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Drug Interactions between belzutifan and sildenafil

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

sildenafil belzutifan

Applies to: sildenafil and belzutifan

GENERALLY AVOID: Coadministration with belzutifan may decrease the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 3A4. The interaction may be significant for sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index. In addition, the extent of the decrease in concentration and effects may be more pronounced in patients who are dual uridine diphosphate glucuronosyltransferase (UGT) 2B17 and CYP450 2C19 poor metabolizers. The proposed mechanism is increased clearance due to belzutifan-mediated induction of CYP450 3A4. Concomitant use of belzutifan (120 mg once daily) with midazolam (a sensitive CYP450 3A4 substrate) decreased the midazolam systemic exposure (AUC) and peak plasma concentration (Cmax) by 40% and 34%, respectively. In patients with higher belzutifan concentrations (e.g., dual UGT 2B17 and CYP450 2C19 poor metabolizers) the AUC of midazolam is predicted to decrease by up to 70%.

MANAGEMENT: Use of belzutifan 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) should generally be avoided. If coadministration is unavoidable, patients should be monitored for diminished therapeutic effects. Clinical and laboratory monitoring should be considered whenever belzutifan is added to or withdrawn from therapy with these drugs, and the dosage of the sensitive CYP450 3A4 substrate drug adjusted as necessary.

References (1)
  1. (2021) "Product Information. Welireg (belzutifan)." Merck & Co., Inc

Drug and food interactions

Moderate

sildenafil food

Applies to: sildenafil

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.

References (1)
  1. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. (2002) "Effects of grapefruit juice on the pharmacokinetics of sildenafil." Clin Pharmacol Ther, 71, p. 21-29

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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