Inc.; 2023 Nov.45458 - Xalkori (crizotinib) capsules and pellets package insert. New York, NY: Pfizer Labs; 2023 Sept.46869 - Firmagon (degarelix) package insert. Parsippany, NJ: Ferring Pharmaceuticals Inc.; 2020 Dec.47129 - Hydroxyzine hydrochloride injection package insert. Miami, FL: Atlantic Biologicals Corp; 2019 Sept.47221 - Propulsid (cisapride) package insert. Titusville, NJ; Janssen Pharmaceutica; 2006 Oct. NOTE: As of May 2000; Propulsid has only been available in the United States via an investigational limited access program to ensure proper patient screening and prescribing.47357 - Quinidine gluconate extended-release tablet package insert. Princeton, NJ: Eywa Pharma Inc.; 2021 Dec.48681 - Sinemet (carbidop-levodopa) tablets package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2018 Apr.48697 - Korlym (mifepristone) tablet package insert. Menlo Park, CA: Corcept Therapeutics; 2019 Nov.50507 - Luvox CR (fluvoxamine maleate extended-release capsules) package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2017 Jan.51111 - Myrbetriq (mirabegron extended-release tablets and oral suspension) package insert. Northbrook, Illinois: Astellas Pharma US, Inc.; 2021 March.51289 - Droperidol injection package insert. Shirley NY: American Regent, Inc. 2023 Mar.52611 - Signifor (pasireotide diaspartate) package insert. Stein, Switzerland: Novartis Pharma Stein AG; 2020 Jan.52746 - Sirturo (bedaquiline) tablets package insert. Horsham, PA: Janssen Products, LP; 2023 Oct.55578 - Owczuk R, Twardowski P, Dylczyk-Sommer A, et al. Influence of promethazine on cardiac repolarization: a double-blind, midazolam-controlled study. Anaesthesia 2009;64:609-614.57094 - Zykadia (ceritinib) package insert. Indianapolis, IN: Novartis; 2021 Oct.57441 - Iribarren C, Round AD, Peng JA, et al. Validation of a population-based method to assess drug-induced alterations in QT interval: a self-controlled crossover study. Pharmacoepidemiol Drug Saf 2013;22;1222-32.57741 - Orbactiv (oritavancin) package insert. Lincolnshire, IL: Melinta Therapeutics, LLC; 2022 Jan.57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.58766 - Tasigna (nilotinib) capsules package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2024 Feb.58782 - Lenvima (lenvatinib) package insert. Woodcliff Lake, NJ:Eisai Inc; 2023 Oct.58821 - Farydak (panobinostat) capsules package insert. Las Vegas, NV: Secura Bio, Inc.; 2021 Sept.59321 - CredibleMeds. QT drug lists. Available on the World Wide Web at http://www.crediblemeds.org.59322 - Howes LG. Cardiovascular effects of drugs used to treat alzheimer's disease. Drug Saf. 2014;37:391–395.59809 - Mamiya K, Sadanaga T, Sekita A, et al. Lithium concentration correlates with QTc in patients with psychosis. J Electrocardiol 2005;38:148-51.59810 - van Noord C, Straus SM, Sturkenboom MC, et al. Psychotropic drugs associated with corrected QT interval prolongation. J Clin Psychopharmacol 2009;29:9-15.59811 - Altinbas K, Guloksuz S, Caglar IM, et al. Electrocardiography changes in bipolar patients during long-term lithium monotherapy. Gen Hosp Psychiatry 2014;36:694-7.60087 - Sprycel (dasatinib) tablet package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2023 Feb.60142 - Varubi (rolapitant) package insert. Waltham, MA: Tesaro Inc; 2018 April.60297 - Tagrisso (osimertinib) tablet package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024 Feb.60748 - Nuplazid (pimavanserin) package insert. San Diego, CA: Acadia; 2023 Sept.60864 - US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. Retrieved June 7, 2016. