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Drug Interactions between armodafinil and sildenafil

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

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Interactions between your drugs

Minor

sildenafil armodafinil

Applies to: sildenafil and armodafinil

Coadministration with modafinil (the racemate) or armodafinil (the R-enantiomer) may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. Modafinil and armodafinil are modest inducers of CYP450 3A4, and pharmacokinetic studies suggest that their effects may be primarily intestinal rather than hepatic. Thus, clinically significant interactions would most likely be expected with drugs that have low oral bioavailability due to significant intestinal CYP450 3A4-mediated first-pass metabolism (e.g., buspirone, cyclosporine, lovastatin, midazolam, saquinavir, simvastatin, sirolimus, tacrolimus, triazolam, calcium channel blockers). However, the potential for interaction should be considered with any drug metabolized by CYP450 3A4, especially given the high degree of interpatient variability with respect to CYP450-mediated metabolism. Pharmacologic response to these drugs may be altered and should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy. Dosage adjustments may be required if an interaction is suspected.

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. Robertson P Jr, Hellriegel ET, Arora S, Nelson M "Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers." Clin Pharmacol Ther 71 (2002): 46-56
  4. Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53
  5. "Product Information. Nuvigil (armodafinil)." Cephalon Inc (2007):
View all 5 references

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Drug and food interactions

Moderate

sildenafil food

Applies to: sildenafil

GENERALLY AVOID: Coadministration with grapefruit juice may slightly increase the oral bioavailability and delay the onset of action of sildenafil. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a randomized, crossover study with 24 healthy male volunteers, ingestion of 250 mL of grapefruit juice one hour before and concurrently with a 50 mg dose of sildenafil increased the mean area under the plasma concentration-time curve (AUC) of sildenafil and its pharmacologically active N-desmethyl metabolite by 23% and 24%, respectively, compared to water. Peak plasma concentrations (Cmax) were unaltered, but the time to reach sildenafil Cmax was prolonged by 0.25 hour. The observed increase in sildenafil bioavailability is unlikely to be of clinical significance in most individuals. However, pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability and may be significant in the occasional susceptible patient. Indeed, one subject in the study had a 2.6-fold increase in sildenafil concentrations.

MANAGEMENT: It may be advisable to avoid administration of sildenafil with grapefruit juice to prevent potential toxicity and delay in onset of action.

References

  1. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. "Effects of grapefruit juice on the pharmacokinetics of sildenafil." Clin Pharmacol Ther 71 (2002): 21-29

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Minor

armodafinil food

Applies to: armodafinil

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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