Exviera

1 
 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 



2 
 

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 
 
Exviera 250 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 250 mg of dasabuvir (as sodium monohydrate). 
 
Excipient with known effect 
 
Each film-coated tablet contains 45 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Beige, ovaloid, film-coated tablets with dimensions of 14.0 mm x 8.0 mm and debossed on one side 
with ‘AV2’. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Exviera is indicated in combination with other medicinal products for the treatment of chronic 
hepatitis C (CHC) in adults (see sections 4.2, 4.4 and 5.1). 
 
For hepatitis C virus (HCV) genotype specific activity, see sections 4.4 and 5.1. 
 
4.2 Posology and method of administration 
 
Treatment with dasabuvir should be initiated and monitored by a physician experienced in the 
management of chronic hepatitis C. 
 
Posology 
 
The recommended dose is 250 mg of dasabuvir (one tablet) twice daily (morning and evening). 
 
 Dasabuvir must not be administered as monotherapy. Dasabuvir should be used in combination with 
other medicinal products for the treatment of HCV (see section 5.1). Refer to the Summary of Product 
Characteristics of the medicinal products that are used in combination with dasabuvir. 
 
The recommended co-administered medicinal product(s) and treatment duration for dasabuvir 
combination therapy are provided in Table 1.  
 



3 
 

Table 1. Recommended co-administered medicinal product(s) and treatment duration for 
dasabuvir by patient population 
 

Patient population Treatment* Duration 

Genotype 1b, without cirrhosis or 
with compensated cirrhosis 

dasabuvir + 
ombitasvir/paritaprevir/ritonavir  

12 weeks  
 

8 weeks may be considered in 
previously untreated genotype 1b-
infected patients with minimal to 

moderate fibrosis** (see section 5.1, 
GARNET study) 

Genotype 1a, 
without cirrhosis 

dasabuvir + 
ombitasvir/paritaprevir/ritonavir + 

ribavirin* 
12 weeks 

Genotype 1a, 
with compensated cirrhosis 

dasabuvir + 
ombitasvir/paritaprevir/ritonavir + 

ribavirin* 
24 weeks (see section 5.1.) 

*Note: Follow the genotype 1a dosing recommendations in patients with an unknown genotype 1 subtype or 
with mixed genotype 1 infection. 
** When assessing severity of liver disease using non-invasive methods, a combination of blood biomarkers or 
the combination of liver stiffness measurement and a blood test improves accuracy and should be undertaken 
prior to 8 week treatment in all patients with moderate fibrosis. 
 
Missed doses 
In case a dose of dasabuvir is missed, the prescribed dose can be taken within 6 hours. If more than 6 
hours have passed since dasabuvir 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. 
 
Special populations 
 
HIV-1 Co-infection 
The dosing recommendations in Table 1 should be followed. For dosing recommendations with HIV 
antiviral medicinal products, refer to sections 4.4 and 4.5. See sections 4.8 and 5.1 for additional 
information. 
 
Liver transplant recipients 
Dasabuvir and ombitasvir/paritaprevir/ritonavir in combination with ribavirin is recommended for 
24 weeks in liver transplant recipients. Lower ribavirin dose at initiation may be appropriate. In the 
post-liver transplant study, ribavirin dosing was individualized and most subjects received 600 to 
800 mg per day (see section 5.1). For dosing recommendations with calcineurin inhibitors refer to 
section 4.5.  
 
Elderly 
 
No dose adjustment of dasabuvir is warranted in elderly patients (see section 5.2). 
 
Renal impairment 
 
No dose adjustment of dasabuvir is required for patients with mild, moderate, or severe renal 
impairment or end-stage-renal disease on dialysis (see section 5.2). For patients that require ribavirin, 
refer to the ribavirin Summary of Product Characteristics for information regarding use in patients 
with renal impairment. 
 



4 
 

Hepatic impairment 
 
No dose adjustment of dasabuvir is required in patients with mild hepatic impairment (Child-Pugh A). 
Dasabuvir should not be used in patients with moderate to severe hepatic impairment (Child-Pugh B 
or C) (see section 5.2).  
 
Paediatric population 
The safety and efficacy of dasabuvir in children less than 18 years of age have not been established. 
No data are available. 
 
Method of administration 
 
The film-coated tablets are for oral use. Patients should be instructed to swallow the tablets whole (i.e. 
patients should not chew, break or dissolve the tablet). To maximise absorption, dasabuvir tablets 
should be taken with food, without regard to fat and calorie content (see section 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Patients with moderate to severe hepatic impairment (Child-Pugh B or C) (see section 5.2). 
 
Use of ethinyloestradiol-containing medicinal products such as those contained in most combined oral 
contraceptives or contraceptive vaginal rings (see sections 4.4 and 4.5). 
 
Co-administration of dasabuvir with medicinal products that are strong or moderate enzyme inducers 
is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect (see section 
4.5. Examples of contraindicated inducers are provided below. 
 
Enzyme inducers: 
 

• carbamazepine, phenytoin, phenobarbital 
• efavirenz, nevirapine, etravirine 
• apalutamide, enzalutamide 
• mitotane 
• rifampicin 
• St. John’s Wort (Hypericum perforatum) 

 
Medicinal products that are strong CYP2C8 inhibitors may increase dasabuvir plasma concentrations 
and must not be co-administered with dasabuvir (see section 4.5). Examples of contraindicated 
CYP2C8 inhibitors are provided below.  
 
CYP2C8 inhibitor: 
 

• gemfibrozil 
 
Dasabuvir is administered with ombitasvir/ paritaprevir /ritonavir. For contra-indications with 
ombitasvir/ paritaprevir /ritonavir refer to the Summary of Product Characteristics. 
 
4.4 Special warnings and precautions for use 
 
General 
 
Dasabuvir is not recommended for administration as monotherapy and must be used in combination 
with other medicinal products for the treatment of hepatitis C infection (see section 4.2 and 5.1). 
 



5 
 

Risk of hepatic decompensation and hepatic failure in patients with cirrhosis 
 
Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have 
been reported post-marketing in patients treated with dasabuvir with ombitasvir/paritaprevir/ritonavir 
with and without ribavirin. Most patients with these severe outcomes had evidence of advanced or 
decompensated cirrhosis prior to initiating therapy. Although causality is difficult to establish due to 
background advanced liver disease, a potential risk cannot be excluded.  
 
Dasabuvir should not be used in patients with moderate to severe hepatic impairment (Child-Pugh B 
or C) (see sections 4.2, 4.3, 4.8 and 5.2). 
 
For patients with cirrhosis: 

• Monitoring should be performed for clinical signs and symptoms of hepatic decompensation 
(such as ascites, hepatic encephalopathy, variceal haemorrhage). 

• Hepatic laboratory testing including direct bilirubin levels should be performed at baseline, 
during the first 4 weeks of starting treatment and as clinically indicated thereafter. 

• Treatment should be discontinued in patients who develop evidence of hepatic 
decompensation. 

 
ALT elevations 
 
During clinical trials with dasabuvir and ombitasvir/paritaprevir/ritonavir with or without ribavirin, 
transient elevations of ALT to greater than 5 times the upper limit of normal occurred in 
approximately 1% of subjects (35 of 3,039). ALT elevations were asymptomatic and generally 
occurred during the first 4 weeks of treatment, without concomitant elevations of bilirubin, and 
declined within approximately two weeks of onset with continued dosing of dasabuvir and 
ombitasvir/paritaprevir/ritonavir with or without ribavirin.  
 
These ALT elevations were significantly more frequent in the subgroup of subjects who were using 
ethinyloestradiol -containing medicinal products such as combined oral contraceptives or 
contraceptive vaginal rings (6 of 25 subjects); (see section 4.3). In contrast, the rate of ALT elevations 
in subjects using other types of oestrogens as typically used in hormonal replacement therapy (i.e., oral 
and topical oestradiol and conjugated oestrogens) was similar to the rate observed in subjects who 
were not using oestrogen-containing products (approximately 1% in each group).  
 
Patients who are taking ethinyloestradiol -containing medicinal products (i.e. most combined oral 
contraceptives or contraceptive vaginal rings) must switch to an alternative method of contraception 
(e.g., progestin only contraception or non-hormonal methods) prior to initiating dasabuvir with 
ombitasvir/paritaprevir/ritonavir therapy (see sections 4.3 and 4.5). 
 
Although ALT elevations associated with dasabuvir and ombitasvir/paritaprevir/ritonavir have been 
asymptomatic, patients should be instructed to watch for early warning signs of liver inflammation, 
such as fatigue, weakness, lack of appetite, nausea and vomiting, as well as later signs such as 
jaundice and discoloured faeces, and to consult a doctor without delay if such symptoms occur. 
Routine monitoring of liver enzymes is not necessary in patients that do not have cirrhosis (for 
cirrhotics, see above). Early discontinuation may result in drug resistance, but implications for future 
therapy are not known. 
 
Pregnancy and concomitant use with ribavirin 
 
Also see section 4.6.  
 
Extreme caution must be taken to avoid pregnancy in female patients and female partners of male 
patients when dasabuvir is taken in combination with ribavirin (see section 4.6 and refer to the 
Summary of Product Characteristics for ribavirin for additional information). 
 



6 
 

Use with tacrolimus, sirolimus and everolimus  
 
Co-administration of dasabuvir and ombitasvir/paritaprevir/ritonavir with systemic tacrolimus, 
sirolimus or everolimus increases the concentrations of the immunosuppressant due to CYP3A 
inhibition by ritonavir (see section 4.5). Serious and/or life threatening events have been observed with 
co-administration of dasabuvir and ombitasvir/paritaprevir/ritonavir with systemic tacrolimus, and a 
similar risk can be expected with sirolimus and everolimus.  
  
Avoid concomitant use of tacrolimus or sirolimus with dasabuvir and ombitasvir/paritaprevir/ritonavir 
unless the benefits outweigh the risks. If tacrolimus or sirolimus are used together with dasabuvir and 
ombitasvir/paritaprevir/ritonavir, caution is advised, and recommended doses and monitoring 
strategies can be found in section 4.5. Everolimus cannot be used due to lack of suitable dose strengths 
for dose adjustments.  
 
Tacrolimus or sirolimus whole blood concentrations should be monitored upon initiation and 
throughout co-administration with dasabuvir and ombitasvir/paritaprevir/ritonavir and the dose and/or 
dosing frequency should be adjusted as needed.  Patients should be monitored frequently for any 
changes in renal function or tacrolimus or sirolimus associated adverse reactions. Refer to the 
tacrolimus or sirolimus Summary of Product Characteristics for additional dosing and monitoring 
instructions. 
 
Depression or psychiatric illness 
 
Cases of depression and more rarely of suicidal ideation and suicide attempt have been reported with 
dasabuvir with or without ombitasvir/paritaprevir/ritonavir treatment in combination with ribavirin in 
the majority of the cases. Although some cases had previous history of depression, psychiatric illness 
and/or substance abuse, a causal relation with dasabuvir with or without 
ombitasvir/paritaprevir/ritonavir treatment cannot be excluded. Caution should be used in patients with 
a pre-existing history of depression or psychiatric illness. Patients and caregivers should be instructed 
to notify the prescriber of any changes in behaviour or mood and of any suicidal ideation. 
 
Genotype-specific activity 
 
Concerning recommended regimens with different HCV genotypes, see section 4.2. Concerning 
genotype-specific virological and clinical activity, see section 5.1. 
 
The efficacy of dasabuvir has not been established in patients with HCV genotypes other than 
genotype 1; dasabuvir should not be used for the treatment of patients infected with other genotypes 
than 1. 
 
Co-administration with other direct-acting antivirals against HCV 
 
Dasabuvir safety and efficacy have been established in combination with ombitasvir/ paritaprevir 
/ritonavir with or without ribavirin. Co-administration of dasabuvir with other antivirals has not been 
studied and, therefore, cannot be recommended. 
 
Retreatment 
 
The efficacy of dasabuvir in patients previously exposed to dasabuvir, or to medicinal products 
anticipated to be cross-resistant, has not been demonstrated. 
 
Use with statins  
 
Rosuvastatin 
Dasabuvir with ombitasvir/paritaprevir/ritonavir is expected to increase the exposure to rosuvastatin 
more than 3-fold. If rosuvastatin treatment is required during the treatment period, the maximum daily 
dose of rosuvastatin should be 5 mg (see section 4.5, Table 2).  



7 
 

 
Pitavastatin and fluvastatin 
The interactions with pitavastatin and fluvastatin have not been investigated. Theoretically, dasabuvir 
with ombitasvir/paritaprevir/ritonavir is expected to increase the exposure to pitavastatin and 
fluvastatin. A temporary suspension of pitavastatin/fluvastatin is recommended for the duration of 
treatment with ombitasvir/paritaprevir/ritonavir. If statin treatment is required during the treatment 
period, a switch to a reduced dose of pravastatin/rosuvastatin is possible (see section 4.5, Table 2). 
 
Treatment of patients with HIV co-infection 
 
Dasabuvir is recommended in combination with paritaprevir/ombitasvir/ritonavir, and ritonavir may 
select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-
infected patients without suppressive antiretroviral therapy should not be treated with dasabuvir. 
Drug interactions need to be carefully taken into account in the setting of HIV co-infection (for details 
see section 4.5, Table 2). 
 
Atazanavir can be used in combination with dasabuvir with ombitasvir/paritaprevir/ritonavir if 
administered at the same time. To be noted, atazanavir should be taken without ritonavir, since 
ritonavir 100 mg once daily is provided as part of the ombitasvir/paritaprevir/ritonavir fixed dose 
combination. The combination carries an increased risk for hyperbilirubinemia (including ocular 
icterus), in particular when ribavirin is part of the hepatitis C regimen. 
 
Darunavir, dosed 800 mg once daily, if administered at the same time as 
ombitasvir/paritaprevir/ritonavir, can be used in the absence of extensive PI resistance (darunavir 
exposure lowered). To be noted, darunavir should be taken without ritonavir, since ritonavir 100 mg 
once daily is provided as part of the ombitasvir/paritaprevir/ritonavir fixed dose combination. 
 
For the use of HIV protease inhibitors other than atazanavir and darunavir refer to the Summary of 
Product Characteristics of ombitasvir/ paritaprevir /ritonavir. 
 
Raltegravir exposure is substantially increased (2-fold). The combination was not linked to any 
particular safety issues in a limited set of patients treated for 12-24 weeks. 
 
Rilpivirine exposure is substantially increased (3-fold) when rilpivirine is given in combination with 
dasabuvir with ombitasvir/paritaprevir/ritonavir, with a consequent potential for QT-prolongation. If 
an HIV protease inhibitor is added (atazanavir, darunavir), rilpivirine exposure may increase even 
further and is, therefore, not recommended. Rilpivirine should be used cautiously, in the setting of 
repeated ECG monitoring. 
 
NNRTIs other than rilpivirine (efavirenz, etravirine, and nevirapine) are contraindicated (see section 
4.3). 
 
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. 
 
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 medicinal products modified when necessary. The physician in 
charge of the diabetic care of the patient should be informed when direct acting antiviral therapy is 
initiated.  



8 
 

 
. 
 
Lactose 
 
Exviera contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase 
deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Dasabuvir must always be administered together with ombitasvir/paritaprevir/ritonavir . When co-
administered they exert mutual effects on each other (see section 5.2). Therefore, the interaction 
profile of the compounds must be considered as a combination. 
 
Pharmacodynamic interactions 
 
Coadministration with enzyme inducers may lead to an increased risk of adverse reactions and ALT 
elevations (see Table 2). 
Coadministration with ethinyloestradiol may lead to increased risk of ALT elevations (see sections 4.3 
and 4.4). Contraindicated enzyme inducers are provided in section 4.3. 
 
Pharmacokinetic interactions 
 
Potential for dasabuvir to affect the pharmacokinetics of other medicinal products 
In vivo drug interaction studies evaluated the net effect of the combination treatment, including 
ritonavir. The following section describes the specific transporters and metabolizing enzymes that are 
affected by dasabuvir when combined with ombitasvir/paritaprevir/ritonavir. See Table 2 for guidance 
regarding potential drug interactions and dosing recommendations for dasabuvir administered with 
ombitasvir/paritaprevir/ritonavir. 
 
Medicinal products metabolised by CYP3A4 
Refer to the ombitasvir/paritaprevir/ritonavir Summary of Product Characteristics for details. (see also 
Table 2).  
 
Medicinal products transported by the OATP family  
Refer to the ombitasvir/paritaprevir/ritonavir Summary of Product Characteristics for details on 
OATP1B1, OATP1B3 and OATP2B1 substrates (see also Table 2). 
 
