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Drug Interactions between Norvir and Tivicay

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

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Interactions between your drugs

Minor

ritonavir dolutegravir

Applies to: Norvir (ritonavir) and Tivicay (dolutegravir)

Theoretically, coadministration with inhibitors of UGT1A or CYP450 3A4 isoenzymes may increase the plasma concentrations of dolutegravir, which is primarily metabolized by UGT1A1 with some contribution from CYP450 3A4. Dolutegravir is also a substrate of UGT1A3, UGT1A9, and P-glycoprotein in vitro. Potent CYP450 3A4 inhibitors such as boceprevir (800 mg every 8 hours) and telaprevir (750 mg every 8 hours) had no significant effects on the pharmacokinetics of dolutegravir given at 50 mg once daily. The interaction has not been studied or reported with UGT1A1 inhibitors such as nilotinib, regorafenib, and sorafenib. However, it is possible that simultaneous inhibition of UGT1A1 and CYP450 3A4 may lead to a clinically significant interaction with dolutegravir. In 12 study subjects, administration of dolutegravir (30 mg once daily) with the dual UGT1A1 and CYP450 3A4 inhibitor, atazanavir (400 mg once daily), increased dolutegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin; 24 hours postdose) by 50%, 91% and 180%, respectively, compared to administration without atazanavir. When the same dosage of dolutegravir was given with atazanavir/ritonavir 300 mg/100 mg once daily, the Cmax, AUC and Cmin of dolutegravir increased by 34%, 62% an 121%, respectively. Because safety data regarding increased dolutegravir exposures are limited, caution may be advisable if dolutegravir is used in combination with both a UGT1A1 inhibitor and a CYP450 3A4 inhibitor.

References

  1. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):

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Drug and food interactions

Moderate

ritonavir food

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

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Minor

dolutegravir food

Applies to: Tivicay (dolutegravir)

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.

References

  1. "Product Information. Tivicay (dolutegravir)." ViiV Healthcare (2013):

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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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