Drug Interaction Report

MONITOR: The use of omacetaxine with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Omacetaxine alone may cause severe myelosuppression, neutropenia, lymphopenia, and opportunistic infections. In clinical trials, infections/infestations (bacterial, viral, fungal, and nonspecified) were reported in up to 56% of patients, and grade 3 or 4 infections/infestations in up to 20% of patients. The risk may theoretically increase when coadministered with other hematotoxic 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 omacetaxine must be used in patients who have recently received or are receiving treatment with other immunosuppressive or myelosuppressive drugs, and vice versa. Close clinical and laboratory monitoring for the development of severe hematologic adverse effects is recommended both during and after discontinuation of therapy. Patients should be advised to seek medical attention if they experience symptoms such as fever, chills, shortness of breath, fatigue, and any unusual bleeding or bruising.

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.