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Drug Interactions between boceprevir and Crixivan

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

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Interactions between your drugs

Moderate

indinavir boceprevir

Applies to: Crixivan (indinavir) 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

indinavir food

Applies to: Crixivan (indinavir)

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References (3)
  1. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S (1998) "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother, 42, p. 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R (2001) "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol, 41, p. 435-42
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:

  • boceprevir
  • Crixivan (indinavir)

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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