VALBENAZINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VALBENAZINE (VALBENAZINE).
Vesicular monoamine transporter 2 (VMAT2) inhibitor, reducing dopamine release in the striatum.
| Metabolism | Primarily via aldo-keto reductase (AKR1C4) to a minor active metabolite, then by CYP3A4, CYP2D6, and other enzymes. |
| Excretion | Primarily hepatic metabolism; less than 30% of the dose excreted unchanged in urine and feces combined. Biliary/fecal excretion accounts for approximately 40-60% as metabolites. |
| Half-life | Terminal elimination half-life is approximately 17-23 hours, allowing for once-daily dosing. |
| Protein binding | Approximately 82-85% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd = 1.0-1.5 L/kg, indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is approximately 75% after administration with food; food increases AUC by 50% and Cmax by 75%. |
| Onset of Action | Oral: 4-8 weeks for therapeutic effect; onset not immediate, requires gradual dose titration. |
| Duration of Action | With once-daily dosing, sustained therapeutic effect over 24 hours; steady-state reached in 1-2 weeks. |
50 mg orally once daily; can be increased to 75 mg orally once daily based on tolerability and response.
| Dosage form | CAPSULE |
| Renal impairment | For GFR 30-89 mL/min: no adjustment. For GFR 15-29 mL/min: maximum 50 mg once daily. For GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: maximum 50 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Start at 50 mg once daily; caution due to potential for QT prolongation and fall risk; monitor electrolytes and cardiac function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VALBENAZINE (VALBENAZINE).
| Breastfeeding | It is unknown if valbenazine is excreted in human breast milk. The molecular weight (approximately 441 Da) suggests possible excretion. No M/P ratio is available. Due to the potential for serious adverse reactions in nursing infants, including sedation and extrapyramidal symptoms, breastfeeding is not recommended during treatment and for at least 5 days after the last dose. |
| Teratogenic Risk | Valbenazine is classified as FDA Pregnancy Category C. In animal studies, fetal developmental toxicity (including reduced fetal weight and skeletal variations) occurred at maternal exposures similar to or greater than the human therapeutic dose at 80 mg/day. There are no adequate and well-controlled studies in pregnant women. First trimester risks cannot be excluded; second and third trimester exposure may be associated with extrapyramidal symptoms or withdrawal in neonates. Use only if potential benefit justifies potential risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days. History of congenital long QT syndrome or QT prolongation. Known hypersensitivity to valbenazine or its components.
| Precautions | May cause QT prolongation, sedation, somnolence, and Parkinsonism-like symptoms. Risk of depression and suicidality. Advise against driving until effects are known. Monitor for akathisia, restlessness, and hypotension. |
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| Fetal Monitoring | Monitor for maternal extrapyramidal symptoms, sedation, QT prolongation (baseline and periodic ECG if at risk), and tardive dyskinesia. In pregnant patients, assess fetal growth and development via ultrasound if clinically indicated. Neonates should be monitored for extrapyramidal symptoms, hypertonia, hypotonia, respiratory depression, and feeding difficulties. |
| Fertility Effects | In animal studies, valbenazine reduced fertility and increased preimplantation loss in female rats at exposures approximately 5 times the human exposure at 80 mg/day. The effects on male fertility are unknown. In humans, no fertility studies have been conducted; valbenazine may impair fertility in females based on animal data. |