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Drug Interactions between Malarone Pediatric and Retrovir

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

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Interactions between your drugs

Minor

zidovudine atovaquone

Applies to: Retrovir (zidovudine) and Malarone Pediatric (atovaquone / proguanil)

Coadministration with atovaquone has been shown to increase the plasma concentrations of zidovudine. The mechanism appears to be inhibition of zidovudine glucuronidation by atovaquone. In 14 HIV-infected volunteers, administration of zidovudine (200 mg every 8 hours) with atovaquone tablets (750 mg every 12 hours) resulted in a 24% decrease in zidovudine apparent oral clearance and a 35% increase in plasma zidovudine area under the concentration-time curve (AUC) compared to administration without atovaquone. Additionally, the formation of the zidovudine glucuronide metabolite was reduced in the presence of atovaquone. These changes are unlikely to be of clinical significance, although the magnitude of interaction may be increased with atovaquone suspension due to its greater bioavailability over the tablets. Zidovudine had no effect on the pharmacokinetics of atovaquone.

References

  1. "Product Information. Mepron (atovaquone)." Glaxo Wellcome PROD (2001):
  2. Taburet AM, Singlas E "Drug interactions with antiviral drugs." Clin Pharmacokinet 30 (1996): 385-401
  3. Lee BL, Tauber MG, Sadler B, Goldstein D, Chambers HF "Atovaquone inhibits the glucuronidation and increases the plasma concentrations of zidovudine." Clin Pharmacol Ther 59 (1996): 14-21

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Drug and food interactions

Moderate

atovaquone food

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

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Minor

zidovudine food

Applies to: Retrovir (zidovudine)

Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration. In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast. In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state. In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting. Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected. The clinical significance of these alterations, if any, is unknown. The product labeling states that zidovudine may be taken with or without food.

References

  1. Lotterer E, Ruhnke M, Trautman M, et al. "Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal." Eur J Clin Pharmacol 40 (1991): 305-8
  2. Unadkat JD, Collier AC, Crosby SS, et al. "Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal." AIDS 4 (1990): 229-32
  3. "Product Information. Retrovir (zidovudine)." Glaxo Wellcome PROD (2001):
  4. Sahai J, Gallicano K, Garber G, et al. "The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients." Br J Clin Pharmacol 33 (1992): 657-60
View all 4 references

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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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