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Drug Interactions between rifapentine and simeprevir

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

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Interactions between your drugs

Major

rifapentine simeprevir

Applies to: rifapentine and simeprevir

GENERALLY AVOID: Coadministration with potent and some moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of simeprevir, which is primarily metabolized by the isoenzyme. In 18 healthy study subjects administered simeprevir (200 mg once daily) in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily) for 7 days, mean simeprevir peak plasma concentration (Cmax) increased by 31% but systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 48% and 92%, respectively. Likewise, when simeprevir (150 mg once daily) was given with the moderate inducer efavirenz (600 mg once daily) to 23 healthy subjects for 14 days, mean simeprevir Cmax, AUC and Cmin decreased by 51%, 71% and 91%, respectively. Simeprevir had no significant effects on the pharmacokinetics of efavirenz or rifampin, but increased the AUC of metabolite 25-desacetyl-rifampin by 24%.

MANAGEMENT: The use of simeprevir in combination with potent and some moderate CYP450 3A4 inducers such as carbamazepine, dexamethasone, efavirenz, enzalutamide, eslicarbazepine, etravirine, nevirapine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifamycins, St. John's wort, and tipranavir should generally be avoided.

References

  1. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
  2. (2013) "Product Information. Olysio (simeprevir)." Janssen Pharmaceuticals

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Drug and food interactions

Moderate

rifapentine food

Applies to: rifapentine

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.

References

  1. (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
  2. (2021) "Product Information. Priftin (rifapentine)." sanofi-aventis

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Moderate

simeprevir food

Applies to: simeprevir

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of simeprevir, although the type of food does not seem to matter. In healthy study subjects, administration of simeprevir after a high-fat, high-caloric (928 kcal) breakfast increased systemic exposure (AUC) by 61% and delayed absorption by 1 hour, while administration after a normal caloric (533 kcal) breakfast increased AUC by 69% and delayed absorption by 1.5 hours.

MANAGEMENT: To ensure maximal oral absorption, simeprevir should be administered with food.

References

  1. (2013) "Product Information. Olysio (simeprevir)." Janssen Pharmaceuticals

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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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