Drug Interactions between levofloxacin and pirtobrutinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pirtobrutinib, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. When pirtobrutinib (200 mg single dose) was administered with itraconazole, a potent CYP450 3A4 inhibitor, pirtobrutinib systemic exposure (AUC) increased by 49%. Concomitant use of diltiazem or verapamil, moderate CYP450 3A4 inhibitors, is predicted to increase pirtobrutinib AUC by 20% and 30%, respectively. 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 pirtobrutinib may increase the risk of infection, bruising, bleeding, fatigue, musculoskeletal pain, diarrhea, edema, and dyspnea.

MANAGEMENT: It may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with pirtobrutinib.

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ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of levofloxacin. According to the drug product labeling, administration of levofloxacin 500 mg with food prolonged the time to peak concentration by 1 hour and decreased the Cmax decreased by 25% following administration of the oral solution and by 14% following administration of the oral tablet.

MANAGEMENT: To ensure maximal and consistent oral absorption, levofloxacin oral solution should be taken at least one hour before or two hours after meals. For administration of the oral solution with continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for one hour before and two hours after the dose of levofloxacin. The oral tablets may be taken without regard to food.

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