Drug Interactions between ganciclovir and Ibrance

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.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the systemic exposure to palbociclib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Increased exposure to palbociclib may increase the risk of adverse effects such as infections, neutropenia, leukopenia, anemia, thrombocytopenia, anorexia, nausea, vomiting, diarrhea, stomatitis, alopecia, asthenia, peripheral neuropathy, and epistaxis.

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of palbociclib capsules and reduce the intersubject variability of palbociclib exposure. According to the product labeling, absorption and exposure of palbociclib from its oral capsule formulation were very low in approximately 13% of the population when taken in the fasted state. Food intake increased the palbociclib exposure in this small subset of the population but did not alter exposure in the rest of the population to a clinically relevant extent. Compared to palbociclib capsules given under overnight fasted conditions, the population average palbociclib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 38% and 21%, respectively, when given with high-fat, high-calorie food (approximately 800 to 1000 calories; 150, 250, and 500 to 600 calories from protein, carbohydrate and fat, respectively); by 27% and 12%, respectively, when given with low-fat, low-calorie food (approximately 400 to 500 calories; 120, 250, and 28 to 35 calories from protein, carbohydrate and fat, respectively); and by 24% and 13%, respectively, when given with moderate-fat, standard calorie food (approximately 500 to 700 calories; 75 to 105, 250 to 350 and 175 to 245 calories from protein, carbohydrate and fat, respectively) one hour before and two hours after palbociclib capsule dosing.

MANAGEMENT: Patients should avoid consumption of grapefruit or grapefruit juice while on treatment with palbociclib. To avoid variability in drug absorption between doses, palbociclib capsules should be taken with food. Palbociclib tablet formulations may be taken with or without food.