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Tetrabenazine

Class: Central Nervous System Agents, Miscellaneous
Chemical Name: cisrac-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-one
Molecular Formula: C19H27NO3
CAS Number: 58-46-8
Brands: Xenazine

Warning(s)

  • Tetrabenazine may increase risk of depression and suicidal thinking and behavior (suicidality) in patients with Huntington's disease; balance this risk with clinical need.1

  • Closely observe all patients initiating tetrabenazine therapy for emergence or clinical worsening of depression, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.1 (See Risk of Depression and Suicidality under Cautions.)

  • Exercise particular caution when treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in Huntington's disease.1

  • Tetrabenazine is contraindicated in patients who are actively suicidal and in patients with untreated or inadequately treated depression.1

REMS:

FDA approved a REMS for tetrabenazine to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of tetrabenazine and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

A monoamine-depleting agent; a benzoquinolizine derivative.1

Uses for Tetrabenazine

Huntington's Chorea

Symptomatic management of chorea associated with Huntington's disease in adults;1 2 17 18 19 20 24 25 38 40 46 48 designated an orphan drug by FDA for this use.3 4 18

Patients receiving tetrabenazine may experience slight worsening of cognition, functional capacity, mood, or rigidity; not known whether these effects persist, worsen, or resolve over time.1 47 Periodically reevaluate long-term risks and benefits of the drug for the individual patient.1 47

Slideshow: Does Your Child Have ADHD? Recognizing Signs & Treatment Options

Other Hyperkinetic Movement Disorders

Has been used with some success for the symptomatic management of other hyperkinetic movement disorders (also called hyperkinesias),22 29 30 31 32 33 35 37 38 39 40 42 47 48 53 including hemiballismus,48 53 senile chorea,48 53 Tourette's syndrome (Gilles de la Tourette's syndrome) (see Pediatric Use under Cautions),30 35 38 42 53 54 tic disorder,47 53 and tardive dyskinesia (including severe and/or refractory cases).30 36 37 38 40 47 48 50 51 53 54

Tetrabenazine Dosage and Administration

General

  • Observe closely for clinical worsening or emergence of depression, suicidal thoughts or behavior (suicidality), or unusual changes in behavior.1 28 47 (See Boxed Warning and see also Risk of Depression and Suicidality under Cautions.)

REMS Program

  • FDA has approved a REMS for tetrabenazine.4 10 13 18 41

  • The goals are to reduce the risk of treatment-emergent depression and suicidality in patients receiving the drug, to promote informed prescribing and proper dosing of tetrabenazine, and to minimize the risk of drug interactions.4 10 13 41

  • The program consists of educational materials for health care professionals, patients, and caregivers, including a medication guide to be dispensed with every tetrabenazine prescription;1 4 10 13 18 41 tetrabenazine must be obtained in the US via a specialty pharmacy network.13 17 For additional information, contact the Xenazine Information Center at 888-882-6013 or consult the Xenazine website at .5 9 13 17 28 43

Administration

Oral Administration

Administer orally without regard to meals.1 18 24 28

Do not double the next dose if a dose is missed.1

Dosage

If used with a potent CYP2D6 inhibitor, dosage adjustment required.1 (See Interactions.)

Carefully titrate dosage over several weeks to determine an individualized dosage for chronic use that reduces chorea and is well tolerated.1 28 48

May discontinue treatment without tapering the dosage.1 Retitrate dosage if therapy is resumed following an interruption of >5 days or a treatment interruption due to a change in medical condition or concomitant drug therapy.1 May resume treatment at the previous maintenance dosage (without titration) following treatment interruption of <5 days.1

Adults

Huntington's Chorea
Oral

Initially, 12.5 mg given once daily in the morning.1 Increase dosage after one week to 12.5 mg twice daily.1 Adjust subsequent dosages in 12.5-mg increments at weekly intervals.1

Administer daily dosages ≥37.5 mg in 3 divided doses.1 If daily dosage is ≤50 mg, the maximum recommended single dose is 25 mg.1

Manufacturer recommends CYP2D6 genotype testing prior to administering dosages >50 mg daily to determine whether patient is poor, intermediate, or extensive metabolizer of CYP2D6 substrates. However, some clinicians prefer to adjust tetrabenazine dosage based on clinical response and tolerability.

