Drug Interactions between Farydak and Ofev

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of nintedanib. After food intake, nintedanib exposure increased by approximately 20% compared to administration under fasted conditions. Absorption was also delayed, as indicated by an increase in the median time to reach maximum plasma concentration (Tmax) from 2 hours in the fasted state to approximately 4 hours under fed conditions, irrespective of the type of food ingested. In an in vitro study, mixing nintedanib capsules with a small amount of apple sauce or chocolate pudding for up to 15 minutes did not have any impact on their pharmaceutical quality, but swelling and deformation of the capsules were observed with longer exposure time due to water uptake of the gelatin capsule shell. Therefore, administration with soft food would not be expected to alter the clinical effect of nintedanib when taken immediately.

GENERALLY AVOID: Grapefruit and grapefruit juice may increase the plasma concentrations of nintedanib, which has been shown to be a substrate of the P-glycoprotein (P-gp) efflux transporter and a minor substrate of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of both P-gp-mediated efflux in the gut wall as well as CYP450 3A4-mediated first-pass metabolism in the intestinal tract by certain compounds present in grapefruit.

MANAGEMENT: Nintedanib should be administered with food to reduce the incidence of gastrointestinal effects. Nintedanib capsules may be taken with a small amount (teaspoonful) of cold or room temperature soft food, such as apple sauce or chocolate pudding, and must be swallowed whole (unchewed) immediately, to ensure the capsule stays intact. Food containing grapefruit, grapefruit juice, or Seville oranges should be avoided during treatment with nintedanib.

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GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of panobinostat. 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 panobinostat may increase the risk of adverse effects such as nausea, vomiting, diarrhea, anorexia, peripheral edema, cardiotoxicity, ECG abnormalities, electrolyte disturbances, bleeding complications, hepatotoxicity, and myelosuppression.

Food may delay the rate of absorption of panobinostat, but does not significantly affect the overall extent of absorption. When a single oral dose of panobinostat was administered to 36 patients with advanced cancer 30 minutes after a high-fat meal, panobinostat peak plasma concentration (Cmax) and systemic exposure (AUC) were approximately 44% and 16% lower, respectively, compared to administration under fasting conditions. The median time to maximum concentration (Tmax) was prolonged by 2.5 hours.

MANAGEMENT: Patients should avoid consumption of grapefruit or grapefruit juice during treatment with panobinostat. The manufacturer also recommends avoiding star fruit, Seville oranges, pomegranate, and pomegranate juice. Panobinostat may be administered with or without food.

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