Drug Interactions between droperidol and entrectinib

GENERALLY AVOID: Grapefruit juice and Seville oranges may increase the plasma concentrations of entrectinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit and Seville oranges Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, itraconazole. When a single 100 mg dose of entrectinib was administered with itraconazole, entrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.7- and 6-fold, respectively. Coadministration of entrectinib with a moderate CYP450 3A4 inhibitor is predicted to increase entrectinib Cmax and AUC by 2.9- and 3-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 entrectinib may increase the risk and/or severity of adverse effects such as cognitive impairment, mood disorders, dizziness, sleep disturbances, liver enzyme elevations, hyperuricemia, congestive heart failure, edema, myocarditis, QT prolongation, vision problems, anemia, and neutropenia.

MANAGEMENT: Patients should avoid consumption of grapefruit, grapefruit juice, and Seville oranges during treatment with entrectinib.

Switch to consumer interaction data

MONITOR CLOSELY: The use of droperidol has been associated with QT interval prolongation, torsade de pointes and other serious arrhythmias, and sudden death. The concurrent administration of agents that can produce hypokalemia and/or hypomagnesemia (e.g., potassium-wasting diuretics, amphotericin B, cation exchange resins), drugs known to increase the QT interval (e.g., phenothiazines, tricyclic antidepressants, antiarrhythmic agents, etc.), certain other drugs (benzodiazepines, volatile anesthetics, intravenous opiates), or alcohol abuse may increase the risk of prolonged QT syndrome. In addition, central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking droperidol with certain other drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: The manufacturer recommends extreme caution if droperidol must be given concomitantly with these agents. The dosage of droperidol should be individualized and titrated to the desired effect. Routine vital sign and ECG monitoring is recommended. When droperidol is used in combination with other drugs that cause CNS and/or respiratory depression, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Switch to consumer interaction data