Administer dosages >50 mg daily in 3 divided doses and make dosage adjustments in 12.5-mg increments at weekly intervals.1

Table 1. Maximum Recommended Adult Dosage of Tetrabenazine Based on CYP2D6 Phenotype1

CYP2D6 Phenotype

Maximum Single Dose

Maximum Daily Dosage

Poor metabolizer

25 mg

50 mg

Intermediate or extensive metabolizer

37.5 mg

100 mg

Stop dosage titration and reduce daily dosage if adverse effects (e.g., excessive sedation, akathisia, restlessness, parkinsonism, depression, insomnia, anxiety) occur; consider drug discontinuance or initiation of specific treatment (e.g., antidepressant therapy) if adverse effects do not resolve.1

Daily dosages >100 mg are not recommended;1 however, higher dosages have been used in some patients.44

Other Hyperkinetic Movement Disorders
Oral

Initial dosage of 25 mg once or twice daily has been used in clinical studies in patients with various hyperkinesias, and then increased in 25-mg daily increments every 1–3 days until optimal therapeutic response, intolerable adverse effects, or maximum dosage of 100–200 mg daily was achieved.38 39 40

One non-US manufacturer recommends initial dosage of 25 mg given 3 times daily, with titration in 25-mg daily increments every 3 or 4 days until maximum tolerated dosage (not exceeding 200 mg daily) is achieved in patients with hyperkinetic movement disorders other than tardive dyskinesia.48 If no improvement occurs at maximum tolerated dosage within 7 days, drug is unlikely to be effective despite increase in dosage or duration of treatment.48

Tardive Dyskinesia
Oral

One non-US manufacturer recommends initial dosage of 12.5 mg daily, with subsequent dosage titration based on response;48 discontinue if no clear benefit or if adverse effects cannot be tolerated.48

Tourette's Syndrome
Oral

Clinical experience is limited; some clinicians recommend initial dosage of 12.5–25 mg given once daily at bedtime or twice daily, with titration to a target dosage of 25 mg given 3 times daily and a maximum dosage of 50 mg given 3 times daily.35 42

Prescribing Limits

Adults

Huntington's Chorea
Oral

100 mg daily.1

Poor metabolizer phenotype: 50 mg daily.1

Other Hyperkinetic Movement Disorders
Oral

100–200 mg daily.35 38 39 40 42

Special Populations

Hepatic Impairment

Contraindicated in hepatic impairment.1 18 (See Hepatic Impairment under Cautions; see Absorption: Special Populations, under Pharmacokinetics; and see also Elimination: Special Populations, under Pharmacokinetics.)

Renal Impairment

No dosage adjustment required.1 43

Geriatric Patients

No dosage adjustment required.1 43 However, at least one manufacturer recommends reduced initial and maintenance dosages.53

Cautions for Tetrabenazine

Contraindications

  • Actively suicidal or untreated or inadequately treated depression.1 18

  • Hepatic impairment.1 18

  • Concomitant therapy with an MAO inhibitor.1 17 18 (See Specific Drugs under Interactions.)

  • Concomitant therapy with reserpine.1 18 (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Periodic Evaluation of Need for Continued Therapy

Slight worsening in mood, cognition, rigidity, and functional capacity may occur; unknown whether these effects persist, resolve, or worsen with continued treatment.1 2

Periodically reevaluate need for continued therapy by assessing benefits on choreiform movements and possible adverse effects (e.g., depression, cognitive decline, parkinsonism, dysphagia, sedation, somnolence, akathisia, restlessness, disability).1 47 Dosage reduction or drug discontinuance may help distinguish between drug-induced adverse effects and disease progression.1 Underlying chorea may improve over time, thereby possibly decreasing the need for tetrabenazine.1

Importance of Careful Dosing

Individualize and carefully titrate dosage slowly over several weeks to determine a dosage that reduces chorea and is well tolerated.1 19 21 47

Possible dose-dependent adverse effects (e.g., depression, fatigue, insomnia, sedation or somnolence, parkinsonism, akathisia) may resolve or lessen with dosage adjustment or specific treatment.1 Consider tetrabenazine discontinuance if adverse effect does not resolve or decrease.1

Dosages >50 mg daily should not be given without CYP2D6 genotyping.1 (See Dosage under Dosage and Administration and see also Determining CYP2D6 Metabolizer Status under Cautions.)