Medicinal products transported by BCRP 
Dasabuvir is an inhibitor of BCRP in vivo. Co-administration of dasabuvir with 
ombitasvir/paritaprevir/ritonavir together with medicinal products that are substrates of BCRP may 
increase plasma concentrations of these transporter substrates, potentially requiring dose 
adjustment/clinical monitoring. Such medicinal products include sulfasalazine, imatinib and some of 
the statins (see Table 2). See also Table 2 for specific advice on rosuvastatin which has been evaluated 
in a drug interaction study. 
 
Medicinal products transported by Pgp in the intestine 
While dasabuvir is an in vitro inhibitor of P-gp, no significant change was observed in the exposure of 
the P-gp substrate, digoxin, when administered with dasabuvir with ombitasvir/paritaprevir/ritonavir. 
It may not be excluded that the systemic exposure of dabigatran etexilate is increased by dasabuvir due 
to inhibition of P-gp in the intestine. 
 
Medicinal products metabolised by glucuronidation 
Dasabuvir is an inhibitor of UGT1A1 in vivo. Co-administration of dasabuvir with medicinal products 
that are primarily metabolized by UGT1A1 result in increased plasma concentrations of such 
medicinal products; routine clinical monitoring is recommended for narrow therapeutic index 
medicinal products (i.e. levothyroxine). See also Table 2 for specific advice on raltegravir and 



9 
 

buprenorphine which have been evaluated in drug interaction studies. Dasabuvir has also been found 
to inhibit UGT1A4, 1A6 and intestinal UGT2B7 in vitro at in vivo relevant concentrations. 
 
Medicinal products metabolised by CYP2C19 
Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir can decrease exposures of 
medicinal products that are metabolized by CYP2C19 (e.g. lansoprazole, esomeprazole, s-
 mephenytoin), which may require dose adjustment/clinical monitoring. CYP2C19 substrates 
evaluated in drug interaction studies include omeprazole and escitalopram (Table 2).  
 
Medicinal products metabolised by CYP2C9 
Dasabuvir administered with ombitasvir/paritaprevir/ritonavir did not affect the exposures of the 
CYP2C9 substrate warfarin. Other CYP2C9 substrates (NSAIDs (e.g. ibuprofen), antidiabetics (e.g. 
glimepiride, glipizide) are not expected to require dose adjustments.  
 
Medicinal products metabolised by CYP2D6 or CYP1A2 
Dasabuvir administered with ombitasvir/paritaprevir/ritonavir did not affect the exposures of the 
CYP2D6 /CYP1A2 substrate duloxetine. Exposures of cyclobenzaprine, a CYP1A2 substrate, were 
decreased. Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates (e.g. 
ciprofloxacin, cyclobenzaprine, theophylline and caffeine). CYP2D6 substrates (e.g. desipramine, 
metoprolol and dextromethorphan) are not expected to require dose adjustments.  
 
Medicinal products renally excreted via transport proteins 
Dasabuvir does not inhibit organic anion transporter (OAT1) in vivo as shown by the lack of 
interaction with tenofovir (OAT1 substrate). In vitro studies show that dasabuvir is not an inhibitor of 
organic cation transporters (OCT2), organic anion transporters (OAT3), or multidrug and toxin 
extrusion proteins (MATE1 and MATE2K) at clinically relevant concentrations.  
 
Therefore, dasabuvir is not expected to affect medicinal products which are primarily excreted by the 
renal route via these transporters (see section 5.2).  
 
Potential for other medicinal products to affect the pharmacokinetics of dasabuvir 
 
Medicinal products that inhibit CYP2C8 
Co-administration of dasabuvir with medicinal products that inhibit CYP2C8 (e.g. teriflunomide, 
deferasirox) may increase dasabuvir plasma concentrations. Strong CYP2C8 inhibitors are 
contraindicated with dasabuvir (see section 4.3 and Table 2). 

 
Enzyme inducers  
Co-administration of dasabuvir with medicinal products that are moderate or strong enzyme inducers 
is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect. 
Contraindicated enzyme inducers are provided in section 4.3 and Table 2.  
 
Dasabuvir is a substrate of P-gp and BCRP and its major metabolite M1 is a substrate of OCT1 in 
vitro. Inhibition of P-gp and BCRP is not expected to show clinically relevant increases in exposures 
of dasabuvir (Table 2). 
 
Dasabuvir M1 metabolite was quantified in all the drug interaction studies. Changes in exposures of 
the metabolite were generally consistent with that observed with dasabuvir except for studies with 
CYP2C8 inhibitor, gemfibrozil, where the metabolite exposures decreased by up to 95% and CYP3A 
inducer, carbamazepine, where the metabolite exposures decreased by only up to 39%. 
 
Patients treated with vitamin K antagonists 
 
As liver function may change during treatment with dasabuvir administered with 
ombitasvir/paritaprevir/ritonavir, a close monitoring of International Normalised Ratio (INR) values is 
recommended. 
 



10 
 

Drug interaction studies 
 
Recommendations for co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir for a 
number of medicinal products are provided in Table 2. 
 
If a patient is already taking medicinal product(s) or initiating a medicinal product while receiving 
dasabuvir and ombitasvir/paritaprevir/ritonavir for which potential for drug interaction is expected, 
dose adjustment of the concomitant medicinal product(s) or appropriate clinical monitoring should be 
considered (Table 2). 
 
If dose adjustments of concomitant medicinal products are made due to treatment with dasabuvir and 
ombitasvir/paritaprevir/ritonavir, doses should be re-adjusted after administration of dasabuvir and 
ombitasvir/paritaprevir/ritonavir is completed. 
 
Table 2 provides the Least Squares Means Ratio (90% Confidence Interval) effect on concentration of 
dasabuvir and ombitasvir/paritaprevir/ritonavir and concomitant medicinal products.  
The direction of the arrow indicates the direction of the change in exposures (Cmax, and AUC) in the 
paritaprevir, ombitasvir, dasabuvir and the co-administered medicinal product (↑= increase more than 
20%, ↓ = decrease more than 20%, ↔ = no change or change less than 20%).  
 
This is not an exclusive list. Dasabuvir is administered with ombitasvir/paritaprevir/ritonavir. For 
interactions with ombitasvir/ paritaprevir /ritonavir refer to the Summary of Product Characteristics. 
 
Table 2. Interactions between dasabuvir with ombitasvir/paritaprevir/ritonavir and other 
medicinal products 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

AMINOSALICYLATE 
Sulfasalazine 
 
Mechanism: 
BCRP 
inhibition by 
paritaprevir, 
ritonavir and 
dasabuvir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Not Studied. Expected: 
 
↑ sulfasalazine 
 
 

Caution should be used 
when sulfasalazine is 
co-administered with 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

 
ANTIARRYTHMICS 
Digoxin 
0.5 mg single 
dose  

Mechanism: 
P-gp 
inhibition by 
dasabuvir, 
paritaprevir, 
and ritonavir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↔ digoxin 1.15 
(1.04-1.27) 

1.16  
(1.09-1.23) 

1.01 
(0.97-1.05) 

While no dose 
adjustment is necessary 
for digoxin, appropriate 
monitoring of serum 
digoxin levels is 
recommended. 

↔ 
dasabuvir 

0.99 
(0.92-1.07) 

0.97 
(0.91-1.02) 

0.99 
(0.92-1.07) 

↔ 
ombitasvir  

1.03 
(0.97-1.10) 

1.00 
(0.98-1.03) 

0.99 
(0.96-1.02) 

↔ 
paritaprevir 

0.92 
(0.80-1.06) 

0.94 
(0.81-1.08) 

0.92 
(0.82-1.02) 

ANTIBIOTICS (SYSTEMIC ADMINISTRATION) 
Sulfameth-
oxazole, 
trimethoprim 
 
800/160 mg 
twice daily 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↑ Sulfameth-
oxazole, 

1.21 
(1.15-1.28) 

1.17 
(1.14-1.20) 

1.15 
(1.10-1.20) 

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↑ 
trimethopri
m 

1.17 
(1.12-1.22) 

1.22 
(1.18-1.26) 

1.25 
(1.19-1.31) 

↑ dasabuvir 1.15 1.33 NA 



11 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

 
Mechanism: 
increase in 
dasabuvir 
possibly due 
to CYP2C8 
inhibition by 
trimethoprim 

(1.02-1.31) (1.23-1.44)  
↔ 
ombitasvir 

0.88 
(0.83-0.94) 

0.85 
(0.80-0.90) NA 

↓ 
paritaprevir 

0.78 
(0.61-1.01) 

0.87 
(0.72-1.06) 

NA 

ANTICANCER AGENTS 
Apalutamide 
 
Enzalutamid
e 
 
Mitotane 
 
Mechanism: 
CYP3A4 
induction by 
apalutamide, 
enzalutamide 
or mitotane. 
 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Not studied. Expected: 
 
↓ dasabuvir 
↓ombitasvir 
↓ paritaprevir 
 

Concomitant use is 
contraindicated (see 
section 4.3). 

 

Imatinib 
 
Mechanism: 
BCRP 
inhibition by 
paritaprevir, 
ritonavir and 
dasabuvir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Not Studied. Expected: 
 
↑ imatinib 
 
 

Clinical monitoring and 
lower doses of imatinib 
are recommended. 

 

ANTICOAGULANTS 
Warfarin 
5 mg single 
dose and 
other vitamin 
K 
antagonists  

dasabu
vir +  
ombitas
vir/parit
aprevir/r
itonavir 

 

↔  
R-warfarin 

1.05 
(0.95-1.17) 

0.88 
(0.81-0.95) 

0.94 
(0.84-1.05) 

While no change in the 
pharmacokinetics of 
warfarin is expected, 
close monitoring of INR 
is recommended with 
all vitamin K 
antagonists. This is due 
to liver function 
changes during 
treatment with 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir 

↔  
S-warfarin 

0.96 
(0.85-1.08) 

0.88 
(0.81-0.96) 

0.95 
(0.88-1.02) 

↔  
dasabuvir 

0.97 
(0.89-1.06) 

0.98 
(0.91-1.06) 

1.03 
(0.94-1.13) 

↔  
ombitasvir 

0.94 
(0.89-1.00) 

0.96 
(0.93-1.00) 

0.98 
(0.95-1.02) 

↔  
paritaprevir 

0.98 
(0.82-1.18) 

1.07 
(0.89-1.27) 

0.96 
(0.85-1.09) 

Dabigatran 
etexilate 
Mechanism: 
Intestinal P-
gp inhibition 
by 
paritaprevir 
and ritonavir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

Not Studied. Expected: 
 
↑ dabigatran etexilate 
 
 

dasabuvir + 
ombitasvir/paritaprevir/
ritonavir may increase 
the plasma 
concentrations of 
dabigatran etexilate. 
Use with caution. 
 

ANTICONVULSANTS 
carbamaze-
pine     

dasabu
vir + 

↔ carba-
mazepine 

1.10 
(1.07-1.14) 

1.17 
(1.13-1.22) 

1.35 
(1.27-1.45) 

Concomitant use is 
contraindicated (see 



12 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

200 mg once 
daily 
followed by 
200 mg twice 
daily 

Mechanism: 
CYP3A4 
induction by 
carbamazepi
ne. 

ombitas
vir/parit
aprevir/
ritonavi
r 

↓ 
carbamaze 

pine 10, 11-
epoxide  

0.84 
(0.82-0.87) 

0.75 
(0.73-0.77) 

0.57 
(0.54-0.61) 

section 4.3). 
 
 

↓  
dasabuvir 

0.45 
(0.41-0.50) 

0.30 
 (0.27-
0.33) 

NA 

↓  
ombitasvir 

0.69 
(0.61-0.78) 

0.69 
(0.64-0.74) 

NA 

↓  
paritaprevir 

0.34 
(0.25-0.48) 

0.30 
(0.23-0.38) 

NA 

Phenobarbita
l 
 
Mechanism: 
CYP3A4 
induction by 
phenobarbita
l. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Not studied. Expected: 
 
↓ dasabuvir 
↓ paritaprevir 
↓ ombitasvir 
 

Concomitant use is 
contraindicated (see 
section 4.3). 

 

Phenytoin 
 
Mechanism: 
CYP3A4 
induction by 
phenytoin. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

Not studied. Expected: 
 
↓ dasabuvir 
↓ paritaprevir 
↓ ombitasvir 
 

Concomitant use is 
contraindicated (see 
section 4.3). 

 

S-
mephenytoin 
Mechanism: 
CYP2C19 
induction by 
ritonavir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

Not studied. Expected: 
 
↓ S-mephenytoin 
 

Clinical monitoring and 
dose adjustment maybe 
needed for s-
mephenytoin. 

ANTIDEPRESSANTS 
Escitalopram 
10 mg single 
dose 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↔ es- 
citalopram 

1.00 
(0.96-1.05) 

0.87 
(0.80-0.95) 

NA No dose adjustment is 
necessary for 
escitalopram. ↑ S-

Desmethyl 
citalopram  

1.15 
(1.10-1.21) 

1.36 
(1.03-1.80) 

NA 

↔  
dasabuvir 

1.10 
(0.95-1.27) 

1.01 
(0.93-1.10) 

0.89 
(0.79-1.00) 

↔  
ombitasvir 

1.09 
(1.01-1.18) 

1.02 
(1.00-1.05) 

0.97 
(0.92-1.02) 

↔  
paritaprevir 

1.12 
(0.88-1.43) 

0.98 
(0.85-1.14) 

0.71 
(0.56-0.89) 

 

Duloxetine 
60 mg single 
dose 
 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 
 

↓  
duloxetine 

0.79 
(0.67-0.94) 

0.75 
(0.67-0.83) 

NA No dose adjustment is 
necessary for 
duloxetine. 
 
No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir
/ritonavir. 

↔  
dasabuvir 

0.94 
(0.81-1.09) 

0.92 
(0.81-1.04) 

0.88 
(0.76-1.01) 

↔  
ombitasvir 

0.98 
(0.88-1.08) 

1.00 
(0.95-1.06) 

1.01 
(0.96-1.06) 

↓  
paritaprevir 

0.79 
(0.53-1.16) 

0.83 
(0.62-1.10) 

0.77 
(0.65-0.91) 

ANTIFUNGALS 
Ketoconazol
e 
400 mg once 
daily  

dasabu
vir + 
ombitas
vir/parit

↑ keto-
conazole 

1.15 
(1.09-1.21) 

2.17 
(2.05-2.29) 

NA Concomitant use is 
contraindicated (see the 
Summary of Product 
Characteristics for 

↑ dasabuvir 1.16 
(1.03-1.32) 

1.42 
(1.26-1.59) 

NA 



13 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

 
Mechanism: 
CYP3A4/P-
gp inhibition 
by 
ketoconazole 
and 
paritaprevir/ 
ritonavir/ 
ombitasvir 
 

aprevir/ 
ritonavi
r 

↔  
ombitasvir 

0.98 
(0.90-1.06) 

1.17 
(1.11-1.24) 

NA ombitasvir/paritaprevir/ 
ritonavir). 
 ↑  

paritaprevir 
1.37 

(1.11-1.69) 
1.98 

(1.63-2.42) 
NA 

ANTIHYPERLIPIDAEMICS 
Gemfibrozil 
600 mg twice 
daily 
 
Mechanism: 
Increase in 
dasabuvir 
exposure is 
due to 
CYP2C8 
inhibition 
and increase 
in 
paritaprevir 
is possibly 
due to 
OATP1B1 
inhibition by 
gemfibrozil. 
 

dasabu
vir + 
paritapr
evir/ 
ritonavi
r 

↑ dasabuvir 2.01 
(1.71-2.38) 

11.25 
(9.05-
13.99) 

NA Concomitant use is 
contraindicated (see 
section 4.3). 
 
 

↑  
paritaprevir 

1.21 
(0.94-1.57) 

1.38 
(1.18-1.61) 

NA 

ANTIMYCOBACTERIALS 
Rifampicin 

Mechanism:  
CYP3A4/CY
P2C8 
induction by 
rifampicin. 

dasabu
vir + 
Ombita
svir/par
itaprevi
r 
/ritonav
ir 

Not Studied. Expected: 
 
↓ dasabuvir 
↓ ombitasvir 
↓ paritaprevir 

Concomitant use is 
contra-indicated (see 
section 4.3). 

 

BIGUANIDE ORAL  ANTIHYPERGLYCEMICS 
Metformin  
 
500 mg 
single dose 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↓ 
metformin  

0.77 
(0.71-0.83) 

0.90 
(0.84-0.97) 

NA No dose adjustment 
needed for metformin 
when co-administered 
with dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

0.83 
(0.74-0.93) 

0.86 
(0.78-0.94) 

0.95 
(0.84-1.07) 

↔ 
ombitasvir 

0.92 
(0.87-0.98) 

1.01 
(0.97-1.05) 

1.01 
(0.98-1.04) 

↓ 
paritaprevir 

0.63 
(0.44-0.91) 

0.80 
(0.61-1.03) 

1.22 
(1.13-1.31) 

CALCIUM CHANNEL BLOCKERS 
Amlodipine 
5 mg single 
dose  
 

dasabu
vir + 
ombitas
vir/parit

↑ 
amlodipine  

1.26 
(1.11-1.44) 

2.57 
(2.31-2.86) 

NA Decrease in amlodipine 
dose by 50% and 
monitor patients for 
clinical effects. 

