Drug Interaction Report

MONITOR: Coadministration with viloxazine may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 and/or CYP450 2D6 leading to increased toxicity. The proposed mechanism is decreased clearance due to viloxazine-mediated inhibition of CYP450 3A4 and/or CYP450 2D6. The product labeling describes viloxazine as a weak inhibitor of CYP450 3A4 and CYP450 2D6.

MANAGEMENT: Caution is advised if viloxazine is used concomitantly with drugs that are substrates of CYP450 3A4 and/or CYP450 2D6, particularly those with a narrow therapeutic range. Monitor for adverse reactions of the CYP450 3A4 or CYP450 2D6 substrate and adjust dosages as needed.

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.