Risk of Depression and Suicidality

Increased risk for depression and for suicidal ideation and behavior (suicidality) in patients with Huntington's disease.1 2 Tetrabenazine increases such risk which may increase with higher dosages.1 18 19 24 49 Depression or worsening of depression reported in 19–35% of tetrabenazine-treated patients; completed suicide, attempted suicide, and suicidal ideation reported.1 43 Depression more likely to occur or worsen in patients with history of depression.49

Closely observe patients for emergence or worsening of depression, suicidality, or unusual changes in behavior.1 Inform patients, caregivers, and families of these risks and instruct them to promptly report any behaviors of concern to the treating clinician.1 Immediately evaluate any patient with Huntington's disease who expresses suicidal ideation.1

Reduce tetrabenazine dosage if depression or suicidality occurs; consider initiating treatment with, or increasing the dosage of, a concomitant antidepressant.1 6 Consider drug discontinuance if depression or suicidality does not resolve.1

Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation; such patients may be at an increased risk for suicidal behavior.1

Contraindicated in patients who are actively suicidal or those with untreated or inadequately treated depression.1

Balance potential risks of depression and suicidality with clinical need for control of choreiform movements.1

Determining CYP2D6 Metabolizer Status

Testing for CYP2D6 status recommended prior to administering tetrabenazine dosages >50 mg daily.1 Limit dosage to 50 mg daily for poor metabolizer phenotype.1 (See Dosage under Dosage and Administration and see also Absorption: Special Populations, under Pharmacokinetics.)

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, has been reported with tetrabenazine and other drugs that reduce dopaminergic transmission.1 16 17 24 25 26 27

Immediately discontinue therapy and initiate supportive and symptomatic therapy if NMS occurs.1 16 17 24 25 26 27 Careful monitoring required if therapy is reinstituted following recovery; the risk that NMS can recur should be carefully considered.1

General Precautions

Akathisia

Possibly dose dependent; reported in up to 20% of tetrabenazine-treated patients.1

Monitor for akathisia and symptoms of restlessness and agitation; reduce tetrabenazine dosage if akathisia develops; drug discontinuance may be necessary in some patients.1

Parkinsonism

Symptoms suggestive of parkinsonism (e.g., bradykinesia, hypertonia, rigidity) reported in 3–15% of tetrabenazine-treated patients and appear to be dose dependent.1 May be difficult to distinguish between drug-induced effect and rigidity associated with progression of Huntington's disease.1 For some patients, drug-induced parkinsonism may result in more functional disability than untreated chorea.1

If parkinsonism develops, consider dosage reduction; some patients may require drug discontinuance.1

Dysphagia

Dysphagia, sometimes associated with aspiration pneumonia, reported in 4–10% of tetrabenazine-treated patients.1 Causal relationship not established, since dysphagia is a manifestation of Huntington's disease and esophageal dysmotility and dysphagia also are reported with drugs that reduce dopaminergic transmission, including tetrabenazine.1

Use tetrabenazine and other drugs that reduce dopaminergic transmission with caution in patients with Huntington's disease at risk for aspiration pneumonia.1

Sedation and Somnolence

Reported in 17–57% of patients receiving the drug in clinical studies.1 Sedation is the most common dose-limiting adverse effect.1 (See Advice to Patients.)

Prolongation of QT Interval

Small increase in corrected QT (QTc) interval reported.1 Avoid use in patients concurrently receiving other drugs known to prolong the QTc interval and in patients with congenital long QT syndrome or history of cardiac arrhythmias.1 18 (See Drugs that Prolong QT Interval under Interactions.)

Factors that may increase the risk of torsades de pointes and/or sudden death in association with drugs that prolong the QTc interval include bradycardia, hypokalemia or hypomagnesemia, concomitant use of other drugs that prolong the QTc interval, and presence of congenital QTc interval prolongation.1

Hypotension and Orthostatic Hypotension

Postural dizziness and dizziness reported.1 2 Consider monitoring orthostatic vital signs in patients who are vulnerable to hypotension.1

Hyperprolactinemia

Elevated prolactin concentrations reported.1 Perform appropriate laboratory testing and consider drug discontinuance if symptomatic hyperprolactinemia suspected.1

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, reported with antipsychotic agents.1 No clear cases reported with tetrabenazine,1 38 47 but other extrapyramidal adverse effects typically associated with antipsychotic agents (e.g., parkinsonism, akathisia) possible.1

Consider drug discontinuance if signs and symptoms suggestive of tardive dyskinesia appear.1

Concomitant Illnesses

Experience in patients with certain concomitant diseases limited.1

Has not been evaluated in patients with recent history of MI or unstable cardiovascular disease.1 (See Prolongation of QT Interval under Cautions and see also Hypotension and Orthostatic Hypotension under Cautions.)

