Company: Teva Pharmaceuticals
Approval Status: Initial approval April 2017
Specific Treatments: chorea associated with Huntington’s disease and tardive dyskinesia
Therapeutic Areas Neurology
Austedo (deutetrabenazine) is a vesicular monoamine transporter 2 (VMAT2) inhibitor.
Austedo is specifically indicated for the treatment of chorea associated with Huntington’s disease and tardive dyskinesia in adults.
Austedo is supplied as a tablet for oral administration. The recommended dose is as follows:
- Huntington’s disease chorea: The dose of Austedo is determined individually for each patient based on reduction of chorea 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. 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.
- Tardive dyskinesia: Initial dose: 12 mg/day; Recommended dose: 12 mg– 48 mg/day; Maximum dose: 48 mg/day
Administer Austedo with food. Swallow Austedo whole. Do not chew, crush, or break tablets. Please see drug label for dosing recommendations in patients switching from tetrabenazine and other dose adjustments.
Chorea associated with Huntington’s disease: The FDA approval of Austedo was based on a randomized, double-blind, placebo-controlled, multi-center trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. Treatment duration was 12 weeks, including an 8-week dose titration period and a 4-week maintenance period, followed by a 1-week washout. Austedo was started at 6 mg per day and titrated upward, at weekly intervals, in 6 mg increments until satisfactory treatment of chorea was achieved, intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached. The primary efficacy endpoint was the Total Maximal Chorea Score, an item of the Unified Huntington’s Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28. Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period (average of Week 9 and Week 12), compared to approximately 1.9 units in the placebo group. The treatment effect of -2.5 units was statistically significant (p<0.0001).
Tardive Dyskinesia: The FDA approval was based on two 12-week, randomized, double-blind, placebo-controlled, multi-center trials conducted in 335 adult ambulatory patients with tardive dyskinesia caused by use of dopamine receptor antagonists. The Abnormal Involuntary Movement Scale (AIMS) was the primary efficacy measure for the assessment of tardive dyskinesia severity. In Study 1, a 12-week, placebo-controlled, fixed-dose trial, 222 adults with tardive dyskinesia were randomized 1:1:1:1 to 12 mg Austedo, 24 mg Austedo, 36 mg Austedo, or placebo. Treatment duration included a 4-week dose escalation period and an 8-week maintenance period followed by a 1-week washout. The dose of Austedo was started at 12 mg per day and increased at weekly intervals in 6 mg/day increments to a dose target of 12 mg, 24 mg or 36 mg per day. In Study 1, the AIMS total score for patients receiving Austedo demonstrated statistically significant improvement, from baseline to Week 12, of 3.3 and 3.2 units for the 36 mg and 24 mg arms, respectively, compared with 1.4 units in placebo. In Study 2, a 12-week, placebo-controlled, flexible-dose trial, adults with tardive dyskinesia (n=113) received daily doses of placebo or Austedo, starting at 12 mg per day with increases allowed in 6-mg increments at 1-week intervals until satisfactory control of dyskinesia was achieved, until intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached. Treatment duration included a 6-week dose titration period and a 6-week maintenance period followed by a 1-week washout. Patients were titrated to an optimal dose over 6 weeks. The average dose of Austedo after treatment was 38.3 mg per day. In Study 2, AIMS total score for patients receiving Austedo demonstrated statistically significant improvement by 3.0 units from baseline to endpoint (Week 12), compared with 1.6 units in the placebo group with a treatment effect of -1.4 units.
Adverse events associated with the use of Austedo may include, but are not limited to, the following:
- dry mouth
Austedo comes with the following Black Box Warning: Austedo can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Anyone considering the use of Austedo must balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Patients, their caregivers, and families should be informed of the risk of depression and suicidality and should be instructed to report behaviors of concern promptly to the treating physician.
Mechanism of Action
Austedo (deutetrabenazine) is a vesicular monoamine transporter 2 (VMAT2) inhibitor. The precise mechanism by which Austedo (deutetrabenazine) exerts its anti-chorea effects is unknown but is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. The major circulating metabolites (α-dihydrotetrabenazine [HTBZ] and β-HTBZ) of deutetrabenazine, are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
For additional information regarding Austedo or chorea associated with Huntington’s disease and tardive dyskinesia, please visit https://austedo.com