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Drug Interactions between boceprevir and elbasvir / grazoprevir

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

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Interactions between your drugs

Major

boceprevir grazoprevir

Applies to: boceprevir and elbasvir / grazoprevir

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of grazoprevir, which is a substrate of the isoenzyme. In 8 study subjects, administration of a single 100 mg dose of grazoprevir with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily) increased grazoprevir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 13%, 200% and 100%, respectively, compared to administration of grazoprevir alone. High plasma levels of grazoprevir may increase the risk of adverse effects such as alanine aminotransferase (ALT) elevations. Ketoconazole also increased the Cmax, AUC and Cmin of a single 50 mg dose of elbasvir by 29%, 80% and 89%, respectively.

MANAGEMENT: Concomitant use of elbasvir-grazoprevir with potent CYP450 3A4 inhibitors should generally be avoided.

References (1)
  1. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc
Moderate

boceprevir elbasvir

Applies to: boceprevir and elbasvir / grazoprevir

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of elbasvir, which is a substrate of the isoenzyme. In 10 study subjects, administration of elbasvir (50 mg once daily) with the potent CYP450 3A4 inhibitors atazanavir/ritonavir (300 mg/100 mg once daily) increased elbasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 4.15-fold, 4.76-fold and 6.45-fold, respectively, compared to elbasvir alone. Likewise, administration with lopinavir/ritonavir 400 mg/100 mg twice daily increased elbasvir Cmax, AUC, and Cmin by 2.87-, 3.71-, and 4.58-fold, respectively (n=10), while administration with darunavir/ritonavir 600 mg/100 mg twice daily increased elbasvir Cmax, AUC, and Cmin by 1.67-, 1.66-, and 1.82-fold, respectively (n=10). Another potent CYP450 3A4 inhibitor, ketoconazole (400 mg once daily), increased the Cmax, AUC, and Cmin of a single 50 mg dose of elbasvir by 1.29-, 1.80, and 1.89-fold, respectively (n=7).

MANAGEMENT: Concomitant use of elbasvir with potent CYP450 3A4 inhibitors should generally be avoided.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc

Drug and food interactions

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
Minor

grazoprevir food

Applies to: elbasvir / grazoprevir

Food does not appear to have clinically significant effects on the pharmacokinetics of elbasvir and grazoprevir. When a single 50 mg-100 mg dose of elbasvir-grazoprevir was administered to healthy study subjects with a high-fat meal (900 kcal; 500 kcal from fat), elbasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 15% and 11%, respectively, while grazoprevir Cmax and AUC increased by 2.8- and 1.5-fold, respectively, compared to administration under fasting conditions. According to the product labeling, elbasvir-grazoprevir may be administered with or without food.

References (1)
  1. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc

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
  • elbasvir/grazoprevir

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.

Medical Disclaimer