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Drug Interactions between atovaquone / proguanil and remdesivir

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

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Interactions between your drugs

Moderate

atovaquone remdesivir

Applies to: atovaquone / proguanil and remdesivir

GENERALLY AVOID: Concomitant use of remdesivir with other agents that are known to induce hepatotoxicity may theoretically increase the risk of liver injury. Data from investigational use and clinical studies suggest that remdesivir may be associated with hepatotoxic effects. Transient treatment-emergent Grade 1 or Grade 2 elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed during multiple-dose Phase 1 studies in healthy volunteers. Some ALT and AST elevations were associated with graded PT elevations, but there were no graded changes in international normalized ratio (INR). Laboratory results for these subjects indicated no systemic sign of drug reaction. Liver transaminase elevations, including grade 3 or higher, were also observed in some participants during compassionate or investigational use of remdesivir and clinical studies for the treatment of COVID-19. The mechanism of potential hepatotoxicity is unknown and the contribution of remdesivir is difficult to determine, as transaminase elevations have also been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of remdesivir.

MANAGEMENT: Until more information is available, concomitant use of remdesivir with known hepatotoxic drugs should be avoided when possible. Liver function should be evaluated prior to starting remdesivir and monitored during treatment as clinically appropriate. Remdesivir should not be initiated in patients with ALT greater than or equal to 5 times the upper limit of normal (ULN) at baseline. Likewise, remdesivir should be discontinued immediately if ALT increases to 5 times ULN or greater during treatment (may be restarted when ALT falls below 5 times ULN), or if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. Gilead Sciences, Inc (2020) About Remdesivir. https://www.gilead.com/purpose/advancing-global-health/covid-19/about-remdesivir
  4. European Medicines Agency (2020) Summary on compassionate use. Remdesivir Gilead. https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf
  5. US Food and Drug Administration (2020) Fact sheet for health care providers emergency use authorization (EUA) of remdesivir (GS-5734TM) https://www.fda.gov/media/137566/download
View all 5 references

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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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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.

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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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