AUSTEDO Coated tablet Ref.[10001] Active ingredients:

2.1 Dosing Information

The dose of AUSTEDO is determined individually for each patient based on reduction of chorea or tardive dyskinesia and tolerability. When first prescribed to patients who are not being switched from tetrabenazine (a related VMAT2 inhibitor), the recommended starting dose of AUSTEDO is 6 mg administered orally once daily for patients with Huntington’s disease and 12 mg per day (6 mg twice daily) for patients with tardive dyskinesia.

• The dose of AUSTEDO may be increased at weekly intervals in increments of 6 mg per day to a maximum recommended daily dosage of 48 mg.
• Administer total daily dosages of 12 mg or above in two divided doses.
• Administer AUSTEDO with food [see Clinical Pharmacology (12.3)].
• Swallow AUSTEDO whole. Do not chew, crush, or break tablets.
• For patients at risk for QT prolongation, assess the QT interval before and after increasing total AUSTEDO dosage above 24 mg per day [see Warnings and Precautions (5.3) and Drug Interactions (7.2)].

2.2 Switching Patients from Tetrabenazine (XENAZINE) to AUSTEDO

Discontinue tetrabenazine (XENAZINE ) and initiate AUSTEDO the following day. The recommended initial dosing regimen of AUSTEDO in patients switching from tetrabenazine (XENAZINE ) to AUSTEDO is shown in Table 1.

Table 1. Recommended Initial Dosing Regimen when Switching from Tetrabenazine (XENAZINE ) to AUSTEDO:

After patients are switched to AUSTEDO, the dose may be adjusted at weekly intervals [see Dosage and Administration (2.1)].

2.3 Dosage Adjustment with Strong CYP2D6 Inhibitors

In patients receiving strong CYP2D6 inhibitors (e.g., quinidine, antidepressants such as paroxetine, fluoxetine, and bupropion), the total daily dosage of AUSTEDO should not exceed 36 mg (maximum single dose of 18 mg) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

2.4 Dosage Adjustment in Poor CYP2D6 Metabolizers

In patients who are poor CYP2D6 metabolizers, the total daily dosage of AUSTEDO should not exceed 36 mg (maximum single dose of 18 mg) [see Use in Specific Populations (8.7)].

2.5 Discontinuation and Interruption of Treatment

Treatment with AUSTEDO can be discontinued without tapering. Following treatment interruption of greater than one week, AUSTEDO therapy should be re-titrated when resumed. For treatment interruption of less than one week, treatment can be resumed at the previous maintenance dose without titration.

Overdoses ranging from 100 mg to 1 g have been reported in the literature with tetrabenazine, a closely related VMAT2 inhibitor. The following adverse reactions occurred with overdosing: acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor.

Treatment should consist of those general measures employed in the management of overdosage with any central nervous system-active drug. General supportive and symptomatic measures are recommended. Cardiac rhythm and vital signs should be monitored. In managing overdosage, the possibility of multiple drug involvement should always be considered. The physician should consider contacting a poison control center on the treatment of any overdose. Telephone numbers for certified poison control centers are listed on the American Association of Poison Control Centers website www.aapcc.org.

Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Protect from light and moisture.