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery61143 - Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm. Retrieved August 31, 2016.61816 - Kisqali (ribociclib) tablets package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2023 Aug.61845 - Austedo and Austedo XR (deutetrabenazine) tablets package insert. Parsippany, NJ: Teva Neuroscience, Inc.; 2023 Sept.61870 - Chiu MH, Al-Majed NS, Stubbins R, et al. A case report of QT prolongation with glycopyrronium bromide in a patient with chronic tamoxifen use. BMC Res Notes. 2016;9:310.61871 - Slovacek L, Priester P, Petera J, et al. Tamoxifen/norfloxacin interaction leading to QT interval prolongation in a female patient with extracranial meningioma. Bratisl Lek Listy. 2011;112(6):353-4.61872 - Slovacek L, Ansorgova V, Macingova Z, et al. Tamoxifen-induced QT interval prolongation. J Clin Pharm Ther. 2008;33(4):453-5.61873 - Ingrezza (valbenazine) capsules package insert. San Diego, CA: Neurocrine Biosciences, Inc.; 2023 Aug.61906 - Rydapt (midostaurin) capsule package insert. East Hanover,NJ: Novartis Pharmaceuticals Corporation; 2023 May.62245 - Besponsa (inotuzumab ozogamicin) injection package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2017 Aug.62292 - Mylotarg (gemtuzumab ozogamicin) injection package insert. Philadelphia, PA: Pfizer Inc.; 2020 Feb.62723 - Macrilen (macimorelin) package insert. Frankfurt am Main, Germany: Aeterna Zentaris GmbH; 2018 Jan.62889 - Apadaz (benzhydrocodone; acetaminophen) tablets package insert. Celebration, FL: Zevra Therapeutics, Inc.; 2023 Dec.63161 - Lucemyra (lofexidine) tablets package insert. Louisville, KY: US WorldMeds, LLC; 2018 May.63309 - Epidiolex (cannabidiol) oral solution package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2023 Oct.63317 - Braftovi (encorafenib) capsules package insert. Boulder, CO: Array BioPharma Inc.; 2023 Oct.63368 - Tibsovo (ivosidenib) tablet package insert. Cambridge, MA: Agios Pharmaceuticals; 2023 Oct.63456 - Diacomit (stiripentol) package insert. Beauvais, France: Biocodex; 2022 Jul.63584 - Vizimpro (dacomitinib) tablet package insert. New York, NY: Pfizer Labs; 2018 Sept.63589 - Soltamox (tamoxifen) oral solution package insert. Raleigh, NC: Midatech Pharma US Inc.; 2019 April.63777 - Daurismo (glasdegib) tablets package insert. New York, NY: Pfizer Labs; 2023 Mar.63787 - Xospata (gilteritinib) tablets package insert. Northbrook, IL: Astellas Pharma US, Inc.; 2022 Jan.63936 - Lamprene (clofazimine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Jan.63962 - Egaten (triclabendazole) package insert. East Hanover, NJ: Novartis Pharmaceuticals; 2022 Feb.63989 - Spravato (esketamine) nasal spray package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2023 Oct.64031 - Mayzent (siponimod) tablets package insert. East Hanover, NJ: Novartis Pharmaceutical Corporation; 2023 Aug.64391 - Beach SR, Kostis WJ, Celano CM, et al. Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. J Clin Psychiatry 2014;75:e441-e449.64392 - Glassman AH, O'Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002;288:701-709.64394 - O'Connor CM, Jiang W, Kuchibhatla M, et al. Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. J Am Coll Cardiol 2010;56:692-699.64395 - Brouillette J, Nattel S. A practical approach to avoiding cardiovascular adverse effects of psychoactive medications. Can J Cardiol 2017;33:1577-1586.64396 - Beach SR, Celano CM, Sugrue AM, et al. QT prolongation, torsades de pointes, and psychotropic medications: a 5-year update. Psychosomatics 2018;59:105-122.64562 - Wakix (pitolisant) tablets package insert. Plymouth Meeting, PA: Harmony Biosciences, LLC; 2022 Dec.64567 - Rozlytrek (entrectinib) package insert. South San Francisco, CA: Genentech Inc.; 2024 Jan.64576 - Xenleta (lefamulin) package insert. Dublin, Ireland: Nabriva Therapeutics US, Inc.; 2021 Mar.64608 - Pentostam (sodium stibogluconate injection) package leaflet: Information for the healthcare professional. Middlesex, United Kingdom: GlaxoSmithKline UK; 2014 Feb.64685 - Reyvow (lasmiditan) tablets