Maviret

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Maviret 100 mg/40 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 100 mg glecaprevir and 40 mg pibrentasvir. 
 
Excipient with known effect 
Each film-coated tablet contains 7.48 mg lactose (as lactose monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Pink, oblong, biconvex, film-coated tablet of dimensions 18.8 mm x 10.0 mm, debossed on one side 
with ‘NXT’. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Maviret is indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults and in 
adolescents aged 12 to <18 years (see sections 4.2, 4.4. and 5.1).  
 
4.2 Posology and method of administration 
 
Maviret treatment should be initiated and monitored by a physician experienced in the management of 
patients with HCV infection. 
 
Posology 
 
Adults and adolescents aged 12 to <18 years 
The recommended dose of Maviret is 300 mg/120 mg (three 100 mg/40 mg tablets), taken orally, once 
daily at the same time with food (see section 5.2). 
 
The recommended Maviret treatment durations for HCV genotype 1, 2, 3, 4, 5, or 6 infected patients 
with compensated liver disease (with or without cirrhosis) are provided in Table 1 and Table 2. 
 
Table 1: Recommended Maviret treatment duration for patients without prior HCV therapy 

Genotype 
Recommended treatment duration  

No cirrhosis Cirrhosis 

GT 1, 2, 3, 4, 5, 6 8 weeks 8 weeks 
 



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Table 2: Recommended Maviret treatment duration for patients who failed prior therapy with 
peg-IFN + ribavirin +/- sofosbuvir, or sofosbuvir + ribavirin 

Genotype Recommended treatment duration 

No cirrhosis Cirrhosis 

GT 1, 2, 4-6 8 weeks 12 weeks 

GT 3 16 weeks 16 weeks 
 
For patients who failed prior therapy with an NS3/4A- and/or an NS5A-inhibitor, see section 4.4. 
 
Missed dose 
In case a dose of Maviret is missed, 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 since Maviret is usually taken, 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 Maviret should be taken. If 
vomiting occurs more than 3 hours after dosing, an additional dose of Maviret is not needed. 
 
Elderly 
No dose adjustment of Maviret is required in elderly patients (see sections 5.1 and 5.2). 
 
Renal impairment 
No dose adjustment of Maviret is required in patients with any degree of renal impairment including 
patients on dialysis (see sections 5.1 and 5.2).  
 
Hepatic impairment 
No dose adjustment of Maviret is required in patients with mild hepatic impairment (Child-Pugh A). 
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 4.3, 4.4, and 
5.2). 
 
Liver or kidney transplant patients  
A 12-week treatment duration has been evaluated and is recommended in liver or kidney transplant 
recipients with or without cirrhosis (see section 5.1). A 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 
Follow the dosing recommendations in Tables 1 and 2. For dosing recommendations with HIV 
antiviral agents, refer to section 4.5.  
 
Paediatric population 
No dose adjustment of Maviret is required in adolescents aged 12 to <18 years (see sections 5.1 and 
5.2). The safety and efficacy of Maviret in children aged less than 12 years have not yet been 
established. 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).  
 



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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. 
 
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. 
 
Use in diabetic patients  
 
Diabetics may experience improved glucose control, potentially resulting in symptomatic 
hypoglycaemia, after initiating HCV direct acting antiviral treatment. Glucose levels of diabetic 
patients initiating direct acting antiviral therapy should be closely monitored, particularly within the 
first 3 months, and their diabetic medication modified when necessary. The physician in charge of the 
diabetic care of the patient should be informed when direct acting antiviral therapy is initiated.  
 
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. 
 



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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. atorvastatin, lovastatin, pravastatin, 
rosuvastatin, simvastatin). See Table 3 for specific recommendations on interactions with sensitive 
substrates of P-gp, BCRP, and OATP1B1/3. For other P-gp, BCRP, or OATP1B1/3 substrates, dose 
adjustment may be needed. 
 
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 Maviret. 
 
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 Maviret, a close monitoring of International 
Normalised Ratio (INR) values is recommended. 
 
Potential for other medicinal products to affect Maviret 
 
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 Maviret or loss of virologic response. Co-administration of such medicinal products with Maviret is 
contraindicated (see section 4.3). 
 
Co-administration of Maviret 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 (see section 4.4). 
 
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 Maviret 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. 
 
Established and other potential medicinal product interactions  
 
Table 3 provides the least-squares mean Ratio (90% Confidence Interval) effect on concentration of 
Maviret and some common concomitant medicinal products. The direction of the arrow indicates the 
direction of the change in exposures (Cmax, AUC, and Cmin) in glecaprevir, pibrentasvir, and the co-
administered medicinal product (↑ = increase (more than 25%), ↓ = decrease (more than 20%), ↔ = 
no change (equal to or less than 20% decrease or 25% increase)). This is not an exclusive list. 
 



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Table 3: Interactions between Maviret and other medicinal products 
Medicinal product 

by therapeutic 
areas/possible 
mechanism of 

interaction 

Effect on 
medicinal 

product levels 
Cmax AUC Cmin Clinical comments 

ANGIOTENSIN-II RECEPTOR BLOCKERS 
Losartan 
50 mg single dose 
 

↑ losartan 2.51  
(2.00, 3.15) 

1.56 
(1.28, 1.89) 

-- No dose adjustment 
is required. 

↑ losartan 
carboxylic 
acid 

2.18  
(1.88, 2.53) 

↔ -- 

Valsartan 
80 mg single dose 
 
(Inhibition of 
OATP1B1/3) 

↑ valsartan 1.36  
(1.17, 1.58) 

1.31  
(1.16, 1.49) 

-- No dose adjustment 
is required. 

ANTIARRHYTHMICS 
Digoxin  
0.5 mg single dose 
 
(Inhibition of P-gp) 

↑ digoxin 1.72 
(1.45, 2.04) 

1.48 
(1.40, 1.57) 

-- Caution and 
therapeutic 
concentration 
monitoring of 
digoxin is 
recommended. 

ANTICOAGULANTS 
Dabigatran etexilate  
150 mg single dose 
 
(Inhibition of P-gp) 

↑ dabigatran 
 

2.05 
(1.72, 2.44) 

2.38 
(2.11, 2.70) 

-- Co-administration 
is contraindicated 
(see section 4.3). 

ANTICONVULSANTS 
Carbamazepine  
200 mg twice daily 
 
(Induction of P-
gp/CYP3A) 

↓ glecaprevir 0.33 
(0.27, 0.41) 

0.34 
(0.28, 0.40) 

-- Co-administration 
may lead to reduced 
therapeutic effect of 
Maviret and is 
contraindicated (see 
section 4.3). 

↓ pibrentasvir 0.50 
(0.42, 0.59) 

0.49 
(0.43, 0.55) 

-- 

Phenytoin, 
phenobarbital, 
primidone 
 

Not studied.   
Expected: ↓ glecaprevir and ↓ pibrentasvir 

ANTIMYCOBACTERIALS 
Rifampicin  
600 mg single dose 
 
(Inhibition of 
OATP1B1/3) 

↑ glecaprevir  6.52 
(5.06, 8.41)  

8.55 
(7.01, 10.4) 

 
-- 

Co-administration 
is contraindicated 
(see section 4.3).  ↔ pibrentasvir ↔ ↔ -- 

Rifampicin 600 mg 
once dailya 
 
(Induction of P-
gp/BCRP/CYP3A) 

↓ glecaprevir  0.14 
(0.11, 0.19) 

0.12 
(0.09, 0.15) 

-- 

↓ pibrentasvir 0.17 
(0.14, 0.20) 

0.13 
(0.11, 0.15) 

-- 

ETHINYL-OESTRADIOL-CONTAINING PRODUCTS 
Ethinyloestradiol 
(EE)/Norgestimate 
35 µg/250 µg once 
daily 

↑ EE 1.31 
(1.24, 1.38) 

1.28 
(1.23, 1.32) 

1.38 
(1.25, 1.52) 

Co-administration 
of Maviret with 
ethinyloestradiol-
containing products 
is contraindicated 
due to the risk of 
ALT elevations (see 
section 4.3). 
No dose adjustment 
is required with 
levonorgestrel, 

↑ 
norelgestromin 

↔ 1.44 
(1.34, 1.54) 

1.45 
(1.33, 1.58) 

↑ norgestrel 1.54 
(1.34, 1.76) 

1.63 
(1.50, 1.76) 

1.75 
(1.62, 1.89) 

EE/Levonorgestrel 
20 µg/100 µg once 
daily 
 

↑ EE 1.30 
(1.18, 1.44) 

1.40 
(1.33, 1.48) 

1.56 
(1.41, 1.72) 

↑ norgestrel 1.37 
(1.23, 1.52) 

1.68 
(1.57, 1.80) 

1.77 
(1.58, 1.98) 



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norethidrone or 
norgestimate as 
contraceptive 
progestagen. 

HERBAL PRODUCTS 
St. John’s wort 
(Hypericum 
perforatum) 
 
(Induction of P-
gp/CYP3A) 

Not studied.   
Expected: ↓ glecaprevir and ↓ pibrentasvir 

Co-administration 
may lead to reduced 
therapeutic effect of 
Maviret and is 
contraindicated (see 
section 4.3).  

