Deutetrabenazine was approved by the US FDA in April 2017 for treating chorea which is associated with Huntingtons disease.
Deutetrabenazine, a vesicular monoamine transporter 2 inhibitor, is used to treat sudden involuntary or repetitive movements (chorea) which is associated with an inherited disease called as Huntington's disease.
It acts by depleting certain chemicals in the nerve endings of the brain.
Deutetrabenazine is not recommended in patients with-
Allergy to the drug
Mood disorders including depressive illness or suicidal tendencies
Severe liver disease
Congenital long QT syndrome or cardiac arrhythmia, or with drugs that prolong the QTc interval
Along with drugs such as reserpine, tetrabenazine or monoamine oxidase inhibitors. A minimum gap of 14 days is required between the treatment with MAO inhibitors and deutetrabenazine, and 20 days between reserpine and deutetrabenazine.
The drug is not recommended during pregnancy and breastfeeding, or in individuals 18 years or younger as safety and efficacy of deutetrabenazine in this population is not established.
The dose of deutetrabenazine depends on individual patients tolerability and the reduction in the episodes of chorea.
The recommended adult initial dose is 6 mg once daily which may be increased up to a maximum daily dose of 48mg in two divided doses with dose increments of 6mg/day at regular weekly intervals. The maximum dose in poor CYPD6 metabolizers is 36 mg per day.
Patients switching from tetrabenazine to deutetrabenazine:
12.5 mg of tetrabenazine - Switch to 6mg of deutetrabenazine once daily
25 mg of tetrabenazine - Switch to 6mg of deutetrabenazine twice daily
37.5 mg of tetrabenazine - Switch to 9 mg twice daily
50 mg of tetrabenazine - Switch to 12 mg twice daily
62.5 mg of tetrabenazine - Switch to 15 mg twice daily
75 mg of tetrabenazine - Switch to 18 mg twice daily
87.5 mg of tetrabenazine - Switch to 21 mg twice daily
100 mg of tetrabenazine - Switch to 24 mg twice daily
Patients taking drugs such as quinidine, paroxetine, fluoxetine, and bupropion:
The maximum single dose per day is 18 mg and the total daily dose is 36 mg.
Deutetrabenazine comes in a tablet form which has to be taken by mouth. It has to be taken with food, initially once daily and later increased to twice daily.
The tablets should be swallowed as a whole without splitting, crushing or chewing. Initially, it is advised to start with a low dose and to gradually increase the dose once weekly.
The dose of deutetrabenazine should be taken exactly as directed by the physician.
Patients should be reassessed at regular intervals for the effect of the medication on chorea and the appearance of some expected adverse effects such as sedation, Parkinsonism, akathisia (strong urge to move), restlessness or decline in cognitive function. In patients with such adverse effects, the dose of deutetrabenazine can either be reduced or the drug can be discontinued.
The risk of suicidal ideation is a possibility with deutetrabenazine therapy. Patients and caregivers should be instructed to report to the physician in case of abnormal behavior.
Monitoring of serum prolactin levels should be carried out regularly to detect hyperprolactinemia.
Regular ophthalmologic monitoring is advised rule out the possibility of eye damage after long-term exposure.
Care should be taken in patients with cardiac illness as deutetrabenazine may lead to prolongation of QT interval resulting in cardiac emergencies.
Neuroleptic malignant syndrome (NMS) has been observed with tetrabenazine therapy and patients on deutetrabenazine also should be advised to recognize the symptoms and signs of NMS such as high fever, altered mental function, and rigidity of muscles. If any of the symptoms are observed, the patient should report to the physician immediately.
Gastrointestinal: Diarrhea, dry mouth, constipation
Cardiovascular: Irregular heartbeat
Central nervous system: Suicidal ideation, dizziness, anxiety, depression, agitation or restlessness, behavioral changes, Parkinsonism, abnormal movements, sedation, cognitive decline, fatigue
Musculoskeletal: Stiffness of arms or legs, jerky movements of face, head or neck
Others: Contusion, urinary tract infection, neuroleptic malignant syndrome
Operating heavy machinery or skilled tasks such as driving should be avoided as deutetrabenazine leads to drowsiness.
The intake of alcohol or other sleep-inducing drugs during deutetrabenazine therapy should be avoided as it may result in severe drowsiness.
Caution is required in patients with a history of depression and caregivers or family members should be instructed to report to the healthcare personnel immediately in case of any abnormal behavior changes.
Several drugs are found to interact with deutetrabenazine. It is therefore necessary to get a physicians approval before taking any prescription or over-the-counter drug or herbal supplement while taking deutetrabenazine.
Deutetrabenazine interacts with MAO Inhibitors. Hence deutetrabenazine and should be taken only after 2 weeks of stopping the intake of MAO Inhibitors.
Reserpine should be stopped at least before 20 days before taking deutetrabenazine because of the possibility of serious interactions.
Antidepressants such as paroxetine, fluoxetine and bupropion and drugs like quinidine decrease the clearance of the drug which results in increased concentration of deutetrabenazine and possible adverse effects. The maximum dose of deutetrabenazine with strong CYPD6 inhibitors is 36 mg per day.
Antipsychotics and other dopamine antagonists may worsen the symptoms of akathisia, Parkinsonism and neuroleptic malignant syndrome caused by deutetrabenazine.
Alcohol and sedative drugs can increase the somnolence caused by deutetrabenazine.
Prolongation of QTc interval may occur when administered with antipsychotic medications like chlorpromazine, haloperidol, thioridazine and ziprasidone, antibiotics like moxifloxacin, and antiarrhythmic medications like quinidine, procainamide, amiodarone and sotalol.
Deutetrabenazine tablets should be stored at a controlled room temperature between 15°C and 25°C.
The tablets should be protected from excess light and moisture.
Keep out of reach of the children.