Section 03 · Monograph
Valbenazine
Reviewed Nov 2026FDA label
IngrezzaVMAT2 inhibitor
- Forms
- Cap: 40, 60, 80mg
- Dose
- 40-80mg once daily
- MOA
- Depletes presynaptic dopamine
Black Box Warning
- VMAT2 inhibitors, including INGREZZA and INGREZZA SPRINKLE, can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington's disease
- Balance the risks of depression and suicidality against the clinical need for treatment of chorea
- Monitor patients for new or worsening depression, suicidal thoughts, or unusual changes in behavior
Indications
- Treatment of tardive dyskinesia in adultsFDA-labeled
- Treatment of chorea associated with Huntington's disease in adultsFDA-labeled
Mechanism of Action
- Selective, reversible inhibitor of vesicular monoamine transporter 2 (VMAT2)
- Reduces uptake of monoamines (notably dopamine) into synaptic vesicles, depleting monoamine stores available for release
- Unlike typical antipsychotics, does not block postsynaptic dopamine receptors directly
Full Dosing
Adult / usual
- Tardive dyskinesia: initiate 40 mg once daily; after 1 week increase to the recommended dose of 80 mg once daily
- Alternative tardive dyskinesia dosing (based on tolerability): 40–60 mg once daily
- Huntington's disease chorea: initiate 40 mg once daily; increase by 20 mg increments no more frequently than every 2 weeks, to the recommended dose of 80 mg once daily
- Strong CYP3A4 inhibitors or CYP2D6 poor metabolizers/strong CYP2D6 inhibitors: maximum dose 40 mg once daily
- May be taken with or without food; INGREZZA SPRINKLE capsules may be opened and sprinkled on soft food (do not chew capsule contents)
Renal
- No dosage adjustment required for renal impairment
Hepatic
- Moderate or severe hepatic impairment: maximum dose 40 mg once daily; avoid the 80 mg dose
Contraindications
- Known hypersensitivity to valbenazine or any component of INGREZZA (e.g., prior angioedema, rash, or urticaria with valbenazine)
Drug Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) — increase valbenazine exposure; limit dose to 40 mg once daily
- Strong CYP3A4 inducers (e.g., rifampin) — reduce valbenazine exposure; concomitant use not recommended
- Strong CYP2D6 inhibitors — increase active metabolite exposure; limit dose to 40 mg once daily
- MAOIs — avoid concomitant use or use within 14 days of MAOI discontinuation
- Digoxin — valbenazine may increase digoxin concentrations; monitor digoxin levels
Adverse Effects
- Somnolence (most common overall)
- Sedation/lethargy
- Urticaria and rash (notably in Huntington's chorea trials)
- Insomnia
- Anticholinergic effects
- Balance disorder/gait disturbance
Monitoring Parameters
- Monitor for emergence or worsening of depression and suicidal ideation, particularly in patients with Huntington's disease
- Monitor for QT interval prolongation, especially in patients with congenital long QT syndrome, arrhythmias, or on other QT-prolonging drugs
- Assess for excessive somnolence/sedation and advise caution with driving or operating machinery
- Monitor for parkinsonism; reduce dose or discontinue if clinically significant
- Monitor for signs/symptoms of neuroleptic malignant syndrome (NMS)
- Monitor for hypersensitivity reactions (angioedema, urticaria, rash); discontinue if these occur
Pregnancy & Lactation
- Pregnancy: may cause fetal harm based on animal data (increased stillbirths and postnatal pup mortality at clinically relevant exposures); no adequate human data
- Lactation: advise patients not to breastfeed during treatment and for 5 days after the final dose; valbenazine is present in animal milk at higher concentrations than plasma