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Drug Interactions between atovaquone / proguanil and sulfamethoxazole

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

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Interactions between your drugs

Minor

sulfamethoxazole atovaquone

Applies to: sulfamethoxazole and atovaquone / proguanil

Coadministration with atovaquone has been shown to slightly decrease the plasma concentrations of trimethoprim (TMP) and sulfamethoxazole (SMX). The mechanism of interaction is unknown. In six HIV-infected adult volunteers, administration of TMP-SMX (160 mg-800 mg orally twice daily) with atovaquone suspension (500 mg orally once daily) resulted in a 17% and 8% decrease in average steady-state concentrations of TMP and SMX in plasma, respectively, compared to administration without atovaquone. These changes are unlikely to be of clinical significance. TMP-SMX had no effect on the pharmacokinetics of atovaquone.

References (1)
  1. (2001) "Product Information. Mepron (atovaquone)." Glaxo Wellcome

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 (3)
  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
Moderate

sulfamethoxazole food

Applies to: sulfamethoxazole

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References (2)
  1. Heelon MW, White M (1998) "Disulfiram-cotrimoxazole reaction." Pharmacotherapy, 18, p. 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA (2020) "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother, 64, e02167-19

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antipneumocystis agents

Therapeutic duplication

The recommended maximum number of medicines in the 'antipneumocystis agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antipneumocystis agents' category:

  • atovaquone/proguanil
  • sulfamethoxazole

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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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