Drug Interaction Report

GENERALLY AVOID: Coadministration of topical tacrolimus with other immunosuppressive agents may potentiate the immunosuppressive effects of topical tacrolimus. However, data concerning its safety and efficacy in combination with immunosuppressants are not available. According to the prescribing information, rare cases of skin malignancy and lymphoma have been reported in patients who have received treatment with topical calcineurin inhibitors, including topical tacrolimus. On the other hand, systemic exposure from topical tacrolimus is reported to be less than 1 ng/mL. In addition, the lowest tacrolimus blood concentration from topical application at which systemic effects can be observed is unknown.

MANAGEMENT: According to the manufacturer, use of topical tacrolimus in immunocompromised patients is not recommended. Therefore, until further information is available, it may be advisable to avoid its concomitant use with other immunosuppressants. Screening for the development of malignancy during and after treatment may also be considered.

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.