Table 1.

Clinically Significant Drug Interactions With Valbenazine¹⁴

Monoamine Oxidase Inhibitors
Clinical implication	Concomitant use of valbenazine with MAOIs may increase the concentration of monoamine neurotransmitters in synapses, potentially leading to increased risk of adverse reactions, such as serotonin syndrome, or attenuated treatment effect of valbenazine.
Prevention or management	Avoid concomitant use of valbenazine with MAOIs.
Examples	Isocarboxazid (Marplan, Validus Pharmaceuticals), phenelzine, selegiline
Strong CYP3A4 Inhibitors
Clinical implication	Concomitant use of valbenazine with strong CYP3A4 inhibitors increased the exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of valbenazine alone. Increased exposure of valbenazine and its active metabolite may increase the risk of exposure-related adverse reactions.
Prevention or management	Reduce valbenazine dose when valbenazine is coadministered with a strong CYP3A4 inhibitor.
Examples	Itraconazole, ketoconazole, clarithromycin
Strong CYP2D6 Inhibitors
Clinical implication	Concomitant use of valbenazine with strong CYP2D6 inhibitors may increase the exposure (Cmax and AUC) to valbenazine’s active metabolite compared with the use of valbenazine alone. Increased exposure of active metabolite may increase the risk of exposure-related adverse reactions.
Prevention or management	Consider reducing valbenazine dose based on tolerability when valbenazine is coadministered with a strong CYP2D6 inhibitor.
Examples	Paroxetine, fluoxetine, quinidine
Strong CYP3A4 Inducers
Clinical implication	Concomitant use of valbenazine with a strong CYP3A4 inducer decreased the exposure of valbenazine and its active metabolite compared with the use of valbenazine alone. Reduced exposure of valbenazine and its active metabolite may reduce efficacy.
Prevention or management	Concomitant use of strong CYP3A4 inducers with valbenazine is not recommended.
Examples	Rifampin, carbamazepine, phenytoin, St. John’s worta
Digoxin
Clinical implication	Concomitant use of valbenazine with digoxin increased digoxin levels because of inhibition of intestinal P-glycoprotein.
Prevention or management	Digoxin concentrations should be monitored when coadministering valbenazine with digoxin. Increased digoxin exposure may increase the risk of exposure-related adverse reactions. Dosage adjustment of digoxin may be necessary.

^aThe induction potency of St. John’s wort may vary widely based on preparation.

AUC = area under the curve; C_max = maximum plasma concentration; CYP = cytochrome P450; MAOIs = monoamine oxidase inhibitors.