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Drug Interactions between macitentan / tadalafil and modafinil

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

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Interactions between your drugs

Moderate

modafinil tadalafil

Applies to: modafinil and macitentan / tadalafil

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of tadalafil, which is primarily metabolized by the isoenzyme. Rifampin (600 mg daily), a potent CYP450 3A4 inducer, has been reported to decrease tadalafil peak plasma concentration (Cmax) and systemic exposure (AUC) from a single 10 mg dose by 46% and 88%, respectively, compared to administration of the drug alone.

MANAGEMENT: For the treatment of benign prostatic hyperplasia and erectile dysfunction, no dosage adjustment of tadalafil is warranted during coadministration with CYP450 3A4 inducers. However, the possibility of diminished pharmacologic effects of tadalafil should be considered. For the treatment of pulmonary arterial hypertension, use of tadalafil should be avoided in patients chronically taking potent inducers of CYP450 3A4.

References (3)
  1. (2003) "Product Information. Cialis (tadalafil)." Lilly, Eli and Company
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. (2009) "Product Information. Adcirca (tadalafil)." United Therapeutics Corporation
Minor

modafinil macitentan

Applies to: modafinil and macitentan / tadalafil

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 (5)
  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

Drug and food interactions

Moderate

tadalafil food

Applies to: macitentan / tadalafil

GENERALLY AVOID: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors such as tadalafil are used with alcohol, as both are mild systemic vasodilators. In clinical pharmacology studies, more subjects administered alcohol at a dose of 0.7 g/kg (equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male; consumed within 10 minutes in study subjects, providing blood alcohol levels of 0.08%) in combination with tadalafil 10 or 20 mg single doses had clinically significant decreases in blood pressure than with alcohol alone. There were reports of postural dizziness, and orthostatic hypotension was observed in some. When tadalafil 20 mg was administered with alcohol at a lower dose of 0.6 g/kg (equivalent to approximately 4 ounces of 80-proof vodka in an 80-kg male), orthostatic hypotension was not observed, dizziness occurred with similar frequency relative to alcohol alone, and the hypotensive effects of alcohol were not potentiated. Neither tadalafil nor alcohol affected the plasma concentrations of the other.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of tadalafil, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients taking tadalafil should avoid consuming large amounts of alcohol (for example, 5 units or more), which may increase the potential for orthostatic signs and symptoms including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. It may also be appropriate to avoid consuming large amounts of grapefruit juice.

References (2)
  1. (2003) "Product Information. Cialis (tadalafil)." Lilly, Eli and Company
  2. (2009) "Product Information. Adcirca (tadalafil)." United Therapeutics Corporation
Minor

modafinil food

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

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

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