Drug Interaction Report

MONITOR CLOSELY: The use of alemtuzumab with other immunosuppressive or antineoplastic agents may increase the risk of infections. Alemtuzumab reduces T and B lymphocytes, but the extent and duration of the reduction is expected to differ based on the dose and indication. Alone, alemtuzumab may cause severe and prolonged myelosuppression, lymphopenia, and rarely, fatal autoimmune cytopenias. Serious, sometimes fatal opportunistic infections have been reported, and the risk may theoretically increase when coadministered with other immunosuppressive therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids.

MANAGEMENT: Caution is advised if alemtuzumab must be used in patients who have recently received or are receiving treatment with other immunosuppressive or antineoplastic drugs, and vice versa. Some authorities consider the combination of alemtuzumab (marketed under the brand name Lemtrada) to be contraindicated in patients receiving antineoplastic or immunosuppressive therapies. Close clinical and laboratory monitoring should be completed as recommended by the manufacturer. The product labeling should be consulted for recommendations on anti-infective prophylaxis to minimize the risks of serious opportunistic infections; as well as, for dosing adjustments and discontinuation recommendations should other toxicities or adverse effects occur. Some authorities recommend that alemtuzumab, marketed under the brand name Campath, not be given within 3 weeks of other chemotherapeutic agents. Since higher dosages are associated with an increased incidence of pancytopenia, the manufacturer of this dosage form of alemtuzumab recommends that single doses not exceed 30 mg and cumulative weekly doses not exceed 90 mg.

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.