Drug Interactions between oliceridine and Retevmo

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selpercatinib. 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 a single dose of selpercatinib (160 mg) was coadministered with multiple doses of itraconazole (200 mg once daily), a potent CYP450 3A4 inhibitor, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 30% and 133%, respectively. Based on pharmacokinetic modeling, administration of multiple doses of selpercatinib (160 mg twice daily) with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem (60 mg three times daily), fluconazole (200 mg once daily), or verapamil (80 mg three times daily) is predicted to increase selpercatinib Cmax by 46% to 76% and AUC by 60% to 99%. 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 selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis).

MANAGEMENT: Until further information is available, it may be advisable for patients to limit or avoid consumption of grapefruit and grapefruit juice during treatment with selpercatinib.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oliceridine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentrations of oliceridine by inhibiting the CYP450 3A4-mediated metabolism of oliceridine, although the interaction has not been studied. 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oliceridine. Any history of alcohol or illicit drug use should be considered when prescribing oliceridine, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oliceridine should preferably avoid the consumption of grapefruit and grapefruit juice.