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Drug Interactions between belzutifan and Paxlovid

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

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Interactions between your drugs

Moderate

ritonavir belzutifan

Applies to: Paxlovid (nirmatrelvir / ritonavir) and belzutifan

MONITOR: Coadministration of belzutifan with inducers of CYP450 2C19 may decrease the plasma concentrations and pharmacologic effects of belzutifan. The proposed mechanism is induction of CYP450 2C19, one of the primary pathways for the metabolic clearance of belzutifan. Clinical data are not available.

MANAGEMENT: Caution and clinical monitoring are recommended whenever belzutifan is prescribed in combination with a CYP450 2C19 inducer. Pharmacologic response to belzutifan should be monitored more closely whenever a CYP450 2C19 inducer is added to or withdrawn from therapy.

References

  1. (2022) "Product Information. Welireg (belzutifan)." Merck Sharp & Dohme (Australia) Pty Ltd

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Moderate

belzutifan nirmatrelvir

Applies to: belzutifan and Paxlovid (nirmatrelvir / ritonavir)

MONITOR: Coadministration with drugs that are inducers of CYP450 3A4 may decrease the plasma concentrations of nirmatrelvir which is primarily metabolized by the isoenzyme. According to the manufacturer, coadministration of nirmatrelvir-ritonavir (300 mg-100 mg twice daily for 5 doses) with the potent CYP450 3A4 inducer carbamazepine (300 mg twice daily for 16 doses) (n=9) decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of nirmatrelvir by approximately 55% and 43%, respectively. Data are unavailable for other, less potent inducers. In addition, the plasma concentrations and pharmacologic effects of the concomitant inducer may be affected; however, clinical data are lacking.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, nirmatrelvir-ritonavir should be used cautiously with agents that induce CYP450 3A4. Antiviral response should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy.

References

  1. US Food and Drug Administration (2021) FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION FOR PAXLOVID. https://www.fda.gov/media/155050/download

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Drug and food interactions

Moderate

ritonavir food

Applies to: Paxlovid (nirmatrelvir / ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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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.

See also

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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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