↔ 
dasabuvir 

1.05 
(0.97-1.14) 

1.01 
(0.96-1.06) 

0.95 
(0.89-1.01) 



14 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

Mechanism: 
CYP3A4 
inhibition by 
ritonavir. 

aprevir/
ritonavi
r 

↔ 
ombitasvir 

1.00 
(0.95-1.06) 

1.00 
(0.97-1.04) 

1.00 
(0.97-1.04) 

↓ 
paritaprevir 

0.77 
(0.64-0.94) 

0.78 
(0.68-0.88) 

0.88 
(0.80-0.95) 

CONTRACEPTIVES 
ethinyloestra
diol/ 
norgestimate 
0.035/0.25 m
g once daily  
 
Mechanism: 
possibly due 
to UGT 
inhibition by 
paritaprevir, 
ombitasvir 
and 
dasabuvir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↔ ethinyl 
oestradiol 

1.16 
(0.90-1.50) 

1.06 
(0.96-1.17) 

1.12 
(0.94-1.33) 

Ethinyloestradiol 
containing oral 
contraceptives are 
contraindicated  
(see section 4.3). 
 

Norgestimate metabolites: 
↑ norgestrel 2.26 

(1.91-2.67) 
2.54 

(2.09-3.09) 
2.93 

(2.39-3.57) 
↑ nor-

elgestromin
e 

2.01 
(1.77-2.29) 

2.60 
(2.30-2.95) 

3.11 
(2.51-3.85) 

↓ dasabuvir 0.51 
(0.22-1.18) 

0.48 
(0.23-1.02) 

0.53 
(0.30- 0.95) 

↔ 
ombitasvir 

1.05 
(0.81-1.35) 

0.97 
(0.81-1.15) 

1.00 
(0.88- 1.12) 

↓  
paritaprevir 

0.70 
(0.40-1.21) 

0.66 
(0.42-1.04) 

0.87 
(0.67-1.14) 

nor-
ethindrone 
(progestin 
only pill) 
0.35 mg once 
daily 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↔ nor-
ethindrone 

0.83 
(0.69-1.01) 

0.91 
(0.76-1.09) 

0.85 
(0.64-1.13) 

No dose adjustment is 
necessary for 
norethindrone or 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

1.01 
(0.90-1.14) 

0.96 
(0.85-1.09) 

0.95 
(0.80-1.13) 

↔ 
ombitasvir 

1.00 
(0.93-1.08) 

0.99 
(0.94-1.04) 

0.97 
(0.90-1.03) 

↑  
paritaprevir 

1.24 
(0.95-1.62) 

1.23 
(0.96-1.57) 

1.43 
(1.13-1.80) 

DIURETICS 
Furosemide 
20 mg single 
dose  

Mechanism: 
possibly due 
to UGT1A1 
inhibition by 
paritaprevir, 
ombitasvir 
and 
dasabuvir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↑ 
furosemide 

1.42 
(1.17-1.72) 

1.08 
(1.00-1.17) 

NA Monitor patients for 
clinical effects; a 
decrease in furosemide 
dose of up to 50% may 
be required. 
 
No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 
 
 

↔ 
dasabuvir 

1.12 
(0.96-1.31) 

1.09 
(0.96-1.23) 

1.06 
(0.98-1.14) 

↔ 
ombitasvir 

1.14 
(1.03-1.26) 

1.07 
(1.01-1.12) 

1.12 
(1.08-1.16) 

↔ 
paritaprevir 

0.93 
(0.63-1.36) 

0.92 
(0.70-1.21) 

1.26 
(1.16-1.38) 



15 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

HCV ANTIVIRAL 
Sofosbuvir 

400 mg once 
daily 

Mechanism: 
BCRP and P-
gp inhibition 
by 
paritaprevir, 
ritonavir and 
dasabuvir 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↑ sofosbuvir 1.61 
(1.38-1.88) 

2.12 
(1.91-2.37) 

NA No dose adjustment 
needed for sofosbuvir 
when administered 
with dasabuvir + 
ombitasvir/paritaprevir
/ritonavir. 

↑ GS-
331007 

1.02 
(0.90-1.16) 

1.27 
(1.14-1.42) 

NA 

↔ dasabuvir 1.09 
(0.98-1.22) 

1.02 
(0.95-1.10) 

0.85 
(0.76-0.95) 

↔ 
ombitasvir 

0.93 
(0.84-1.03) 

0.93 
(0.87-0.99) 

0.92 
(0.88-0.96) 

↔ 
paritaprevir 

0.81 
(0.65-1.01) 

0.85 
(0.71-1.01) 

0.82 
(0.67-1.01) 

HERBAL PRODUCTS 
St. John's 
Wort 
(hypericum 
perforatum) 
Mechanism: 
CYP3A4 
induction by 
St. John's 
Wort. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Not Studied. Expected: 
 
↓ dasabuvir 
↓ ombitasvir 
↓ paritaprevir 
 

Concomitant use is 
contraindicated (see 
section 4.3). 

 

HIV ANTIVIRALS: PROTEASE INHIBITORS  
For a general comment on treatment of HIV co-infected patients, including a discussion on different 
antiretroviral regimens that may be used, please see section 4.4 (Treatment of HIV co-infected patients) and the 
Summary of Product Characteristics of ombitasvir/ paritaprevir /ritonavir. 
Atazanavir 

300 mg once 
daily (given 
at the same 
time) 
 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↔ 
atazanavir 

0.91 
(0.84-0.99) 

1.01 
(0.93-1.10) 

0.90 
(0.81-1.01) 

The recommended dose 
of atazanavir is 300 mg, 
without ritonavir, in 
combination with 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. Atazanavir 
must be administered at 

↔ 
dasabuvir 

 

0.83 
(0.71-0.96) 

0.82 
(0.71-0.94) 

0.79 
(0.66-0.94) 

↓ 
ombitasvir 

0.77 
(0.70-0.85) 

0.83 
 (0.74-
0.94) 

0.89 
(0.78-1.02) 



16 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

Mechanism: 
Increase in 
paritaprevir 
exposures 
may be due 
to inhibition 
of OATPs by 
atazanavir. 
 

↑ 
paritaprevir 

1.46 
(1.06-1.99) 

1.94 
(1.34-2.81) 

3.26 
(2.06-5.16) 

the same time as 
dasabuvir 
+ombitasvir/paritaprevi
r/ritonavir. Ritonavir 
dose in 
ombitasvir/paritaprevir/
ritonavir will provide 
atazanavir 
pharmacokinetic 
enhancement. 

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 
 
The combination of 
atazanavir and 
ombitasvir/paritaprevir/
ritonavir + dasabuvir 
increase bilirubin 
levels, in particular 
when ribavirin is part 
of the hepatitis C 
regimen, see sections 
4.4 and 4.8. 

Atazanavir/ 
ritonavir 
300/100 mg 
once daily 

(administere
d in the 
evening) 
 
Mechanism: 
Increase in 
paritaprevir 
exposures 
may be due 
to inhibition 
of 
OATP1B1/B
3 and 
CYP3A by 
atazanavir 
and CYP3A 
inhibition by 
the 
additional 
dose of 
ritonavir. 
 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↔ 
atazanavir 

1.02 
(0.92-1.13) 

1.19 
(1.11-1.28) 

1.68 
(1.44-1.95) 

 
 

↔ 
dasabuvir 

0.81 
(0.73-0.91) 

0.81 
(0.71-0.92) 

0.80 
(0.65-0.98) 

↔ 
ombitasvir 

0.83 
(0.72-0.96) 

0.90 
(0.78-1.02) 

1.00 
(0.89-1.13) 

↑ 
paritaprevir 

2.19 
(1.61-2.98) 

3.16 
(2.40-4.17) 

11.95 
(8.94-15.98) 



17 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

Darunavir 

800 mg once 
daily (given 
at the same 
time) 
 
Mechanism: 
Unknown 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↓ darunavir 0.92 
(0.87-0.98) 

0.76 
(0.71-0.82) 

0.52 
(0.47-0.58) 

The recommended dose 
of darunavir is 800 mg 
once daily, without 
ritonavir, when 
administered at the 
same time as 
ombitasvir/paritaprevir/
ritonavir + dasabuvir 
(ritonavir dose in 
ombitasvir/paritaprevir/
ritonavir will provide 
darunavir 
pharmacokinetic 
enhancement). This 
regimen can be used in 
the absence of 
extensive PI resistance 
(i.e. lack of darunavir 
associated RAMs), see 
also section 4.4. 
 
Darunavir combined 
with 
ombitasvir/paritaprevir/
ritonavir + dasabuvir is 
not recommended in 
patients with extensive 
PI resistance. 

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

1.10 
(0.88-1.37 

0.94 
(0.78-1.14) 

0.90 
(0.76-1.06) 

↔  
ombitasvir 

0.86 
(0.77-0.95) 

0.86 
(0.79-0.94) 

0.87 
(0.82-0.92) 

↑  
paritaprevir 

1.54 
(1.14-2.09) 

1.29 
(1.04-1.61) 

1.30 
(1.09-1.54) 

Darunavir/ 
ritonavir 
600/100 mg 
twice daily 

Mechanism: 
Unknown 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↔ 
darunavir 

0.87 
(0.79-0.96) 

0.80 
(0.74-0.86) 

0.57 
(0.48-0.67) 

 

↓ dasabuvir 0.84 
(0.67-1.05) 

0.73 
(0.62-0.86) 

0.54 
(0.49-0.61) 

↓ 
ombitasvir 

0.76 
(0.65-0.88) 

0.73 
(0.66-0.80) 

0.73 
(0.64-0.83) 

↓ 
paritaprevir 

0.70 
(0.43-1.12) 

0.59 
(0.44-0.79) 

0.83 
(0.69-1.01) 

Darunavir/ 
ritonavir 
800/100 mg 
once daily 
(administere
d in the 
evening) 

Mechanism: 
Unknown 
 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↑ darunavir 0.79 
(0.70-0.90) 

1.34 
(1.25-1.43) 

0.54 
(0.48-0.62) 

 

↓ dasabuvir  0.75 
(0.64-0.88) 

0.72 
(0.64-0.82) 

0.65 
(0.58-0.72) 

↔  
ombitasvir 

0.87 
(0.82-0.93) 

0.87 
(0.81-0.93) 

0.87 
(0.80-0.95) 

↓ 
paritaprevir 

0.70 
(0.50-0.99) 

0.81 
(0.60-1.09) 

1.59 
(1.23-2.05) 

lopinavir / 
ritonavir 
400/100 mg 

dasabu
vir + 
ombitas
vir/parit

↔ 
lopinavir 

0.87 
(0.76-0.99) 

0.94 
(0.81-1.10) 

1.15 
(0.93-1.42) 

Lopinavir/ritonavir 
400/100 mg twice daily 
or 800/200 mg once 
daily is contraindicated 

↔ 
dasabuvir 

0.99  
(0.75-1.31) 

0.93  
(0.75-1.15) 

0.68  
(0.57-0.80) 



18 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

twice daily1 

Mechanism: 
Increase in 
paritaprevir 
exposures 
may be due 
to inhibition 
of 
CYP3A/efflu
x 
transporters 
by lopinavir 
and higher 
dose of 
ritonavir. 

aprevir/
ritonavi
r 

↔ 
ombitasvir 

1.14  
(1.01-1.28) 

1.17  
(1.07-1.28) 

1.24  
(1.14-1.34) 

with dasabuvir and 
ombitasvir/paritaprevir/r
itonavir due to increase 
in paritaprevir exposures 
(see Summary of 
Product Characteristics 
of 
ombitasvir/paritaprevir/r
itonavir). 

 

↑ 
paritaprevir 

2.04  
(1.30-3.20) 

2.17  
(1.63-2.89) 

2.36  
(1.00-5.55) 

HIV ANTIVIRALS: NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS  
Rilpivirine2  
25 mg once 
daily 
administered 
in the 
morning, 
with food 

Mechanism: 
CYP3A 
inhibition by 
ritonavir. 

 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↑ rilpivirine 2.55 
(2.08-3.12) 

3.25 
(2.80-3.77) 

3.62 
(3.12-4.21) 

Co-administration of 
dasabuvir and 
ombitasvir/paritaprevir/
ritonavir with 
rilpivirine once daily 
should only be 
considered in patients 
without known QT-
prolongation, and 
without other QT-
prolongation co-
administered medicinal 
products. If the 
combination is used, 
repeated ECG-
monitoring should be 
done, see section 4.4.  

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

1.18 
(1.02-1.37) 

1.17 
(0.99-1.38) 

1.10 
(0.89-1.37) 

↔ 
ombitasvir 

1.11 
(1.02-1.20) 

1.09 
(1.04-1.14) 

1.05 
(1.01-1.08) 

↑ 
paritaprevir 

 

1.30 
(0.94-1.81) 

1.23 
(0.93-1.64) 

0.95 
(0.84-1.07) 

Efavirenz/ 
emtricitabine
/ tenofovir 
disoproxil 
fumarate 
600/300/200 
mg once 
daily 

Mechanism: 
possible 
enzyme 
induction by 
efavirenz. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Co-administration of efavirenz (enzyme inducer) based 
regimens with paritaprevir /ritonavir + dasabuvir resulted 
in ALT elevations and therefore, early discontinuation of 

the study. 

Concomitant use with 
efavirenz containing 
regimens is 
contraindicated (see 
section 4.3). 

 



19 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

Nevirapine 
etravirine 

 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Not Studied. Expected: 
 
↓ dasabuvir  
↓ ombitasvir 
↓ paritaprevir 

 

Concomitant use is 
contraindicated (see 
section 4.3). 

HIV ANTIVIRALS: INTEGRASE STRAND TRANSFER INHIBITOR 
Dolutegravir 

50 mg once 
daily 

Mechanism: 
possibly due 
to UGT1A1 
inhibition by 
paritaprevir, 
dasabuvir 
and 
ombitasvir 
and CYP3A4 
inhibition by 
ritonavir 

dasabuvi
r + 
ombitas
vir/parit
aprevir/r
itonavir 

↑ 
dolutegravir 

1.22 
(1.15-1.29) 

1.38 
(1.30-1.47) 

1.36 
(1.19-1.55) 

No dose adjustment 
needed for dolutegravir 
when administered 
with dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

1.01 
(0.92-1.11) 

0.98 
(0.92-1.05) 

0.92 
(0.85-0.99) 

↔ 
ombitasvir 

0.96 
(0.89-1.03) 

0.95 
(0.90-1.00) 

0.92 
(0.87-0.98) 

↔ 
paritaprevir 

0.89 
(0.69-1.14) 

0.84 
(0.67-1.04) 

0.66 
(0.59-0.75) 

Raltegravir 

400 mg twice 
daily 

Mechanism: 
UGT1A1 
inhibition by 
paritaprevir, 
ombitasvir 
and 
dasabuvir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↑ 
raltegravir 

 

2.33 
(1.66-3.27) 

2.34 
(1.70-3.24) 

2.00 
(1.17-3.42) 

No dose adjustment is 
necessary for 
raltegravir or dasabuvir 
+ 
ombitasvir/paritaprevir/
ritonavir. 

 

No clinically relevant changes in dasabuvir, paritaprevir, 
and ombitasvir exposures (based on comparison with 

historical data) were observed during the co-
administration. 

