WARNING: DEPRESSION AND SUICIDALITY
See full prescribing information for complete boxed warning.
- Increases the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington's disease.
- Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of XENAZINE.
- Monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior.
- Inform patients, caregivers, and families of the risk of depression and suicidality and instruct to report behaviors of concern promptly to the treating physician.
- Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation.
- XENAZINE is contraindicated in patients who are actively suicidal, and in patients with untreated or inadequately treated depression.
- XENAZINE is also contraindicated in patients with hepatic impairment and patients taking monoamine oxidase inhibitors (MAOIs), reserpine, and deutetrabenazine or valbenazine. XENAZINE should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI. XENAZINE should not be used concomitantly with reserpine, and at least 20 days should elapse after stopping reserpine before starting XENAZINE.
- Prescribers should periodically re-evaluate the need for XENAZINE in their patients by assessing the effect on chorea and possible adverse effects, including depression and suicidality, cognitive decline, parkinsonism, dysphagia, sedation/somnolence, akathisia, restlessness, and disability.
- XENAZINE should be titrated slowly over several weeks and individualized for each patient. Before a dose >50 mg/day is administered, determine a patient’s CYP2D6 metabolizer status. Individualize doses according to a patient’s status. Do not exceed a dose of 50 mg/day or 25 mg/dose in poor metabolizers and when administering XENAZINE with strong CYP2D6 inhibitors. XENAZINE therapy should be re-titrated if there is a treatment interruption of >5 days.
- A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with XENAZINE. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria, rhabdomyolysis, and acute renal failure. The management of NMS should include immediate discontinuation of XENAZINE, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems. Recurrence of NMS has been reported with resumption of drug therapy.
- XENAZINE may increase the risk of akathisia, restlessness, and agitation and can also cause other serious adverse reactions, including parkinsonism. These adverse reactions may require a dose reduction or discontinuation of XENAZINE.
- XENAZINE may induce sedation/somnolence, which may impair a patient’s ability to drive or operate dangerous machinery. Concomitant use of alcohol or other sedating drugs can worsen sedation/somnolence. In some patients, sedation occurred at doses that were lower than recommended doses.
- XENAZINE causes a small prolongation of QTc (about 8 msec) and should not be used in combination with drugs known to prolong QTc (which in certain circumstances can lead to torsades de pointes and/or sudden death), in patients with congenital long QT syndrome, and in patients with a history of cardiac arrhythmias.
- The risk of Parkinsonism, NMS, and akathisia may be increased by concomitant use of XENAZINE and dopamine antagonists or antipsychotics.
- Monitoring of vital signs on standing should be considered in patients who are vulnerable to hypotension.
- XENAZINE elevates serum prolactin concentrations. If symptomatic hyperprolactinemia is suspected, conduct appropriate laboratory testing and consider discontinuing XENAZINE.
- Some adverse events, such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety, or sedation, may be dose-dependent. Stop titration and reduce the dose of XENAZINE if observed. If the adverse reaction does not resolve, consider withdrawing XENAZINE or initiating other specific treatment.
- The most commonly reported adverse reactions with XENAZINE (>10% and at least 5% greater than placebo) were sedation/somnolence (31% vs 3%), fatigue (22% vs 13%), insomnia (22% vs 0%), depression (19% vs 0%), akathisia (19% vs 0%), anxiety/anxiety aggravated (15% vs 3%), and nausea (13% vs 7%).
For more information, please see the Medication Guide and full Prescribing Information, including Boxed Warning for depression and suicidality, or go to www.XenazineUSA.com.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.