HIV-ANTIVIRAL AGENTS 
Atazanavir + 
ritonavir 
300/100 mg once 
dailyb 

↑ glecaprevir ≥4.06  
(3.15, 5.23) 

≥6.53  
(5.24, 8.14) 

≥14.3 
(9.85, 20.7) 

Co-administration 
with atazanavir is 
contraindicated due 
to the risk of ALT 
elevations (see 
section 4.3).  

↑ pibrentasvir ≥1.29  
(1.15, 1.45) 

≥1.64  
(1.48, 1.82) 

≥2.29 
(1.95, 2.68) 

Darunavir + 
ritonavir  
800/100 mg once 
daily 

↑ glecaprevir 3.09 
(2.26, 4.20) 

4.97 
(3.62, 6.84) 

8.24 
(4.40, 15.4) 

Co-administration 
with darunavir is 
not recommended. ↔ pibrentasvir ↔ ↔ 1.66 

(1.25, 2.21) 
Efavirenz/emtricitab
ine/tenofovir 
disoproxil fumarate 
600/200/300 mg 
once daily 
 

↑ tenofovir ↔ 1.29 
(1.23, 1.35) 

1.38 
(1.31, 1.46) 

Co-administration 
with efavirenz may 
lead to reduced 
therapeutic effect of 
Maviret and is not 
recommended. No 
clinically 
significant 
interactions are 
expected with 
tenofovir disoproxil 
fumarate. 

The effect of efavirenz/emtricitabine/tenofovir disoproxil 
fumarate on glecaprevir and pibrentasvir was not directly 
quantified within this study, but glecaprevir and pibrentasvir 
exposures were significantly lower than historical controls. 

Elvitegravir/cobicist
at/emtricitabine/ 
tenofovir 
alafenamide 
 
(P-gp, BCRP, and 
OATP inhibition by 
cobicistat, OATP 
inhibition by 
elvitegravir) 

↔ tenofovir ↔ ↔ ↔ No dose adjustment 
is required. ↑ glecaprevir 2.50 

(2.08, 3.00) 
3.05 

(2.55, 3.64) 
4.58  

(3.15, 6.65) 
↑ pibrentasvir ↔ 1.57 

(1.39, 1.76) 
1.89 

(1.63, 2.19) 

Lopinavir/ritonavir 
400/100 mg twice 
daily 

↑ glecaprevir 2.55 
(1.84, 3.52) 

4.38 
(3.02, 6.36) 

18.6 
(10.4, 33.5) 

Co-administration 
is not 
recommended. 
 

↑ pibrentasvir 1.40 
(1.17, 1.67) 

2.46 
(2.07, 2.92) 

5.24 
(4.18, 6.58) 

Raltegravir 
400 mg twice daily 
 
(Inhibition of 
UGT1A1) 

↑ raltegravir 1.34  
(0.89, 1.98) 

1.47  
(1.15, 1.87) 

2.64  
(1.42, 4.91) 

No dose adjustment 
is required. 

HCV-ANTIVIRAL AGENTS 
Sofosbuvir  
400 mg single dose 
 
(P-gp/BCRP 
inhibition) 

↑ sofosbuvir 1.66 
(1.23, 2.22) 

2.25  
(1.86, 2.72) 

-- No dose adjustment 
is required. 
 ↑ GS-331007 ↔ ↔ 

 
1.85 

(1.67, 2.04) 
↔ glecaprevir ↔ ↔ ↔ 
↔ pibrentasvir ↔ ↔ ↔ 



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HMG-COA REDUCTASE INHIBITORS 
Atorvastatin  
10 mg once daily 
 
(Inhibition of 
OATP1B1/3, P-gp, 
BCRP, CYP3A) 

↑ atorvastatin 22.0 
(16.4, 29.5) 

8.28 
(6.06, 11.3) 

-- Co-administration 
with atorvastatin 
and simvastatin is 
contraindicated (see 
section 4.3). 

Simvastatin  
5 mg once daily 
 
(Inhibition of  
OATP1B1/3, P-gp, 
BCRP) 

↑ simvastatin 1.99 
(1.60, 2.48) 

2.32 
(1.93, 2.79) 

-- 

↑ simvastatin 
acid 

10.7 
(7.88, 14.6) 

4.48 
(3.11, 6.46) 

-- 

Lovastatin  
10 mg once daily 
 
(Inhibition of  
OATP1B1/3, P-gp, 
BCRP) 

↑ lovastatin ↔ 1.70 
(1.40, 2.06) 

-- Co-administration 
is not 
recommended. If 
used, lovastatin 
should not exceed a 
dose of 20 mg/day 
and patients should 
be monitored.   

↑ lovastatin 
acid 

5.73 
(4.65, 7.07) 

4.10 
(3.45, 4.87) 

-- 

Pravastatin  
10 mg once daily 
 
(Inhibition of 
OATP1B1/3) 

↑ pravastatin 2.23 
(1.87, 2.65) 

2.30 
(1.91, 2.76) 

-- Caution is 
recommended. 
Pravastatin dose 
should not exceed 
20 mg per day and 
rosuvastatin dose 
should not exceed 
5 mg per day. 

Rosuvastatin 
5 mg once daily 
 
(Inhibition of 
OATP1B1/3, 
BCRP) 

↑ rosuvastatin 5.62 
(4.80, 6.59) 

2.15 
(1.88, 2.46) 

-- 

Fluvastatin, 
Pitavastatin  

Not studied.   
Expected: ↑ fluvastatin and ↑ pitavastatin  

Interactions with 
fluvastatin and 
pitavastatin are 
likely and caution is 
recommended 
during the 
combination. A low 
dose of the statin is 
recommended at the 
initiation of the 
DAA treatment. 

IMMUNOSUPPRESSANTS 
Ciclosporin 
100 mg single dose 

↑ glecaprevirc 1.30 
(0.95, 1.78) 

1.37 
(1.13, 1.66) 

1.34 
(1.12, 1.60) 

Maviret is not 
recommended for 
use in patients 
requiring stable 
ciclosporin doses 
> 100 mg per day. 
If the combination 
is unavoidable, use 
can be considered if 
the benefit 
outweighs the risk 
with a close clinical 
monitoring. 

↑ pibrentasvir ↔ ↔ 1.26 
(1.15, 1.37) 

Ciclosporin  
400 mg single dose 

↑ glecaprevir 4.51 
(3.63, 6.05) 

5.08 
(4.11, 6.29) 

-- 

↑ pibrentasvir ↔ 1.93 
(1.78, 2.09) 

-- 

Tacrolimus 
1 mg single dose 
 
(CYP3A4 and P-gp 
inhibition) 

↑ tacrolimus 1.50 
(1.24, 1.82) 

1.45 
(1.24, 1.70) 

-- The combination of 
Maviret with 
tacrolimus should 
be used with 
caution. Increase of 

↔ glecaprevir ↔ ↔ ↔ 
↔ pibrentasvir ↔ ↔ ↔ 



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 tacrolimus exposure 
is expected. 
Therefore, a 
therapeutic drug 
monitoring of 
tacrolimus is 
recommended and a 
dose adjustment of 
tacrolimus made 
accordingly. 

PROTON PUMP INHIBITORS 
Omeprazole  
20 mg once daily 
 
(Increase gastric pH 
value) 

↓ glecaprevir 0.78 
(0.60, 1.00) 

0.71 
(0.58, 0.86) 

-- No dose adjustment 
is required. 

↔ pibrentasvir ↔ ↔ -- 

Omeprazole  
40 mg once daily (1 
hour before 
breakfast) 

↓ glecaprevir 0.36 
(0.21, 0.59) 

0.49 
(0.35, 0.68) 

-- 

↔ pibrentasvir ↔ ↔ -- 

Omeprazole  
40 mg once daily 
(evening without 
food) 

↓ glecaprevir 0.54 
(0.44, 0.65) 

0.51 
(0.45, 0.59) 

-- 

↔ pibrentasvir ↔ ↔ -- 

VITAMIN K ANTAGONISTS 
Vitamin K 
antagonists 

Not studied. Close monitoring of 
INR is 
recommended with 
all vitamin K 
antagonists. This is 
due to liver function 
changes during 
treatment with 
Maviret. 

DAA=direct acting antiviral  
a. Effect of rifampicin on glecaprevir and pibrentasvir 24 hours after final rifampicin dose. 
b. Effect of atazanavir and ritonavir on the first dose of glecaprevir and pibrentasvir is reported. 
c. HCV-infected transplant recipients who received a median ciclosporin dose of 100 mg per day had increased 
glecaprevir exposures to 2.4-fold of those not receiving ciclosporin. 
 
Additional drug-drug interaction studies were performed with the following medical products and 
showed no clinically significant interactions with Maviret: abacavir, amlodipine, buprenorphine, 
caffeine, dextromethorphan, dolutegravir, emtricitabine, felodipine, lamivudine, lamotrigine, 
methadone, midazolam, naloxone, norethindrone or other progestin-only contraceptives, rilpivirine, 
tenofovir alafenamide and tolbutamide. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of glecaprevir 
or pibrentasvir in pregnant women. 
 