HIV ANTIVIRALS: NUCLEOSIDE INHIBITORS  
Abacavir/ 
lamivudine 

600/300 mg 
once daily 

 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↔ abacavir 0.87 
(0.78-0.98) 

0.94 
(0.90-0.99) 

NA No dose adjustment 
needed for abacavir or 
lamivudine when 
administered with 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↓ 
lamivudine 

0.78 
(0.72-0.84) 

0.88 
(0.82-0.93) 

1.29 
(1.05-1.58) 

↔ 
dasabuvir 

0.94 
(0.86-1.03) 

0.91 
(0.86-0.96) 

0.95 
(0.88-1.02) 

↔ 
ombitasvir 

0.82 
(0.76-0.89) 

0.91 
(0.87-0.95) 

0.92 
(0.88-0.96) 

↔ 
paritaprevir 

0.84 
(0.69-1.02) 

0.82 
(0.70-0.97) 

0.73 
(0.63-0.85) 



20 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

Em-
tricitabine/ 
tenofovir 
200 mg once 
daily/300 mg 
once daily 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↔ em-
tricitabine 

1.05 
(1.00-1.12) 

1.07 
(1.00-1.14) 

1.09 
(1.01-1.17) 

No dose adjustment is 
necessary for 
emtricitabine/tenofovir 
and dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
tenofovir 

1.07 
(0.93-1.24) 

1.13 
(1.07-1.20) 

1.24 
(1.13-1.36) 

↔ 
dasabuvir 

0.85 
(0.74-0.98) 

0.85 
(0.75-0.96) 

0.85 
(0.73-0.98) 

↔ 
ombitasvir 

0.89 
(0.81-0.97) 

0.99 
(0.93-1.05) 

0.97 
(0.90-1.04) 

↓ 
paritaprevir  

0.68 
(0.42-1.11) 

0.84 
(0.59-1.17) 

1.06 
(0.83-1.35) 

HMG CoA REDUCTASE INHIBITOR 
Rosuvastatin 
5 mg once 
daily  

Mechanism: 
OATP1B 
inhibition by 
paritaprevir 
and BCRP 
inhibition by 
dasabuvir 
paritaprevir, 
and ritonavir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↑ 
rosuvastatin 

7.13 
(5.11-9.96) 

2.59 
(2.09-3.21) 

0.59 
(0.51-0.69) 

The maximum daily 
dose of rosuvastatin 
should be 5 mg (see 
section 4.4). 

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 
 

 

↔ 
dasabuvir 

 

1.07 
(0.92-1.24) 

1.08 
(0.92-1.26) 

1.15 
(1.05-1.25) 

↔ 
ombitasvir 

0.92 
(0.82-1.04) 

0.89 
(0.83-0.95) 

0.88 
(0.83-0.94) 

↑ 
paritaprevir 

1.59 
(1.13-2.23) 

1.52 
(1.23-1.90) 

1.43 
(1.22-1.68) 

Pravastatin 
10 mg once 
daily 

Mechanism: 
OATP1B1 
inhibition by 
paritaprevir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↑ 
pravastatin 

1.37 
(1.11-1.69) 

1.82 
(1.60-2.08) 

 Reduce pravastatin 
dose by 50%.  

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir
/ritonavir. 

↔ 
dasabuvir 

 

1.00 
(0.87-1.14) 

0.96 
(0.85-1.09) 

1.03 
(0.91-1.15) 

↔ 
ombitasvir 

 0.95 
(0.89-1.02) 

0.94 
(0.89-0.99) 

 0.94 
(0.89-0.99) 

↔ 
paritaprevi
r 

0.96 
(0.69-1.32) 

1.13 
 (0.92-1.38) 

1.39 
(1.21-1.59) 

Fluvastatin 
 
Mechanism: 
OATP1B/BC
RP inhibition 
by 
paritaprevir. 
 
Pitavastatin 
 
Mechanism: 
OATP1B 
inhibition by 
paritaprevir. 
 
 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

Not studied. Expected: 
 
↑   fluvastatin 
↑   pitavastatin 
↔ dasabuvir 
↔ ombitasvir 
↔ paritaprevir 
 

Concomitant use with 
fluvastatin and 
pitavastatin is not 
recommended (see 
section 4.4). 
A temporary 
suspension of 
fluvastatin and 
pitavastatin is 
recommended for the 
duration of treatment. If 
statin treatment is 
required during the 
treatment period, a 
switch to dose reduced 
pravastatin or 
rosuvastatin is possible. 

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 



21 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

IMMUNOSUPPRESSANTS 
Ciclosporin 
30 mg once 
daily single 
dose3 

Mechanism: 
Effect on 
ciclosporin is 
due to 
CYP3A4 
inhibition by 
ritonavir and 
increase in 
paritaprevir 
exposures 
may be due 
to 
OATP/BCRP
/P-gp 
inhibition by 
ciclosporin. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↑ 
ciclosporin 

1.01 
(0.85-1.20) 

5.82 
(4.73-7.14) 

15.8 
(13.8-18.09) 

When starting co-
administration with 
dasabuvir and 
ombitasvir/paritaprevir/
ritonavir, give one fifth 
of the total daily dose 
of ciclosporin once 
daily with ombitasvir/ 
paritaprevir /ritonavir. 
Monitor ciclosporin 
levels and adjust dose 
and/or dosing 
frequency as needed.  
 
No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir.  
 

↓ dasabuvir 0.66 
(0.58-0.75) 

0.70 
(0.65-0.76) 

0.76 
(0.71-0.82) 

↔ 
ombitasvir 

0.99 
(0.92-1.07) 

1.08 
(1.05-1.11) 

1.15 
(1.08-1.23) 

↑ 
paritaprevir 

1.44 
(1.16-1.78) 

1.72 
(1.49-1.99) 

1.85 
(1.58-2.18) 

Everolimus 

0.75 mg 
single dose 

Mechanism: 
Effect on 
everolimus is 
due to 
CYP3A4 
inhibition by 
ritonavir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↑ 
everolimus 

 

4.74 
(4.29-5.25) 

27.1 
(24.5-30.1) 

16.1 
(14.5-17.9)4 

Co-administration of 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir with 
everolimus is not 
recommended because 
of a significant increase 
in everolimus 
exposures which cannot 
be properly dose 
adjusted with available 
dose strengths. 

↔ 
dasabuvir 

1.03 
(0.90-1.18) 

1.08 
(0.98-1.20) 

1.14 
(1.05-1.23) 

↔ 
ombitasvir 

0.99 
(0.95-1.03) 

1.02 
(0.99-1.05) 

1.02 
(0.99-1.06) 

↔ 
paritaprevir 

1.22 
(1.03-1.43) 

1.26 
(1.07-1.49) 

1.06 
(0.97-1.16) 

Sirolimus 

0.5 mg single 
dose5 

Mechanism: 
Effect on 
sirolimus is 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

 

↑ Sirolimus 
 

6.40 
(5.34-7.68) 

38.0 
(31.5-45.8) 

19.6  
(16.7-22.9)6 

Concomitant use of 
sirolimus with 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir is not 
recommended unless 
the benefits outweigh 
the risks (see section 
4.4). If sirolimus is 

↔ 
dasabuvir 

1.04 
(0.89-1.22) 

1.07 
(0.95-1.22) 

1.13 
(1.01-1.25) 

↔ 
ombitasvir 

1.03 
(0.93-1.15) 

1.02 
(0.96-1.09) 

1.05 
(0.98-1.12) 



22 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

due to 
CYP3A4 
inhibition by 
ritonavir. 

↔ 
paritaprevir 

1.18 
(0.91-1.54) 

1.19 
(0.97-1.46) 

1.16 
(1.00-1.34) 

used together with 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir, administer 
sirolimus 0.2 mg twice 
a week (every 3 or 4 
days on the same two 
days each week). 
Sirolimus blood 
concentrations should 
be monitored every 4 to 
7 days until 3 
consecutive trough 
levels have shown 
stable concentrations of 
sirolimus. Sirolimus 
dose and/or dosing 
frequency should be 
adjusted as needed. 
 
5 days after completion 
of dasabuvir + 
ombitasvir/paritaprevir/
ritonavir treatment, the 
sirolimus dose and 
dosing frequency prior 
to receiving dasabuvir 
+ 
ombitasvir/paritaprevir/
ritonavir should be 
resumed, along with 
routine monitoring of 
sirolimus blood 
concentrations. 

Tacrolimus    
2 mg single 
dose7 

Mechanism: 
Effect on 

dasabu
vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

↑ 
tacrolimus 

3.99 
(3.21-4.97) 

57.1 
 (45.5-
71.7) 

16.6 
(13.0-21.2) 

Concomitant use of 
tacrolimus with 
dasabuvir and 
ombitasvir/paritaprevir/
ritonavir is not 
recommended unless 
the benefits outweigh 

↔ 
dasabuvir 

0.85 
(0.73-0.98) 

0.90 
(0.80-1.02) 

1.01 
(0.91-1.11) 

↔ 
ombitasvir 

0.93 
(0.88-0.99) 

0.94 
(0.89-0.98) 

0.94 
(0.91-0.96) 



23 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

tacrolimus is 
due to 
CYP3A4 
inhibition by 
ritonavir. 

↓ 
paritaprevir  

0.57 
(0.42-0.78) 

0.66 
(0.54-0.81) 

0.73 
(0.66-0.80) 

the risks (see section 
4.4).  
If tacrolimus with 
dasabuvir and 
ombitasvir/paritaprevir/
ritonavir are used 
concomitantly, 
tacrolimus should not 
be administered on the 
day dasabuvir and 
ombitasvir/paritaprevir/
ritonavir are initiated. 
Beginning the day after 
dasabuvir and 
ombitasvir/paritaprevir/
ritonavir are initiated; 
reinitiate tacrolimus at 
a reduced dose based 
on tacrolimus blood 
concentrations. The 
recommended 
tacrolimus dosing is 
0.5 mg every 7 days. 

Tacrolimus whole 
blood concentrations 
should be monitored 
upon initiation and 
throughout co-
administration with 
dasabuvir and 
ombitasvir/paritaprevir/
ritonavir and the dose 
and/or dosing 
frequency should be 
adjusted as 
needed.  Upon 
completion of 
dasabuvir and 
ombitasvir/paritaprevir/
ritonavir treatment, the 
appropriate dose and 
dosing frequency of 
tacrolimus should be 
guided by assessment 
of tacrolimus blood 
concentrations.  

IRON CHELATORS 
Deferasirox dasabu

vir + 
ombitas
vir/parit
aprevir/
ritonavi
r 

Not studied. Expected: 
 

↑ dasabuvir 

Deferasirox may 
increase dasabuvir 
exposures and should be 
used with caution. 



24 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

MEDICINAL PRODUCTS USED IN MULTIPLE SCLEROSIS 
Teriflunomid
e 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

Not studied. Expected: 

↑ dasabuvir 

Teriflunomide may 
increase dasabuvir 
exposures and should be 
used with caution. 

OPIOIDS 
Methadone 

20-120 mg 
once daily8 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↔ R-
Methadone 

1.04 
(0.98-1.11) 

1.05 
(0.98-1.11) 

0.94 
(0.87-1.01) 

No dose adjustment is 
necessary for 
methadone and 
dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ S-
Methadone 

0.99 
(0.91-1.08) 

0.99 
(0.89-1.09) 

0.86 
(0.76-0.96) 

↔ ombitasvir/paritaprevir and dasabuvir (based on the 
cross-study comparison) 

buprenorphin
e/ naloxone  
4-24 mg/1-
6 mg once 
daily8 

Mechanism: 
CYP3A4 
inhibition by 
ritonavir and 
UGT 
inhibition by 
paritaprevir, 
ombitasvir 
and 
dasabuvir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↑ bu-
prenorphine 

2.18 
(1.78-2.68) 

2.07 
(1.78-2.40) 

3.12 
(2.29-4.27) 

No dose adjustment is 
necessary for 
buprenorphine/naloxon
e and dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

 

↑ norbu-
prenorphine 

2.07 
(1.42-3.01) 

1.84 
(1.30-2.60) 

2.10 
(1.49- 2.97) 

↑ naloxone 1.18 
(0.81-1.73) 

1.28 
(0.92-1.79) 

NA 

↔ ombitasvir /paritaprevir  and dasabuvir (based on the 
cross-study comparison) 

MUSCLE RELAXANTS 
Carisoprodol 
250 mg 
single dose 

Mechanism: 
CYP2C19 
induction by 
ritonavir 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↓ 
Carisoprodol 

0.54 
(0.47-0.63) 

0.62 
(0.55-0.70) 

NA No dose adjustment 
required for 
carisoprodol; increase 
dose if clinically 
indicated. 

↔ dasabuvir 0.96 
(0.91-1.01) 

1.02 
(0.97-1.07) 

1.00 
(0.92-1.10) 

↔ 
ombitasvir 

0.98 
(0.92-1.04) 

0.95 
(0.92-0.97) 

0.96 
(0.92-0.99) 

↔ 
paritaprevir 

0.88 
(0.75-1.03) 

0.96 
(0.85-1.08) 

1.14 
(1.02-1.27) 

Cyclobenzap
rine 5 mg 
single dose 

Mechanism: 
decrease 
possibly due 
to CYP1A2 
induction by 
ritonavir 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↓ 
cyclobenzap
rine 

0.68 
(0.61-0.75) 

 

0.60 
(0.53-0.68) 

NA No dose adjustment for 
cyclobenzaprine 
required; increase dose 
if clinically indicated. ↔ dasabuvir 0.98 

(0.90-1.07) 
1.01 

(0.96-1.06) 
1.13 

(1.07-1.18) 
↔ 
ombitasvir 

0.98 
(0.92-1.04) 

1.00 
(0.97-1.03) 

1.01 
(0.98-1.04) 

↔ 
paritaprevir 

1.14 
(0.99-1.32) 

1.13 
(1.00-1.28) 

1.13 
(1.01-1.25) 

NARCOTIC ANALGESICS 
Paracetamol 
(given as 
fixed dose 
hydrocodone
/paracetamol

dasabu
vir + 
ombitas
vir/parit
aprevir/r

↔ 
Paracetamo
l 

1.02 
(0.89-1.18) 

1.17 
(1.09-1.26) 

NA No dose adjustment is 
necessary for 
paracetamol when 
administered with 
dasabuvir + 

↔ 
dasabuvir 

1.13 
 (1.01-1.26) 

1.12 
 (1.05-

1.16 
(1.08-1.25) 



25 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

) 

300 mg 
single dose 

itonavir 1.19) ombitasvir/paritaprevir/
ritonavir. ↔ 

ombitasvir 
1.01 

(0.93-1.10) 
0.97 

(0.93-1.02) 
0.93 

(0.90-0.97) 
↔ 
paritaprevir 

1.01 
(0.80-1.27) 

1.03 
(0.89-1.18) 

1.10 
(0.97-1.26) 

Hydrocodone 
(as given in a 
fixed-dose 
hydrocodone
/paracetamol
) 

5 mg single 
dose 

Mechanism: 
CYP3A4 
inhibition by 
ritonavir  

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↑  hydrocod
one 

1.27 
(1.14-
1.40) 

1.90 
(1.72-
2.10) 

NA A reduction of 
hydrocodone dose by 
50% and/or clinical 
monitoring should be 
considered when 
administered with 
dasabuvir + 
ombitasvir/paritaprevir
/ritonavir. 

 

Changes for dasabuvir and ombitasvir, paritaprevir 
are the same as shown for paracetamol above 

PROTON PUMP INHIBITORS 
Omeprazole 
40 mg once 
daily  

Mechanism: 
CYP2C19 
induction by 
ritonavir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↓ 
omeprazole 

0.62 
(0.48-0.80) 

0.62 
(0.51-0.75) 

NA If clinically indicated, 
higher doses of 
omeprazole should be 
used.  
No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

1.13 
(1.03-1.25) 

1.08 
(0.98-1.20) 

1.05 
(0.93-1.19) 

↔ 
ombitasvir 

1.02 
(0.95-1.09) 

1.05 
(0.98-1.12) 

1.04 
(0.98-1.11) 

↔ 
paritaprevir 

1.19 
(1.04-1.36) 

1.18 
(1.03-1.37) 

0.92 
(0.76-1.12) 

Esomeprazol
e 
Lansoprazole 
Mechanism: 
CYP2C19 
induction by 
ritonavir. 

 
dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

Not studied. Expected: 
↓ esomeprazole, lansoprazole 
 

 

If clinically indicated,  
higher doses of 
esomeprazole/lansopraz
ole may be needed. 

 

SEDATIVES / HYPNOTICS 
Zolpidem 
5 mg single 
dose 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↔ 
zolpidem 

 

0.94 
(0.76-1.16) 

0.95 
(0.74-1.23) 

NA No dose adjustment is 
necessary for zolpidem. 

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

0.93 
(0.84-1.03) 

0.95 
(0.84-1.08) 

0.92 
(0.83-1.01) 

↔ 
ombitasvir 

1.07 
(1.00-1.15) 

1.03 
(1.00-1.07) 

1.04 
(1.00-1.08) 

↓ 
paritaprevir 

0.63 
(0.46-0.86) 

0.68 
(0.55-0.85) 

1.23 
(1.10-1.38) 

Diazepam 

2 mg single 
dose 

Mechanism: 
CYP2C19 
induction by 
ritonavir 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↓diazepam 1.18 
(1.07-1.30) 

0.78 
(0.73-0.82) NA 

No dose adjustment 
required for diazepam; 
increase dose if 
clinically indicated. 

