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Drug Interactions between givosiran and ritonavir

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

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Interactions between your drugs

Moderate

ritonavir givosiran

Applies to: ritonavir and givosiran

MONITOR: Coadministration with givosiran may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 1A2 and/or CYP450 2D6. The proposed mechanism is decreased clearance due to givosiran-mediated inhibition of CYP450 1A2 and 2D6 isoenzymes. Concomitant administration of a single subcutaneous dose of givosiran (2.5 mg/kg) increased the systemic exposure (AUC) and peak plasma concentration (Cmax) of caffeine (sensitive CYP450 1A2 substrate) by 3.1-fold and 1.3-fold, respectively, and dextromethorphan (sensitive CYP450 2D6 substrate) by 2.4-fold and 2.0-fold, respectively.

MANAGEMENT: Caution and monitoring are recommended when givosiran is given with drugs that are substrates of CYP450 1A2 and/or 2D6. Concomitant use should generally be avoided with CYP450 1A2 or 2D6 substrates that have a narrow therapeutic range where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, the dosage of the CYP450 1A2 or 2D6 substrate should be reduced according to approved product labeling or clinical response and tolerance. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever givosiran is added to or withdrawn from therapy with these drugs.

References (1)
  1. (2019) "Product Information. Givlaari (givosiran)." Alnylam Pharmaceuticals

Drug and food interactions

Moderate

ritonavir food

Applies to: 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.

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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