Drug Interaction Report

GENERALLY AVOID: Coadministration with ticagrelor may increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 3A4 by ticagrelor, which is a mild inhibitor. The interaction may be significant for sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index.

MANAGEMENT: Concomitant use of ticagrelor with sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index (e.g., cisapride, ergot alkaloids, colchicine, fentanyl, macrolide immunosuppressants, midazolam, pimozide, triazolam, vinca alkaloids) is not recommended.

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.