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Drug Interactions between fostemsavir and nirmatrelvir / ritonavir

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

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Interactions between your drugs

Moderate

ritonavir fostemsavir

Applies to: nirmatrelvir / ritonavir and fostemsavir

MONITOR: Coadministration with potent inhibitors of CYP450 3A4, P-glycoprotein (P-gp), and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of temsavir, the active moiety of fostemsavir. According to the prescribing information, temsavir is a substrate of CYP450 3A4, esterases, P-gp, and BCRP. In pharmacokinetic studies, mean temsavir peak plasma concentration (Cmax) increased by approximately 50% to 80% and systemic exposure (AUC) increased by approximately 35% to 100% when fostemsavir 600 mg twice daily was administered with various potent CYP450 3A4 inhibitors (atazanavir/ritonavir 300 mg/100 mg once daily; darunavir/ritonavir 600 mg/100 mg twice daily; darunavir/ritonavir/etravirine 600 mg/100 mg/200 mg twice daily; ritonavir 100 mg once daily; cobicistat 150 mg once daily; darunavir/cobicistat 800 mg/150 mg once daily). These changes are not considered clinically relevant. However, increased temsavir exposure may increase the risk of QT prolongation.

MANAGEMENT: No dosage adjustments are recommended for fostemsavir when used with potent CYP450 3A4, P-gp, and/or BCRP inhibitors. It may be advisable to monitor patients for increased adverse effects such as QT prolongation during coadministration, particularly in the elderly and patients with risk factors for torsade de pointes.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2020) "Product Information. Rukobia (fostemsavir)." ViiV Healthcare

Drug and food interactions

Moderate

ritonavir food

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

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

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