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Drug Interactions between Agenerase and etravirine

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

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Interactions between your drugs

Moderate

amprenavir etravirine

Applies to: Agenerase (amprenavir) and etravirine

GENERALLY AVOID: Coadministration of etravirine and protease inhibitors without concomitant ritonavir as a pharmacokinetic booster may produce significant alterations in plasma concentrations of the protease inhibitor. Etravirine is an inducer of CYP450 3A4 and inhibitor of CYP450 2C19 and 2C9, thus it may variously affect the metabolism and clearance of protease inhibitors. In unboosted pharmacokinetic regimens, etravirine has reduced plasma levels of atazanavir and indinavir and increased levels of amprenavir and nelfinavir. However, significant interactions affecting either etravirine and/or protease inhibitor plasma concentrations have also been observed with boosted regimens, including atazanavir/ritonavir, fosamprenavir/ritonavir, and tipranavir/ritonavir.

MANAGEMENT: Protease inhibitors should not be prescribed with etravirine in the absence of low-dose ritonavir as a pharmacokinetic booster.

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

Drug and food interactions

Moderate

amprenavir food

Applies to: Agenerase (amprenavir)

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References (2)
  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM (2002) "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother, 46, p. 1589-1590
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

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