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Drug Interactions between eplerenone and Provigil

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

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Interactions between your drugs

Minor

modafinil eplerenone

Applies to: Provigil (modafinil) and eplerenone

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to these drugs may be altered and should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy.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. (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
  2. Robertson P, Decory HH, Madan A, Parkinson A (2000) "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos, 28, p. 664-71
  3. Robertson P Jr, Hellriegel ET, Arora S, Nelson M (2002) "Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers." Clin Pharmacol Ther, 71, p. 46-56
  4. Doherty MM, Charman WN (2002) "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet, 41, p. 235-53
  5. (2007) "Product Information. Nuvigil (armodafinil)." Cephalon Inc
View all 5 references

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Drug and food interactions

Major

eplerenone food

Applies to: eplerenone

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

References

  1. (2002) "Product Information. Inspra (eplerenone)." Searle
  2. (2021) "Product Information. Eplerenone (eplerenone)." MSN Laboratories Europe Ltd
  3. (2023) "Product Information. Eplerenone (Apotex) (eplerenone)." Apotex Pty Ltd

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

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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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