Valbenazine for tardive dyskinesia

Clinical considerations

Unique properties. Valbenazine is metabolized slowly to a potent, selective VMAT2 antagonist (NBI-98782) in a manner that permits once daily dosing, removes the need for CYP2D6 genotyping, and provides significant efficacy.

Why Rx? The reasons to prescribe valbenazine for TD patients include:

• currently the only agent with FDA approval for TD
• fewer tolerability issues seen with the only other effective agent, tetrabenazine
• no signal for effects on mood parameters or rates of parkinsonism
• lack of multiple daily dosing and possible need for 2D6 genotyping involved with TBZ prescribing.

Dosing

The recommended dosage of valbenazine is 80 mg/d administered as a single dose with or without food, starting at 40 mg once daily for 1 week. There is no dosage adjustment required in those with mild to moderate renal impairment; however, valbenazine is not recommended in those with severe renal impairment. The maximum dose is 40 mg/d for those who with moderate or severe hepatic impairment (Child-Pugh score, 7 to 15) however, valbenazine is not recommended for patients with severe renal impairment (creatinine clearance <30 mL/min) because the exposure to the active metabolite is reduced by approximately 75%. The combined efficacy and tolerability of dosages >80 mg/d has not been evaluated. Adverse effects seen with tetrabenazine at higher dosages include akathisia, anxiety, insomnia, parkinsonism, fatigue, and depression.

A daily dose of 40 mg may be considered for some patients based on tolerability, including those who are known CYP 2D6 poor metabolizers, and those taking strong CYP2D6 inhibitors.² For those taking strong 3A4 inhibitors, the maximum daily dose is 40 mg. Concomitant use of valbenazine with strong 3A4 inducers is not recommended as the exposure to the active metabolite is reduced by approximately 75%.² Lastly, because VMAT2 inhibition may alter synaptic levels of other monoamines, it is recommended that valbenazine not be administered with monoamine oxidase inhibitors, such as isocarboxazid, phenelzine, or selegiline.

Contraindications

There are no reported contraindications for valbenazine. As with most medications, there is limited available data on valbenazine use in pregnant women; however, administration of valbenazine to pregnant rats during organogenesis through lactation produced an increase in the number of stillborn pups and postnatal pup mortalities at doses under the maximum recommended human dose (MRHD) using body surface area based dosing (mg/m²). Pregnant women should be advised of the potential risk to a fetus. Valbenazine and its metabolites have been detected in rat milk at concentrations higher than in plasma after oral administration of valbenazine at doses 0.1 to 1.2 times the MRHD (based on mg/m²). Based on animal findings of increased perinatal mortality in exposed fetuses and pups, woman are advised not to breastfeed during valbenazine treatment and for 5 days after the final dose. No dosage adjustment is required for geriatric patients.