↓ 
nordiazepam 

1.10 
(1.03-1.19) 

0.56 
(0.45-0.70) 

NA 

↔ 
dasabuvir 

1.05 
(0.98-1.13) 

1.01 
(0.94-1.08) 

1.05 
(0.98-1.12) 

↔ 
ombitasvir 

1.00 
(0.93-1.08) 

0.98 
(0.93-1.03) 

0.93 
(0.88-0.98) 

↔ 
paritaprevir 

0.95 
(0.77-1.18) 

0.91 
(0.78-1.07) 

0.92 
(0.82-1.03) 



26 
 

Medicinal 
Product/ 
Possible 

Mechanism 
of 

Interaction 

GIVE
N 

WITH 

EFFECT Cmax AUC Ctrough Clinical Comments 

Alprazolam 
0.5 mg single 
dose   

Mechanism: 
CYP3A4 
inhibition by 
ritonavir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

↑ 
alprazolam 

1.09 
(1.03-1.15) 

1.34 
(1.15-1.55) 

NA Clinical monitoring of 
patients is 
recommended. A 
decrease in alprazolam 
dose can be considered 
based on clinical 
response.  

No dose adjustment 
needed for dasabuvir + 
ombitasvir/paritaprevir/
ritonavir. 

↔ 
dasabuvir 

0.93 
(0.83-1.04) 

0.98 
(0.87-1.11) 

1.00 
(0.87-1.15) 

↔ 
ombitasvir 

0.98 
(0.93-1.04) 

1.00 
(0.96-1.04) 

0.98 
(0.93-1.04) 

↔ 
paritaprevir  

0.91 
(0.64-1.31) 

0.96 
(0.73-1.27) 

1.12 
(1.02-1.23) 

THYROID HORMONES 
Levothyroxin
e 
 
Mechanism: 
UGT1A1 
inhibition by 
paritaprevir, 
ombitasvir 
and 
dasabuvir. 

dasabu
vir + 
ombitas
vir/parit
aprevir/r
itonavir 

Not studied. Expected: 
 
↑ levothyroxine 
 
 

Clinical monitoring and 
dose adjustment may be 
required for 
levothyroxine. 

 

1. Lopinavir/ritonavir 800/200 mg once daily (administered in the evening) was also administered with 
dasabuvir with ombitasvir/paritaprevir/ritonavir. The effect on Cmax and AUC of DAAs and lopinavir 
was similar to that observed when lopinavir/ritonavir 400/100 mg twice daily was administered with 
dasabuvir and ombitasvir/paritaprevir/ritonavir. 

2. Rilpivirine was also administered with food in the evening and 4 hours after dinner with dasabuvir + 
ombitasvir/paritaprevir/ritonavir in the study. The effect on rilpivirine exposures was similar to that 
observed when rilpivirine was administered in the morning with food with dasabuvir + 
ombitasvir/paritaprevir/ritonavir. 
 

3. Ciclosporin 100 mg dosed alone and 30 mg administered with dasabuvir + 
ombitasvir/paritaprevir/ritonavir. Dose normalized cyclosporine ratios are shown for interaction with 
dasabuvir + ombitasvir/paritaprevir/ritonavir.  
 

4. C12:= concentration at 12 hours following single dose of everolimus. 
 

5. Sirolimus 2 mg was dosed alone, 0.5 mg administered with dasabuvir + 
ombitasvir/paritaprevir/ritonavir. Dose normalized sirolimus ratios are shown for interaction with 
ombitasvir/paritaprevir/ritonavir + dasabuvir. 
 

6. C24:= concentration at 24 hours following single dose of cyclosporine, tacrolimus or sirolimus. 
 

7. Tacrolimus 2 mg was dosed alone and 2 mg was administered with dasabuvir + 
ombitasvir/paritaprevir/ritonavir. Dose normalized tacrolimus ratios are shown for interaction with 
dasabuvir + ombitasvir/paritaprevir/ritonavir. 
 

8. Dose normalised parameters reported for methadone, buprenorphine and naloxone. 
 

Note: Doses used for dasabuvir + ombitasvir/paritaprevir/ritonavir were: ombitasvir 25 mg paritaprevir 150 mg, 
ritonavir 100 mg, once daily and dasabuvir 400 mg twice daily or 250 mg twice daily. The dasabuvir exposures 
obtained with the 400 mg formulation and the 250 mg tablet are similar. dasabuvir + 
ombitasvir/paritaprevir/ritonavir was administered as multiple doses in all the drug interaction studies except 
the drug interaction studies with carbamazepine, gemfibrozil, ketoconazole, and 
sulfamethoxazole/trimethoprim. 
 



27 
 

 
Paediatric population 
 
Drug interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential /contraception in males and females 
 
Extreme caution must be taken to avoid pregnancy in female patients and female partners of male 
patients when dasabuvir is used with ribavirin. Significant teratogenic and/or embryocidal effects have 
been demonstrated in all animal species exposed to ribavirin; therefore, ribavirin is contraindicated in 
women who are pregnant and in the male partners of women who are pregnant. Refer to the Summary 
of Product Characteristics for ribavirin for additional information. 
 
Female patients: Women of childbearing potential should not receive ribavirin unless they are using 
an effective form of contraception during treatment with ribavirin and for 4 months after treatment.  
 
Male patients and their female partners: Either male patients or their female partners of childbearing 
potential must use a form of effective contraception during treatment with ribavirin and for 7 months 
after treatment.  
 
Ethinyloestradiol is contraindicated in combination with dasabuvir (see section 4.3). See additional 
information on specific hormonal contraceptives in sections 4.3 and 4.4. 
 
Pregnancy 
 
There are very limited data from the use of dasabuvir in pregnant women. Animal studies do not 
indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a 
precautionary measure, it is preferable to avoid the use of dasabuvir during pregnancy. 
 
If ribavirin is co-administered with dasabuvir and ombitasvir/paritaprevir/ritonavir, the 
contraindications regarding use of ribavirin during pregnancy apply (see also the Summary of Product 
Characteristics of ribavirin).  
 
Breast-feeding 
 
It is not known whether dasabuvir and metabolites are excreted in human breast milk. Available 
pharmacokinetic data in animals have shown excretion of dasabuvir and metabolites in milk (see 
section 5.3). Because of the potential for adverse reactions from the medicinal product in breastfed 
infants, a decision must be made whether to discontinue breastfeeding or discontinue treatment with 
dasabuvir, taking into account the importance of the therapy to the mother. Patients receiving ribavirin 
should also refer to the Summary of Product Characteristics of ribavirin. 
 
Fertility 
 
No human data on the effect of dasabuvir on fertility are available. Animal studies do not indicate 
harmful effects on fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Dasabuvir has no or negligible influence on the ability to drive and use machines.  Patients should be 
informed that fatigue has been reported during treatment with dasabuvir in combination with 
ombitasvir/paritaprevir/ritonavir and ribavirin (see section 4.8). 



28 
 

 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
 
In subjects receiving dasabuvir and ombitasvir/paritaprevir/ritonavir with ribavirin, the most 
commonly reported adverse reactions (greater than 20% of subjects) were fatigue and nausea. The 
proportion of subjects who permanently discontinued treatment due to adverse reactions was 0.2% 
(5/2,044) and 4.8% (99/2,044) of subjects had ribavirin dose reductions due to adverse reactions. 
 
 
 
Tabulated list of adverse reactions 
 
The safety summary is based on pooled data from phase 2 and 3 clinical trials in subjects who received 
dasabuvir and ombitasvir/paritaprevir/ritonavir with or without ribavirin.  The majority of adverse 
reactions presented in Table 3 were of grade 1 severity in dasabuvir- and 
ombitasvir/paritaprevir/ritonavir-containing regimens. 
 
The adverse reactions are listed below by 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) or very rare (<1/10,000).  
 
Table 3. Adverse reactions identified with dasabuvir in combination with 
ombitasvir/paritaprevir/ritonavir or ombitasvir/paritaprevir/ritonavir and ribavirin 
 

Frequency 

dasabuvir and 
ombitasvir/paritaprevir/ritonavir 

+ ribavirin* 
N = 2,044 

dasabuvir and 
ombitasvir/paritaprevir/ritonavir 

 
N = 588 

Blood and lymphatic system disorders 
Common Anaemia  
Immune system disorders 
Frequency 
unknown Anaphylactic reactions Anaphylactic reactions 

Metabolism and nutrition disorders 
Uncommon Dehydration  
Psychiatric disorders 
Very common Insomnia  
Gastrointestinal disorders 
Very common Nausea, Diarrhoea   
Common Vomiting  
Hepatobiliary disorders 
Frequency 
unknown 

Hepatic decompensation and 
hepatic failure  

Hepatic decompensation and 
hepatic failure  

Skin and subcutaneous tissue disorders 
Very common Pruritus  
Common  Pruritus 
Rare Angioedema Angioedema 
General disorders and administration and administration site conditions 

Very common 
Asthenia 

Fatigue 
 



29 
 

*Data set includes all genotype 1-infected subjects in Phase 2 and 3 trials including subjects with cirrhosis. Note: 
For laboratory abnormalities refer to Table 4.  
 
Description of selected adverse reactions 
 
Compared to subjects without cirrhosis, in subjects with compensated cirrhosis there was an increased 
rate of indirect hyperbilirubinemia when ribavirin was part of the regimen.  
 
Laboratory abnormalities 
Changes in selected laboratory parameters are described in Table 4. A side-by-side tabulation is 
provided to simplify presentation; direct comparisons should not be made across trials that differ in 
trial designs. 
 
Table 4. Selected treatment emergent laboratory abnormalities 
 

Laboratory parameters 

SAPPHIRE I and II PEARL II, III, and IV TURQUOISE II 
(subjects with cirrhosis) 

dasabuvir and 
ombitasvir/paritaprevir

/ritonavir + ribavirin 

12 weeks 
N = 770 
n (%) 

dasabuvir and 
ombitasvir/paritaprevir

/ritonavir 

12 weeks  
N = 509 
n (%) 

dasabuvir and 
ombitasvir/paritaprevir
/ritonavir  + ribavirin 

12 or 24 weeks 
N = 380 
n (%) 

ALT    
>5-20 × ULN* (Grade 3) 6/765 (0.8%) 1/509 (0.2%) 4/380 (1.1%) 
>20 × ULN (Grade 4) 3/765 (0.4%) 0 2/380 (0.5%) 
Haemoglobin    
<100-80 g/L (grade 2) 41/765 (5.4%) 0 30/380 (7.9%) 
<80-65 g/L (grade 3) 1/765 (0.1%) 0 3/380 (0.8%) 
<65 g/L (Grade 4) 0 0 1/380 (0.3%) 
Total bilirubin    
>3-10 × ULN (grade 3) 19/765 (2.5%) 2/509 (0.4%) 37/380 (9.7%) 
>10 × ULN (grade 4) 1/765 (0.1%) 0 0 

*ULN: Upper Limit of Normal 
 
Serum ALT elevations 
 
In a pooled analysis of clinical trials with dasabuvir and ombitasvir/paritaprevir/ritonavir with and 
without ribavirin, 1% of subjects experienced serum ALT levels greater than 5 times the upper limit of 
normal (ULN) after starting treatment. As the incidence of such elevations was 26% among women 
taking a concomitant ethinyloestradiol-containing medicine, such medicinal products are 
contraindicated with dasabuvir and ombitasvir/paritaprevir/ritonavir. No increase in incidence of ALT 
elevations was observed with other types of systemic oestrogens commonly used for hormone 
replacement therapy (e.g., oestradiol and conjugated oestrogens). ALT elevations were typically 
asymptomatic, generally occurred during the first 4 weeks of treatment (mean time 20 days, range 8-
57 days) and most resolved with ongoing therapy. Two patients discontinued dasabuvir and 
ombitasvir/paritaprevir/ritonavir due to elevated ALT, including one on ethinyloestradiol. Three 
interrupted dasabuvir and ombitasvir/paritaprevir/ritonavir for one to seven days, including one on 
ethinyloestradiol. The majority of these ALT elevations were transient and assessed as related to 
dasabuvir and ombitasvir/paritaprevir/ritonavir. Elevations in ALT were generally not associated with 
bilirubin elevations. Cirrhosis was not a risk factor for elevated ALT (see section 4.4). 
 
Serum bilirubin elevations  
 
Transient elevations in serum bilirubin (predominantly indirect) were observed in subjects receiving 
dasabuvir and ombitasvir/paritaprevir/ritonavir with ribavirin, related to the inhibition of the bilirubin 



30 
 

transporters OATP1B1/1B3 by paritaprevir and ribavirin-induced haemolysis. Bilirubin elevations 
occurred after initiation of treatment, peaked by study Week 1, and generally resolved with ongoing 
therapy. Bilirubin elevations were not associated with aminotransferase elevations. The frequency of 
indirect bilirubin elevations was lower among subjects who did not receive ribavirin. 
 
Liver transplant recipients 
 
The overall safety profile in HCV-infected transplant recipients who were administered dasabuvir and 
ombitasvir/paritaprevir/ritonavir and ribavirin (in addition to their immunosuppressant medicinal 
products) was similar to subjects treated with dasabuvir and ombitasvir/paritaprevir/ritonavir and 
ribavirin in phase 3 clinical trials, although some adverse reactions were increased in frequency. 10 
subjects (29.4%) had at least one post baseline haemoglobin value of less than 10 g/dL. 10 of 34 
subjects (29.4%) dose modified ribavirin due to decrease in haemoglobin and 2.9% (1/34) had an 
interruption of ribavirin. Ribavirin dose modification did not impact SVR rates. 5 subjects required 
erythropoietin, all of whom initiated ribavirin at the starting dose of 1000 to 1200 mg daily. No subject 
received a blood transfusion. 
 
HIV/HCV co-infected patients 
 
The overall safety profile in HCV/HIV-1 co-infected subjects was similar to that observed in HCV 
mono-infected subjects. Transient elevations in total bilirubin >3 x ULN (mostly indirect) occurred in 
17 (27.0%) subjects; 15 of these subjects were receiving atazanavir. None of the subjects with 
hyperbilirubinemia had concomitant elevations of aminotransferases. 
 
GT1-infected subjects with or without cirrhosis with severe renal impairment or end-stage renal 
disease (ESRD) 
Dasabuvir and ombitasvir/paritaprevir/ritonavir with or without ribavirin were assessed in 68 subjects 
with genotype 1 infection with or without cirrhosis who have severe renal impairment or ESRD (see 
Section 5.1). The overall safety profile in subjects with severe renal impairment was similar to that 
seen in prior Phase 3 studies in subjects without severe renal impairment, except that a greater 
proportion of subjects required intervention due to ribavirin-associated decreases in serum 
haemoglobin. The mean baseline haemoglobin level was 12.1 g/dL and the mean decline in 
haemoglobin at the end of treatment for subjects taking RBV was 1.2 g/dL.  Thirty-nine of the 50 
subjects who received ribavirin required interruption of ribavirin, and 11 of these subjects were also 
treated with erythropoietin. Four subjects experienced a haemoglobin level < 8 g/dL.  Two subjects 
received a blood transfusion.  Adverse events of anaemia were not seen in the 18 GT1b-infected 
subjects who did not receive ribavirin. Ombitasvir/paritaprevir/ritonavir with or without dasabuvir was 
also evaluated without ribavirin in 18 GT1a- and GT4-infected patients; no adverse events of anaemia 
were seen in these subjects. 
 
 
Paediatric population 
 
The safety of dasabuvir in children and adolescents aged < 18 years has not yet been established. No 
data are available. 
 
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 single dose of dasabuvir administered to healthy volunteers was 2 g. No 
study drug-related adverse reactions or clinically significant laboratory abnormalities were observed. 

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


31 
 

In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of 
adverse reactions or effects and appropriate symptomatic treatment instituted immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use; direct-acting antivirals, ATC code: J05AP09 
 
Mechanism of action 
 
Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the 
NS5B gene, which is essential for replication of the viral genome.  
 
Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir combines three direct-acting 
antiviral medicinal products with distinct mechanisms of action and non-overlapping resistance 
profiles to target HCV at multiple steps in the viral lifecycle. Refer to the Summary of Product 
Characteristics of ombitasvir/paritaprevir/ritonavir for its pharmacological properties. 
 
Activity in cell culture and biochemical studies 
 
The EC50 of dasabuvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture 
assays was 7.7 and 1.8 nM, respectively. The replicon activity of dasabuvir was attenuated 12- to 13-
fold in the presence of 40% human plasma. The mean EC50 of dasabuvir against replicons containing 
NS5B from a panel of treatment-naïve genotype 1a and 1b isolates in the HCV replicon cell culture 
assay was 0.77 nM (range 0.4 to 2.1 nM; n=11) and 0.46 nM (range 0.2 to 2 nM; n=10), respectively. 
In biochemical assays, dasabuvir inhibited a panel of genotype 1a and 1b polymerases with a mean 
IC50 value of 4.2 nM (range 2.2 to 10.7 nM; n=7). 
 
