Drug Interactions between atovaquone / proguanil and ritonavir
This report displays the potential drug interactions for the following 2 drugs:
- atovaquone/proguanil
- ritonavir
Interactions between your drugs
atovaquone ritonavir
Applies to: atovaquone / proguanil and ritonavir
GENERALLY AVOID: Coadministration with ritonavir may decrease the plasma concentrations of atovaquone and proguanil. The mechanism of interaction has not been established, but may involve ritonavir induction of the glucuronidation of atovaquone and the CYP450 2C19-mediated metabolism of proguanil. According to an open-label study from the Netherlands, HIV patients stabilized on antiretroviral regimens containing efavirenz (600 mg once daily; n=20), atazanavir/ritonavir (300 mg/100 mg once daily; n=19), or lopinavir/ritonavir (400 mg/100 mg twice daily or 800 mg/200 mg once daily; n=19) had significantly lower plasma concentrations of atovaquone and proguanil compared to healthy volunteers (n=18) following a single 250 mg/100 mg dose of atovaquone/proguanil. Specifically, atovaquone systemic exposure (AUC) was 46% lower in the atazanavir/ritonavir group and 74% lower in the lopinavir/ritonavir group than in the control group. Likewise, proguanil AUC was 41% and 38% lower in the atazanavir/ritonavir and lopinavir/ritonavir groups, respectively. The clinical significance is unknown. There are no published reports in the medical literature regarding atovaquone/proguanil treatment failure in HIV patients receiving ritonavir-boosted protease inhibitor regimens.
MANAGEMENT: The potential for treatment failure should be considered when atovaquone or atovaquone/proguanil is used with ritonavir. Some experts recommend avoiding concomitant use. If coadministration is required, an increased dosage of atovaquone and proguanil may be required.
References
- (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
- Van Luin M, Van der Ende ME, Richter C, et al. (2010) "Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir." AIDS, 24, p. 1223-6
ritonavir proguanil
Applies to: ritonavir and atovaquone / proguanil
GENERALLY AVOID: Coadministration with ritonavir may decrease the plasma concentrations of atovaquone and proguanil. The mechanism of interaction has not been established, but may involve ritonavir induction of the glucuronidation of atovaquone and the CYP450 2C19-mediated metabolism of proguanil. According to an open-label study from the Netherlands, HIV patients stabilized on antiretroviral regimens containing efavirenz (600 mg once daily; n=20), atazanavir/ritonavir (300 mg/100 mg once daily; n=19), or lopinavir/ritonavir (400 mg/100 mg twice daily or 800 mg/200 mg once daily; n=19) had significantly lower plasma concentrations of atovaquone and proguanil compared to healthy volunteers (n=18) following a single 250 mg/100 mg dose of atovaquone/proguanil. Specifically, atovaquone systemic exposure (AUC) was 46% lower in the atazanavir/ritonavir group and 74% lower in the lopinavir/ritonavir group than in the control group. Likewise, proguanil AUC was 41% and 38% lower in the atazanavir/ritonavir and lopinavir/ritonavir groups, respectively. The clinical significance is unknown. There are no published reports in the medical literature regarding atovaquone/proguanil treatment failure in HIV patients receiving ritonavir-boosted protease inhibitor regimens.
MANAGEMENT: The potential for treatment failure should be considered when atovaquone or atovaquone/proguanil is used with ritonavir. Some experts recommend avoiding concomitant use. If coadministration is required, an increased dosage of atovaquone and proguanil may be required.
References
- (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
- Van Luin M, Van der Ende ME, Richter C, et al. (2010) "Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir." AIDS, 24, p. 1223-6
Drug and food interactions
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
- (2001) "Product Information. Mepron (atovaquone)." Glaxo Wellcome
- (2001) "Product Information. Malarone (atovaquone-proguanil)." Glaxo Wellcome
- 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
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
- (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
Report options
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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