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. |
| Molecular Weight | 331.46 |
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 | Valbenazine is not recommended during the first trimester due to potential teratogenic effects; animal studies have shown developmental toxicity, and human data are lacking. |
| 2nd trimester | Limited human data; valbenazine should be used in the second trimester only if potential benefit justifies potential risk to the fetus, as there is a possibility of fetal harm. |
| 3rd trimester | Use in the third trimester may cause adverse effects in the neonate, such as extrapyramidal symptoms or withdrawal; avoid unless clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for VALBENAZINE (VALBENAZINE).
| Placental transfer | Valbenazine crosses the placenta based on animal studies; specific extent in humans is unknown but likely due to its molecular weight and lipophilicity. |
| Breastfeeding | Valbenazine is likely excreted into human breast milk based on its molecular weight and lipophilicity. Not recommended during breastfeeding due to potential for serious adverse reactions in the breastfed infant, including sedation, extrapyramidal symptoms, and neuroleptic malignant syndrome-like effects. |
■ FDA Black Box Warning
None.
| Serious Effects |
Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuationHypersensitivity to valbenazine or any of 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. |
| Food/Dietary | No specific food restrictions. Grapefruit has no known interaction. Valbenazine may be taken with or without food. Avoid alcohol due to additive central nervous system effects. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
| Valbenazine is a VMAT2 inhibitor used for tardive dyskinesia. Titrate slowly: start 40 mg daily, increase to 80 mg after 1 week. Monitor for somnolence and QT prolongation; avoid in congenital long QT syndrome. Do not use with strong CYP2D6 inducers or inhibitors. Can be given with or without food. |
| Patient Advice | Take valbenazine exactly as prescribed; do not change dose without consulting your doctor. · May cause drowsiness; avoid driving or operating heavy machinery until you know how valbenazine affects you. · Report any new or worsening depression, suicidal thoughts, or unusual changes in mood or behavior. · Avoid alcohol while taking valbenazine. · If you miss a dose, skip it and take the next dose at the regular time. Do not take two doses at once. · Tell your doctor about all medications you take, including over-the-counter drugs and supplements. · Do not stop taking valbenazine abruptly; it may worsen your condition. |