What are the drug-to-drug interactions when taking Deutetrabenazine (Austedo)?

From the FDA Drug Label

7 DRUG INTERACTIONS

7.1 Strong 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. 7.2 Reserpine Reserpine binds irreversibly to VMAT2 and the duration of its effect is several days. 7.3 Monoamine Oxidase Inhibitors (MAOIs) AUSTEDO XR and AUSTEDO are contraindicated in patients taking MAOIs. 7.4 Neuroleptic Drugs The risk of parkinsonism, NMS, and akathisia may be increased by concomitant use of AUSTEDO XR or AUSTEDO with dopamine antagonists or antipsychotics. 7.5 Alcohol or Other Sedating Drugs Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence 7.6 Concomitant Tetrabenazine or Valbenazine AUSTEDO XR and AUSTEDO are contraindicated in patients currently taking tetrabenazine or valbenazine.

The drug to drug interactions when taking deutetrabenazine include:

• Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, bupropion): may increase systemic exposure to active dihydro-metabolites of deutetrabenazine, requiring a dose reduction [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)] 1
• Reserpine: should not be used concomitantly with deutetrabenazine, and at least 20 days should elapse after stopping reserpine before starting deutetrabenazine 1
• Monoamine Oxidase Inhibitors (MAOIs): contraindicated in patients taking MAOIs, and deutetrabenazine should not be used within 14 days of discontinuing therapy with an MAOI 1
• Neuroleptic Drugs: may increase the risk of parkinsonism, NMS, and akathisia when used concomitantly with deutetrabenazine 1
• Alcohol or Other Sedating Drugs: may have additive effects and worsen sedation and somnolence when used concomitantly with deutetrabenazine 1 1
• Tetrabenazine or Valbenazine: contraindicated in patients currently taking these drugs, but deutetrabenazine may be initiated the day following discontinuation of tetrabenazine 1

From the Research

Deutetrabenazine has several important drug interactions that patients should be aware of, particularly with strong CYP2D6 inhibitors, other VMAT2 inhibitors, MAO inhibitors, reserpine, CNS depressants, and QT-prolonging medications, which can increase the risk of adverse effects or interactions 2. When taking deutetrabenazine, it is essential to consider the potential interactions with other medications.

• Strong CYP2D6 inhibitors like paroxetine, fluoxetine, and quinidine can significantly increase deutetrabenazine levels in the body, potentially leading to increased side effects.
• Combining deutetrabenazine with other VMAT2 inhibitors such as tetrabenazine or valbenazine should be avoided due to the risk of additive effects.
• MAO inhibitors (like phenelzine or selegiline) can cause serious reactions when taken with deutetrabenazine and should not be used together, as evidenced by the potential for increased serotonergic effects and serotonin syndrome 3.
• Reserpine depletes monoamines and should be discontinued at least 20 days before starting deutetrabenazine.
• Caution is needed when combining deutetrabenazine with CNS depressants like alcohol, benzodiazepines, or opioids as this may increase sedation and drowsiness.
• QT-prolonging medications should be used cautiously with deutetrabenazine due to potential cardiac effects. These interactions occur because deutetrabenazine works by inhibiting vesicular monoamine transporter 2 (VMAT2), affecting neurotransmitter storage, and is metabolized primarily through the CYP2D6 enzyme pathway 4. Patients should always inform all healthcare providers about all medications they are taking to prevent potentially dangerous interactions, and monitoring for adverse events such as depression, somnolence, and suicidal ideation is crucial 2.