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Drug Interactions between Agenerase and ixabepilone

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

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Interactions between your drugs

Moderate

amprenavir ixabepilone

Applies to: Agenerase (amprenavir) and ixabepilone

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ixabepilone, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of ixabepilone in combination with the CYP450 3A4 inhibitor ketoconazole resulted in a 79% increase in ixabepilone systemic exposure (AUC) compared to treatment without ketoconazole.

MANAGEMENT: Concomitant use of ixabepilone with potent CYP450 3A4 inhibitors should generally be avoided. If coadministration is necessary, a reduction of the ixabepilone dosage to 20 mg/m2 should be considered. Based on pharmacokinetic studies, this dosage is predicted to adjust the ixabepilone systemic exposure (AUC) to the range observed without inhibitors. However, clinical data are lacking. Following discontinuation of the potent CYP450 3A4 inhibitor, a washout period of approximately one week should be allowed before the ixabepilone dosage is adjusted upward to the indicated dosage.

References (1)
  1. (2007) "Product Information. Ixempra (ixabepilone)." Bristol-Myers Squibb

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

ixabepilone food

Applies to: ixabepilone

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ixabepilone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with ixabepilone should avoid the consumption of grapefruit or grapefruit juice.

References (1)
  1. (2007) "Product Information. Ixempra (ixabepilone)." Bristol-Myers Squibb

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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