ed. No data are available.
Method of administration
For oral use.
Patients should be instructed to swallow tablets whole with food and not to chew, crush or break the tablets as it may alter the bioavailability of the agents (see section 5.2).
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Patients with severe hepatic impairment (Child-Pugh C) (see sections 4.2, 4.4, and 5.2).
Concomitant use with atazanavir containing products, atorvastatin, simvastatin, dabigatran etexilate, ethinyl oestradiol-containing products, strong P-gp and CYP3A inducers (e.g., rifampicin, carbamazepine, St. John's wort (Hypericum perforatum), phenobarbital, phenytoin, and primidone) (see section 4.5).
4.4 Special warnings and precautions for use
Hepatitis B Virus reactivation
Cases of hepatitis B virus (HBV) reactivation, some of them fatal, have been reported during or after treatment with direct-acting antiviral agents. HBV screening should be performed in all patients before initiation of treatment. HBV/HCV co-infected patients are at risk of HBV reactivation, and should, therefore, be monitored and managed according to current clinical guidelines.
Liver transplant patients
The safety and efficacy of Maviret in patients who are post-liver transplant have not yet been assessed. Treatment with Maviret in this population in accordance with the recommended posology (see section 4.2) should be guided by an assessment of the potential benefits and risks for the individual patient.
Hepatic impairment
Maviret is not recommended in patients with moderate hepatic impairment (Child-Pugh B) and is contraindicated in patients with severe hepatic impairment (Child-Pugh C) (see sections 4.2, 4.3, and 5.2).
Patients who failed a prior regimen containing an NS5A- and/or an NS3/4A-inhibitor
Genotype 1-infected (and a very limited number of genotype 4-infected) patients with prior failure on regimens that may confer resistance to glecaprevir/pibrentasvir were studied in the MAGELLAN-1 study (section 5.1). The risk of failure was, as expected, highest for those exposed to both classes. A resistance algorithm predictive of the risk for failure by baseline resistance has not been established. Accumulating double class resistance was a general finding for patients who failed re-treatment with glecaprevir/pibrentasvir in MAGELLAN-1. No re-treatment data is available for patients infected with genotypes 2, 3, 5 or 6. Maviret is not recommended for the re-treatment of patients with prior exposure to NS3/4A- and/or NS5A-inhibitors.
Drug-drug interactions
Co-administration is not recommended with several medicinal products as detailed in section 4.5.
Lactose
Maviret contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
Potential for Maviret to affect other medicinal products
Glecaprevir and pibrentasvir are inhibitors of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide (OATP) 1B1/3. Co-administration with Maviret may increase plasma concentrations of medicinal products that are substrates of P-gp (e.g. dabigatran etexilate, digoxin), BCRP (e.g. rosuvastatin), or OATP1B1/3 (e.g. atorva |
