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 juice may significantly increase the plasma concentrations of olaparib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a drug interaction study with 57 patients, mean olaparib systemic exposure (AUC) was increased approximately 2.7-fold by the potent CYP450 3A4 inhibitor itraconazole. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that a moderate inhibitor (fluconazole) may increase the AUC of olaparib by 2.2-fold. The interaction has not been studied with grapefruit juice. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to olaparib may increase the risk of adverse effects such as hematologic toxicity, nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain or discomfort.

MANAGEMENT: Food containing grapefruit, grapefruit juice, Seville orange (a citrus relative of the grapefruit), or Seville orange juice should be avoided during treatment with olaparib. Some authorities also recommend avoiding starfruit (carambola) and pomegranate.