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The following serious adverse reactions are described below and elsewhere in the labeling:
- Depression and suicidality [see WARNINGS AND PRECAUTIONS]
- Akathisia, restlessness, and agitation [see WARNINGS AND PRECAUTIONS]
- Parkinsonism [see WARNINGS AND PRECAUTIONS]
- Dysphagia [see WARNINGS AND PRECAUTIONS]
- Sedation and somnolence [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
During its development, XENAZINE was administered to 773 unique subjects and patients. The conditions and duration of exposure to XENAZINE varied greatly, and included single and multiple dose clinical pharmacology studies in healthy volunteers (n=259) and open-label (n=529) and double-blind studies (n=84) in patients.
In a randomized, 12-week, placebo-controlled clinical trial of HD patients, adverse reactions were more common in the XENAZINE group than in the placebo group. Forty-nine of 54 (91%) patients who received XENAZINE experienced one or more adverse reactions at any time during the study. The most common adverse reactions were (over 10%, and at least 5% greater than placebo) were sedation/somnolence, fatigue, insomnia, depression, akathisia, and nausea.
Adverse Reactions Occurring in ≥ 4% Patients
The number and percentage of the most common adverse reactions that occurred at any time during the study in ≥ 4% of XENAZINE-treated patients, and with a greater frequency than in placebo-treated patients, are presented in Table 1.
Table 1: Adverse Reactions in a 12-Week,
Double-Blind, Placebo-Controlled Trial in Patients with Huntington’s Disease
n = 54 %
n = 30 %
|Upper respiratory tract infection||11||7|
|Shortness of breath||4||0|
Dose escalation was discontinued or dosage of study drug was reduced because of one or more adverse reactions in 28 of 54 (52%) patients randomized to XENAZINE. These adverse reactions consisted of sedation (15), akathisia (7), parkinsonism (4), depression (3), anxiety (2), fatigue (1) and diarrhea (1). Some patients had more than one AR and are, therefore, counted more than once.
Adverse Reactions Due to Extrapyramidal Symptoms
Table 2 describes the incidence of events considered to be extrapyramidal adverse reactions which occurred at a greater frequency in XENAZINE-treated patients compared to placebo-treated patients.
Table 2: Adverse Reactions
Due to Extrapyramidal Symptoms in a 12-Week, Double-Blind, Placebo-Controlled
Trial in Patients with Huntington’s disease
n = 54%
n = 30%
|Extrapyramidal event 2||15%||0|
|Any extrapyramidal event||33%||0|
|1Patients with the following adverse event preferred terms
were counted in this category: akathisia, hyperkinesia, restlessness.
2Patients with the following adverse event preferred terms were counted in this category: bradykinesia, parkinsonism, extrapyramidal disorder, hypertonia.
Patients may have had events in more than one category.
The following adverse reactions have been identified during post-approval use of XENAZINE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Nervous system disorders: tremor
Psychiatric disorders: confusion, worsening aggression
Respiratory, thoracic and mediastinal disorders: pneumonia
Skin and subcutaneous tissue disorders: hyperhidrosis, skin rash
Read the Xenazine (tetrabenazine tablets) Side Effects Center for a complete guide to possible side effects
Strong CYP2D6 Inhibitors
In vitro studies indicate that α-HTBZ and β-HTBZ are substrates for CYP2D6. Strong CYP2D6 inhibitors (e.g., paroxtine, fluoxetine, quinidine) markedly increase exposure to these metabolites. A reduction in XENAZINE dose may be necessary when adding a strong CYP2D6 inhibitor (e.g., fluoxetine, paroxetine, quinidine) in patients maintained on a stable dose of XENAZINE. The daily dose of XENAZINE should not exceed 50 mg per day and the maximum single dose of XENAZINE should not exceed 25 mg in patient staking strong CYP2D6 inhibitors [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, Use in Specific Populations, CLINICAL PHARMACOLOGY].
Reserpine binds irreversibly to VMAT2 and the duration of its effect is several days. Prescribers should wait for chorea to reemerge before administering XENAZINE to avoid overdosage and major depletion of serotonin and norepinephrine in the CNS. At least 20 days should elapse after stopping reserpine before starting XENAZINE. XENAZINE and reserpine should not be used concomitantly [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS].
Monoamine Oxidase Inhibitors (MAOIs)
XENAZINE is contraindicated in patients taking MAOIs. XENAZINE should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS].
Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.
Drugs That Cause QTc Prolongation
XENAZINE causes a small prolongation of QTc (about 8 msec), concomitant use with other drugs that are known to cause QTc prolongation should be avoided, these including antipsychotic medications (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), Class 1A (e.g., quinidine, procainamide), and Class III (e.g., amiodarone, sotalol) antiarrhythmic medications or any other medications known to prolong the QTc interval. XENAZINE should be avoided in patients with congenital long QT syndrome, and in patients with a history of cardiac arrhythmias. Certain conditions may increase the risk for torsade de pointes or sudden death such as, (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].
The risk for Parkinsonism, NMS, and akathisia may be increased by concomitant use of XENAZINE and dopamine antagonists or antipsychotics (e.g., chlorpromazine, haloperidol, olanzapine, risperidone, thioridazine, ziprasidone).
Drug Abuse And Dependence
XENAZINE is not a controlled substance.
Clinical trials did not reveal patients developed drug seeking behaviors, though these observations were not systematic. Abuse has not been reported from the postmarketing experience in countries where XENAZINE has been marketed.
As with any CNS-active drug, prescribers should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of XENAZINE misuse or abuse (such as development of tolerance, increasing dose requirements, drug-seeking behavior).
Abrupt discontinuation of XENAZINE from patients did not produce symptoms of withdrawal or a discontinuation syndrome; only symptoms of the original disease were observed to re-emerge [see DOSAGE AND ADMINISTRATIONS].
Read the Xenazine Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/19/2015
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