Studies in rats/mice with glecaprevir or pibrentasvir do not indicate direct or indirect harmful effects 
with respect to reproductive toxicity. Maternal toxicity associated with embryo-foetal loss has been 
observed in the rabbit with glecaprevir which precluded evaluation of glecaprevir at clinical exposures 
in this species (see section 5.3). As a precautionary measure, Maviret use is not recommended in 
pregnancy. 
 



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Breast-feeding 
 
It is unknown whether glecaprevir or pibrentasvir are excreted in human milk. Available 
pharmacokinetic data in animals have shown excretion of glecaprevir and pibrentasvir in milk (for 
details see section 5.3). A risk to the suckling child cannot be excluded. A decision must be made 
whether to discontinue breast-feeding or to discontinue/abstain from Maviret therapy taking into 
account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
No human data on the effect of glecaprevir and/or pibrentasvir on fertility are available. Animal 
studies do not indicate harmful effects of glecaprevir or pibrentasvir on fertility at exposures higher 
than the exposures in humans at the recommended dose (see Section 5.3).  
 
4.7 Effects on ability to drive and use machines 
 
Maviret has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety assessment of Maviret in subjects treated for 8, 12 or 16 weeks with compensated liver 
disease (with or without cirrhosis) was based on registrational Phase 2 and 3 studies which evaluated 
approximately 2,300 subjects. The most commonly reported adverse reactions (incidence ≥ 10%) were 
headache and fatigue. Less than 0.1% of subjects treated with Maviret had serious adverse reactions 
(transient ischaemic attack). The proportion of subjects treated with Maviret who permanently 
discontinued treatment due to adverse reactions was 0.1%. The type and severity of adverse reactions 
in subjects with cirrhosis were overall comparable to those seen in subjects without cirrhosis. 
 
Tabulated summary of adverse reactions 
 
The following adverse reactions were identified in patients treated with Maviret. The adverse reactions 
are listed below by body system organ class and frequency. Frequencies are defined as follows: very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare 
(≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) or not known (cannot be estimated from the available 
data). 
 
Table 4: Adverse reactions identified with Maviret  

Frequency Adverse reactions 
Immune system disorders 
Uncommon angioedema 
Nervous system disorders 
Very common headache  
Gastrointestinal disorders 
Common diarrhoea, nausea  
Skin and subcutaneous tissue disorders  
Not known pruritus 
General disorders and administration site conditions 
Very common fatigue  
Common asthenia 

 
Description of selected adverse reactions 
 
Adverse reactions in subjects with severe renal impairment including subjects on dialysis 



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The safety of Maviret in subjects with chronic kidney disease (including subjects on dialysis) and 
genotypes 1, 2, 3, 4, 5 or 6 chronic HCV infection with compensated liver disease (with or without 
cirrhosis) was assessed in EXPEDITION-4 (n=104) and EXPEDITION-5 (n=101).  The most common 
adverse reactions in subjects with severe renal impairment were pruritus (17%) and fatigue (12%) in 
EXPEDITION-4 and pruritus (14.9%) in EXPEDITION-5. 
 
Adverse Reactions in Subjects with Liver or Kidney Transplant 
The safety of Maviret was assessed in 100 post-liver or -kidney transplant recipients with genotypes 1, 
2, 3, 4, or 6 chronic HCV infection without cirrhosis (MAGELLAN-2). The overall safety profile in 
transplant recipients was comparable to that observed in subjects in the Phase 2 and 3 studies. Adverse 
reactions observed in greater than or equal to 5% of subjects receiving Maviret for 12 weeks were 
headache (17%), fatigue (16%), nausea (8%) and pruritus (7%). 
 
Safety in HCV/HIV-1 Co-infected Subjects  
The overall safety profile in HCV/HIV-1 co-infected subjects (ENDURANCE-1 and EXPEDITION-
2) was comparable to that observed in HCV mono-infected subjects.  
 
Paediatric population 
The safety of Maviret in HCV GT1-6 infected adolescents is based on data from a Phase 2/3 open-
label study in 47 subjects aged 12 years to <18 years treated with Maviret for 8 to 16 weeks (DORA-
Part 1). The adverse reactions observed were comparable with those observed in clinical studies of 
Maviret in adults. 
 
Serum bilirubin elevations 
Elevations in total bilirubin of at least 2x upper limit normal (ULN) were observed in 1.3% of subjects 
related to glecaprevir-mediated inhibition of bilirubin transporters and metabolism. Bilirubin 
elevations were asymptomatic, transient, and typically occurred early during treatment. Bilirubin 
elevations were predominantly indirect and not associated with ALT elevations. Direct 
hyperbilirubinemia was reported in 0.3% of subjects.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
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 (see section 4.8). Appropriate symptomatic 
treatment should be instituted immediately. Glecaprevir and pibrentasvir are not significantly removed 
by haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Direct-acting antiviral, ATC code:  J05AP57 glecaprevir and pibrentasvir 
 
Mechanism of action 
 

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12 

Maviret is a fixed-dose combination of two pan-genotypic, direct-acting antiviral agents, glecaprevir 
(NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor), targeting multiple steps in the HCV 
viral lifecycle. 
  
Glecaprevir 
Glecaprevir is a pan-genotypic inhibitor of the HCV NS3/4A protease, which is necessary for the 
proteolytic cleavage of the HCV encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, 
NS5A, and NS5B proteins) and is essential for viral replication.  
 
Pibrentasvir 
Pibrentasvir is a pan-genotypic inhibitor of HCV NS5A, which is essential for viral RNA replication 
and virion assembly. The mechanism of action of pibrentasvir has been characterized based on cell 
culture antiviral activity and drug resistance mapping studies. 
 
Antiviral activity 
 
The EC50 values of glecaprevir and pibrentasvir against full-length or chimeric replicons encoding 
NS3 or NS5A from laboratory strains are presented in Table 5.  
 
Table 5. Activity of glecaprevir and pibrentasvir against HCV genotypes 1-6 replicon cell lines 

HCV Subtype Glecaprevir EC50, nM Pibrentasvir EC50, nM 
1a 0.85 0.0018 
1b 0.94 0.0043 
2a 2.2 0.0023 
2b 4.6 0.0019 
3a 1.9 0.0021 
4a 2.8 0.0019 
5a NA 0.0014 
6a 0.86 0.0028 

NA = not available 
 
The in vitro activity of glecaprevir was also studied in a biochemical assay, with similarly low IC50 
values across genotypes.  
 
EC50 values of glecaprevir and pibrentasvir against chimeric replicons encoding NS3 or NS5A from 
clinical isolates are presented in Table 6.  
 



13 

Table 6. Activity of glecaprevir and pibrentasvir against transient replicons containing NS3 or 
NS5A from HCV genotypes 1-6 clinical isolates 

HCV 
subtype 

Glecaprevir Pibrentasvir 
Number of clinical 

isolates 
Median EC50, nM 

(range) 
Number of clinical 

isolates 
Median EC50, nM 

(range) 

1a 11 0.08   (0.05 – 0.12) 11 
0.0009  

 (0.0006 – 0.0017) 

1b 9 0.29   (0.20 – 0.68) 8 
0.0027  

 (0.0014 – 0.0035) 

2a 4 1.6   (0.66 – 1.9) 6 
0.0009  

 (0.0005 – 0.0019) 

2b 4 2.2   (1.4 – 3.2) 11 
0.0013  

 (0.0011 – 0.0019) 

3a 2 2.3   (0.71 – 3.8) 14 
0.0007  

 (0.0005 – 0.0017) 

4a 6 0.41   (0.31 – 0.55) 8 
0.0005  

 (0.0003 – 0.0013) 

4b NA NA 3 0.0012   (0.0005 – 0.0018) 

4d 3 0.17   (0.13 – 0.25) 7 
0.0014  

 (0.0010 – 0.0018) 
5a 1 0.12 1 0.0011 

6a NA NA 3 0.0007   (0.0006 – 0.0010) 
6e NA NA 1 0.0008 
6p NA NA 1 0.0005 

NA = not available 
 
Resistance  
 
In cell culture 
Amino acid substitutions in NS3 or NS5A selected in cell culture or important for the inhibitor class 
were phenotypically characterized in replicons.  
 
Substitutions important for the HCV protease inhibitor class at positions 36, 43, 54, 55, 56, 155, 166, 
or 170 in NS3 had no impact on glecaprevir activity. Substitutions at amino acid position 168 in NS3 
had no impact in genotype 2, while some substitutions at position 168 reduced glecaprevir 
susceptibility by up to 55-fold (genotypes 1, 3, 4), or reduced susceptibility by > 100-fold (genotype 
6). Some substitutions at position 156 reduced susceptibility to glecaprevir (genotypes 1 to 4) by 
> 100-fold.  Substitutions at amino acid position 80 did not reduce susceptibility to glecaprevir except 
for Q80R in genotype 3a, which reduced susceptibility to glecaprevir by 21-fold.   
 