The M1 metabolite of dasabuvir had EC50 values of 39 and 8 nM against genotype 1a-H77 and 1b-
Con1 strains in HCV replicon cell culture assays, respectively, and the activity of the M1 metabolite 
was attenuated 3- to 4-fold in the presence of 40% human plasma. Dasabuvir had reduced activity in 
biochemical assays against NS5B polymerases from HCV genotypes 2a, 2b, 3a and 4a (IC50 values 
ranging from 900 nM to >20 μM). 
 
Resistance 
 
In cell culture 
Resistance to dasabuvir conferred by variants in NS5B selected in cell culture or identified in Phase 2b 
and 3 clinical trials were phenotypically characterised in the appropriate genotype 1a or 1b replicons. 
 
In genotype 1a, substitutions C316Y, M414T, Y448H, A553T, G554S, S556G/R, and Y561H in HCV 
NS5B reduced susceptibility to dasabuvir. In the genotype 1a replicon, the activity of dasabuvir was 
reduced 21- to 32-fold by the M414T, S556G or Y561H substitutions; 152- to 261-fold by the A553T, 
G554S or S556R substitutions; and 1472- and 975-fold by the C316Y and Y448H substitutions, 
respectively. G558R and D559G/N were observed as treatment-emergent substitutions but the activity 
of dasabuvir against these variants could not be evaluated due to poor replication capacity. In genotype 
1b, substitutions C316N, C316Y, M414T, Y448H, and S556G in HCV NS5B reduced susceptibility to 
dasabuvir. The activity of dasabuvir was reduced by 5- and 11-fold by C316N and S556G, 
respectively; 46-fold by M414T or Y448H; and 1569-fold by the C316Y substitutions in the genotype 
1b replicon. Dasabuvir retained full activity against replicons containing substitutions S282T in the 
nucleoside binding site, M423T in the lower thumb site, and P495A/S, P496S or V499A in the upper 
thumb site.  
 
Effect of baseline HCV substitutions/polymorphisms on treatment response 



32 
 

A pooled analysis of subjects with genotype 1 HCV infection, who were treated with dasabuvir, 
ombitasvir and paritaprevir with or without ribavirin in Phase 2b and 3 clinical trials, was conducted to 
explore the association between baseline NS3/4A, NS5A or NS5B substitutions/polymorphisms and 
treatment outcome in these recommended regimens.  
 
In the greater than 500 genotype 1a baseline samples in this analysis, the most frequently observed 
resistance-associated variants were M28V (7.4%) in NS5A and S556G (2.9%) in NS5B. Q80K, 
although a highly prevalent polymorphism in NS3 (41.2% of samples), confers minimal resistance to 
paritaprevir. Resistance-associated variants at amino acid positions R155 and D168 in NS3 were rarely 
observed (less than 1%) at baseline. In the greater than 200 genotype 1b baseline samples in this 
analysis, the most frequently observed resistance-associated variants observed were Y93H (7.5%) in 
NS5A, and C316N (17.0%) and S556G (15%) in NS5B. Given the low virologic failure rates observed 
with recommended treatment regimens for HCV genotype 1a- and 1b-infected subjects, the presence 
of baseline variants appears to have little impact on the likelihood of achieving SVR. 
 
In clinical studies 
Of the 2,510 HCV genotype 1 infected subjects who were treated with regimens containing dasabuvir, 
ombitasvir and paritaprevir with or without ribavirin (for 8, 12 or 24 weeks) in Phase 2b and 3 clinical 
trials, a total of 74 subjects (3%) experienced virologic failure (primarily post-treatment relapse). 
Treatment-emergent variants and their prevalence in these virologic failure populations are shown in 
Table 5. In the 67 genotype 1a infected subjects, NS3 variants were observed in 50 subjects, NS5A 
variants were observed in 46 subjects, NS5B variants were observed in 37 subjects, and treatment-
emergent variants were seen in all 3 drug targets in 30 subjects. In the 7 genotype 1b infected subjects, 
treatment-emergent variants were observed in NS3 in 4 subjects, in NS5A in 2 subjects, and in both 
NS3 and NS5A in 1 subject. No genotype 1b infected subjects had treatment-emergent variants in all 3 
drug targets. 
 
Table 5. Treatment-emergent amino acid substitutions in the pooled analysis of dasabuvir and 
ombitasvir/paritaprevir/ritonavir, with and without RBV regimens in Phase 2b and Phase 3 
clinical trials (N=2510) 
 

Target Emergent amino acid substitutionsa 

Genotype 1a 
 N=67b 
% (n) 

Genotype 1b 
N=7 
% (n) 

NS3 V55Ic 6 (4) -- 
Y56Hc 9 (6) 42.9 (3)d 
I132Vc 6 (4) -- 
R155K 13.4 (9) -- 
D168A 6 (4) -- 
D168V 50.7 (34) 42.9 (3)d 
D168Y 7.5 (5) -- 
V36Ac, V36Mc, F43Lc, D168H, E357Kc < 5% -- 

NS5A M28T 20.9 (14) -- 
M28Ve 9 (6) -- 
Q30Re 40.3 (27) -- 
Y93H  28.6 (2) 
H58D, H58P, Y93N < 5% -- 

NS5B A553T 6.1 (4) -- 
S556G 33.3 (22) -- 
C316Y, M414T, G554S, S556R, G558R, 
D559G, D559N, Y561H 

< 5% -- 

a. Observed in at least 2 subjects of the same subtype. 
b. N=66 for the NS5B target. 
c. Substitutions were observed in combination with other emergent substitutions at NS3 position R155 or 

D168. 
d. Observed in combination in genotype 1b-infected subjects. 
e. Observed in combination in 6% (4/67) of the subjects. 
Note: The following variants were selected in cell culture but were not treatment-emergent: NS3 variants 
A156T in genotype 1a, and R155Q and D168H in genotype 1b; NS5A variants Y93C/H in genotype 1a, and 



33 
 

L31F/V or Y93H in combination with L28M, L31F/V or P58S in genotype 1b; and NS5B variants Y448H 
in genotype 1a, and M414T and Y448H in genotype 1b. 
 

Persistence of resistance-associated substitutions 
 
The persistence of dasabuvir, ombitasvir and paritaprevir resistance-associated amino acid 
substitutions in NS5B, NS5A and NS3, respectively, was assessed in genotype 1a-infected subjects in 
Phase 2b trials. Dasabuvir treatment-emergent variants M414T, G554S, S556G, G558R or D559G/N 
in NS5B were observed in 34 subjects. Ombitasvir treatment-emergent variants M28T, M28V or 
Q30R in NS5A were observed in 32 subjects. Paritaprevir treatment-emergent variants V36A/M, 
R155K or D168V were observed in NS3 in 47 subjects. 
 
NS3 variants V36A/M and R155K and NS5B variants M414T and S556G remained detectable at post-
treatment Week 48, whereas NS3 variant D168V and all other NS5B variants were not observed at 
post-treatment Week 48. All treatment-emergent variants in NS5A remained detectable at post-
treatment Week 48. Due to high SVR rates in genotype 1b, trends in persistence of treatment-emergent 
variants in this genotype could not be established. 
 
The lack of detection of virus containing a resistance-associated substitution does not indicate that the 
resistant virus is no longer present at clinically significant levels. The long-term clinical impact of the 
emergence or persistence of virus containing dasabuvir and ombitasvir/paritaprevir/ritonavir -
resistance-associated substitutions on future treatment is unknown. 
 
Cross-resistance 
 
Cross-resistance is expected among NS5A inhibitors, NS3/4A protease inhibitors, and non-nucleoside 
NS5B inhibitors by class. The impact of prior dasabuvir, ombitasvir, or paritaprevir treatment 
experience on the efficacy of other NS5A inhibitors, NS3/4A protease inhibitors, or NS5B inhibitors 
has not been studied. 
 
Clinical efficacy and safety 
 
The efficacy and safety of dasabuvir in combination with ombitasvir/paritaprevir/ritonavir with and 
without ribavirin was evaluated in eight Phase 3 clinical trials, including two trials exclusively in 
subjects with compensated cirrhosis (Child-Pugh A), in over 2,360 subjects with genotype 1 chronic 
hepatitis C infection as summarised in Table 6. 
 
Table 6. Phase 3 global multicentre trials conducted with dasabuvir and 
ombitasvir/paritaprevir/ritonavir with or without ribavirin (RBV). 
 

Trial Number of subjects treated 
HCV genotype 

(GT) Summary of study design 

Treatment-naïve, without cirrhosis 

SAPPHIRE I 631 GT1 
Arm A: dasabuvir and 
ombitasvir/paritaprevir/ritonavir + RBV 
Arm B: Placebo 

PEARL III 419 GT1b 

Arm A: dasabuvir and 
ombitasvir/paritaprevir/ritonavir + RBV 
Arm B: dasabuvir and 
ombitasvir/paritaprevir/ritonavir  

PEARL IV 305 GT1a 

Arm A: dasabuvir and 
ombitasvir/paritaprevir/ritonavir + RBV 
Arm B: dasabuvir and 
ombitasvir/paritaprevir/ritonavir   

GARNET 
(open-label) 166 GT1b 

dasabuvir and 
ombitasvir/paritaprevir/ritonavir (8 weeks) 

Peginteferon+ribavirin-experienced, without cirrhosis 

SAPPHIRE II 394 GT1 Arm A: dasabuvir and ombitasvir/paritaprevir/ritonavir + RBV 



34 
 

Arm B: Placebo 

PEARL II  
(open-label) 179 GT1b 

Arm A: dasabuvir and 
ombitasvir/paritaprevir/ritonavir + RBV 
Arm B: dasabuvir and 
ombitasvir/paritaprevir/ritonavir    

Treatment-naïve and peginterferon+ribavirin-experienced, with compensated cirrhosis 

TURQUOISE II 
(open-label) 380 GT1 

Arm A: dasabuvir and 
ombitasvir/paritaprevir/ritonavir + RBV 
(12 weeks) 
Arm B: dasabuvir and 
ombitasvir/paritaprevir/ritonavir + RBV 
(24 weeks) 

TURQUOISE III 
(open-label) 60 GT1b 

dasabuvir and 
ombitasvir/paritaprevir/ritonavir (12 
weeks) 

 
In all eight trials, the dasabuvir dose was 250 mg twice daily and the ombitasvir/paritaprevir/ritonavir 
dose was 25 mg/150 mg/100 mg once daily. For subjects who received ribavirin, the ribavirin dose 
was 1000 mg per day for subjects weighing less than 75 kg or 1200 mg per day for subjects weighing 
greater than or equal to 75 kg. 
 
Sustained virologic response (SVR) was the primary endpoint to determine the HCV cure rate in the 
Phase 3 studies and was defined as unquantifiable or undetectable HCV RNA 12 weeks after the end 
of treatment (SVR12). Treatment duration was fixed in each trial and was not guided by subjects’ 
HCV RNA levels (no response guided algorithm). Plasma HCV RNA values were measured during 
the clinical trials using the COBAS TaqMan HCV test (version 2.0), for use with the High Pure 
System (except GARNET which used COBAS AmpliPrep/COBAS TaqMan HCV Test v2.0). The 
High Pure system assay had a lower limit of quantification (LLOQ) of 25 IU per mL and the 
AmpliPrep assay had a LLOQ of 15 IU per mL. 
 
Clinical trials in treatment-naïve adults 
 
SAPPHIRE-I – genotype 1, treatment-naïve, without cirrhosis 
 
Design:  randomised, global multicentre, double-blind, placebo-controlled 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir with weight-based ribavirin for 12 

weeks 
 
Treated subjects (N=631) had a median age of 52 years (range: 18 to 70); 54.5% were male; 5.4% 
were Black; 15.2% had a history of depression or bipolar disorder; 79.1% had baseline HCV RNA 
levels of at least 800,000 IU/mL; 15.4% had portal fibrosis (F2) and 8.7% had bridging fibrosis (F3); 
67.7% had HCV genotype 1a infection; 32.3% had HCV genotype 1b infection. 
 
Table 7. SVR12 for genotype 1-infected treatment-naïve subjects in SAPPHIRE-I 
 

Treatment outcome 

dasabuvir and 
ombitasvir/paritaprevir/ritonavir with RBV 

for 12 weeks 
n/N % 95% CI 

Overall SVR12 456/473 96.4 94.7, 98.1 
  HCV genotype 1a 308/322 95.7 93.4, 97.9 
  HCV genotype 1b 148/151 98.0 95.8, 100.0 
Outcome for subjects without SVR12    

On-treatment VFa 1/473 0.2  
Relapse 7/463 1.5  
Otherb 9/473 1.9  

a. Confirmed HCV ≥ 25 IU/mL after HCV RNA < 25 IU/mL during treatment, confirmed 1 log10 IU/mL 
increase in HCV RNA from nadir, or HCV RNA persistently ≥ 25 IU/mL with at least 6 weeks of treatment. 



35 
 

b. Other includes early drug discontinuation not due to virologic failure and missing HCV RNA values in the 
SVR12 window. 

 
No subjects with HCV genotype 1b infection experienced on-treatment virologic failure and one 
subject with HCV genotype 1b infection experienced relapse. 
 
PEARL-III – genotype 1b, treatment-naïve, without cirrhosis 
 
Design:  randomised, global multicentre, double-blind, regimen-controlled 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir without ribavirin or with weight-based 

ribavirin for 12 weeks 
 
Treated subjects (N=419) had a median age of 50 years (range: 19 to 70); 45.8% were male; 4.8% 
were Black; 9.3% had a history of depression or bipolar disorder; 73.3% had baseline HCV RNA of at 
least 800,000 IU/mL; 20.3% had portal fibrosis (F2) and 10.0% had bridging fibrosis (F3). 
 
Table 8. SVR12 for genotype 1b-infected treatment-naïve subjects in PEARL III 
 

Treatment outcome 
dasabuvir and ombitasvir/paritaprevir/ritonavir for 12 weeks 

With RBV Without RBV 
n/N % 95% CI n/N % 95% CI 

Overall SVR12 209/210 99.5 98.6, 100.0 209/209 100 98.2, 100.0 
Outcome for subjects without SVR12     
On-treatment VF 1/210 0.5  0/209 0  
Relapse 0/210 0  0/209 0  
Other 0/210 0  0/209 0  
 
PEARL-IV – genotype 1a, treatment-naïve, without cirrhosis 
 
Design:  randomised, global multicentre, double-blind, regimen-controlled 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir without ribavirin or with weight-based 

ribavirin for 12 weeks 
 
Treated subjects (N=305) had a median age of 54 years (range: 19 to 70); 65.2% were male; 11.8% 
were Black; 20.7% had a history of depression or bipolar disorder; 86.6% had baseline HCV RNA 
levels of at least 800,000 IU/mL; 18.4% had portal fibrosis (F2) and 17.7% had bridging fibrosis (F3).  
 
Table 9. SVR12 for genotype 1a-infected treatment-naïve subjects in PEARL IV 
 

Treatment outcome 

dasabuvir and ombitasvir/paritaprevir/ritonavir for 12 weeks 
With RBV Without RBV 

n/N % 95% CI n/N % 95% CI 

Overall SVR12 97/100 97.0 93.7, 100.0 185/205 90.2 86.2, 94.3 
Outcome for subjects without SVR12     
On-treatment VF 1/100 1.0  6/205 2.9  
Relapse 1/98 1.0  10/194 5.2  
Other 1/100 1.0  4/205 2.0  
 
GARNET – Genotype 1b, Treatment-Naïve without cirrhosis. 
 
Design:  open-label, single-arm, global multicentre 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir for 8 weeks 
 
Treated subjects (N=166) had a median age of 53 years (range: 22 to 82); 56.6% were female; 3.0% 
were Asian; 0.6% were Black; 7.2% had baseline HCV RNA levels of at least 6,000,000 IU per mL; 



36 
 

9% had advanced fibrosis (F3) and 98.2% had HCV genotype 1b infection (one subject each had 
genotype 1a, 1d, and 6 infection). 
 
Table 10. SVR12 for Genotype 1b-infected treatment-naïve subjects without cirrhosis 
 

 
dasabuvir and ombitasvir/paritaprevir/ritonavir for 8 weeks 

n/N (%) 

SVR12 160/163 (98.2) 

 95% CIa 96.1, 100.0 
F0-F1 138/139 (99.3)b 

F2 9/9 (100) 
F3 13/15 (86.7)c 

a. Calculated using the normal approximation to the binomial distribution 
b. 1 patient discontinued due to non-compliance  
c. Relapse in 2/15 patients (confirmed HCV RNA ≥ 15 IU/mL post-treatment before or during SVR12 window 
among subjects with HCV RNA < 15 IU/mL at last observation with at least 51 days of treatment).  
 