Use with caution in patients with a history of depression or suicidality or with diseases, conditions, or treatments that may cause depression or increased suicidality.1

Contraindicated in patients with untreated or inadequately treated depression, those who are actively suicidal, or those with hepatic impairment.1 18 (See Contraindications and see also Risk of Depression and Suicidality under Cautions and see also Hepatic Impairment under Cautions.)

Binding to Melanin-containing Tissues

Binds to melanin-containing tissues, possibly resulting in accumulation and toxicity with long-term use; clinical importance unknown.1 18 Opthalmologic monitoring in clinical studies was inadequate to exclude possibility of injury after long-term drug exposure.1 18

Specific Populations

Pregnancy

Category C.1 18

Lactation

Not known whether tetrabenazine or its metabolites distribute into milk;1 18 however, at least one study suggests that the drug is distributed into human milk.53 54 57 Discontinue nursing or the drug.1 18

Pediatric Use

Safety and efficacy not established in pediatric patients.1 18 28

Has been effective in a limited number of pediatric patients with hyperkinetic movement disorders, including Tourette's syndrome and severe chorea, to date.33 35 42 54 55 May have a similar adverse effect profile in pediatric patients as in adults, possibly with fewer parkinsonian adverse effects.33

Based on clinical experience, one manufacturer suggests starting tetrabenazine at approximately 50% of the adult dose and titrating the dosage slowly according to tolerance and patient response.53 54 55

Geriatric Use

Pharmacokinetics not evaluated in geriatric individuals.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Decreased tetrabenazine metabolism in patients with mild to moderate hepatic impairment.1 Safety and efficacy of increased exposure to the drug and its metabolites unknown; dosage adjustments to ensure safe use are not possible in hepatic impairment.1 Use contraindicated.1

Renal Impairment

Pharmacokinetics not evaluated in renal impairment.1

Common Adverse Effects

Sedation, somnolence, insomnia, fatigue, depression, anxiety, irritability, balance difficulties, extrapyramidal adverse effects (e.g., akathisia, bradykinesia, parkinsonism, hypertonia), nausea, vomiting, ecchymosis, falls, laceration of the head, upper respiratory tract infection.1 2 18 21 22 25 38 47

Interactions for Tetrabenazine

Metabolized by carbonyl reductase to the active metabolites α-dihydrotetrabenazine and β-dihydrotetrabenazine, which are metabolized principally by CYP2D6.1

Neither tetrabenazine nor its α- and β-dihydrotetrabenazine metabolites are substrates or inhibitors of the P-glycoprotein transport system.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP2D6 inhibitors: Potential pharmacokinetic interaction (increased exposure to α-dihydrotetrabenazine and β-dihydrotetrabenazine).1 7 18 When therapy with a potent CYP2D6 inhibitor is initiated in a patient already stabilized on tetrabenazine, use caution and reduce tetrabenazine dosage by 50%.1 17 When tetrabenazine is initiated in a patient already stabilized on a potent CYP2D6 inhibitor, maximum recommended tetrabenazine dosage is 50 mg daily, with maximum single dose of 25 mg.1 (See Specific Drugs under Interactions.)

Moderate or weak CYP2D6 inhibitors: Effects on pharmacokinetics of tetrabenazine not established.1 18

Inducers or inhibitors of CYP isoenzymes 1A2, 2A6, 2C9, 2C19, or 2E1: Pharmacokinetic interaction unlikely.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP 1A2, 2B6, 2D6, 2C8, 2C9, 2C19, 2E1, 3A, 3A4: Pharmacokinetic interaction unlikely.1

Drugs Affecting or Affected by P-glycoprotein Transport

Clinically important interactions unlikely.1

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT-interval prolongation); avoid concomitant use of other drugs known to prolong the QTc interval.1 18 (See Specific Drugs under Interactions and see Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Alcohol

Potential worsening of sedation and somnolence1

Antiarrhythmics (class Ia and III; e.g., amiodarone, procainamide, quinidine, sotalol)

