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Drug Interactions between glecaprevir / pibrentasvir and rifampin

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

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Interactions between your drugs

Major

rifAMPin glecaprevir

Applies to: rifampin and glecaprevir / pibrentasvir

CONTRAINDICATED: The plasma concentrations of glecaprevir may increase significantly during acute coadministration with rifampin, but decreases after chronic coadministration. Pibrentasvir plasma concentrations are not affected during acute coadministration with rifampin, but also decreases significantly after chronic coadministration. The proposed mechanism is rifampin inhibition of organic anion transporting polypeptide (OATP) 1B1-mediated hepatic uptake of glecaprevir initially, followed by induction of P-glycoprotein-mediated intestinal efflux and CYP450 3A4-mediated metabolism of glecaprevir and pibrentasvir after chronic dosing. In 12 study subjects, glecaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 6.5- and 8.6-fold, respectively, after a single 300 mg-120 mg dose of glecaprevir-pibrentasvir was administered with the first 600 mg dose of rifampin. Following multiple dosing of rifampin 600 mg once daily, however, glecaprevir Cmax and AUC decreased by 86% and 88%, respectively, while pibrentasvir Cmax and AUC decreased by 83% and 87%, respectively. High plasma levels of glecaprevir may increase the risk of adverse effects such as alanine aminotransferase (ALT) and bilirubin elevations, whereas low plasma levels of glecaprevir and pibrentasvir may reduce viral susceptibility and increase the risk of resistance development.

MANAGEMENT: Concomitant use of glecaprevir and pibrentasvir with rifampin is considered contraindicated.

References

  1. "Product Information. Mavyret (glecaprevir-pibrentasvir)." Abbott Pharmaceutical (2017):

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Drug and food interactions

Moderate

rifAMPin food

Applies to: rifampin

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References

  1. "Product Information. Rifampin (rifAMPin)." Akorn Inc (2022):
  2. "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc (2022):
  3. "Product Information. Rifadin (rifampicin)." Sanofi (2023):
  4. "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd (2024):
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE "Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/" (2024):
  6. "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc. (2019):
View all 6 references

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Moderate

glecaprevir food

Applies to: glecaprevir / pibrentasvir

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of glecaprevir and pibrentasvir. Relative to fasting conditions, mean glecaprevir systemic exposure (AUC) increased by 83% to 163% and mean pibrentasvir AUC increased by 40% to 53% when administered with moderate to high fat meals.

MANAGEMENT: Glecaprevir-pibrentasvir should be administered with food.

References

  1. "Product Information. Mavyret (glecaprevir-pibrentasvir)." Abbott Pharmaceutical (2017):

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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.

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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