in transport and metabolism, including direct and indirect bilirubin. No subjects experienced jaundice and total bilirubin levels decreased after completing MAVYRET.
7 DRUG INTERACTIONS
7.1 Mechanisms for the Potential Effect of MAVYRET on Other Drugs
Glecaprevir and pibrentasvir are inhibitors of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide (OATP) 1B1/3. Coadministration with MAVYRET may increase plasma concentration of drugs that are substrates of P-gp, BCRP, OATP1B1 or OATP1B3. Glecaprevir and pibrentasvir are weak inhibitors of cytochrome P450 (CYP) 3A, CYP1A2, and uridine glucuronosyltransferase (UGT) 1A1.
Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment, including treatment with MAVYRET. If MAVYRET is coadministered with warfarin, close monitoring of INR values is recommended during treatment and post-treatment follow-up.
7.2 Mechanisms for the Potential Effect of Other Drugs on MAVYRET
Glecaprevir and pibrentasvir are substrates of P-gp and/or BCRP. Glecaprevir is a substrate of OATP1B1/3. Coadministration of MAVYRET with drugs that inhibit hepatic P-gp, BCRP, or OATP1B1/3 may increase the plasma concentrations of glecaprevir and/or pibrentasvir.
Coadministration of MAVYRET with drugs that induce P-gp/CYP3A may decrease glecaprevir and pibrentasvir plasma concentrations.
Carbamazepine, efavirenz, and St. John’s wort may significantly decrease plasma concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect of MAVYRET. The use of these agents with MAVYRET is not recommended [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].
7.3 Established and Other Potential Drug Interactions
TABLE 5 provides the effect of MAVYRET on concentrations of coadministered drugs and the effect of coadministered drugs on glecaprevir and pibrentasvir [see Contraindications (4) and Clinical Pharmacology (12.3)].
Table 5. Potentially Significant Drug Interactions Identified in Drug Interaction Studies
Concomitant
Drug Class:
Drug Name Effect on
Concentration Clinical Comments
Antiarrhythmics:
Digoxin ↑ digoxin Measure serum digoxin concentrations before initiating MAVYRET. Reduce digoxin concentrations by decreasing the dose by approximately 50% or by modifying the dosing frequency and continue monitoring.
Anticoagulants:
Dabigatran etexilate ↑ dabigatran If MAVYRET and dabigatran etexilate are coadministered, refer to the dabigatran etexilate prescribing information for dabigatran etexilate dose modifications in combination with P-gp inhibitors in the setting of renal impairment.
Anticonvulsants:
Carbamazepine ↓ glecaprevir
↓ pibrentasvir Coadministration may lead to reduced therapeutic effect of MAVYRET and is not recommended.
Antimycobacterials:
Rifampin ↓ glecaprevir
↓ pibrentasvir Coadministration is contraindicated because of potential loss of therapeutic effect [see Contraindications (4)].
Ethinyl Estradiol-Containing Products:
Ethinyl estradiol-containing
medications such as
combined oral contraceptives ↔ glecaprevir
↔ pibrentasvir Coadministration of MAVYRET may increase the risk of ALT elevations and is not recommended.
Herbal Product |