Single substitutions important for the NS5A inhibitor class at positions 24, 28, 30, 31, 58, 92, or 93 in 
NS5A in genotypes 1 to 6 had no impact on the activity of pibrentasvir. Specifically in genotype 3a, 
A30K or Y93H had no impact on pibrentasvir activity. Some combinations of substitutions in 
genotypes 1a and 3a (including A30K+Y93H in genotype 3a) showed reductions in susceptibility to 
pibrentasvir. In genotype 3b replicon, the presence of naturally occurring polymorphisms K30 and 
M31 in NS5A reduced susceptibility to pibrentasvir by 24-fold relative to the activity of pibrentasvir 
in genotype 3a replicon. 
 
In clinical studies 
 
Studies in treatment-naïve and peginterferon (pegIFN), ribavirin (RBV) and/or sofosbuvir treatment-
experienced subjects with or without cirrhosis 
Twenty two of the approximately 2,300 subjects treated with Maviret for 8, 12, or 16 weeks in 
registrational Phase 2 and 3 clinical studies experienced virologic failure (2 with genotype 1, 2 with 
genotype 2, 18 with genotype 3 infection).  
 



14 

Among the 2 genotype 1-infected subjects who experienced virologic failure, one had treatment-
emergent substitutions A156V in NS3 and Q30R/L31M/H58D in NS5A, and one had Q30R/H58D 
(while Y93N was present at baseline and post-treatment) in NS5A.  
 
Among the 2 genotype 2-infected subjects, no treatment-emergent substitutions were observed in NS3 
or NS5A (the M31 polymorphism in NS5A was present at baseline and post-treatment in both 
subjects). 
 
Among the 18 genotype 3-infected subjects treated with Maviret for 8, 12, or 16 weeks who 
experienced virologic failure, treatment-emergent NS3 substitutions Y56H/N, Q80K/R, A156G, or 
Q168L/R were observed in 11 subjects. A166S or Q168R were present at baseline and post-treatment 
in 5 subjects. Treatment-emergent NS5A substitutions M28G, A30G/K, L31F, P58T, or Y93H were 
observed in 16 subjects, and 13 subjects had A30K (n=9) or Y93H (n=5) at baseline and post-
treatment. 
 
Studies in subjects with or without compensated cirrhosis who were treatment-experienced to NS3/4A 
protease and/or NS5A inhibitors  
Ten of 113 subjects treated with Maviret in the MAGELLAN-1 study for 12 or 16 weeks experienced 
virologic failure.  
 
Among the 10 genotype 1-infected subjects with virologic failure, treatment-emergent NS3 
substitutions V36A/M, R155K/T, A156G/T/V, or D168A/T were observed in 7 subjects. Five of the 
10 had combinations of V36M, Y56H, R155K/T, or D168A/E in NS3 at baseline and post-treatment. 
All of the genotype 1-infected virologic failure subjects had one or more NS5A substitutions 
L/M28M/T/V, Q30E/G/H/K/L/R, L31M, P32 deletion, H58C/D, or Y93H at baseline, with additional 
treatment-emergent NS5A substitutions M28A/G, P29Q/R, Q30K, H58D, or Y93H observed in 7 of 
the subjects at the time of failure.   
 
Effect of baseline HCV amino acid polymorphisms on treatment response 
A pooled analysis of treatment-naïve and pegylated interferon, ribavirin and/or sofosbuvir treatment-
experienced subjects receiving Maviret in the Phase 2 and Phase 3 clinical studies was conducted to 
explore the association between baseline polymorphisms and treatment outcome and to describe 
substitutions seen upon virologic failure. Baseline polymorphisms relative to a subtype-specific 
reference sequence at amino acid positions 155, 156, and 168 in NS3, and 24, 28, 30, 31, 58, 92, and 
93 in NS5A were evaluated at a 15% detection threshold by next-generation sequencing. Baseline 
polymorphisms in NS3 were detected in 1.1% (9/845), 0.8% (3/398), 1.6% (10/613), 1.2% (2/164), 
41.9% (13/31), and 2.9% (1/34) of subjects with HCV genotype 1, 2, 3, 4, 5, and 6 infection, 
respectively. Baseline polymorphisms in NS5A were detected in 26.8% (225/841), 79.8% (331/415), 
22.1% (136/615), 49.7% (80/161), 12.9% (4/31), and 54.1% (20/37) of subjects with HCV genotype 1, 
2, 3, 4, 5, and 6 infection, respectively. 
 
Genotype 1, 2, 4, 5, and 6: Baseline polymorphisms in genotypes 1, 2, 4, 5 and 6 had no impact on 
treatment outcome.   
 
Genotype 3: For subjects who received the recommended regimen (n=313), baseline polymorphisms 
in NS5A (Y93H included) or NS3 did not have a relevant impact on treatment outcomes. All subjects 
(15/15) with Y93H and 77% (17/22) with A30K in NS5A at baseline achieved SVR12. The overall 
prevalence of A30K and Y93H at baseline was 7.0% and 4.8%, respectively. The ability to assess the 
impact of baseline polymorphisms in NS5A was limited among treatment-naïve subjects with cirrhosis 
and treatment-experienced subjects due to low prevalence of A30K (3.0%, 4/132) or Y93H (3.8%, 
5/132).  
 
Cross-resistance 
 
In vitro data indicate that the majority of the resistance-associated substitutions in NS5A at amino acid 
positions 24, 28, 30, 31, 58, 92, or 93 that confer resistance to ombitasvir, daclatasvir, ledipasvir, 
elbasvir, or velpatasvir remained susceptible to pibrentasvir. Some combinations of NS5A 



15 

substitutions at these positions showed reductions in susceptibility to pibrentasvir. Glecaprevir was 
fully active against resistance-associated substitutions in NS5A, while pibrentasvir was fully active 
against resistance-associated substitutions in NS3. Both glecaprevir and pibrentasvir were fully active 
against substitutions associated with resistance to NS5B nucleotide and non-nucleotide inhibitors. 
 
Clinical efficacy and safety 
 
Table 7 summarizes clinical studies conducted with Maviret in subjects with HCV genotype 1, 2, 3, 4, 
5 or 6 infection.  
 
Table 7: Clinical studies conducted with Maviret in subjects with HCV genotype 1, 2, 3, 4, 5 or 6 
Infection 

Genotype (GT) Clinical study  Summary of study design  
TN and PRS-TE subjects without cirrhosis 

GT1 ENDURANCE-1
a Maviret for 8 weeks (n=351) or 12 weeks (n=352)  

SURVEYOR-1  Maviret for 8 weeks (n=34) 

GT2 ENDURANCE-2  Maviret (n=202) or Placebo (n=100) for 12 weeks SURVEYOR-2b Maviret for 8 weeks (n=199) or 12 weeks (n=25) 

GT3 
ENDURANCE-3 Maviret for 8 weeks (n=157) or 12 weeks (n=233)  Sofosbuvir + daclatasvir for 12 weeks (n=115) 

SURVEYOR-2  Maviret for 8 weeks (TN only, n=29) or 12 weeks (n=76) or 16 weeks (TE only, n=22) 

GT4, 5, 6 

ENDURANCE-4 Maviret for 12 weeks (n=121) 
ENDURANCE-5,6 Maviret for 8 weeks (n=75) 
SURVEYOR-1  Maviret for 12 weeks (n=32) 
SURVEYOR-2c  Maviret for 8 weeks (n=58) 

GT1-6 VOYAGE-1f Maviret for 8 weeks (GT1, 2, 4, 5, and 6 and GT3 TN) (n=356) or 16 weeks (GT3 TE only) (n=6) 
TN and PRS-TE subjects with cirrhosis 
GT1, 2, 4, 5, 6 EXPEDITION-1 Maviret for 12 weeks (n=146) 
GT3 SURVEYOR-2d Maviret for 12 weeks (TN only, n=64) or 16 weeks (TE only, n=51)  
GT5, 6 ENDURANCE-5,6 Maviret for 12 weeks (n=9) 
GT1-6 VOYAGE-2f Maviret for 12 weeks (GT1, 2, 4, 5, and 6 and GT3 TN) (n=157) or 16 weeks (GT3 TE only) (n=3) 
GT1-6 EXPEDITION-8 Maviret for 8 weeks (n=343) (TN only) 
Subjects with CKD stage 3b, 4 and 5 with or without cirrhosis 
GT1-6 EXPEDITION-4 Maviret for 12 weeks (n=104) 
GT1-6 EXPEDITION-5 Maviret for 8 weeks (n=84) or 12 weeks (n=13) or 16 weeks (n=4)  
NS5A inhibitor and/or PI-experienced subjects with or without cirrhosis 
GT1, 4 MAGELLAN-1e  Maviret for 12 weeks (n=66) or 16 weeks (n=47) 
HCV/HIV-1 Co-Infected Subjects with or without Cirrhosis 
GT1-6 EXPEDITION-2 Maviret for 8 weeks (n=137) or 12 weeks (n=16) 
Liver or Kidney Transplant Recipients 
GT1-6 MAGELLAN-2 Maviret for 12 weeks (n=100)  
Adolescent subjects (12 to <18 years) 
GT1-6 DORA (Part 1) Maviret for 8 weeks (n=44) or 16 weeks (n=3)  

