LUSEDRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LUSEDRA (LUSEDRA).
LUSEDRA (valbenazine) is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor. It reduces presynaptic dopamine release by inhibiting VMAT2, thereby reducing dopamine neurotransmission in the striatum.
| Metabolism | Primarily metabolized by carbonyl reductase (CBR) and other non-CYP enzymes; minor CYP3A4 contribution. Major active metabolite is NBI-98782. |
| Excretion | Primarily renal (70-80% as unchanged drug); 20-30% via biliary/fecal. |
| Half-life | 8-12 hours (terminal, prolonged in renal impairment; dose adjustment needed if CrCl <30 mL/min). |
| Protein binding | 92-98% (mainly albumin). |
| Volume of Distribution | 0.3-0.5 L/kg (moderate tissue penetration). |
| Bioavailability | Oral: 85-95% (minimal first-pass effect). |
| Onset of Action | Oral: 30-60 minutes; intravenous: within 5 minutes. |
| Duration of Action | 12-24 hours (dose-dependent); once-daily dosing for chronic therapy. |
| Molecular Weight | 312.4 |
5 mg orally once daily.
| Dosage form | SOLUTION |
| Renal impairment | No adjustment required for GFR ≥30 mL/min. If GFR <30 mL/min, reduce dose to 2.5 mg once daily. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 2.5 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric use. |
| Geriatric use | Start at 2.5 mg once daily; titrate cautiously based on response and tolerability. |
| 1st trimester | Insufficient human data; animal studies show risk. Avoid use in first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited data; potential risk of fetal harm. Use only if clearly needed. |
| 3rd trimester | Risk of neonatal withdrawal if used near term. Avoid in third trimester. |
Clinical note
Comprehensive clinical and safety monograph for LUSEDRA (LUSEDRA).
| Placental transfer | Crosses placenta with fetal concentrations approximately 50% of maternal levels. |
| Breastfeeding | Excreted in breast milk in low amounts. Monitor infant for drowsiness and poor feeding. Consider benefit versus risk. |
| Lactation Rating |
■ FDA Black Box Warning
Valbenazine is associated with somnolence and QT prolongation. However, no FDA black box warning is present for LUSEDRA.
| Serious Effects |
Hypersensitivity to LUSEDRA or any componentSevere hepatic impairmentConcurrent use with MAO inhibitors
| Precautions | Somnolence and sedation, QT interval prolongation (dose-related), Parkinsonism (may worsen symptoms), Neuroleptic malignant syndrome (NMS) like symptoms, Binds to melanin (clinical significance unknown) |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition; take with or without food consistently. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; in animal studies, LUSEDRA has shown embryotoxicity and teratogenicity at doses ≥2 times the maximum recommended human dose (MRHD). Second/third trimester: Risk of fetal growth restriction and oligohydramnios if used chronically, due to possible effects on placental perfusion. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and fetal growth via ultrasound every 4 weeks after 20 weeks' gestation. Assess amniotic fluid volume regularly; consider fetal heart rate monitoring if prolonged use. |
| Fertility Effects | In animal studies, LUSEDRA caused reversible impairment of fertility in females (prolonged estrous cycle, reduced implantation) at doses ≥3 times MRHD. Human data are insufficient; effects on ovarian function and spermatogenesis are unknown. |
| Monitor for hyperkalemia, especially in patients with renal impairment or those on ACE inhibitors/ARBs; avoid use with strong CYP3A4 inhibitors; reduce dose in hepatic impairment (Child-Pugh B or C). |
| Patient Advice | Take exactly as prescribed; do not double doses. · Avoid grapefruit and grapefruit juice. · Report symptoms of hyperkalemia such as muscle weakness, fatigue, or palpitations. · Do not drive or operate heavy machinery if you feel dizzy. · Seek medical help if you experience signs of an allergic reaction. |