valbenazine

General Information

Valbenazine (Ingrezza) is an oral vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for adults with tardive dyskinesia who remain on dopamine receptor–blocking agents.

Randomized trials demonstrate clinically meaningful Abnormal Involuntary Movement Scale (AIMS) reductions within two weeks that persist through 48-week extensions, supporting guideline placement as first-line VMAT2 therapy despite access hurdles such as prior authorization and copay costs.

The contrast view can help compare dosing cadence, QT risk, and sedation across VMAT2 options and align AIMS-driven monitoring with site tardive dyskinesia protocols.

Frequently preferred over deutetrabenazine because of once-daily dosing and a modest monitoring burden; financial assistance is often required to initiate or continue therapy.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Reversibly inhibits VMAT2, reducing vesicular packaging and synaptic release of dopamine within the nigrostriatal pathway.

Minimal affinity for serotonin, adrenergic, muscarinic, or histamine receptors preserves antipsychotic efficacy while dampening dyskinetic movements.

• High-affinity VMAT2 inhibitor (parent and active metabolite).
• Negligible binding to dopamine D2, serotonin 5-HT2, adrenergic, or muscarinic receptors.

Metabolism and Pharmacokinetics

• Median Tmax 4–8 hours; >99% protein bound with an apparent volume of distribution ≈92 L.
• Extensively metabolized by CYP3A4/5 and CYP2D6 to the active metabolite NBI-98782; exposure increases in CYP2D6 poor metabolizers and with strong inhibitors.
• Mean half-life ≈15–22 hours (parent) and ≈18–20 hours (active metabolite); ~60% of the dose is recovered in urine and ~30% in feces, primarily as metabolites (<2% unchanged).

Dosing and Administration

• Initiate 40 mg once daily for 7 days, then increase to 80 mg once daily if tolerated.
• Limit to 40 mg once daily with strong CYP3A4 inhibitors or in moderate/severe hepatic impairment (Child-Pugh B/C); avoid use in Child-Pugh C when risk outweighs benefit.
• Avoid strong CYP3A4 inducers (rifampin, carbamazepine, St. John’s wort) and consider 40 mg maintenance in CYP2D6 poor metabolizers or with strong CYP2D6 inhibitors.
• Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m^2).

Monitoring & Labs

• Baseline and follow-up AIMS scoring (and functional impact) to document benefit and support payer renewals.
• Sedation and falls risk, especially in older adults and when other CNS depressants are co-prescribed.
• QTc monitoring when cardiac risk exists or when other QT-prolonging drugs are used.
• Medication reconciliation for CYP3A4/2D6 inhibitors/inducers that can shift exposure and tolerability.

Valbenazine treats TD symptoms while the dopamine-blocking agent often continues; monitoring focuses on AIMS response and on sedation/QT-related safety.

Adverse Effects

Interactions

• Contraindicated with strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John’s wort) due to markedly reduced exposure.
• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) and strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) increase exposure—limit to 40 mg/day and monitor for somnolence and QTc effects.
• Additive QT prolongation with other QT-active agents (e.g., ziprasidone, methadone, class Ia/III antiarrhythmics); avoid or monitor closely.
• Avoid concomitant reserpine or other VMAT2 inhibitors because of theoretical additive monoamine depletion.

Other Useful Information

• Document baseline AIMS score and reassess every 4–12 weeks to gauge benefit and guide payer renewals.
• Maintain the underlying antipsychotic when clinically feasible; valbenazine treats TD symptoms rather than the primary psychiatric disorder.
• If two or more consecutive doses are missed, instruct patients to restart at 40 mg for one week before re-escalating.
• Discuss pregnancy registry participation and lactation data limitations when applicable.
• Review other QT-active medications and CYP3A4/2D6 modulators before dose increases; this helps prevent avoidable sedation or QTc effects.

References

1. INGREZZA (valbenazine) prescribing information — DailyMed (2025)
2. Kinect 3: A Phase 3 Randomized, Double Blind, Placebo Controlled Trial OF Valbenazine FOR Tardive Dyskinesia — American Journal of Psychiatry (2017)
3. A Long Term, Open Label Study OF Valbenazine FOR Tardive Dyskinesia — CNS Spectrums (2021)
4. Tardive dyskinesia: placing vesicular monoamine transporter type 2 (VMAT2) inhibitors into clinical perspective — Expert Review of Neurotherapeutics (2018)