Austedo

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Depression and Suicidality in Patients with Huntington's disease [see WARNINGS AND PRECAUTIONS]
• QTc Prolongation [see WARNINGS AND PRECAUTIONS]
• Neuroleptic Malignant Syndrome (NMS) [see WARNINGS AND PRECAUTIONS]
• Akathisia, Agitation, and Restlessness [see WARNINGS AND PRECAUTIONS]
• Parkinsonism [see WARNINGS AND PRECAUTIONS]
• Sedation and Somnolence [see WARNINGS AND PRECAUTIONS]
• Hyperprolactinemia [see WARNINGS AND PRECAUTIONS]
• Binding to Melanin-Containing Tissues [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.

Patients With Huntington's Disease

Study 1 was a randomized, 12-week, placebo-controlled study in patients with chorea associated with Huntington's disease. A total of 45 patients received AUSTEDO, and 45 patients received placebo. Patients ranged in age between 23 and 74 years (mean 54 years); 56% were male, and 92% were Caucasian. The most common adverse reactions occurring in greater than 8% of AUSTEDO-treated patients were somnolence, diarrhea, dry mouth, and fatigue. Adverse reactions occurring in 4% or more of patients treated with AUSTEDO, and with a greater incidence than in patients on placebo, are summarized in Table 2.

Table 2: Adverse Reactions in Patients with Huntington's Disease (Study 1) Experienced by at Least 4% of Patients on AUSTEDO and with a Greater  Incidence than on Placebo

One or more adverse reactions resulted in a reduction of the dose of study medication in 7% of patients in Study 1. The most common adverse reaction resulting in dose reduction in patients receiving AUSTEDO was dizziness (4%).

Agitation led to discontinuation in 2% of patients treated with AUSTEDO in Study 1.

Patients With Tardive Dyskinesia

The data described below reflect 410 tardive dyskinesia patients participating in clinical trials. AUSTEDO was studied primarily in two 12-week, placebo-controlled trials (fixed dose, dose escalation). The population was 18 to 80 years of age, and had tardive dyskinesia and had concurrent diagnoses of mood disorder (33%) or schizophrenia/schizoaffective disorder (63%). In these studies, AUSTEDO was administered in doses ranging from 12-48 mg per day. All patients continued on previous stable regimens of antipsychotics; 71% and 14% respective atypical and typical antipsychotic medications at study entry.

The most common adverse reactions occurring in greater than 3% of AUSTEDO-treated patients and greater than placebo were nasopharyngitis and insomnia. The adverse reactions occurring in >2% or more patients treated with AUSTEDO (12-48 mg per day) and greater than in placebo patients in two double-blind, placebo-controlled studies in patients with tardive dyskinesia (Study 1 and Study 2) are summarized in Table 3.

Table 3: Adverse Reactions in2 Placebo-Controlled Tardive Dyskinesia Studies (Study1 and Study 2)of 12-week Treatment on AUSTEDO Reported in at Least 2% of Patients and Greater than Placebo

One or more adverse reactions resulted in a reduction of the dose of study medication in 4% of AUSTEDO-treated patients and in 2% of placebo-treated patients.

DRUG INTERACTIONS

Strong CYP2D6 Inhibitors

A reduction in AUSTEDO dose may be necessary when adding astrong CYP2D6 inhibitor in patients maintained on a stable dose of AUSTEDO. Concomitant use of strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, bupropion) has been shown to increase the systemic exposure to the active dihydro-metabolites of deutetrabenazine by approximately 3fold. The daily dose of AUSTEDO should not exceed 36 mg per day, and the maximum single dose of AUSTEDO should not exceed 18 mg in patients taking strong CYP2D6 inhibitors [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Reserpine

Reserpine binds irreversibly to VMAT2 and the duration of its effect is several days. Prescribers should wait for chorea or dyskinesia to reemerge before administering AUSTEDO to help reduce the risk of overdosage and major depletion of serotonin and norepinephrine in the central nervous system. At least 20 days should elapse after stopping reserpine before starting AUSTEDO. AUSTEDO and reserpine should not be used concomitantly [see CONTRAINDICATIONS].

Monoamine Oxidase Inhibitors (MAOIs)

AUSTEDO is contraindicated in patients taking MAOIs. AUSTEDO should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI [see CONTRAINDICATIONS].

Neuroleptic Drugs

The risk of parkinsonism, NMS, and akathisia may be increased by concomitant use of AUSTEDO and dopamine antagonists or antipsychotics.

Alcoholor Other Sedating Drugs

Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence [see WARNINGS AND PRECAUTIONS].

Concomitant Tetrabenazine or Valbenazine

AUSTEDO is contraindicated in patients currently taking tetrabenazine or valbenazine. AUSTEDO may be initiated the day following discontinuation of tetrabenazine [see DOSAGE AND ADMINISTRATION].

Read the entire FDA prescribing information for Austedo (Deutetrabenazine Tablets)