Increased risk of QT interval prolongation1 18

Avoid concomitant use1 18

Antipsychotic agents

Possible exaggeration of QTc prolongation, NMS, and/or extrapyramidal reactions1

Avoid concomitant use1

Chlorpromazine

Increased risk of QT interval prolongation1 18

Avoid concomitant use1 18

CNS depressants

Potential worsening of sedation and somnolence1

Desipramine

Possible CNS excitation and hypertension53

Digoxin

Pharmacokinetic interaction unlikely1 7 13

Dopamine antagonists

Possible exaggeration of QTc prolongation, NMS, and/or extrapyramidal reactions1

Fluoxetine

Possible increased exposure to tetrabenazine's active metabolites1 7 18

Patient already stabilized on tetrabenazine: Initiate fluoxetine with caution; reduce tetrabenazine dosage by 50%1 17

Patient already stabilized on fluoxetine: Maximum tetrabenazine dosage of 50 mg daily and 25 mg as single dose1

Levodopa

Possible reduced therapeutic effects of levodopa, exacerbation of Parkinson's disease symptoms; amelioration of tetrabenazine-induced parkinsonism34 43

MAO inhibitors

Possible CNS excitation and hypertension53

Concomitant use contraindicated;1 17 18 use caution when initiating tetrabenazine therapy following MAO inhibitor discontinuance13 15

At least one manufacturer recommends allowing at least 14 days to elapse between discontinuance of tetrabenazine and initiation of MAO inhibitor and vice versa53

Moxifloxacin

Increased risk of QT interval prolongation1 18

Avoid concomitant use1 18

Paroxetine

Increased peak plasma concentrations, AUC, and half-lives of tetrabenazine's active metabolites1 7 18

Patient already stabilized on tetrabenazine: Initiate paroxetine with caution; reduce tetrabenazine dosage by 50%1 17

Patient already stabilized on paroxetine: Maximum tetrabenazine dosage of 50 mg daily and 25 mg as single dose1

Quinidine

Possible increased exposure to tetrabenazine's active metabolites1 7 18

Patient already stabilized on tetrabenazine: Initiate quinidine with caution; reduce tetrabenazine dosage by 50%1 17

Patient already stabilized on quinidine: Maximum tetrabenazine dosage of 50 mg daily and 25 mg as single dose1

Reserpine

Possible serotonin and norepinephrine depletion in the CNS1

Concomitant use contraindicated1 17

Wait for signs of chorea to re-emerge after discontinuing reserpine before initiating tetrabenazine therapy1

Allow at least 20 days to elapse after reserpine discontinuance prior to initiating tetrabenazine therapy1 17 18

Thioridazine

Increased risk of QT interval prolongation1 18

Avoid concomitant use1 18

Ziprasidone

Increased risk of QT interval prolongation1 18

Avoid concomitant use1 18

Tetrabenazine Pharmacokinetics

Absorption

Bioavailability

Following oral administration, ≥75% absorbed.1

Peak plasma concentrations of active metabolites α-dihydrotetrabenazine and β-dihydrotetrabenazine reached within 1–1.5 hours; peak plasma concentration of O-dealkylated-dihydrotetrabenazine (another major metabolite) is reached approximately 2 hours following a dose.1

Duration

16–24 hours.53

Food

No effect on mean or peak plasma concentrations or AUC of α-dihydrotetrabenazine and β-dihydrotetrabenazine.1

Special Populations

Patients with mild to moderate chronic hepatic impairment: Mean peak plasma tetrabenazine concentrations were 7- to 190-fold higher and AUCs of α-dihydrotetrabenazine and β-dihydrotetrabenazine were approximately 30–39% greater compared with values in healthy individuals.1

Poor CYP2D6 metabolizers: Exposures to α-dihydrotetrabenazine and β-dihydrotetrabenazine were about threefold and ninefold higher, respectively, compared with values in extensive metabolizers.1

Distribution

Extent

Not known whether the drug or its metabolites are distributed into milk in humans;1 18 one study suggests that the drug is distributed into human milk and crosses the placenta.53 54 57

Plasma Protein Binding

Tetrabenazine: 82–85%.1

α-Dihydrotetrabenazine: 60–68%.1

β-Dihydrotetrabenazine: 59–63%.1

Elimination

Metabolism

Rapidly and extensively metabolized mainly in the liver by carbonyl reductase to active metabolites α-dihydrotetrabenazine and β-dihydrotetrabenazine, which are further O-dealkylated, principally by CYP2D6, to O-dealkylated-dihydrotetrabenazine.1