TN=treatment naïve, PRS-TE=treatment experienced (includes previous treatment that included pegIFN (or 
IFN), and/or RBV and/or sofosbuvir), PI=Protease Inhibitor, CKD=chronic kidney disease 
a. Included 33 subjects co-infected with HIV-1. 
b. GT2 from SURVEYOR-2 Parts 1 and 2 - Maviret for 8 weeks (n=54) or 12 weeks (n=25); GT2 from 
SURVEYOR-2 Part 4 - Maviret for 8 weeks (n=145). 
c. GT3 without cirrhosis from SURVEYOR-2 Parts 1 and 2 - Maviret for 8 weeks (n=29) or 12 weeks (n=54); 
GT3 without cirrhosis from SURVEYOR-2 Part 3 - Maviret for 12 weeks (n=22) or 16 weeks (n=22). 
d. GT3 with cirrhosis from SURVEYOR-2 Part 2 - Maviret for 12 weeks (n=24) or 16 weeks (n=4); GT3 with 
cirrhosis from SURVEYOR-2 Part 3 - Maviret for 12 weeks (n=40) or 16 weeks (n=47). 
e. GT1, 4 from MAGELLAN-1 Part 1 - Maviret for 12 weeks (n=22); GT1, 4 from MAGELLAN-1 Part 2 - 
Maviret for 12 weeks (n=44) or 16 weeks (n=47). 



16 

f. VOYAGE-1 and VOYAGE-2 were Asian regional studies. 
 
Serum HCV RNA values were measured during the clinical studies using the Roche COBAS 
AmpliPrep/COBAS Taqman HCV test (version 2.0) with a lower limit of quantification (LLOQ) of 
15 IU/mL (except for SURVEYOR-1 and SURVEYOR-2 which used the Roche COBAS TaqMan 
real-time reverse transcriptase-PCR (RT-PCR) assay v. 2.0 with an LLOQ of 25 IU/mL). Sustained 
virologic response (SVR12), defined as HCV RNA less than LLOQ at 12 weeks after the cessation of 
treatment, was the primary endpoint in all the studies to determine the HCV cure rate. 
 
Clinical studies in treatment-naïve or treatment-experienced subjects with or without cirrhosis 
Of the 2,409 subjects with compensated liver disease (with or without cirrhosis) treated who were 
treatment-naïve or treatment-experienced to combinations of peginterferon, ribavirin and/or 
sofosbuvir, the median age was 53 years (range: 19 to 88); 73.3% were treatment-naïve, 26.7% were 
treatment-experienced to a combination containing either sofosbuvir, ribavirin and/or peginterferon; 
40.3% were HCV genotype 1; 19.8% were HCV genotype 2; 27.8% were HCV genotype 3; 8.1% 
were HCV genotype 4; 3.4% were HCV genotype 5-6; 13.1% were ≥65 years; 56.6% were male; 6.2% 
were Black; 12.3% had cirrhosis; 4.3% had severe renal impairment or end stage renal disease; 20.0% 
had a body mass index of at least 30 kg per m2; 7.7% had HIV-1 coinfection and the median baseline 
HCV RNA level was 6.2 log10 IU/mL 
 
Table 8: SVR12 in treatment-naïve and treatment-experienceda subjects to peginterferon, 
ribavirin and/or sofosbuvir with genotype 1, 2, 4, 5 and 6 infection who received the 
recommended duration (pooled data from ENDURANCE-1b, SURVEYOR-1, -2, and 
EXPEDITION-1, 2b, -4 and 8) 

 Genotype 1 Genotype 2 Genotype 4 Genotype 5 Genotype 6 
SVR12 in subjects without cirrhosis  
    8 weeks 99.2%  

(470/474)  
98.1% 

(202/206)  
95.2% 
(59/62)  

100% 
(2/2)  

92.3%  
(12/13)  

   Outcome for subjects without SVR12 
   On-treatment VF 0.2% 

(1/474)  
0% 

(0/206)  
0% 

(0/62)  
0% 

(0/2)  
0% 

(0/13)  
    Relapsec 0%  

(0/471)  
1.0% 

(2/204)  
0% 

(0/61)  
0% 

(0/2)  
0% 

(0/13)  
    Otherd 0.6% 

(3/474)  
1.0% 

(2/206)  
4.8% 
(3/62)  

0% 
(0/2)  

7.7% 
(1/13)  

SVR12 in subjects with cirrhosis 
    8 weeks  97.8% 

(226/231) 
100%  

(26/26) 
100%  

(13/13) 
100%  
(1/1) 

100%  
(9/9) 

    12 weeks 96.8% 
(30/31) 

90.0% 
(9/10) 

100% 
(8/8) 

 
--- 

100% 
(1/1) 

    Outcome for subjects without SVR12 
  On-treatment VF 0% 

(0/262) 
0% 

(0/36) 
0% 

(0/21) 
0% 

(0/1) 
0% 

(0/10) 
  Relapsec 0.4% 

(1/256) 
0% 

(0/35) 
0% 

(0/20) 
0% 

(0/1) 
0% 

(0/10) 
  Otherd 1.9%(5/262) 2.8% 

(1/36) 
0% 

(0/21) 
0% 

(0/1) 
0% 

(0/10) 
VF=virologic failure 
a. Percent of subjects with prior treatment experience to PRS is 26%, 14%, 24%, 0%, and 13% for genotypes 1, 
2, 4, 5, and 6, respectively. None of the GT5 subjects were TE-PRS, and 3 GT6 subjects were TE-PRS. 
b. Includes a total of 154 subjects coinfected with HIV-1 in ENDURANCE-1 and EXPEDITION-2 who received 
the recommended duration.  
c. Relapse is defined as HCV RNA ≥ LLOQ after end-of-treatment response among those who completed 
treatment. 
d. Includes subjects who discontinued due to adverse event, lost to follow-up, or subject withdrawal.  
 
Of the genotype 1-, 2-, 4-, 5-, or 6-infected subjects with end stage renal disease enrolled in 
EXPEDITION-4, 97.8% (91/93) achieved SVR12 with no virologic failures.  
 



17 

Clinical Study in Subjects with Genotype 5 or 6 Infection 
ENDURANCE-5,6 was an open-label study in 84 HCV GT5 (N=23) or 6-infected (N=61) TN or TE-
PRS subjects.  Subjects without cirrhosis received Maviret for 8 weeks, and subjects with 
compensated cirrhosis received Maviret for 12 weeks. Of the 84 subjects treated, the median age was 
59 years (range 24-79); 27% had HCV genotype 5, 73% had HCV genotype 6; 54% were female, 30% 
were White, 68% were Asian; 90% were HCV TN; 11% had compensated cirrhosis.  
 
The overall SVR12 rate was 97.6% (82/84).  The SVR12 rate was 95.7% (22/23) for GT5-infected 
subjects and 98.4% (60/61) for GT6-infected subjects.  One TN GT5-infected subject without cirrhosis 
experienced relapse, and one TN GT6-infected subject with compensated cirrhosis experienced on-
treatment virologic failure. 
 
Subjects with Genotype 1, 2, 4, 5, or 6 Infection with Cirrhosis who received 8 weeks of Maviret 
The safety and efficacy of Maviret given for 8 weeks in GT 1, 2, 4, 5 or 6 treatment naïve subjects 
with compensated cirrhosis was evaluated in a single-arm, open-label study (EXPEDITION-8).  
Of the 280 subjects treated, the median age was 60 years (range: 34 to 88); 81.8% had HCV genotype 
1, 10% had HCV genotype 2, 4.6% had HCV genotype 4, 0.4% had HCV genotype 5; 3.2% had HCV 
genotype 6; 60% were male; 9.6% were Black. 
 
The overall SVR12 rate was 98.2% (275/280). There were no virologic failures. 
 
Subjects with genotype 3 infection  
The efficacy of Maviret in subjects who were treatment-naïve or treatment-experienced to 
combinations of peginterferon, ribavirin and/or sofosbuvir with genotype 3 chronic hepatitis C 
infection was demonstrated in the ENDURANCE-3 (treatment-naïve without cirrhosis), 
EXPEDITION-8 (treatment-naïve with cirrhosis), and SURVEYOR-2 Part 3 (subjects with and 
without cirrhosis and/or treatment-experienced) clinical studies. 
 
ENDURANCE-3 was a partially-randomized, open-label, active-controlled study in treatment-naïve 
genotype 3-infected subjects. Subjects were randomized (2:1) to either Maviret for 12 weeks or the 
combination of sofosbuvir and daclatasvir for 12 weeks; subsequently the study included a third arm 
(which was non-randomized) with Maviret for 8 weeks. EXPEDITION-8 was a single-arm, open-label 
study in treatment-naïve subjects with compensated cirrhosis and genotype 1, 2, 3, 4, 5 or 6 infection 
who received Maviret for 8 weeks.  SURVEYOR-2 Part 3 was an open-label study that evaluated the 
efficacy of Maviret in treatment-experienced genotype 3-infected subjects without cirrhosis and with 
compensated cirrhosis for 16-weeks. Among treatment-experienced subjects, 46% (42/91) failed a 
previous regimen containing sofosbuvir. 
 
