FDA

Austedo XR

Approved 17 Feb 2023OralTablet, extended release

The FDA lists this product in 8 strengths and forms.

Indications

AUSTEDO XR ® and AUSTEDO ® are indicated in adults for the treatment of: chorea associated with Huntington’s disease [see Clinical Studies ( 14.1 )] tardive dyskinesia [see Clinical Studies ( 14.2 )] AUSTEDO XR and AUSTEDO are vesicular monoamine transporter 2 (VMAT2) inhibitors indicated in adults for the treatment of: Chorea associated with Huntington’s disease ( 1 ) Tardive dyskinesia ( 1 )

Contraindications

AUSTEDO XR and AUSTEDO are contraindicated in patients: With Huntington’s disease who are suicidal, or have untreated or inadequately treated depression [see Warnings and Precautions ( 5.1 )] . With hepatic impairment [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] . Taking reserpine. At least 20 days should elapse after stopping reserpine before starting AUSTEDO XR or AUSTEDO [see Drug Interactions ( 7.2 )] .

Taking monoamine oxidase inhibitors (MAOIs). AUSTEDO XR and AUSTEDO should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI [see Drug Interactions ( 7.3 )] . Taking tetrabenazine or valbenazine [see Drug Interactions ( 7.6 )] . Suicidal, or untreated/inadequately treated depression in patients with Huntington’s disease ( 4 , 5.1 ) Hepatic impairment ( 4 , 8.6 , 12.3 ) Taking reserpine, MAOIs, tetrabenazine, or valbenazine ( 4 , 7.2 , 7.3 , 7.6 )

Warnings and precautions

QT Prolongation: Avoid use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval ( 5.3 ) Neuroleptic Malignant Syndrome (NMS): Discontinue if this occurs ( 5.4 ) Akathisia, agitation, restlessness, and parkinsonism: Reduce dose or discontinue if this occurs ( 5.5 , 5.6 ) Sedation/somnolence: May impair the patient’s ability to drive or operate complex machinery ( 5.7 )

5.1 Depression and Suicidality in Patients with Huntington’s Disease Patients with Huntington’s disease are at increased risk for depression, and suicidal ideation or behaviors (suicidality). AUSTEDO XR and AUSTEDO may increase the risk for suicidality in patients with Huntington’s disease. In a 12-week, double-blind, placebo-controlled trial, suicidal ideation was reported by 2% of patients treated with AUSTEDO, compared to no patients on placebo; no suicide attempts and no completed suicides were reported.

Indications

Contraindications

Warnings and precautions

Interactions

Concomitant use of strong CYP2D6 inhibitors: Maximum recommended dose of AUSTEDO XR or AUSTEDO is 36 mg per day ( 2.3 , 7.1 ) Alcohol or other sedating drugs: May have additive sedation and somnolence ( 7.5 )

7.1Strong CYP2D6 Inhibitors

A reduction in AUSTEDO XR or AUSTEDO dose may be necessary when adding a strong CYP2D6 inhibitor in patients maintained on a stable dose of AUSTEDO XR or 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 3-fold. The daily dose of AUSTEDO XR or AUSTEDO should not exceed 36 mg per day in patients taking strong CYP2D6 inhibitors [see Dosage and Administration ( 2.3 ) and Clinical Pharmacology ( 12.3 )].

7.2Reserpine

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 XR or 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 XR or AUSTEDO. AUSTEDO XR and AUSTEDO should not be used concomitantly with reserpine [see Contraindications ( 4 )] .

7.3Monoamine Oxidase Inhibitors (MAOIs)

AUSTEDO XR and AUSTEDO are contraindicated in patients taking MAOIs. AUSTEDO XR and AUSTEDO should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI [see Contraindications ( 4 )] .

7.4Neuroleptic Drugs

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

7.5Alcohol or Other Sedating Drugs

Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence [see Warnings and Precautions ( 5.7 )].

7.6Concomitant Tetrabenazine or Valbenazine

AUSTEDO XR and AUSTEDO are contraindicated in patients currently taking tetrabenazine or valbenazine. AUSTEDO XR or AUSTEDO may be initiated the day following discontinuation of tetrabenazine [see Dosage and Administration ( 2.2 )].

Adverse reactions

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 ( 5.1 )] QTc Prolongation [see Warnings and Precautions ( 5.3 )] Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions ( 5.4 )] Akathisia, Agitation, and Restlessness [see Warnings and Precautions ( 5.5 )] Parkinsonism [see Warnings and Precautions ( 5.6 )] Sedation and Somnolence [see Warnings and Precautions ( 5.7 )] Hyperprolactinemia [see Warnings and Precautions ( 5.8 )] Binding to Melanin-Containing Tissues [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (>8% of AUSTEDO-treated patients with Huntington’s disease and greater than placebo): somnolence, diarrhea, dry mouth, and fatigue ( 6.1 ) Most common adverse reactions (that occurred in 4% of AUSTEDO-treated patients with tardive dyskinesia and greater than placebo): nasopharyngitis and insomnia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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. The studies described below were conducted with AUSTEDO tablets; adverse reactions with AUSTEDO XR extended-release tablets are expected to be similar to AUSTEDO tablets.

Patients with Huntington’s Disease Study 1 [see Clinical Studies ( 14.1 )] 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 3. Table 3: 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 Adverse Reaction AUSTEDO (N = 45) % Placebo (N = 45) % Somnolence 11 4 Diarrhea 9 0 Dry mouth 9 7 Fatigue 9 4 Urinary tract infection 7 2 Insomnia 7 4 Anxiety 4 2 Constipation 4 2 Contusion 4 2 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) [see Clinical Studies ( 14.2 )] .

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 4. Table 4: Adverse Reactions in 2 Placebo-Controlled Tardive Dyskinesia Studies (Study 1 and Study 2) of 12-week Treatment on AUSTEDO Reported in at Least 2% of Patients and Greater than Placebo Adverse Reaction AUSTEDO (N=279) (%) Placebo (N=131) (%) Nasopharyngitis 4 2 Insomnia 4 1 Depression/ Dysthymic disorder 2 1 Akathisia/Agitation/Restlessness 2 1 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.

Austedo XR

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Austedo XR

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.2Clinical Worsening and Adverse Events in Patients with Huntington’s Disease

5.3QTc Prolongation

5.4Neuroleptic Malignant Syndrome (NMS)

5.5Akathisia, Agitation, and Restlessness

5.6Parkinsonism

5.7Sedation and Somnolence

Interactions

7.1Strong CYP2D6 Inhibitors

7.2Reserpine

7.3Monoamine Oxidase Inhibitors (MAOIs)

7.4Neuroleptic Drugs

7.5Alcohol or Other Sedating Drugs

7.6Concomitant Tetrabenazine or Valbenazine

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information

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