Drug Interactions between Cytovene and Ingrezza

ADJUST DOSE: Coadministration with grapefruit juice may increase the plasma concentration of valbenazine. The mechanism is inhibition of CYP450 3A4-mediated first-metabolism in the gut wall by certain compounds present in grapefruits. The use of valbenazine has been associated with modest prolongation of the QT interval. However, clinically significant QT prolongation may occur in patients taking a strong CYP450 3A4 inhibitor due to increased concentrations of valbenazine and its active metabolite (+)-alfa-dihydrotetrabenazine. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drugs involved and dosages of the drugs.

MANAGEMENT: Pharmacologic response to valbenazine should be monitored more closely whenever a strong inhibitor of CYP450 3A4 is added to or withdrawn from therapy. Assessment of baseline QT interval and periodic monitoring during therapy may be considered. The manufacturer recommends reducing the dose of valbenazine to 40 mg once daily during concomitant administration with strong CYP450 3A4 inhibitors. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. In addition, patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

ADJUST DOSING INTERVAL: Food delays but enhances the oral absorption and bioavailability of ganciclovir capsules, possibly due to prolongation of gastrointestinal transit time. In 20 HIV- and CMV-seropositive subjects, ganciclovir dosing (1000 mg every 8 hours) following a standardized high-fat breakfast increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ganciclovir by an average of 15% and 22%, respectively, compared to dosing after an overnight fast. The time to reach peak plasma concentration (Tmax) was prolonged from 1.8 to 3 hours. In another study of 15 such patients, administration of ganciclovir (2000 mg) within 30 minutes following a high-fat breakfast increased the Cmax and AUC an average of 111% and 114%, respectively, compared to administration in the fasting state (i.e. at least 1 hour before or 2 hours after a meal or snack). Over the total day of dosing (2000 mg orally three times a day), there was a mean increase of 48% and 97% in Cmax and AUC, respectively, and a 36% decrease in half-life during administration with meals.

MANAGEMENT: To ensure maximal oral absorption, oral ganciclovir should be administered with or immediately after a meal.