Clinical trials in peginterferon+ribavirin-experienced adults 
 
SAPPHIRE-II – genotype 1, pegIFN+RBV-experienced, without cirrhosis 
 
Design:  randomised, global multicentre, double-blind, placebo-controlled 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir with weight-based ribavirin for 12 

weeks 
 
Treated subjects (N=394) had a median age of 54 years (range: 19 to 71); 49.0% were prior 
pegIFN/RBV null responders; 21.8/% were prior pegIFN/RBV partial responders; and 29.2% were 
prior pegIFN/RBV relapsers; 57.6% were male; 8.1% were Black; 20.6% had a history of depression 
or bipolar disorder;  87.1% had baseline HCV RNA levels of at least 800,000 IU per mL; 17.8% had 
portal fibrosis (F2) and 14.5% had bridging fibrosis (F3); 58.4% had HCV genotype 1a infection; 
41.4% had HCV genotype 1b infection. 
 
Table 11. SVR12 for genotype 1-infected peginterferon+ribavirin-experienced subjects in 
SAPPHIRE-II 
 

Treatment outcome 

dasabuvir and 
ombitasvir/paritaprevir/ritonavir with RBV for 

12 weeks 
n/N % 95% CI 

Overall SVR12 286/297 96.3 94.1, 98.4 
HCV genotype 1a 166/173 96.0 93.0, 98.9 
  Prior pegIFN/RBV null responder 83/87 95.4 91.0, 99.8 
  Prior pegIFN/RBV partial responder 36/36 100 100.0, 100.0 
  Prior pegIFN/RBV relapser 47/50 94.0 87.4, 100.0 
HCV genotype 1b 119/123 96.7 93.6, 99.9 
  Prior pegIFN/RBV null responder 56/59 94.9 89.3, 100.0 
  Prior pegIFN/RBV partial responder 28/28 100 100.0, 100.0 
  Prior pegIFN/RBV relapser 35/36 97.2 91.9, 100.0 
Outcome for subjects without SVR12    
  On-treatment VF 0/297 0  
  Relapse 7/293 2.4  
  Other 4/297 1.3  
 
No subjects with HCV genotype 1b infection experienced on-treatment virologic failure and 2 subjects 
with HCV genotype 1b infection experienced relapse. 
 



37 
 

PEARL-II – genotype 1b, pegIFN+RBV-experienced, without cirrhosis 
 
Design:  randomised, global multicentre, open-label, regimen-controlled 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir without ribavirin or with weight-based 

ribavirin for 12 weeks 
 
Treated subjects (N=179) had a median age of 57 years (range: 26 to 70); 35.2% were prior 
pegIFN/RBV null responders; 28.5% were prior pegIFN/RBV partial responders; and 36.3% were 
prior pegIFN/RBV relapsers; 54.2% were male; 3.9% were Black; ; 12.8% had a history of depression 
or bipolar disorder; 87.7% had baseline HCV RNA levels of at least 800,000 IU/mL; 17.9% had portal 
fibrosis (F2) and 14.0% had bridging fibrosis (F3). 
 
Table 12. SVR12 for genotype 1b-infected peginterferon+ribavirin-experienced subjects in 
PEARL II 
 

Treatment outcome 

dasabuvir and ombitasvir/paritaprevir/ritonavir for 12 
weeks 

With RBV Without RBV 
n/N % 95% CI n/N % 95% CI 

Overall SVR12 86/88 97.7 94.6, 100.0 91/91 100 95.9, 100.0 
Prior pegIFN/RBV null responder 30/31 96.8 90.6, 100.0 32/32 100 89.3, 100.0 
Prior pegIFN/RBV partial 
responder 

24/25 96.0 88.3, 100.0 26/26 100 87.1, 100.0 

Prior pegIFN/RBV relapser 32/32 100 89.3, 100.0 33/33 100 89.6, 100.0 
Outcome for subjects without SVR12     
 On-treatment VF 0/88 0  0/91 0  
 Relapse 0/88 0  0/91 0  
 Other 2/88 2.3  0/91 0  
 
Clinical trial in subjects with compensated cirrhosis 
 
TURQUOISE-II – treatment-naïve or pegIFN + RBV-experienced with compensated cirrhosis 
 
Design:  randomised, global multicentre, open-label 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir with weight-based ribavirin for 12 or 

24 weeks 
 
Treated subjects (N=380) had a median age of 58 years (range: 21 to 71); 42.1% were treatment-naïve, 
36.1% were prior pegIFN/RBV null responders; 8.2% were prior pegIFN/RBV partial responders, 
13.7% were prior pegIFN/RBV relapsers; 70.3% were male; 3.2% were Black; 14.7% had platelet 
counts of less than 90 x 109/L; 49.7% had albumin less than 40 g/L; 86.1% had baseline HCV RNA 
levels of at least 800,000 IU/mL; 24.7% had a history of depression or bipolar disorder; 68.7% had 
HCV genotype 1a infection, 31.3% had HCV genotype 1b infection. 
 



38 
 

Table 13. SVR12 for genotype 1-infected subjects with compensated cirrhosis who were 
treatment-naïve or previously treated with pegIFN/RBV 
 
Treatment outcome dasabuvir and ombitasvir/paritaprevir/ritonavir with RBV 

 12 weeks 24 weeks 
n/N % CIa n/N % CIa 

Overall SVR12 191/208 91.8 87.6, 96.1 166/172 96.5 93.4, 99.6 
HCV genotype 1a 124/140 88.6 83.3, 93.8 115/121 95.0 91.2, 98.9 

Treatment naïve 59/64 92.2  53/56 94.6  
Prior pegIFN/RBV null 
responders 

40/50 80.0  39/42 92.9  

Prior pegIFN/RBV partial 
responders 

11/11 100  10/10 100  

Prior pegIFN/RBV Prior 
relapsers 

14/15 93.3  13/13 100  

HCV genotype 1b 67/68 98.5 95.7, 100 51/51 100 93.0, 100 
Treatment naïve 22/22 100  18/18 100  
Prior pegIFN/RBV null 
responders 

25/25 100  20/20 100  

Prior pegIFN/RBV partial 
responders 

6/7 85.7  3/3 100  

Prior pegIFN/RBV Prior 
relapsers 

14/14 100  10/10 100  

Outcome for subjects 
without SVR12 

      

 On-treatment VF 1/208 0.5  3/172 1.7  
 Relapse 12/203 5.9  1/164 0.6  
 Other 4/208 1.9  2/172 1.21  

a. 97.5% confidence intervals are used for the primary efficacy endpoints (overall SVR12 rate); 95% 
confidence intervals are used for additional efficacy endpoints (SVR12 rates in HCV genotype 1a and 
1b-infected subjects). 

 
Relapse rates in GT1a cirrhotic subjects by baseline laboratory values are presented in Table 14.   
 
Table 14. TURQUOISE-II: relapse rates by baseline laboratory values after 12 and 24 weeks of 
treatment in subjects with genotype 1a infection and compensated cirrhosis 
 
 dasabuvir and 

ombitasvir/paritaprevir/ritonavir 
with RBV 

12-week arm 

dasabuvir and 
ombitasvir/paritaprevir/ritonavir 

with RBV 
24-week arm 

Number of Responders at 
the End of Treatment 

135 113 

AFP* < 20 ng/mL, platelets ≥ 90 x 109/L, AND albumin ≥ 35 g/L prior to treatment 
   Yes (for all three 
parameters listed above) 

1/87 (1%) 0/68 (0%) 

   No (for any parameter 
listed above) 

10/48 (21%) 1/45 (2%) 

*AFP= serum alpha fetoprotein 
 
In subjects with all three favourable baseline laboratory values (AFP < 20 ng/mL, platelets ≥ 90 x 
109/L, and albumin ≥ 35 g/L), relapse rates were similar in subjects treated for 12 or 24 weeks.  
 
TURQUOISE-III: treatment-naïve or pegIFN + RBV-experienced with compensated cirrhosis  
 
Design:  global multicentre, open-label 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir without ribavirin for 12 weeks 



39 
 

 
60 patients were randomized and treated, and 60/60 (100%) achieved SVR12. Main characteristics are 
shown below. 
 
Table 15. Main demographics in TURQUOISE-III 
 

Characteristics N = 60 
Age, median (range) years 60.5 (26-78) 
Male gender, n (%) 37 (61) 
  
Prior HCV Treatment:    
     naïve, n (%) 27 (45) 
     Peg-IFN + RBV, n (%) 33 (55) 
Baseline albumin, median g/L 40.0 
     < 35, n (%) 10 (17) 
     ≥ 35, n (%)  50 (83) 
Baseline platelet count, median (× 109/L) 132.0 
     < 90, n (%) 13 (22) 
     ≥ 90, n (%)  47 (78) 

 
Pooled analyses of clinical trials 
 
Durability of response 
Overall, 660 subjects in Phase 2 and 3 clinical trials had HCV RNA results for both the SVR12 and 
SVR24 time points. Among these subjects, the positive predictive value of SVR12 on SVR24 was 
99.8%. 
 
Pooled efficacy analysis 
In Phase 3 clinical trials, 1075 subjects (including 181 with compensated cirrhosis) received the 
recommended regimen (see section 4.2). Table 16 shows SVR rates for these subjects. 
 
In subjects who received the recommended regimen, 97% achieved SVR overall (among which 181 
subjects with compensated cirrhosis achieved 97% SVR), while 0.5% experienced virologic 
breakthrough and 1.2% experienced post-treatment relapse. 
 



40 
 

Table 16. SVR12 rates for recommended treatment regimens by patient population 
 
 HCV Genotype 1b  

dasabuvir and 
ombitasvir/paritaprevir/ritonavir 

HCV Genotype 1a  
dasabuvir and 

ombitasvir/paritaprevir/ritonavir  
with RBV 

 Without 
cirrhosis 

 

With 
compensated 

cirrhosis 

 

Without 
cirrhosis 

 

With 
compensated 

cirrhosis 
  
 

Treatment duration 12 weeks 12 weeks 12 weeks 24 weeks 
Treatment-naïve 100% (210/210) 100% (27/27)  96% (403/420) 95% (53/56) 
pegIFN + RBV-
experienced 

100% (91/91) 100%  (33/33) 96% (166/173) 95% (62/65) 

Prior relapse 100% (33/33) 100% (3/3) 94% (47/50) 100% (13/13) 
Prior partial 
response 

100% (26/26) 100% (5/5) 100% (36/36) 100% (10/10) 

Prior null response 100% (32/32) 100% (7/7) 95% (83/87) 93% (39/42) 
Other pegIFN/RBV 
failures 0 100% (18/18)

+ 0 0 

TOTAL 100% (301/301) 100% (60/60) 96% (569/593) 95% (115/121) 
+Other types of pegIFN/RBV failure include less well documented non-response, relapse/breakthrough or other 
pegIFN failure. 
 
Impact of ribavirin dose adjustment on probability of SVR 
In Phase 3 clinical trials, 91.5% of subjects did not require ribavirin dose adjustments during therapy. 
In the 8.5% of subjects who had ribavirin dose adjustments during therapy, the SVR rate (98.5%) was 
comparable to subjects who maintained their starting ribavirin dose throughout treatment. 
 
TURQUOISE-I: treatment-naïve or pegIFN + RBV-experienced with HCV GT1 or GT4/HIV-1 co-
infection, without cirrhosis or with compensated cirrhosis 
 
Design:  randomised, global multicentre, open-label 
Treatment:  ombitasvir/paritaprevir/ritonavir with or without dasabuvir coadminstered with or 

without weight-based ribavirin for 12 or 24 weeks  
 
See section 4.2 for dosing recommendations in HCV/HIV-1 co-infected patients. Subjects were on a 
stable HIV-1 antiretroviral therapy (ART) regimen that included ritonavir-boosted atazanavir or 
raltegravir, dolutegravir (Part 2 only), or darunavir (Part 1b and Part 2 GT4 only)-, co-administered 
with a backbone of tenofovir plus emtricitabine or lamivudine. Part 1 of the study was a Phase 2 pilot 
cohort consisting of 2 parts, Part 1a (63 subjects) and Part 1b (22 subjects). Part 2 was a Phase 3 
cohort consisting of 233 subjects.   
 
In Part 1a, all subjects received dasabuvir and ombitasvir/paritaprevir/ritonavir with ribavirin for 12 or 
24 weeks.  Treated subjects (N = 63) had a median age of 51 years (range: 31 to 69); 24% were Black; 
19% had compensated cirrhosis; 67% were treatment-naïve; 33% had failed prior treatment with 
pegIFN/RBV; 89% had HCV genotype 1a infection. 
 
In Part 1b, all subjects received dasabuvir and ombitasvir/paritaprevir/ritonavir with ribavirin for 12 
weeks.  Treated subjects (N = 22) had a median age of 54 years (range: 34 to 68); 41% were Black; 
14% had compensated cirrhosis; 86% were HCV treatment-naïve; 14% had failed prior treatment with 
pegIFN/RBV; 68% had HCV genotype 1a infection. 
 
In Part 2, subjects with HCV GT1 received dasabuvir and ombitasvir/paritaprevir/ritonavir with or 
without ribavirin for 12 or 24 weeks.  Subjects with HCV GT4 received 
ombitasvir/paritaprevir/ritonavir with ribavirin for 12 or 24 Weeks.  Treated subjects (N = 233) had a 
median age of 49 years (range: 26 to 69); 10% were Black; 12% had compensated cirrhosis; 66% were 



41 
 

treatment-naïve; 32% had failed prior treatment with pegIFN/RBV; 2% had failed prior treatment with 
sofosbuvir. 
 
Table 17 shows the primary efficacy analysis of SVR12 performed on subjects with HCV GT1/HIV-1 
co-infection that received recommended regimen in Part 2 of the TURQUOISE-I study.  

Table 17. Primary SVR12 Assessment for Part 2, Subjects with HCV GT1/HIV-1 co-infection in 
TURQUOISE-I 

Endpoint 

dasabuvir and ombitasvir/paritaprevir/ritonavir with or 
without ribavirin for  

12 or 24 Weeks 
N = 200a 

SVR12, n/N (%) [95% CI]  194/200 (97.0) [93.6, 98.6] 

Outcome for subjects not achieving SVR12  
 On-treatment virologic failure 1 
 Post-treatment relapse 1 
 Otherb 4 

a. Includes all HCV GT1 subjects in Part 2 excluding Arm G subjects that did not receive recommended 
regimen.  
b. Includes subjects who discontinued due to adverse event, lost to follow-up or subject withdrawal, and 
subjects with reinfection  

 
Efficacy analyses performed on other parts of the study demonstrated similarly high SVR12 rates. In 
Part 1a, SVR12 was achieved by 29/31 (93.5%) subjects on the 12-week arm (95% CI: 79.3% – 
98.2%) and by 29/32 (90.6%) subjects on the 24-week arm (95% CI: 75.8% – 96.8%). There was 1 
relapse in the 12-week arm and 1 on-treatment virologic failure in the 24-week arm. In Part 1b, 
SVR12 was achieved by 22/22 (100%) subjects (95% CI: 85.1%, 100%). In Part 2, SVR12 was 
achieved by 27/28 (96.4%) subjects with HCV GT4/HIV-1 coinfection (95% CI: 82.3%, 99.4%) with 
no virologic failures. 
 
The SVR12 rates in HCV/HIV-1 co-infected subjects were thus consistent with SVR12 rates in the 
phase 3 trials of HCV mono-infected subjects.  
CORAL-I: treatment-naïve or pegIFN + RBV-experienced, GT 1 or GT4 infected, at least 3 months 
post liver transplant or 12 months post renal transplant  
 
Design:  randomised, global multicentre, open-label 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir for 12 or 24 weeks with or without 
ribavirin (investigator chosen dose) for GT1 and GT4 infection 
 
In subjects with liver transplant, no cirrhosis and GT1 infection, patients were dosed with dasabuvir 
and ombitasvir/paritaprevir/ritonavir for 12-24 weeks, with and without RBV. Liver transplant 
subjects with cirrhosis were dosed with dasabuvir and ombitasvir/paritaprevir/ritonavir with RBV 
(GT1a for 24 weeks [n=4], GT1b for 12 weeks [n=2]). Subjects with renal transplant and no cirrhosis 
were dosed for 12 weeks (with RBV for GT1a [n=9], without RBV for GT1b [n=3]). Subjects with 
liver transplant and GT4 infection were dosed with ombitasvir/paritaprevir/ritonavir with RBV (non-
cirrhotic for 12 weeks [n=2] and cirrhotic for 24 weeks [n=1]. The dose of ribavirin was individualized 
at the discretion of the investigator, with most subjects receiving 600 to 800 mg as a starting dose, and 
most subjects also receiving 600 to 800 mg per day at the end of treatment. 
 
