Drug Interactions between Mepron and oxycodone

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. 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 juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, 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 oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.

ADJUST DOSING INTERVAL: Food, particularly high-fat food, significantly enhances the oral absorption and bioavailability of atovaquone. In 16 healthy volunteers, administration of a single 750 mg dose of atovaquone suspension following a standard breakfast (23 g fat: 610 kCal) resulted in an approximately 3.4-fold increase in the mean peak plasma concentration (Cmax) and a 2.5-fold increase in the mean area under the plasma concentration-time curve (AUC) of atovaquone compared to administration following an overnight fast. In a study consisting of 19 HIV-infected volunteers receiving atovaquone suspension 500 mg/day, Cmax and AUC of atovaquone increased by 72% and 66%, respectively, in the fed state relative to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atovaquone products (suspension, tablet, or in combination with proguanil) should be administered with a meal or milky drink, or enteral nutrition at the same time(s) each day. Because plasma atovaquone concentrations have been shown to correlate with the likelihood of successful treatment and in some cases, survival, alternative therapies may be appropriate for patients who have difficulty taking atovaquone with food.