Elimination Route

Eliminated in urine (about 75%) and feces (7–16%).1 In urine, <10% eliminated as α-dihydrotetrabenazine or β-dihydrotetrabenazine.1

Half-life

α-Dihydrotetrabenazine: 4–8 hours.1

β-Dihydrotetrabenazine: 2–4 hours.1

Special Populations

Patients with hepatic impairment: Elimination half-lives prolonged to approximately 17.5 hours for tetrabenazine, 10 hours for α-dihydrotetrabenazine, and 8 hours for β-dihydrotetrabenazine.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Reversibly inhibits uptake of monoamines (e.g., dopamine, norepinephrine, serotonin, histamine) into synaptic vesicles and depletes monoamine stores from nerve terminals.1 2 13 17 18 19 20 21 23 24 25

  • Precise mechanism of antichorea effects not established, but appears to be related to drug's ability to reversibly and selectively inhibit vesicular monoamine transporter type 2 (VMAT2) in CNS, thereby decreasing uptake of monoamines into synaptic vesicles and depleting monoamine stores from nerve terminals.1 2 7 8 13 17 18 19 20 21 23 24 25

  • Preferentially depletes dopamine; dose required to deplete norepinephrine or serotonin is approximately fivefold higher than that required to deplete dopamine.2 7 17 21 23 Preferential depletion of dopamine in striatum may contribute to antichorea effects.4 13 18 22

  • Exhibits weak in vitro binding affinity for dopamine type 2 (D2) receptors.1 13 21 23 Does not possess binding affinity for GABA, glutamate, glycine, histamine, or norepinephrine receptors or ion channels.7

Advice to Patients

  • Tetrabenazine medication guide must be provided to the patient each time the drug is dispensed;4 10 importance of patient and caregiver reading the medication guide prior to initiation of tetrabenazine therapy and each time the prescription is refilled.1 4 13 28

  • Risk of new or worsening depression and suicidality; importance of patients or their families being alert to and immediately reporting emergence of suicidality, new or worsening depression, or other unusual changes in behavior.1 28

  • Importance of informing patients that tetrabenazine is used to treat the involuntary movements (chorea) of Huntington's disease and that the drug does not cure the cause of the involuntary movements and does not treat other symptoms of Huntington's disease (e.g., problems with thinking and emotions).28

  • Importance of informing patients and their families that the dosage of tetrabenazine will be gradually increased to reach the optimal dosage.1 28 Importance of being alert to possible development of adverse effects (e.g., sedation, akathisia, parkinsonism, depression, difficulty swallowing, fatigue, insomnia) that may require a dosage reduction or tetrabenazine discontinuance.1 25 47 Importance of informing patient that a blood test may be needed if a dosage exceeding 50 mg daily is considered.1 28

  • Importance of taking tetrabenazine exactly as prescribed at the correct time each day.10 Importance of informing patients not to take a double dose of the drug if a dose of tetrabenazine is missed.1 28

  • Importance of informing patients that involuntary movements may return or worsen within 12–18 hours after the last dose if therapy is discontinued or a dose is missed.28 Importance of patients informing clinicians if tetrabenazine has been discontinued for >5 days and importance of patients not taking additional doses of the drug until they notify their clinician.10 28

  • Risk of sedation, somnolence, and psychomotor impairment; importance of exercising caution while operating hazardous machinery, including driving a motor vehicle, until patient is receiving a maintenance dosage of tetrabenazine and has gained experience with the drug's effects.1 18 28

  • Importance of informing patients that concomitant use of alcohol or other CNS depressants may worsen the sedative effects of tetrabenazine.1 18 28

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses (e.g., liver disease).1 28

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 28

  • Importance of informing patients of other important precautionary information.1 28 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Distribution of tetrabenazine is restricted.4 10 13 17 18 41 (See REMS Program under Dosage and Administration.)

Tetrabenazine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

12.5 mg

Xenazine

Lundbeck

25 mg

Xenazine (scored)

Lundbeck

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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3. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA website. Accessed 2008 Sep 12.

4. Food and Drug Administration: FDA News: FDA approves first drug for treatment of chorea in Huntington's disease. Rockville, MD; 2008 Aug 15. From FDA website.

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9. Ovation Pharmaceuticals, Deerfield, IL: Personal communication.

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