Drug Interactions between Dilaudid Cough Syrup and ifosfamide

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydromorphone. 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: Consumption of alcohol while taking sustained-release formulations of hydromorphone may cause rapid release of the drug, resulting in high systemic levels of hydromorphone that may be potentially lethal even in opioid-tolerant patients. Alcohol appears to disrupt the extended release mechanism, causing 'dose-dumping' into the bloodstream. In 48 healthy volunteers, coadministration of a 12 mg dose of sustained-release hydromorphone with 240 mL of 40% (80 proof) alcohol resulted in a mean peak hydromorphone concentration (Cmax) approximately six times greater than when taken with water. One subject had a 16-fold increase in hydromorphone Cmax with 40% alcohol compared to water. In some subjects, coadministration with 8 ounces of 4% alcohol (equivalent to 2/3 of a typical serving of beer) resulted in almost twice the hydromorphone Cmax than when coadministered with water. The effect of alcohol was more pronounced in a fasted state.

MANAGEMENT: Patients taking sustained-release formulations of hydromorphone should not consume alcohol or use medications that contain alcohol on days of hydromorphone dosing. In general, potent narcotics such as hydromorphone should not be combined with alcohol.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may reduce the efficacy of ifosfamide, whose anticancer effect is dependent on its activation to the 4-hydroxyifosfamide metabolite via CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4 metabolism by certain compounds present in grapefruit. There are no data available about the effects of grapefruit on ifosfamide. However, in a small study, 8 patients with incurable malignancies received ifosfamide 3 g/m2 by infusion with the potent CYP450 3A4 inhibitor ketoconazole 200 mg orally twice daily for 4 days starting 1 day before the ifosfamide infusion. Ketoconazole decreased the clearance of ifosfamide by 11%, decreased systemic exposure (AUC) of the active metabolite 4-hydroxyifosfamide by 30%, and increased the AUC of the inactive but potentially neurotoxic metabolite 2-dechloroethylifosfamide by 23%, as compared to control. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

GENERALLY AVOID: Alcohol may potentiate the neurotoxic effects of ifosfamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, ifosfamide therapy may cause gastrointestinal disorders and alcohol consumption may increase nausea and vomiting.

MANAGEMENT: Given the potential for reduced efficacy of ifosfamide and increased risk of neurotoxicity and nephrotoxicity it may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with ifosfamide. In addition, patients receiving ifosfamide should be warned of the increased risk of neurotoxicity, nausea and vomiting when used in combination with alcohol. Patients should avoid or limit the consumption of alcohol during treatment with ifosfamide.