ADVERSE REACTIONS
During its development, tetrabenazine was administered to 773 unique subjects and patients. The conditions and duration of exposure to tetrabenazine 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.
The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of adverse effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.
In a randomized, 12-week, placebo-controlled clinical trial of HD subjects, adverse events (AEs) were more common in the tetrabenazine group than in the placebo group. Forty-nine of 54 (91%) patients who received XENAZINE experienced one or more AEs at any time during the study. The AEs most commonly reported (over 10%, and at least 5% greater than placebo) were sedation/somnolence (31% vs. 3% on placebo), fatigue (22% vs. 13% on placebo), insomnia (22% vs. 0% on placebo), depression (19% vs. 0% on placebo), akathisia (19% vs. 0% on placebo), and nausea (13% vs. 7% on placebo). The number and percentage of the most commonly reported AEs that occurred at any time during the study in ≥4% of tetrabenazine-treated patients, and with a greater frequency than in placebo-treated patients, are presented in Table 1 in decreasing order of frequency within body systems for the tetrabenazine group.
Table 1. Treatment Emergent Adverse Events in Patients Treated with Tetrabenazine and with a Greater Frequency than Placebo in the 12-Week, Double-Blind, Placebo-Controlled Trial of XENAZINE | Body System | AE Term | Tetrabenazine
n = 54
n (%) | Placebo
n = 30
n (%) |
| PSYCHIATRIC DISORDERS | Sedation/somnolence | 17 (31%) | 1 (3%) |
| Insomnia | 12 (22%) | - |
| Depression | 10 (19%) | - |
| Anxiety/anxiety aggravated | 8 (15%) | 1 (3%) |
| Irritability | 5 (9%) | 1 (3%) |
| Appetite decreased | 2 (4%) | - |
| Obsessive reaction | 2 (4%) | - |
| CENTRAL & PERIPHERAL NERVOUS SYSTEM | Akathisia | 10 (19%) | - |
| Balance difficulty | 5 (9%) | - |
| Parkinsonism/bradykinesia | 5 (9%) | - |
| Dizziness | 2 (4%) | - |
| Dysarthria | 2 (4%) | - |
| Gait unsteady | 2 (4%) | - |
| Headache | 2 (4%) | 1 (3%) |
| GASTROINTESTINAL SYSTEM DISORDERS | Nausea | 7 (13%) | 2 (7%) |
| Vomiting | 3 (6%) | 1 (3%) |
| BODY AS A WHOLE – GENERAL | Fatigue | 12 (22%) | 4 (13%) |
| Fall | 8 (15%) | 4 (13%) |
| Laceration (head) | 3 (6%) | - |
| Ecchymosis | 3 (6%) | - |
| RESPIRATORY SYSTEM DISORDERS | Upper respiratory tract infection | 6 (11%) | 2 (7%) |
| Shortness of breath | 2 (4%) | - |
| Bronchitis | 2 (4%) | - |
| URINARY SYSTEM DISORDERS | Dysuria | 2 (4%) | - |
Dose titration was discontinued or dosage of study drug was reduced because of one or more AEs in 28 of 54 (52%) patients randomized to tetrabenazine. These AEs consisted of sedation (15), akathisia (7), parkinsonism (4), depression (3), anxiety (2), fatigue (1) and diarrhea (1). Some patients had more than one AE and are therefore counted more than once.
The following table describes the incidence of events considered to be extrapyramidal adverse reactions.
Table 2. Treatment Emergent Extrapyramidal Symptoms in Patients Treated with Tetrabenazine and with a Greater Frequency than Placebo in the 12-Week, Double-Blind, Placebo-Controlled Trial of XENAZINE | Event | Patients (%) reporting event |
XENAZINE
n = 54 | Placebo
n = 30 |
| 1Patients with the following adverse event preferred terms were counted in this category: akathisia, hyperkinesia, restlessness. |
| 2 Patients 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. |
| Akathisia 1 | 10 (19%) | 0 |
| Extrapyramidal event 2 | 8 (15%) | 0 |
| Any extrapyramidal event | 18 (33%) | 0 |
Laboratory Tests
No clinically significant changes in laboratory parameters were reported in clinical trials with XENAZINE. In controlled clinical trials, XENAZINE caused a small mean increase in ALT and AST laboratory values as compared to placebo.
Vital Signs
In controlled clinical trials, tetrabenazine did not affect blood pressure, pulse, and body weight. Orthostatic blood pressure was not consistently measured in the XENAZINE clinical trials.
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class
Tetrabenazine is not a controlled substance.
Physical and Psychological Dependence
Clinical trials did not reveal any tendency for drug seeking behavior, though these observations were not systematic. Abuse has not been reported from the postmarketing experience in countries where tetrabenazine has been marketed. Abrupt discontinuation of tetrabenazine from patients did not produce symptoms of withdrawal or a discontinuation syndrome; only symptoms of the original disease were observed to re-emerge. As with any CNS-active drug, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of tetrabenazine misuse or abuse (such as development of tolerance, incrementation of dose, drug-seeking behavior).
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REPORTS OF SUSPECTED XENAZINE SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Xenazine. The information is not vetted and should not be considered as verified clinical evidence.
Possible Xenazine side effects / adverse reactions in 60 year old male
Reported by a pharmacist from United States on 2011-10-03
Patient: 60 year old male
Reactions: Death
Adverse event resulted in: death
Suspect drug(s):
Xenazine
Possible Xenazine side effects / adverse reactions in 49 year old female
Reported by a pharmacist from United States on 2011-10-05
Patient: 49 year old female
Reactions: Huntington's Disease, Disease Progression
Adverse event resulted in: death
Suspect drug(s):
Xenazine
Possible Xenazine side effects / adverse reactions in 75 year old male
Reported by a pharmacist from United States on 2011-10-11
Patient: 75 year old male
Reactions: Death
Adverse event resulted in: death
Suspect drug(s):
Xenazine
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