Table 9: SVR12 in treatment-naïve, genotype 3-infected subjects without cirrhosis 
(ENDURANCE-3) 

SVR 
 

Maviret 8 weeks 
N=157 

Maviret 12 weeks 
N=233 

SOF+DCV 12 weeks 
N=115 

94.9% (149/157) 95.3% (222/233) 96.5% (111/115) 
 Treatment difference -1.2%; 

95% confidence interval (-5.6% to 3.1%) 
Treatment difference -0.4%; 

97.5% confidence interval (-5.4% to 4.6%) 
 

Outcome for subjects without SVR12 
     On-treatment VF 0.6% (1/157) 0.4% (1/233) 0% (0/115) 
     Relapsea 3.3% (5/150) 1.4% (3/222) 0.9% (1/114) 
     Otherb 1.3% (2/157) 3.0% (7/233) 2.6% (3/115) 

a. Relapse is defined as HCV RNA ≥ LLOQ after end-of-treatment response among those who completed 
treatment. 
b. Includes subjects who discontinued due to adverse event, lost to follow-up, or subject withdrawal. 

 
In a pooled analysis of treatment naïve patients without cirrhosis (including Phase 2 and 3 data) where 
SVR12 was assessed according to the presence of baseline A30K, a numerically lower SVR12 rate 



18 

was achieved in patients with A30K treated for 8 weeks as compared to those treated for 12 weeks 
[78% (14/18) vs 93% (13/14)]. 
 
Table 10: SVR12 in genotype 3-infected subjects with or without cirrhosis (SURVEYOR-2 Part 
3 and EXPEDITION-8) 

 Treatment-naïve  
with cirrhosis 

Treatment-naïve  
with cirrhosis 

Treatment-experienced 
with or without cirrhosis 

Maviret 
8 weeks 
(N=63) 

Maviret 
12 weeks 
(N=40) 

Maviret 
16 weeks 
(N=69) 

SVR 95.2% (60/63) 97.5% (39/40) 95.7% (66/69) 
 Outcome for subjects without SVR12 
   On-treatment VF 0% (0/63) 0% (0/40) 1.4% (1/69) 
   Relapsea 1.6% (1/62) 0% (0/39) 2.9% (2/68) 
   Otherb 3.2% (2/63) 2.5% (1/40) 0% (0/69) 
 SVR by cirrhosis status 
   No Cirrhosis NA NA 95.5% (21/22) 
   Cirrhosis 95.2% (60/63) 97.5% (39/40) 95.7% (45/47) 

a. Relapse is defined as HCV RNA ≥ LLOQ after end-of-treatment response among those who completed 
treatment. 
b. Includes subjects who discontinued due to adverse event, lost to follow-up, or subject withdrawal. 
 
Of the genotype 3-infected subjects with end stage renal disease enrolled in EXPEDITION-4, 100% 
(11/11) achieved SVR12. 
 
Subjects with genotype 3b infection  
GT3b is a subtype reported in a relatively small number of HCV infected patients in China and a few 
countries in South and Southeast Asia, but rarely outside of this region. Studies VOYAGE-1 and 
VOYAGE-2 were conducted in China, Singapore, and South Korea in HCV genotype 1-6 subjects 
without cirrhosis (VOYAGE-1) or with compensated cirrhosis (VOYAGE-2) that were treatment-
naïve (TN) or treatment-experienced to combinations of interferon, peg-interferon, ribavirin and/or 
sofosbuvir (TE-PRS). All subjects without cirrhosis or with compensated cirrhosis received 8 or 12 
weeks of Maviret, respectively, except GT3 TE-PRS subjects who received 16 weeks of Maviret. The 
overall SVR12 rates were 97.2% (352/362) and 99.4% (159/160) in VOYAGE-1 and VOYAGE-2, 
respectively. 
 
Among GT3b subjects without cirrhosis, a numerically lower SVR12 rate of 58.3% (7/12) [62.5% 
(5/8) for TN subjects and 50% (2/4) for TE-PRS subjects] was observed compared to GT3a subjects 
without cirrhosis (92.9% (13/14)). Three GT3b TN subjects experienced relapse and two GT3b TE-
PRS subjects experienced on-treatment virologic failure. Among subjects with compensated cirrhosis, 
the overall SVR12 rate for GT3b infected subjects was 87.5% (7/8) [85.7% (6/7) for TN subjects and 
100% (1/1) for TE-PRS subjects] and 100% (6/6) for GT3a infected subjects. One GT3b TN subject 
experienced relapse. 
 
Overall SVR12 Rate from the Clinical Studies in Treatment-Naïve or Treatment-Experienced Subjects 
with or without Cirrhosis 
In subjects who are treatment-naïve (TN) or treatment-experienced to combinations of interferon, 
peginterferon, ribavirin and/or sofosbuvir (TE-PRS) who received the recommended duration, 97.5% 
(1,395/1,431) achieved SVR12 overall, while  0.2% (3/1,431) experienced on-treatment virologic 
failure and 0.9% (12/1,407) experienced post-treatment relapse. 
 
In TN or TE-PRS subjects with compensated cirrhosis who received the recommended duration, 
97.1%  (431/444) achieved SVR12 (among which 97.7% [335/343] of TN subjects achieved SVR12), 
while 0.2% (1/444) experienced on-treatment virologic failure and 0.9% (4/434) experienced post-
treatment relapse. 
 



19 

In TN subjects without cirrhosis who received the recommended duration of 8 weeks, 97.5% 
(749/768) achieved SVR12, while 0.1% (1/768) experienced on-treatment virologic failure and 0.7% 
(5/755) experienced post-treatment relapse. 
 
In TE-PRS subjects without cirrhosis who received the recommended duration, 98.2% (215/219) 
achieved SVR12, while 0.5% (1/219) experienced on-treatment virologic failure and 1.4% (3/218) 
experienced post-treatment relapse. 
 
The presence of HIV-1 coinfection did not impact efficacy. The SVR12 rate in TN or TE-PRS 
HCV/HIV-1 co-infected subjects treated for 8 or 12 weeks (without cirrhosis and with compensated 
cirrhosis, respectively) was 98.2% (165/168) from ENDURANCE-1 and EXPEDITION-2. One 
subject experienced on-treatment virologic failure (0.6%, 1/168) and no subjects relapsed (0%, 0/166).  
 
Clinical Study in Liver or Kidney Transplant Recipients  
MAGELLAN-2 was a single-arm, open-label study in 100 post-liver or -kidney transplant HCV 
GT1-6 infected subjects without cirrhosis who received Maviret for 12 weeks. The study included 
subjects who were HCV treatment-naïve or treatment-experienced to combinations of (peg) interferon, 
ribavirin, and/or sofosbuvir, with the exception of GT3-infected subjects who were all treatment-
naïve.   
 
Of the 100 subjects treated, the median age was 60 years (range: 39 to 78); 57% had HCV genotype 1, 
13% had HCV genotype 2, 24% had HCV genotype 3, 4% had HCV genotype 4, 2% had HCV 
genotype 6; 75% were male; 8% were Black; 66% were HCV treatment-naïve; none had cirrhosis and 
80% had a baseline fibrosis state of F0 or F1; 80% of subjects were post-liver transplant and 20% were 
post-kidney transplant. Immunosuppressants allowed for co-administration were ciclosporin 
≤100 mg/day, tacrolimus, sirolimus, everolimus, azathioprine, mycophenolic acid, prednisone, and 
prednisolone.  
 
The overall SVR12 rate in post-transplant subjects was 98.0% (98/100). There was one relapse and no 
on-treatment virologic failure. 
 
Clinical Study in Renally Impaired Subjects 
EXPEDITION-5 was an open-label study in 101 HCV GT1-6 infected subjects without cirrhosis or 
with compensated cirrhosis and chronic kidney disease (CKD) stage 3b, 4, or 5. Subjects were either 
treatment-naïve or treatment-experienced to combinations of (peg) interferon, ribavirin, and/or 
sofosbuvir and received Maviret for 8, 12, or 16 weeks per approved treatment durations. 
 
Of the 101 subjects treated, the median age was 58 years (range 32-87); 53% had HCV genotype 1; 
27% had HCV genotype 2; 15% had HCV genotype 3; 4% had HCV genotype 4; 59% were male; 
73% were White; 80% were HCV treatment-naïve; 13% had cirrhosis and 65% had a baseline fibrosis 
state of F0 or F1; 7% were CKD stage 3b; 17% were CKD Stage 4, and 76% were CKD Stage 5 (all 
receiving dialysis); 84 subjects received 8 weeks of treatment, 13 subjects received 12 weeks of 
treatment, and 4 subjects received 16 weeks of treatment. 
 
The overall SVR12 rate was 97% (98/101).  There were no virologic failures. 
 
