Maviret

/ AbbVie

The recommended dose is 300 mg/120 mg (three 100 mg/40 mg tablets), taken orally, once daily with food.
The recommended treatment durations for HCV genotype 1, 2, 3, 4, 5, or 6 infected patients with compensated liver disease (with or without cirrhosis):
Recommended  treatment duration for patients without prior HCV therap:
All HCV genotypes with NO cirrhosis – 8 weeks, patients with all  HCV genotypes WITH cirrhosis-12 weeks.
Recommended treatment duration for patients who failed prior therapy with peg-IFN + ribavirin +/- sofosbuvir, or sofosbuvir + ribavirin:
Genotype 1, 2, 4-6 with NO cirrhosis: 8 weeks, patients WITH cirrhosis: 12 weeks.
Genotype GT 3 WITH/WITHOUT cirrhosis: 16 weeks.
Missed dose: In case of missed dose, the prescribed dose can be taken within 18 hours after the time it was supposed to be taken. If more than 18 hours have passed the missed dose should not be taken and the patient should take the next dose per the usual dosing schedule. Patients should be instructed not to take a double dose.
If vomiting occurs within 3 hours of dosing, an additional dose of the drug should be taken. If vomiting occurs more than 3 hours after dosing, an additional dose of this drug is not needed.
Elderly: No dose adjustment is required in elderly patients.
Renal impairment: No dose adjustment is required in patients with any degree of renal impairment including patients on dialysis.
Hepatic impairment: No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh A).
The drug is not recommended in patients with moderate hepatic impairment (Child Pugh-B) and is contraindicated in patients with severe hepatic impairment (Child-Pugh C).
Liver transplant patients: The drug  may be used for a minimum of 12 weeks in liver transplant recipients. 16 week treatment duration should be considered in genotype 3-infected patients who are treatment experienced with peg-IFN + ribavirin +/- sofosbuvir, or sofosbuvir + ribavirin.
Patients with HIV-1 Co-infection: See prescribing information for full details.
Paediatric population: The safety and efficacy of this drug in children and adolescents aged less than 18 years have not yet been established. No data are available.

Treatment of chronic hepatitis C virus (HCV) infection in adults.

Hypersensitivity to the active substances or to any of the excipients.
Patients with severe hepatic impairment (Child-Pugh C).
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).

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 this drug in patients who are post-liver transplant have not yet been assessed. See prescribing information for full details.
Hepatic impairment: This drug is not recommended in patients with moderate hepatic impairment (Child-Pugh B) and is contraindicated in patients with severe hepatic impairment (Child-Pugh C).
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. 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. This drug 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. See prescribing information for full details.
Lactose: The drug contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
See prescribing information for full details.

Very common: Headache, fatigue.
Common: Diarrhea, nausea, asthenia.
See prescribing information for full details.

Potential for this drug 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 this drug 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. atorvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin). See prescribing information for full details.
Glecaprevir and pibrentasvir are weak inhibitors of cytochrome P450 (CYP) 3A and uridine glucuronosyltransferase (UGT) 1A1 in vivo. Clinically significant increases in exposure were not observed for sensitive substrates of CYP3A (midazolam, felodipine) or UGT1A1 (raltegravir) when administered with this drug.
Both glecaprevir and pibrentasvir inhibit the bile salt export pump (BSEP) in vitro.
Significant inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, UGT1A6, UGT1A9, UGT1A4, UGT2B7, OCT1, OCT2, OAT1, OAT3, MATE1 or MATE2K are not expected.
Patients treated with vitamin K antagonists: As liver function may change during treatment with this drug, a close monitoring of International Normalised Ratio (INR) values is recommended.
Potential for other medicinal products to affect this drug: See prescribing information for full details.
Use with strong P-gp/CYP3A inducers: Medicinal products that are strong P-gp and CYP3A inducers (e.g., rifampicin, carbamazepine, St. John’s wort (Hypericum perforatum), phenobarbital, phenytoin, and primidone) could significantly decrease glecaprevir or pibrentasvir plasma concentrations and may lead to reduced therapeutic effect of this drug  or loss of virologic response. Co-administration of such medicinal products with this drug  is contraindicated.
Co-administration of this drug with medicinal products that are moderate inducers P-gp/CYP3A may decrease glecaprevir and pibrentasvir plasma concentrations (e.g. oxcarbazepine, eslicarbazepine, lumacaftor, crizotinib). Co-administration of moderate inducers is not recommended.
Glecaprevir and pibrentasvir are substrates of the efflux transporters P-gp and/or BCRP. Glecaprevir is also a substrate of the hepatic uptake transporters OATP1B1/3. Co-administration of this drug  with medicinal products that inhibit P-gp and BCRP (e.g. ciclosporin, cobicistat, dronedarone, itraconazole, ketoconazole, ritonavir) may slow elimination of glecaprevir and pibrentasvir and thereby increase plasma exposure of the antivirals. Medicinal products that inhibit OATP1B1/3 (e.g. elvitegravir, ciclosporin, darunavir, lopinavir) increase systemic concentrations of glecaprevir.

Pregnancy: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of glecaprevir or pibrentasvir in pregnant women. This drug is not recommended in pregnancy.
Lactation: It is unknown whether glecaprevir or pibrentasvir are excreted in human milk.
See prescribing information for full details.

The highest documented doses administered to healthy volunteers is 1,200 mg once daily for 7 days for glecaprevir and 600 mg once daily for 10 days for pibrentasvir. Asymptomatic serum ALT elevations (>5x ULN) were observed in 1 out of 70 healthy subjects following multiple doses of glecaprevir (700 mg or 800 mg) once daily for ≥ 7 days. In case of overdose, the patient should be monitored for any signs and symptoms of toxicities.  Appropriate symptomatic treatment should be instituted immediately. Glecaprevir and pibrentasvir are not significantly removed by haemodialysis.

Storage: below 30°C