Drug Interaction Report

MONITOR: Acute intake of opiates during sildenafil use may result in prolonged erections. The proposed mechanism is an opiate-induced acute increase in cyclic guanosine monophosphate concentrations in peripheral nerve endings, which can be additive with that produced by sildenafil. The interaction has been reported specifically with dihydrocodeine but could conceivably occur with other opiates. In two patients who had been using sildenafil for erectile dysfunction, prolonged erections lasting 2 to 5 hours occurred on several occasions of sildenafil use within the first week after initiation of treatment with dihydrocodeine. One patient discontinued the dihydrocodeine, whereupon his erections from sildenafil returned to normal. The other patient continued taking dihydrocodeine for an additional 2 weeks but had no further problems.

MANAGEMENT: Patients using sildenafil should be advised of the potential for prolonged erections during acute intake of opiates, and to contact their physician if problems occur. The interaction may not occur during chronic use of opiates.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including buprenorphine. 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.

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

GENERALLY AVOID: Coadministration with grapefruit juice may slightly increase the oral bioavailability and delay the onset of action of sildenafil. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a randomized, crossover study with 24 healthy male volunteers, ingestion of 250 mL of grapefruit juice one hour before and concurrently with a 50 mg dose of sildenafil increased the mean area under the plasma concentration-time curve (AUC) of sildenafil and its pharmacologically active N-desmethyl metabolite by 23% and 24%, respectively, compared to water. Peak plasma concentrations (Cmax) were unaltered, but the time to reach sildenafil Cmax was prolonged by 0.25 hour. The observed increase in sildenafil bioavailability is unlikely to be of clinical significance in most individuals. However, pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability and may be significant in the occasional susceptible patient. Indeed, one subject in the study had a 2.6-fold increase in sildenafil concentrations.

MANAGEMENT: It may be advisable to avoid administration of sildenafil with grapefruit juice to prevent potential toxicity and delay in onset of action.