Elderly  
Clinical studies of Maviret included 328 patients aged 65 and over (13.8% of the total number of 
subjects). The response rates observed for patients ≥ 65 years of age were similar to that of patients 
< 65 years of age, across treatment groups. 
 
Paediatric population 
DORA (Part 1) was an open-label study to evaluate safety and efficacy in adolescents aged 12 years to 
less than 18 years who received Maviret 300 mg/120 mg (three 100 mg/40 mg film-coated tablets), for 
8, or 16 weeks. 47 subjects were enrolled in DORA (Part 1). The median age was 14 years (range: 12 
to 17); 79% had HCV genotype 1, 6% had HCV genotype 2, 9% had HCV genotype 3, 6% had HCV 
genotype 4; 55% were female; 11% were Black; 77% were HCV treatment-naïve; 23% were 



20 

treatment-experienced to interferon; 4% had HIV-coinfection; none had cirrhosis; the mean weight 
was 59 kg (range: 32 to 109 kg). 
 
The overall SVR12 rate was 100% (47/47). No subject experienced virologic failure. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
glecaprevir/pibrentasvir in one or more subsets of the paediatric population from 3 years to less than 
12 years in the treatment of chronic hepatitis C (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetic properties of the components of Maviret are provided in Table 11.  
 
Table 11: Pharmacokinetic properties of the components of Maviret in healthy adult subjects 

 Glecaprevir Pibrentasvir 
Absorption 
Tmax (h)a 5.0 5.0 
Effect of meal (relative to fasting)b ↑ 83-163%  ↑ 40-53%  
Distribution 
% Bound to human plasma proteins  97.5 >99.9 
Blood-to-plasma ratio  0.57 0.62 
Biotransformation 
Metabolism secondary none 
Elimination 
Major route of elimination  Biliary excretion Biliary excretion 
t1/2 (h) at steady-state 6 - 9 23 - 29 
% of dose excreted in urinec 0.7 0 
% of dose excreted in faecesc 92.1d 96.6 
Transport 
Substrate of transporter P-gp, BCRP, and 

OATP1B1/3 
P-gp and not 

excluded BCRP 
a. Median Tmax following single doses of glecaprevir and pibrentasvir in healthy subjects. 
b. Mean systemic exposure with moderate to high fat meals.  
c. Single dose administration of [14C]glecaprevir or [14C]pibrentasvir in mass balance studies.  
d. Oxidative metabolites or their byproducts accounted for 26% of radioactive dose. No glecaprevir metabolites 

were observed in plasma. 
 
In patients with chronic hepatitis C infection without cirrhosis, following 3 days of monotherapy with 
either glecaprevir 300 mg per day (N=6) or pibrentasvir 120 mg per day (N=8) alone, geometric mean 
AUC24 values were 13600 ng∙h/mL for glecaprevir and 459 ng∙h/mL for pibrentasvir. Estimation of 
the pharmacokinetic parameters using population pharmacokinetic models has inherent uncertainty 
due to dose non-linearity and cross interaction between glecaprevir and pibrentasvir. Based on 
population pharmacokinetic models for Maviret in chronic hepatitis C patients, steady-state AUC24 
values for glecaprevir and pibrentasvir were 4800 and 1430 ng∙h/mL in subjects without cirrhosis 
(N=1804), and 10500 and 1530 ng∙h/mL in subjects with cirrhosis (N=280), respectively. Relative to 
healthy subjects (N=230), population estimates of AUC24, ss were similar (10% difference) for 
glecaprevir and 34% lower for pibrentasvir in HCV-infected patients without cirrhosis.  
 
Linearity/non-linearity 
 
Glecaprevir AUC increased in a greater than dose-proportional manner (1200 mg QD had 516-fold 
higher exposure than 200 mg QD) which may be related to saturation of uptake and efflux 
transporters. 
 
Pibrentasvir AUC increased in a greater than dose-proportional manner at doses up to 120 mg, (over 
10-fold exposure increase at 120 mg QD compared to 30 mg QD), but exhibited linear 



21 

pharmacokinetics at doses ≥ 120 mg. The non-linear exposure increase <120 mg may be related to 
saturation of efflux transporters. 
 
Pibrentasvir bioavailability when coadministered with glecaprevir is 3-fold of pibrentasvir alone. 
Glecaprevir is affected to a lower extent by coadministration with pibrentasvir. 
 
Pharmacokinetics in special populations  
 
Race/ethnicity 
No dose adjustment of Maviret is required based on race or ethnicity. 
 
Gender/weight 
No dose adjustment of Maviret is required based on gender or body weight. 
 
Elderly 
No dose adjustment of Maviret is required in elderly patients. Population pharmacokinetic analysis in 
HCV-infected subjects showed that within the age range (12 to 88 years) analysed, age did not have a 
clinically relevant effect on the exposure to glecaprevir or pibrentasvir. 
 
Paediatric Population 
No dose adjustment of Maviret is required in adolescents 12 years and older. Exposures of glecaprevir 
and pibrentasvir in adolescents aged 12 to <18 years were comparable to those in adults from Phase 
2/3 studies. The pharmacokinetics of glecaprevir and pibrentasvir have not been established in 
paediatric patients <12 years of age. 
 
Renal impairment 
Glecaprevir and pibrentasvir AUC were increased ≤ 56% in non-HCV infected subjects with mild, 
moderate, severe, or end-stage renal impairment not on dialysis compared to subjects with normal 
renal function. Glecaprevir and pibrentasvir AUC were similar with and without dialysis (≤ 18% 
difference) in dialysis-dependent non-HCV infected subjects. In population pharmacokinetic analysis 
of HCV-infected subjects, 86% higher glecaprevir and 54% higher pibrentasvir AUC were observed 
for subjects with end stage renal disease, with or without dialysis, compared to subjects with normal 
renal function.  Larger increases may be expected when unbound concentration is considered. 
 
Overall, the changes in exposures of Maviret in HCV-infected subjects with renal impairment with or 
without dialysis were not clinically significant. 
 
Hepatic impairment 
At the clinical dose, compared to non-HCV infected subjects with normal hepatic function, glecaprevir 
AUC was 33% higher in Child-Pugh A subjects, 100% higher in Child-Pugh B subjects, and increased 
to 11-fold in Child-Pugh C subjects. Pibrentasvir AUC was similar in Child-Pugh A subjects, 26% 
higher in Child-Pugh B subjects, and 114% higher in Child-Pugh C subjects. Larger increases may be 
expected when unbound concentration is considered.  
 
Population pharmacokinetic analysis demonstrated that following administration of Maviret in HCV-
infected subjects with compensated cirrhosis, exposure of glecaprevir was approximately 2-fold and 
pibrentasvir exposure was similar to non-cirrhotic HCV-infected subjects. The mechanism for the 
differences between glecaprevir exposure in chronic Hepatitis C patients with or without cirrhosis is 
unknown. 
 
5.3 Preclinical safety data 
 
Glecaprevir and pibrentasvir were not genotoxic in a battery of in vitro or in vivo assays, including 
bacterial mutagenicity, chromosome aberration using human peripheral blood lymphocytes and in vivo 
rodent micronucleus assays. Carcinogenicity studies with glecaprevir and pibrentasvir have not been 
conducted.  
 



22 

No effects on mating, female or male fertility, or early embryonic development were observed in 
rodents at up to the highest dose tested. Systemic exposures (AUC) to glecaprevir and pibrentasvir 
were approximately 63 and 102 times higher, respectively, than the exposure in humans at the 
recommended dose.  
 
In animal reproduction studies, no adverse developmental effects were observed when the components 
of Maviret were administered separately during organogenesis at exposures up to 53 times (rats; 
glecaprevir) or 51 and 1.5 times (mice and rabbits, respectively; pibrentasvir) the human exposures at 
the recommended dose of Maviret. Maternal toxicity (anorexia, lower body weight, and lower body 
weight gain) with some embryofoetal toxicity (increase in post-implantation loss and number of 
resorptions and a decrease in mean foetal body weight), precluded the ability to evaluate glecaprevir in 
the rabbit at clinical exposures.  There were no developmental effects with either compound in rodent 
peri/postnatal developmental studies in which maternal systemic exposures (AUC) to glecaprevir and 
pibrentasvir were approximately 47 and 74 times, respectively, the exposure in humans at the 
recommended dose. Unchanged glecaprevir was the main component observed in the milk of lactating 
rats without effect on nursing pups. Pibrentasvir was the only component observed in the milk of 
lactating rats without effect on nursing pups. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Copovidone (Type K 28) 
Vitamin E (tocopherol) polyethylene glycol succinate 
Silica, colloidal anhydrous 
Propylene glycol monocaprylate (Type II) 
Croscarmellose sodium 
Sodium stearyl fumarate 
 
Film coating 
 
Hypromellose 2910 (E464) 
Lactose monohydrate 
Titanium dioxide 
Macrogol 3350 
Iron oxide red (E172)   
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
36 months. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container  
 
PVC/PE/PCTFE aluminium foil blister packs. 
Pack containing 84 (4 x 21) film-coated tablets. 



