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Drug Interactions between etravirine and macitentan / tadalafil

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

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Interactions between your drugs

Moderate

tadalafil etravirine

Applies to: macitentan / tadalafil and etravirine

MONITOR: Coadministration with etravirine may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is accelerated clearance due to induction of CYP450 3A4 activity by etravirine. In 15 study subjects coadministered etravirine and the CYP450 3A4 substrate sildenafil (50 mg single dose), sildenafil peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 45% and 57%, respectively, while Cmax and AUC of its active N-desmethyl metabolite decreased by 25% and 41%, respectively.

MANAGEMENT: Caution is advised if etravirine must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever etravirine is added to or withdrawn from therapy.

References (1)
  1. (2008) "Product Information. Intelence (etravirine)." Ortho Biotech Inc
Moderate

etravirine macitentan

Applies to: etravirine and macitentan / tadalafil

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of macitentan, which is primarily metabolized by the isoenzyme. In ten healthy male subjects pretreated with macitentan (30 mg initially, followed by 10 mg once daily) for 5 days, coadministration with the potent CYP450 3A4 inducer rifampin (600 mg once daily) on days 6 through 12 reduced macitentan systemic exposure (AUC) by 79% and trough plasma concentration (Cmin) by 93% compared to macitentan administered alone. There was no significant effect on the AUC of the active metabolite, which has been reported to be approximately 5-fold less potent than macitentan in vitro, but whose systemic exposure in human is 2.5-fold higher than that of macitentan.

MANAGEMENT: Caution is advised when macitentan is used with CYP450 3A4 inducers. The possibility of diminished therapeutic effects should be considered.

References (2)
  1. (2013) "Product Information. Opsumit (macitentan)." Actelion Pharmaceuticals US Inc
  2. Bruderer S, Aanismaa P, Homery MC, et al. (2012) "Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist." AAPS J, 14, p. 68-78

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
Moderate

etravirine food

Applies to: etravirine

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.

References (1)
  1. (2008) "Product Information. Intelence (etravirine)." Ortho Biotech 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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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