DOSAGE AND ADMINISTRATION
In patients with chorea associated with Huntington’s disease, proper dosing of XENAZINE involves careful titration of therapy to determine an individualized dose for each patient. When first prescribed, XENAZINE therapy should be titrated slowly over several weeks to allow the identification of a dose for chronic use that reduces chorea and is well tolerated. Doses above 100 mg/day are not recommended for any patient.
Dosing Recommendations up to 50 mg per day
The dose of XENAZINE should be individualized. The starting dose should be 12.5 mg per day given once in the morning. After one week, the dose should be increased to 25 mg per day given as 12.5 mg twice a day. XENAZINE should be titrated up slowly at weekly intervals by 12.5 mg, to allow the identification of a dose that reduces chorea and is well tolerated. If a dose of 37.5 to 50 mg per day is needed, it should be given in a three times a day regimen. The maximum recommended single dose is 25 mg. If adverse events such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety or intolerable sedation occur, titration should be stopped and the dose should be reduced. If the adverse event does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants).
Dosing Recommendations above 50 mg per day
Patients who appear to require doses greater than 50 mg per day should be genotyped for CYP2D6.
The dose of XENAZINE should be individualized.
For CYP2D6 Extensive and Intermediate Metabolizers (patients who express CYP2D6)
At doses above 50 mg per day, XENAZINE should be titrated up slowly at weekly intervals by 12.5 mg, to allow the identification of a dose that reduces chorea and is well tolerated. Doses above 50 mg per day should be given in a three times a day regimen. The maximum recommended daily dose is 100 mg and the maximum recommended single dose is 37.5 mg. If adverse events such as akathisia, parkinsonism, depression, insomnia, anxiety or intolerable sedation occur, titration should be stopped and the dose should be reduced. If the adverse event does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants).
For CYP2D6 Poor Metabolizers (patients who do not express CYP2D6)
In patients who are CYP2D6 poor metabolizers, dosing is similar to EMs except that the recommended maximum single dose is 25 mg, and the maximum recommended daily dose is 50 mg.
Discontinuation of Treatment with XENAZINE
Treatment with XENAZINE can be discontinued without tapering. Re-emergence of chorea may occur within 12 to 18 hours after the last dose of tetrabenazine.
Resumption of Treatment
Following treatment interruption of greater than five (5) days or a treatment interruption occurring due to a change in the patient’s medical condition or concomitant medications, XENAZINE therapy should be retitrated when resumed. For short-term treatment interruption of less than five (5) days, treatment can be resumed at the previous maintenance dose without titration.
SPECIAL POPULATIONS
Hepatically Impaired Patients: The use of XENAZINE in patients with liver disease is contraindicated (see CLINICAL PHARMACOLOGY – Liver Disease under Special Populations; CONTRAINDICATIONS; and PRECAUTIONS - Use in Patients with Concomitant Illness).
Patients taking CYP2D6 Inhibitors
Caution should be used when adding a strong CYP2D6 inhibitor (such as fluoxetine, paroxetine, quinidine), to a patient already receiving a stable dose of tetrabenazine. In patients receiving co-administered strong CYP2D6 inhibitors, the daily dose of tetrabenazine should be halved. To initiate treatment with XENAZINE in patients on a stable dose of a strong CYP2D6 inhibitor, the dosing recommendations for the CYP2D6 poor metabolizers should be followed. The effect of moderate or weak CYP2D6 inhibitors such as duloxetine, terbinafine, amiodarone, or sertraline has not been evaluated (see CLINICAL PHARMACOLOGY and PRECAUTIONS).
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