Drug Interaction Report

MONITOR: Coadministration with fenofibrate may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of CYP450 2C19, 2A6, and 2C9 isoenzymes. The proposed mechanism, based on in vitro data, is decreased clearance due to fenofibrate-mediated inhibition of CYP450 2C19, 2A6, and 2C9.

MANAGEMENT: Until more information is available, caution is advised if fenofibrate is used concomitantly with drugs that are substrates of CYP450 2C19, 2A6, or 2C9 isoenzymes, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever fenofibrate is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. 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 some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.