Drug Interactions between Phenytoin Sodium, Prompt and repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and adverse effects of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4, and is also a substrate of P-gp in vitro. 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 repotrectinib and grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Drug interaction studies have shown that the administration of repotrectinib with itraconazole, a potent CYP450 3A4 and P-gp inhibitor, increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of repotrectinib by 1.7-fold and 5.9-fold, 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 repotrectinib may increase the risk of adverse reactions such as dizziness, fatigue, cognitive disorders, ataxia, dysgeusia, peripheral neuropathy, muscular weakness, and dyspnea as well as more serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, myalgia with creatinine phosphokinase (CPK) elevation, hyperuricemia, and skeletal fractures.

MANAGEMENT: The manufacturer advises that concomitant use of repotrectinib with grapefruit, grapefruit juice, or supplements that contain grapefruit should be avoided.

Phenytoin levels may decrease when the suspension is given with enteral feedings. This could lead to a loss of seizure control. You could interrupt the feeding for 2 hours before and after the phenytoin dose. Alternatively, you may give the phenytoin suspension diluted in water and flush the tube with water after administration. These would make it easier for your body to absorb the medication. However, this still may not entirely avoid the interaction and may not always be feasible. You should have your phenytoin levels checked upon starting and stopping of enteral feedings. In addition, using phenytoin together with food may alter the effects of phenytoin. Contact your doctor if you experience worsening of seizure control or symptoms of toxicity, including twitching eye movements, slurred speech, loss of balance, tremor, muscle stiffness or weakness, nausea, vomiting, feeling light-headed, fainting, and slow or shallow breathing. If your doctor does prescribe these medications together, you may need a dose adjustment or special test to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Ask your doctor before making any changes to your therapy.

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