23 

 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/17/1213/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26th July 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu 
  

http://www.ema.europa.eu/


24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 



25 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
GERMANY 
 
AbbVie Logistics B.V 
Zuiderzeelaan 53 
8017 JV Zwolle 
NETHERLANDS 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  
 
• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are 
set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-
portal. 
 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk 
profile or as the result of an important (pharmacovigilance or risk minimisation) 
milestone being reached.  



26 

 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 
Non-interventional post-authorisation safety study (PASS): 
In order to evaluate the recurrence of hepatocellular carcinoma associated with 
Maviret, the MAH shall conduct and submit the results of a prospective safety study 
using data deriving from a cohort of a well-defined group of patients, based on an 
agreed protocol. The final study report shall be submitted by: 

 
Q2 2023 

  



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Maviret 100 mg/40 mg film-coated tablets 
glecaprevir/pibrentasvir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each film-coated tablet contains 100 mg of glecaprevir and 40 mg of pibrentasvir. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
film-coated tablets  
 
84 (4 x 21) film-coated tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



30 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER  
 
EU/1/17/1213/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
maviret 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Maviret 100 mg/40 mg film-coated tablets 
glecaprevir/pibrentasvir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each film-coated tablet contains 100 mg of glecaprevir and 40 mg of pibrentasvir. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
film-coated tablets  
 
21 film-coated tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
Take all 3 tablets in 1 blister once daily with food 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



32 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER  
 
EU/1/17/1213/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
maviret 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



33 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Maviret 100 mg/40 mg tablets 
glecaprevir/pibrentasvir 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
  



34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

 
  



35 

Package leaflet: Information for the user 
 

Maviret 100 mg/40 mg film-coated tablets 
glecaprevir/pibrentasvir 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Maviret is and what it is used for 
2. What you need to know before you take Maviret 
3. How to take Maviret 
4. Possible side effects  
5. How to store Maviret 
6. Contents of the pack and other information 
 
 
1. What Maviret is and what it is used for 
 
Maviret is an antiviral medicine used to treat adults and adolescents (12 to less than 18 years old) with 
long-term (‘chronic’) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C 
virus). It contains the active substances glecaprevir and pibrentasvir. 
 
Maviret works by stopping the hepatitis C virus from multiplying and infecting new cells. This allows 
the infection to be eliminated from the body.  
 
 
2. What you need to know before you take Maviret 
 
Do not take Maviret if: 
• you are allergic to glecaprevir, pibrentasvir or any of the other ingredients of this medicine (listed 
in section 6 of this leaflet). 
• you have severe liver problems other than from hepatitis C. 
• you are taking the following medicines: 

• atazanavir (for HIV infection)  
• atorvastatin or simvastatin (to lower blood cholesterol)  
• carbamazepine, phenobarbital, phenytoin, primidone (normally used for epilepsy) 
• dabigatran etexilate (to prevent blood clots)  
• ethinyl oestradiol-containing medicines (such as contraception medicines, including 

vaginal rings and tablets) 
• rifampicin (for infections)  
• St. John’s wort (Hypericum perforatum), (herbal remedy used for mild depression). 

 
Do not take Maviret if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before taking Maviret. 
 



36 

Warnings and precautions 
Talk to your doctor if you have the following because your doctor may want to check you more 
closely:  
• liver problems other than hepatitis C 
• current or previous infection with the hepatitis B virus 
• diabetes. You may need closer monitoring of your blood glucose levels and/or adjustment of your 

diabetes medication after starting Maviret. Some diabetic patients have experienced low sugar 
levels in the blood (hypoglycaemia) after starting treatment with medicines like Maviret. 

 
Blood tests  
Your doctor will test your blood before, during and after your treatment with Maviret. This is so that 
your doctor can decide if:  
• you should take Maviret and for how long 
• your treatment has worked and you are free of the hepatitis C virus.  
 
Children 
Do not give this medicine to children under 12 years of age. The use of Maviret in children under 12 
years of age has not yet been studied. 
 
Other medicines and Maviret 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Tell your doctor or pharmacist before taking Maviret, if you are taking any of the medicines in the 
table below. The doctor may need to change your dose of these medicines.  
 

Medicines you must tell your doctor about before taking Maviret 
Medicine Purpose of the medicine 
ciclosporin, tacrolimus to suppress the immune system 
darunavir, efavirenz, lopinavir, ritonavir for HIV infection  
digoxin for heart problems 
fluvastatin, lovastatin, pitavastatin, pravastatin, 
rosuvastatin  

to lower blood cholesterol 

warfarin and other similar medicines* to prevent blood clots 
*Your doctor may need to increase the frequency of your blood tests to check how well your blood 
can clot. 
 
If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking 
Maviret. 
 
Pregnancy and contraception  
The effects of Maviret during pregnancy are not known. If you are pregnant, think you may be 
pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine, as the 
use of Maviret in pregnancy is not recommended. Contraceptive medicines that contain 
ethinylestradiol must not be used in combination with Maviret. 
 
Breast-feeding 
Talk to your doctor before taking Maviret if you are breast-feeding. It is not known whether the two 
medicines in Maviret pass into breast milk. 
 
Driving and using machines 
Maviret should not affect your ability to drive or use any tools or machines.  
 



37 

Maviret contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, talk to your doctor 
before taking this medicine. 
 
 
3. How to take Maviret 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. Your doctor will tell you how long you need to take Maviret for. 
 
How much to take 
The recommended dose for adults and adolescents (12 to <18 years old) is three tablets of Maviret 
100mg/40mg taken together, once a day.  
Three tablets in one blister is the daily dose. 
 
How to take 
• Take the tablets with food.  
• Swallow the tablets whole. 
• Do not chew, crush or break the tablets as it may affect the amount of Maviret in your blood.  
 
If you are sick (vomit) after taking Maviret it may affect the amount of Maviret in your blood. This 
may make Maviret work less well. 
• If you vomit less than 3 hours after taking Maviret, take another dose. 
• If you vomit more than 3 hours after taking Maviret, you do not need to take 

another dose until your next scheduled dose. 
 
If you take more Maviret than you should 
If you accidentally take more than the recommended dose, contact your doctor or go to the nearest 
hospital straight away. Take the medicine pack with you so that you can show the doctor what you 
have taken. 
 
If you forget to take Maviret  
It is important not to miss a dose of this medicine.  
 
If you do miss a dose, work out how long it is since you should have last taken Maviret:  
• If you notice within 18 hours of the time you usually take Maviret take the dose as soon as 

possible. Then take the next dose at your usual time.  
• If you notice 18 hours or more after the time you usually take Maviret, wait and take the next 

dose at your usual time. Do not take a double dose (two doses too close together).  

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor or pharmacist if you notice any of the following side effects: 
 
Very common: may affect more than 1 in 10 people 
• feeling very tired (fatigue) 
• headache 

 
Common: may affect up to 1 in 10 people 
• feeling sick (nausea) 
• diarrhoea 
• feeling weak or lack of energy (asthenia) 



38 

Uncommon: may affect up to 1 in 100 people  
• swelling of the face, lips, tongue, throat, abdomen, arms or legs 

 
Not known: cannot be estimated from the available data 
• itching 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Maviret 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and blister after ‘EXP’. 
 
This medicine does not require any special storage. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Maviret contains  
• The active substances are glecaprevir and pibrentasvir. Each tablet contains 100 mg of glecaprevir 

and 40 mg of pibrentasvir. 
• The other ingredients are: 

− Tablet core: copovidone (Type K 28), vitamin E polyethylene glycol succinate, silica, 
anhydrous colloidal, propylene glycol monocaprylate (type II), croscarmellose sodium, 
sodium stearyl fumarate. 

− Tablet film-coating: hypromellose (E464), lactose monohydrate, titanium dioxide, macrogol 
3350, iron oxide red (E172). 

 
What Maviret looks like and contents of the pack 
Maviret tablets are pink, oblong, curved on both sides (biconvex), film-coated tablets with dimensions 
of 18.8 mm x 10.0 mm and debossed on one side with ‘NXT’. 
 
Maviret tablets are packed into foil blisters, each containing 3 tablets. Maviret is available in a pack of 
84 tablets as 4 cartons, each containing 21 film-coated tablets. 
 
Marketing Authorisation Holder and Manufacturer 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 
 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


39 

България 
АбВи ЕООД 
Тел.: +359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811 
 

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 
 

Magyarország 
AbbVie Kft. 
Tel.: +36 1 455 8600 

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 
 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201 

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0 
 

Nederland 
AbbVie B.V. 
Tel: +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 
 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00 

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 
 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U.  
Tel: +34 91 384 09 10 
 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00  

France 
AbbVie 
Tél: +33 (0)1 45 60 13 00 
 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel: +385 (0)1 5625 501 
 

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35 

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900 

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777 

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel: +358 (0)10 2411 200 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ: +357 22 34 74 40 
 

Sverige 
AbbVie AB 
Tel: +46 (0)8 684 44 600 

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090 



40 

 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please 
contact the local representative of the Marketing Authorisation Holder. 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET