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Drug Interactions between atovaquone / proguanil and rifapentine

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

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Interactions between your drugs

Moderate

atovaquone rifapentine

Applies to: atovaquone / proguanil and rifapentine

GENERALLY AVOID: Coadministration with a rifamycin may decrease the plasma concentrations of atovaquone. The exact mechanism is unknown but may be related to the enzyme-inducing effects of rifamycins. In 13 HIV-infected volunteers, administration of atovaquone suspension (750 mg orally every 12 hours) with rifampin (600 mg orally every 24 hours) resulted in a 52% decrease in the average steady-state plasma atovaquone concentration and a 39% reduction in atovaquone half-life (from 82 hours to 50 hours) compared to administration without rifampin. Similarly, concomitant administration of rifabutin has been shown to reduce atovaquone plasma concentrations by approximately 34%.

MANAGEMENT: The use of atovaquone in combination with rifampin or rifabutin is not recommended. The same precaution may be applicable to rifapentine, although clinical data are lacking.

References

  1. (2001) "Product Information. Mepron (atovaquone)." Glaxo Wellcome
  2. Goodwin SD, Fish DN (1995) "Criteria for use of atovaquone oral suspension in adult inpatients and outpatients." Am J Health Syst Pharm, 52, p. 2460-2
  3. (2001) "Product Information. Malarone (atovaquone-proguanil)." Glaxo Wellcome

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Drug and food interactions

Moderate

atovaquone food

Applies to: atovaquone / proguanil

ADJUST DOSING INTERVAL: Food, particularly high-fat food, significantly enhances the oral absorption and bioavailability of atovaquone. In 16 healthy volunteers, administration of a single 750 mg dose of atovaquone suspension following a standard breakfast (23 g fat: 610 kCal) resulted in an approximately 3.4-fold increase in the mean peak plasma concentration (Cmax) and a 2.5-fold increase in the mean area under the plasma concentration-time curve (AUC) of atovaquone compared to administration following an overnight fast. In a study consisting of 19 HIV-infected volunteers receiving atovaquone suspension 500 mg/day, Cmax and AUC of atovaquone increased by 72% and 66%, respectively, in the fed state relative to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atovaquone products (suspension, tablet, or in combination with proguanil) should be administered with a meal or milky drink, or enteral nutrition at the same time(s) each day. Because plasma atovaquone concentrations have been shown to correlate with the likelihood of successful treatment and in some cases, survival, alternative therapies may be appropriate for patients who have difficulty taking atovaquone with food.

References

  1. (2001) "Product Information. Mepron (atovaquone)." Glaxo Wellcome
  2. (2001) "Product Information. Malarone (atovaquone-proguanil)." Glaxo Wellcome
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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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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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

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