Dosing & Uses
Dosage Forms & Strengths
capsule
- 40mg
- 80mg
Tardive Dyskinesia
Indicated for treatment of tardive dyskinesia in adults
40 mg PO qDay x1 week, then increase to the recommended dose of 80 mg PO qDay
Continuation of 40 mg once daily may be considered for some patients
Also see Administration
Dosage Modifications
Strong CYP3A4 inducers: Coadministration not recommended
Strong CYP3A4 inhibitors: If coadministered, reduce valbenazine dose to 40 mg/day
Strong CYP2D6 inhibitors or known CYP2D6 poor metabolizers: If coadministered, consider reducing dose
Hepatic impairment
- Mild: No dose adjustment required
- Moderate-to-severe (Child-Pugh 7-15): Not to exceed 40 mg/day
Renal impairment
- Mild-to-moderate (CrCl 30-90 mL/min): No dose adjustment required
- Severe (CrCl <30 mL/min): Use not recommended
Tardive dyskinesia: Safety and efficacy not established
Tourette Syndrome (Orphan)
Orphan designation for treatment of Tourette syndrome
Sponsor
- Neurocrine Biosciences, Inc; 12780 El Camino Real; San Diego, California 92130
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Somnolence (10.9%)
1-10%
Anticholinergic effects (5.4%)
Balance disorders/fall (4.1%)
Headache (3.4%)
Akathisia (2.7%)
Vomiting (2.6%)
Nausea (2.3%)
Arthralgia (2.3%)
Postmarketing Reports
Hypersensitivity
QT prolongation
Skin and subcutaneous tissue disorders: rash
Warnings
Contraindications
Patients with a history of hypersensitivity to drug or components of the formulation
Cautions
Can cause somnolence; warn patients not to perform activities requiring mental alertness (eg, driving or operating hazardous machinery) until they know how they will be affected
QT prolongation
- May prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing
- If coadministered with a strong CYP2D6 or CYP3A4 inhibitor, or patients who are CYP2D6 poor metabolizers, valbenazine concentrations may increase and cause clinically significant QT prolongation (see Dosage Modifications)
- Avoid in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval
- For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage
Drug interaction overview
- MAOIs
- Avoid coadministration
- Concomitant use may increase concentration of monoamine neurotransmitters in synapses, potentially leading to increased risk of adverse reactions (eg, serotonin syndrome) or attenuated treatment effect of valbenazine
- Strong CYP3A4 inhibitors
- Reduce valbenazine dose (see Dosage Modifications)
- Coadministration increases exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of valbenazine alone
- Strong CYP2D6 inhibitors
- Consider reducing valbenazine dose based on tolerability
- Coadministration increases exposure (Cmax and AUC) to valbenazine’s active metabolite compared with the use of valbenazine alone
- Strong CYP3A4 inducers
- Concomitant use not recommended
- Coadministration decreases systemic exposure of valbenazine and its active metabolite, thereby decreasing efficacy
- Digoxin
- Coadministration increases digoxin levels owing to P-gp inhibition
- Monitor digoxin levels if coadministered; dosage adjustment of digoxin may be necessary
Pregnancy
Pregnancy
Data are limited on use in pregnant women
Based on animal studies, may cause fetal harm; advise pregnant women of the potential risk
Animal studies
- Administration to pregnant rats during organogenesis through lactation produced an increase in the number of stillborn pups and postnatal pup mortalities at doses <1 times the maximum recommended human dose (MRHD) of 80 mg/day based on mg/m² body surface area
- However, no malformations were observed when administered orally to rats and rabbits during the period of organogenesis at doses up to 1.8 or 24 times, respectively, the MRHD
Lactation
Unknown if distributed in human breast milk
Valbenazine and its metabolites have been detected in rat milk at concentrations higher than in plasma following oral administration at doses 0.1-1.2 times the MRHD based on mg/m²
Based on animal findings of increased perinatal mortality in exposed fetuses and pups, advise a woman not to breastfeed during treatment and for 5 days after the final dose
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
The mechanism of action of valbenazine in the treatment of tardive dyskinesia is unknown, but is thought to be mediated through the reversible inhibition of vesicular monoamine transporter 2 (VMAT2), a transporter that regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release
Absorption
Bioavailability: ~49%
Peak plasma time: 0.5-1 hr (parent); 4-8 hr (active metabolite)
Steady-state: 1 week
Distribution
Protein bound: >99% (parent); ~64% (active metabolite)
Vd: 92 L
Metabolism
Extensively metabolized after oral administration by hydrolysis of the valine ester to form the active metabolite ([+]-alpha-HTBZ) and by oxidative metabolism, primarily by CYP3A4/5, to form mono-oxidized valbenazine and other minor metabolites
[+]-alpha-HTBZ appears to be further metabolized in part by CYP2D6
Elimination
Half-life: 15-22 hr (parent drug and active metabolite)
Total plasma clearance: 7.2 L/hr
Excretion: 60% urine; 30% feces; <2% excreted as unchanged valbenazine or [+]-alpha-HTBZ
Pharmacogenomics
CYP2D6 poor metabolizers
- Consider reducing valbenazine dose based on tolerability for known CYP2D6 poor metabolizers
- Increased exposure (Cmax and AUC) to the active metabolite is anticipated in CYP2D6 poor metabolizers, which may increase risk for exposure-related adverse effects
Administration
Oral Administration
May take with or without food
Also see Dosage Modifications
Storage
Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
Images
Patient Handout
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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- Compare formulary status to other drugs in the same class.
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