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Drug Interactions between Malarone Pediatric and Provigil

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

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Interactions between your drugs

Moderate

modafinil proguanil

Applies to: Provigil (modafinil) and Malarone Pediatric (atovaquone / proguanil)

MONITOR: Coadministration with modafinil (the racemate) or armodafinil (the R-enantiomer) may increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 2C19 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2C19 activity by modafinil and armodafinil. In pharmacokinetic studies, coadministration of a single 400 mg dose of armodafinil with omeprazole 40 mg increased systemic exposure to omeprazole by approximately 40%. A case report implicated modafinil in the development of clozapine toxicity characterized by dizziness, ataxia, and tachycardia. Clozapine serum levels increased from 761 ng/mL to 1400 ng/mL several weeks after initiation of modafinil therapy.

MANAGEMENT: Caution is advised if modafinil or armodafinil must be used concurrently with medications that undergo metabolism by CYP450 2C19, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever modafinil or armodafinil is added to or withdrawn from therapy.

References

  1. "Product Information. Provigil (modafinil)." Cephalon, Inc PROD (2001):
  2. Robertson P, Decory HH, Madan A, Parkinson A "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos 28 (2000): 664-71
  3. Dequardo JR "Modafinil-associated clozapine toxicity." Am J Psychiatry 159 (2002): 1243-1244
  4. "Product Information. Nuvigil (armodafinil)." Cephalon Inc (2007):
  5. Cerner Multum, Inc. "Australian Product Information." O 0
View all 5 references

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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

modafinil food

Applies to: Provigil (modafinil)

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.

References

  1. "Product Information. Provigil (modafinil)." Cephalon, Inc PROD (2001):
  2. "Product Information. Nuvigil (armodafinil)." Cephalon Inc (2007):

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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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