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Drug Interactions between Agenerase and boceprevir

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

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Interactions between your drugs

Moderate

amprenavir boceprevir

Applies to: Agenerase (amprenavir) and boceprevir

MONITOR: Coadministration of boceprevir and some ritonavir-boosted protease inhibitor regimens has been associated with decreased plasma concentrations of both boceprevir and the protease inhibitors. The mechanism of interaction has not been described. In a pharmacokinetic study of 39 healthy volunteers, boceprevir reduced the mean trough plasma concentrations (Cmin) of ritonavir-boosted atazanavir, darunavir, and lopinavir by 49%, 59%, and 43%, respectively. Mean reductions of 34% to 44% were observed in the systemic exposure (AUC) and 25% to 36% were observed in the peak concentration (Cmax) of atazanavir, lopinavir, and darunavir. Conversely, ritonavir-boosted atazanavir did not alter the AUC of boceprevir, whereas ritonavir-boosted darunavir and lopinavir decreased the AUC of boceprevir by 32% and 45%, respectively. When boceprevir (400 mg three times daily for 15 days) was given in combination with ritonavir alone (100 mg once daily for 12 days), boceprevir Cmax and AUC decreased by 27% and 19%, respectively. Data are currently unavailable regarding a potential interaction between boceprevir and other protease inhibitors, whether alone or ritonavir-boosted.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, caution is advised if boceprevir is used in combination with ritonavir-boosted protease inhibitor regimens. Patients coinfected with chronic HCV and HIV who have been started on one of these combinations should be closely monitored for treatment response and potential HCV and HIV virologic rebound. The safety and efficacy of boceprevir has not been established in the HCV/HIV coinfected population. As such, the manufacturer does not recommend the coadministration of boceprevir and ritonavir-boosted HIV protease inhibitors.

References (2)
  1. (2011) "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation
  2. FDA. U.S. Food and Drug Administration (2012) FDA Drug Safety Communication: Important drug interactions between (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs. http://www.fda.gov/Drugs/DrugSafety/ucm291119.htm

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

boceprevir food

Applies to: boceprevir

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.

References (1)
  1. (2011) "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Protease inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'protease inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'protease inhibitors' category:

  • Agenerase (amprenavir)
  • boceprevir

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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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