Drug Interactions between Acid Reducer-Cimetidine and Percocet 7.5/325

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.

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GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

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Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

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Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

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H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

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