package insert. Indianapolis, IN: Eli Lilly and Company; 2022 Sep.64768 - Xcorpi (cenobamate) tablets package insert. Paramus, NJ: SK Life Science, Inc.; 2024 Jan.64848 - Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). https://www.fda.gov/media/133681/download. Retrieved December 19, 2019.64870 - Dayvigo (lemborexant) tablets package insert. Nutley, NJ: Eisai Inc.; 2023 Apr.64885 - Caplyta (lumateperone) capsules package insert. New York, NY; Intra-Cellular Therapies, Inc.; 2023 Jun.65068 - Barhemsys (amisulpride) package insert. Indianapolis, IN: Acacia Pharma Inc; 2021 May.65098 - Isturisa (osilodrostat) tablet package insert. Lebanon, NJ: Recordati Rare Disease, Inc.; 2020 Mar.65157 - CredibleMeds. COVID-19 experimental therapies and TdP risk. Available on the World Wide Web at http://https://crediblemeds.org/blog/covid-19-experimental-therapies-and-tdp-risk. Accessed March 23, 2020.65159 - American Society of Transplantation and Cellular Therapy Infectious Diseases Special Interest Group. Interim Guidelines for COVID-19: Management in Hematopoietic Cell Transplant and Cellular Therapy Patients. March 18, 2020. Available on the world wide web at: https://higherlogicdownload.s3.amazonaws.com/ASBMT/a1e2ac9a-36d2-4e23-945c-45118b667268/UploadedImages/COVID-19_Interim_Patient_Guidelines_3_18_20.pdf65170 - Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19 [published online ahead of print, March 25, 2020]. Mayo Clin Proc 2020;95.65338 - Ongentys (opicapone) package insert. San Diego, CA: Neurocrine Biosciences, Inc.; 2020 Apr.65387 - Retevmo (selpercatinib) capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2022 Sept.65634 - Fintepla (fenfluramine) oral solution package insert. Smyrna, GA: UCB, Inc.; 2023 Dec.65666 - Rukobia (fostemsavir) package insert. Durham, NC: ViiV Healthcare; 2024 Feb.65809 - Olinvyk (oliceridine) injection package insert. Chesterbrook, PA: Trevana, Inc. 2023 Dec.66183 - Orgovyx (relugolix) tablets package insert. Brisbane, CA: Myovant Sciences, Inc.; 2023 Mar.66336 - Lupkynis (voclosporin) capsules package insert. Rockville, MD: Aurinia Pharma U.S., Inc.; 2021 Jan.66527 - Ponvory (ponesimod) tablet package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2023 Aug.66812 - Fexinidazole package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2021 Dec.66926 - Korsuva (Difelikefalin) injection package insert. Stamford, CT: Cara Therapeutics, Inc.; 2021 Aug.66990 - Exkivity (mobocertinib) capsules package insert. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2023 Sept.67231 - Recorlev (levoketoconazole) package insert. Chicago, IL: Xeris Pharmaceuticals, Inc.; 2021 Dec.67427 - Vonjo (pacritinib) capsules package insert. Seattle, WA: CTI BioPharma Corp; 2023 Aug.67473 - Arellano AL, Papaseit E, Romaguera A, et al. Neuropsychiatric and general interactions of natural and synthetic cannabinoids with drugs of abuse and medicines. CNS Neurol Disord - Drug Targets 2017;16:554-566.67509 - Igalmi (dexmedetomidine) sublingual film package insert. New Haven, CT: BioXcel Therapeutics, Inc.; 2022 Apr.68325 - Krazati (adagrasib) tablets package insert. San Diego, CA: Mirati Therapeutics, Inc.; 2022 Dec.68784 - Brusa L, Orlacchio A, Stefani A, Galati S, Pierantozzi M, Iani C, Mercuri NB. Tetrabenazine improves levodopa-induced peak-dose dyskinesias in patients with Parkinson's disease. Funct Neurol. 2013 Apr-May;28(2):101-5.69114 - Velsipity (etrasimod) package insert. New York, NY: Pfizer, Inc.; 2023 June69220 - Vanflyta (quizartinib) tablets package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2023 July.69264 - Zurzuvae (zuranolone) capsules package insert. Cambridge, MA: Biogen Inc; 2023 Aug.

      Monitoring Parameters

      • laboratory monitoring not necessary

      US Drug Names

      • Xenazine
      ;