Tetrabenazine Drug Interactions: What to Avoid and What to Tell Your Doctor

Tetrabenazine has several significant drug interactions that patients and caregivers need to understand. Some interactions are outright contraindications — meaning the combination must be completely avoided — while others require dose adjustments or increased monitoring. This guide covers the most important Tetrabenazine interactions and gives you a checklist of what to tell your doctor and pharmacist.

Contraindicated Combinations: Never Take With Tetrabenazine

The following combinations are contraindicated — they must be avoided entirely:

MAOIs (monoamine oxidase inhibitors): Including phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), selegiline (Emsam patch), and linezolid (an antibiotic that has MAOI activity). The combination risks a severe hypertensive crisis. At least 14 days must pass after stopping an MAOI before starting Tetrabenazine. This is a serious, potentially life-threatening interaction.

Reserpine: Another monoamine depletor. Combining it with Tetrabenazine causes excessive CNS depletion of serotonin and norepinephrine. At least 20 days must pass after stopping reserpine before starting Tetrabenazine.

Deutetrabenazine (Austedo) or Valbenazine (Ingrezza): Using two VMAT2 inhibitors simultaneously is contraindicated due to additive monoamine depletion. Deutetrabenazine can be started the day after stopping Tetrabenazine.

CYP2D6 Inhibitors: Major Interaction Requiring Dose Adjustment

Tetrabenazine is metabolized primarily by the CYP2D6 enzyme in the liver. Drugs that strongly inhibit CYP2D6 can dramatically increase blood levels of Tetrabenazine's active metabolites (alpha-HTBZ and beta-HTBZ), increasing the risk of side effects.

Major CYP2D6 inhibitors to discuss with your doctor:

Fluoxetine (Prozac): Commonly prescribed for depression in HD patients — but it's a strong CYP2D6 inhibitor. If you take fluoxetine, your Tetrabenazine dose may need to be reduced, and you should be treated as a CYP2D6 poor metabolizer for dosing purposes.

Paroxetine (Paxil): One of the most potent CYP2D6 inhibitors. Requires dose adjustment of Tetrabenazine.

Quinidine: Antiarrhythmic drug that is also a strong CYP2D6 inhibitor.

Bupropion (Wellbutrin): Moderate CYP2D6 inhibitor — should be used cautiously with Tetrabenazine.

QT-Prolonging Drugs: Increased Heart Rhythm Risk

Tetrabenazine causes a small QT interval prolongation (~8 ms). When combined with other QT-prolonging drugs, this can increase the risk of serious cardiac arrhythmias including torsade de pointes. Avoid or use extreme caution with:

Antipsychotics: Chlorpromazine, haloperidol, thioridazine, ziprasidone

Class 1A antiarrhythmics: Quinidine, procainamide

Class III antiarrhythmics: Amiodarone, sotalol

Antibiotics: Moxifloxacin (Avelox), azithromycin (Z-pack), clarithromycin

Other agents: Methadone, adagrasib, some antiemetics (ondansetron at high doses)

CNS Depressants: Additive Sedation

Tetrabenazine causes sedation. Combining it with other central nervous system depressants increases this effect and can impair your ability to drive, operate machinery, or perform tasks requiring attention. Use caution with:

Alcohol

Opioid pain medications (oxycodone, hydrocodone, codeine, fentanyl)

Benzodiazepines (Xanax, Valium, Klonopin, Ativan)

Sleep medications (zolpidem, eszopiclone)

Muscle relaxants (cyclobenzaprine, carisoprodol)

What to Tell Your Doctor and Pharmacist

Before starting Tetrabenazine, give your neurologist a complete list of all your medications, including:

All prescription medications (including antidepressants, antipsychotics, antiarrhythmics, and antibiotics)

Over-the-counter medications

Herbal supplements and vitamins (St. John's Wort, in particular, affects CYP enzymes)

Any history of cardiac arrhythmias, congenital long QT syndrome, or electrolyte abnormalities

For a complete overview of Tetrabenazine side effects, see our guide: Tetrabenazine Side Effects: What to Expect and When to Call Your Doctor.