Deutetrabenazine

What is Deutetrabenazine?

Deutetrabenazine (AUSTEDO) is a vesicular monoamine transporter 2 (VMAT2) inhibitor used to treat chorea associated with huntington’s disease and tardive dyskinesia.

What are the uses of this medicine?

This medicine used to treat:

• the involuntary movements (chorea) of Huntington’s disease. AUSTEDO does not cure the cause of the involuntary movements, and it does not treat other symptoms of Huntington’s disease, such as problems with thinking or emotions.
• movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia).

How does this medicine work?

• The precise mechanism by which deutetrabenazine exerts its effects in the treatment of tardive dyskinesia and chorea in patients with Huntington’s disease 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.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• have Huntington’s disease and are depressed or have thoughts of suicide.
• have liver problems.
• are taking a monoamine oxidase inhibitor (MAOI) medicine. Do not take an MAOI within 14 days after you stop taking AUSTEDO. Do not start AUSTEDO if you stopped taking an MAOI in the last 14 days. Ask your healthcare provider or pharmacist if you are not sure.
• are taking reserpine. Do not take medicines that contain reserpine (such as Serpalan and Renese-R) with AUSTEDO. If your healthcare provider plans to switch you from taking reserpine to AUSTEDO, you must wait at least 20 days after your last dose of reserpine before you start taking AUSTEDO.
• are taking tetrabenazine (Xenazine). If your healthcare provider plans to switch you from tetrabenazine (Xenazine) to AUSTEDO, take your first dose of AUSTEDO on the day after your last dose of tetrabenazine (Xenazine).
• are taking valbenazine (Ingrezza).

What drug interactions can this medicine cause?

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. Maximum recommended dose of AUSTEDO is 36 mg per day (18 mg twice daily). AUSTEDO and reserpine should not be used concomitantly. AUSTEDO is contraindicated in patients taking MAOIs (eg: isocarboxazid, phenelzine, selegiline). Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence. AUSTEDO is contraindicated in patients currently taking tetrabenazine or valbenazine. The risk of parkinsonism, NMS, and akathisia may be increased by concomitant use of AUSTEDO and dopamine antagonists or antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone).

Is this medicine FDA approved?

• It was approved for use in the United States in 2017.

How should this medicine be used?

Recommended Dosageː

• 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.

• Maximum recommended dosage of AUSTEDO in poor CYP2D6 metabolizers is 36 mg per day (i.e., 18 mg twice daily).

Administration

• Take AUSTEDO exactly as your healthcare provider tells you to take it.
• Take AUSTEDO by mouth and with food.
• Swallow AUSTEDO tablets whole with water. Do not chew, crush, or break AUSTEDO tablets before swallowing. If you cannot swallow AUSTEDO tablets whole, tell your healthcare provider. You may need a different medicine.
• If your dose of AUSTEDO is 12 mg or more each day, take AUSTEDO tablets 2 times a day in equal doses with food.
• Your healthcare provider will increase your dose of AUSTEDO each week for several weeks, until you and your healthcare provider find the right dose for you.
• Tell your healthcare provider if you stop taking AUSTEDO for more than 1 week. Do not take another dose until you talk to your healthcare provider.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 6 mg, 9 mg, and 12 mg

This medicine is available in fallowing brand namesː

• AUSTEDO

What side effects can this medication cause?

The most common side effects of AUSTEDO in people with Huntington’s disease include:

• sleepiness (sedation)
• diarrhea
• tiredness
• dry mouth

The most common side effects of AUSTEDO in people with tardive dyskinesia include:

• inflammation of the nose and throat (nasopharyngitis)
• problems sleeping (insomnia)

AUSTEDO can cause serious side effects, including:

• Depression and suicidal thoughts or actions in people with Huntington’s disease
• Irregular heartbeat (QT prolongation)
• Neuroleptic malignant syndrome (NMS)
• Restlessness
• Parkinsonism

What special precautions should I follow?

• Sleepiness (sedation) is a common side effect of AUSTEDO. While taking AUSTEDO, do not drive a car or operate dangerous machinery until you know how AUSTEDO affects you. Drinking alcohol and taking other drugs that may also cause sleepiness while you are taking AUSTEDO may increase any sleepiness caused by AUSTEDO.
• AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO is administered within the recommended dosage range. Avoid use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval.
• AUSTEDO may increase the risk for suicidality in patients with Huntington’s disease. 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.
• Neuroleptic Malignant Syndrome (NMS) may occur with AUSTEDO .Discontinue if this occurs.
• AUSTEDO may increase the risk of akathisia, agitation, and restlessness in patients with Huntington’s disease and tardive dyskinesia. Reduce dose or discontinue if this occurs.

What to do in case of emergency/overdose?

The following adverse reactions occurred with overdosing: acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor.

Management for overdosage:

• 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.

Can this medicine be used in pregnancy?

• There are no adequate data on the developmental risk associated with the use of AUSTEDO in pregnant women.

Can this medicine be used in children?

• The safety and effectiveness of AUSTEDO have not been established in pediatric patients for the treatment of Tourette syndrome.

What are the active and inactive ingredients in this medicine?

• Active ingredient: deutetrabenazine
• Inactive ingredients: ammonium hydroxide, black iron oxide, n‑butyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, polyethylene oxide, polysorbate 80, polyvinyl alcohol, povidone, propylene glycol, shellac, talc, titanium dioxide, and FD&C blue #2 lake. The 6 mg tablets also contain FD&C red #40 lake. The 12 mg tablets also contain FD&C yellow #6 lake.

Who manufactures and distributes this medicine?

• Distributed by:

Teva Pharmaceuticals USA, Inc. Parsippany, NJ 07054

What should I know about storage and disposal of this medication?

• Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF).
• Protect from light and moisture.

• Dailymed label info on Deutetrabenazine
• FDA Deutetrabenazine