A total of 129 subjects were treated, 84 with GT1a, 41 with GT1b, 1 with GT1 other, 3 with GT4 
infection. Overall, 61% had fibrosis stage F0-F1, 26% F2, 9% F3, and 4% F4.  61% had prior HCV 
treatment experience before transplant. For immunosuppressive medication, most subjects were taking 
tacrolimus (81%), with the remainder taking cyclosporine. 
 



42 
 

Among all GT1 subjects who were post liver transplant, 111/114 (97.4%) achieved SVR12; with 2 
relapsing post treatment and 1 breakthrough on treatment.  Among the GT1 subjects who were post 
renal transplant, 9/12 (75%) achieved SVR12; however, there were no virologic failures.  All 3 
(100%) subjects with GT 4 infection who were post liver transplant achieved SVR12 
 
Clinical Trial in patients receiving chronic opioid substitution therapy 
 
In a phase 2, multicentre, open-label, single arm study, 38 treatment-naïve or pegIFN/RBV treatment 
experienced, non-cirrhotic subjects with genotype 1 infection who were on stable doses of methadone 
(N=19) or buprenorphine with or without naloxone (N=19) received 12 weeks of dasabuvir in 
combination with ombitasvir/paritaprevir/ritonavir and ribavirin. Treated subjects had a median age of 
51 years (range: 26 to 64); 65.8% were male and 5.3% were Black. A majority (86.8%) had baseline 
HCV RNA levels of at least 800,000 IU/mL and a majority (84.2%) had genotype 1a infection; 15.8% 
had portal fibrosis (F2) and 5.3% had bridging fibrosis (F3); and 94.7% were naïve to prior HCV 
treatment. 
 
Overall, 37 (97.4%) of 38 subjects achieved SVR12. No subjects experienced on-treatment virologic 
failure or relapse.  
 
RUBY-I; treatment-naïve or pegIFN + RBV experienced with or without cirrhosis who have severe 
renal impairment or end stage renal disease (ESRD) 
 
Design:  multicentre, open-label 
Treatment:  dasabuvir and ombitasvir/paritaprevir/ritonavir with or without RBV for 12 or 24 

weeks 
 
Severe renal impairment or ESRD includes CKD Stage 4 defined as eGFR <30-15 mL/min/1.73 m2 or 
CKD Stage 5 defined as <15 mL/min/1.73 m2 or requiring haemodialysis. Treated subjects (N=68) had 
a median age of 58 years (range: 32-77 years); 83.8% were male; 58.8% were Black; 73.5% of 
subjects were infected with HCV GT1a; 75.0%% had Stage 5 CKD and 69.1% were on haemodialysis.  
 
Sixty four of 68 (94.1%) subjects achieved SVR12. One subject experienced relapse at Post-Treatment 
Week 4, 2 subjects prematurely discontinued study drug and 1 subject had missing SVR12 data. 
 
See also Section 4.8 for discussion of safety information for RUBY-I. 
 
In another open-label phase 3b study evaluating 12 weeks of ombitasvir/paritaprevir/ritonavir with or 
without dasabuvir and without RBV in non-cirrhotic, treatment-naive GT1a and GT4 patients with 
CKD stage 4 or 5 (Ruby II), the SVR12 rate was 94.4% (17/18), with no subjects experiencing on-
treatment virologic failure or relapse. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
dasabuvir and ombitasvir/paritaprevir/ritonavir in one or more subsets of the paediatric populations 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 combination of dasabuvir with ombitasvir/paritaprevir/ritonavir 
have been evaluated in healthy adult subjects and in subjects with chronic hepatitis C. Table 18 shows 
mean Cmax and AUC of dasabuvir 250 mg twice daily with ombitasvir/paritaprevir/ritonavir 
25 mg/150 mg/100 mg once daily following multiple doses with food in healthy volunteers. 
 



43 
 

Table 18. Geometric mean Cmax, AUC of multiple doses of dasabuvir 250 mg twice daily and 
ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily with food in healthy 
volunteers 
 

 Cmax (ng/ml) (CV%) AUC (ng*hr/ml) (CV%) 
Dasabuvir 1030 (31) 6840 (32) 

 
Absorption 
 
Dasabuvir was absorbed after oral administration with mean Tmax of approximately 4 to 5 hours. 
Dasabuvir exposures increased in a dose proportional manner and accumulation is minimal. 
Pharmacokinetic steady state for dasabuvir when coadministered with ombitasvir/paritaprevir/ritonavir 
is achieved after approximately 12 days of dosing. 
 
Effects of food 
 
Dasabuvir should be administered with food. All clinical trials with dasabuvir have been conducted 
following administration with food. 
 
Food increased the exposure (AUC) of dasabuvir by up to 30% relative to the fasting state. The 
increase in exposure was similar regardless of meal type (e.g., high-fat versus moderate-fat) or calorie 
content (approximately 600 kcal versus approximately 1000 kcal). To maximise absorption, dasabuvir 
should be taken with food without regard to fat or calorie content. 
 
Distribution 
 
Dasabuvir is highly bound to plasma proteins. Plasma protein binding is not meaningfully altered in 
patients with renal or hepatic impairment. The blood to plasma concentration ratios in human ranged 
from 0.5 to 0.7 indicating that dasabuvir was preferentially distributed in the plasma compartment of 
whole blood. Dasabuvir was greater than 99.5%, and M1 major metabolite of dasabuvir was 94.5% 
bound to human plasma proteins over a concentration range of 0.05 to 5 µg/mL. At steady-state the 
exposures ratio of M1 to dasabuvir is approximately 0.6. Taking into account the protein binding and 
in vitro activity of M1 against HCV genotype 1, its contribution to efficacy is expected to be similar to 
that of dasabuvir. In addition, M1 is a substrate of the hepatic uptake transporters OATP family and 
OCT1 and thus, the hepatocyte concentration and thereby contribution to efficacy, may be larger than 
dasabuvir.  
 
Biotransformation 
 
Dasabuvir is predominantly metabolised by CYP2C8 and to a lesser extent by CYP3A. Following a 
400 mg 14C-dasabuvir dose in humans, unchanged dasabuvir was the major component (approximately 
60%) of drug related radioactivity in plasma. Seven metabolites were identified in plasma. The most 
abundant plasma metabolite was M1, which represented 21% of drug-related radioactivity (AUC) in 
circulation following single dose; it’s formed via oxidative metabolism predominantly by CYP2C8. 
 
Elimination 
 
Following dosing of dasabuvir with ombitasvir/ paritaprevir /ritonavir, mean plasma half-life of 
dasabuvir was approximately 6 hours. Following a 400 mg 14C-dasabuvir dose, approximately 94% of 
the radioactivity was recovered in faeces with limited radioactivity (approximately 2%) in urine. 
Unchanged dasabuvir accounted for 26.2% and M1 for 31.5% of the total dose in faeces. M1 is mainly 
cleared through direct biliary excretion with the contribution of UGT-mediated glucuronidation and, to 
a small extent, oxidative metabolism. 
 
Dasabuvir does not inhibit organic anion transporter (OAT1) in vivo and is not expected to inhibit 
organic cation transporters (OCT2), organic anion transporters (OAT3), or multidrug and toxin 



44 
 

extrusion proteins (MATE1 and MATE2K) at clinically relevant concentrations; therefore, dasabuvir 
does not affect medicinal product transport by these proteins. 
 
Special populations 
 
Elderly 
Based on population pharmacokinetic analysis of data from Phase 3 clinical studies, a 10 year increase 
or decrease in age from 54 years (median age in the Phase 3 studies) would results in <10% change in 
dasabuvir exposures. There is no pharmacokinetic information in patients >75 years. 
 
Sex or body weight 
Based on population pharmacokinetic analysis of data from Phase 3 clinical studies, female subjects 
would have approximately 14 to 30% higher dasabuvir exposures than male subjects. A 10 kg change 
in body weight from 76 kg (median weight in the Phase 3 studies) would result in <10% change in 
dasabuvir exposures. 
 
Race or ethnicity 
Based on population pharmacokinetic analysis of data from Phase 3 clinical studies, Asian subjects 
had 29% to 39% higher dasabuvir exposures than non-Asian subjects. 
  
Renal impairment 
Pharmacokinetics of the combination of ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, 
with dasabuvir 400 mg were evaluated in subjects with mild (CrCl: 60 to 89 ml/min), moderate (CrCl: 
30 to 59 ml/min) and severe (CrCl: 15 to 29 ml/min) renal impairment, relative to subjects with 
normal renal function. 
 
In subjects with mild, moderate and severe renal impairment, dasabuvir mean AUC values were 21% 
higher, 37% higher and 50% higher, respectively. Dasabuvir M1 AUC values were 6% lower, 10% 
lower, and 13% lower, respectively.  
 
The changes in dasabuvir exposures in subjects with mild, moderate and severe renal impairment are 
not considered to be clinically significant. Limited data in patients with end-stage renal disease 
indicate no clinically significant changes in exposure also in this patient group. No dose adjustment of 
dasabuvir is required for patients with mild, moderate, or severe renal impairment, or end-stage-renal 
disease on dialysis (see section 4.2). 
 
Hepatic impairment 
Pharmacokinetics of the combination of dasabuvir 400 mg, with ombitasvir 25 mg, paritaprevir 
200 mg, and ritonavir 100 mg were evaluated in subjects with mild (Child-Pugh A), moderate (Child-
Pugh B) and severe (Child-Pugh C) hepatic impairment, relative to subjects with normal hepatic 
function. 
 
In subjects with mild, moderate and severe hepatic impairment, dasabuvir AUC values were 17% 
higher, 16% lower and 325% higher, respectively. The AUC values of dasabuvir M1 metabolite were 
unchanged, 57% lower, and 77% higher, respectively. Plasma protein binding of dasabuvir and its M1 
metabolite were not meaningfully different in subjects with hepatic impairment compared to normal 
control subjects (see sections 4.2, 4.4 and 4.8). 
 
Paediatric population 
The pharmacokinetics of dasabuvir with ombitasvir/paritaprevir/ritonavir in paediatric patients has not 
been investigated (see section 4.2). 



45 
 

 
5.3 Preclinical safety data 
 
Dasabuvir was 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 rat micronucleus 
assays. 
 
Dasabuvir was not carcinogenic in a 6-month transgenic mouse study up to the highest dosage tested 
(2 g/kg/day), resulting in dasabuvir AUC exposures approximately 19-fold higher than those in 
humans at the recommended dose of 500 mg (250 mg twice daily). 
 
Similarly, dasabuvir was not carcinogenic in a 2-year rat study up to the highest dose tested (800 
mg/kg/day), resulting in dasabuvir exposures approximately 19-fold higher than those in humans at 
500 mg. 
 
Dasabuvir had no effects on embryo-foetal viability or on fertility in rodents and were not teratogenic 
in two species. No adverse effects on behaviour, reproduction or development of offspring were 
reported. The highest dasabuvir dose tested produced exposures equal to 16 to 24-fold (rat) or 6-fold 
(rabbit) the exposures in humans at the maximum recommended clinical dose.  
 
Dasabuvir was the predominant component observed in the milk of lactating rats, without effect on 
nursing pups. Elimination half-life in rat milk was slightly shorter than in plasma, AUC was about 2 
fold of that in plasma. Since dasabuvir is a BCRP substrate, distribution to the milk may change if this 
transporter is inhibited or induced by co-administration of other medicinal products. Dasabuvir-
derived material was minimally transferred through the placenta in pregnant rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core  
 
Microcrystalline cellulose (E 460(i)) 
Lactose monohydrate 
Copovidone 
Croscarmellose sodium 
Colloidal anhydrous silica (E 551) 
Magnesium stearate (E 470b) 
 
Film-coating  
 
Poly(vinyl alcohol) (E 1203) 
Titanium dioxide (E 171)  
Macrogol (3350) 
Talc (E 553b)  
Iron oxide yellow (E 172) 
Iron oxide red (E 172) 
Iron oxide black (E 172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 



46 
 

 
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-size of 56 tablets (multipack carton containing 4 inner cartons of 14 tablets each). 
  
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(S)  
 
EU/1/14/983/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 15 January 2015 
Date of latest renewal: 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

  

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


47 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 

ANNEX II 
 

A. MANUFACTURER(S) 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 

 
 



48 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
GERMANY 
 
 
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 (PSURs)  
 
The requirements for submission of PSURs 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 marketing authorisation holder (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.  

 
 

• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 
In order to evaluate the recurrence of hepatocellular carcinoma associated with 
dasabuvir, 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 

  



49 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



50 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

  



51 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton of multipack containing 56 (4 packs of 14) film-coated tablets - including blue box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exviera 250 mg film-coated tablets 
dasabuvir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 250 mg of dasabuvir (as sodium monohydrate).  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 56 (4 packs of 14) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use 
Take one tablet in the morning. 
Take one tablet in the evening. 
 
 
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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 



52 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/983/001 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
exviera  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



53 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Inner carton of multipack of 14 film-coated tablets – without blue box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exviera 250 mg film-coated tablets 
dasabuvir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 250 mg of dasabuvir (as sodium monohydrate).  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 film-coated tablets 
Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use 
Take one tablet in the morning. 
Take one tablet in the evening. 
 
 
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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



54 
 

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(S)  
 
EU/1/14/983/001 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
exviera  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
  



55 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER FOIL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exviera 250 mg tablets 
dasabuvir 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP  
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
  



56 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 

  



57 
 

Package leaflet: Information for the patient 
 

Exviera 250 mg film-coated tablets 
dasabuvir 

 
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 Exviera is and what it is used for 
2. What you need to know before you take Exviera 
3. How to take Exviera 
4. Possible side effects  
5. How to store Exviera 
6. Contents of the pack and other information 
 
 
1. What Exviera is and what it is used for 
 
Exviera contains the active substance dasabuvir. Exviera is an antiviral medicine used to treat adults 
with chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis 
C virus).  
 
Exviera works by stopping the hepatitis C virus from multiplying and infecting new cells, thus 
clearing the virus from your blood over a period of time. 
 
Exviera tablets do not work on their own. They are always taken with another antiviral medicine 
containing ombitasvir/paritaprevir/ritonavir. Some patients may also take an antiviral medicine called 
ribavirin. Your doctor will talk with you about which of these medicines to take with Exviera. 
 
It is very important that you also read the package leaflets for the other antiviral medicines that you 
take with Exviera. If you have any questions about your medicines, please ask your doctor or 
pharmacist. 
 
 
2. What you need to know before you take Exviera 
 
Do not take Exviera: 
• If you are allergic to dasabuvir or any of the other ingredients of this medicine (listed in section 6). 
• If you have moderate to severe liver problems other than hepatitis C. 
• If you are taking any of the medicines listed in the following table. This is because serious or life-

threatening effects can occur when Exviera and ombitasvir/paritaprevir/ritonavir are taken with 
these medicines. These medicines can affect the way Exviera and ombitasvir/paritaprevir/ritonavir 
work and Exviera and ombitasvir/paritaprevir/ritonavir can affect the way these other medicines 
work. 

 



58 
 

Medicines you must not take with Exviera 
Medicine or active substance Purpose of the medicine 
carbamazepine, phenytoin, phenobarbital for epilepsy 
efavirenz, etravirine, nevirapine for HIV infection 
Apalutamide, enzalutamide for prostate cancer 
ethinyloestradiol containing medicines such as 
those contained in most contraceptive pills 
and vaginal rings used for contraception 

for contraception 

gemfibrozil to lower cholesterol and other fats in the 
blood 

mitotane for some tumours of the adrenal glands 
rifampicin for bacterial infections 
St. John’s Wort (hypericum perforatum) a herbal medicine for anxiety and mild 

depression. This medicine is available 
without a prescription 

 
Do not take Exviera if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before taking Exviera. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Exviera if you: 
- have liver disease other than hepatitis C; 
- have a current or previous infection with the hepatitis B virus, since your doctor may want to monitor 
you more closely. 
- have diabetes. You may need closer monitoring of your blood glucose levels and/or adjustment of 
your diabetes medicines after starting Exviera. Some diabetic patients have experienced low sugar 
levels in the blood (hypoglycaemia) after starting treatment with medicines like Exviera. 
 
When taking Exviera and ombitasvir/paritaprevir/ritonavir, tell your doctor if you have the following 
symptoms as they may be a sign of worsening liver problems:  
- Feel sick (nauseous), are sick (vomit) or lose your appetite. 
- Notice yellowing of your skin or eyes. 
- Your urine is darker than normal. 
- Confusion 
- Notice swelling of your stomach area 
 
If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking 
Exviera. 
 
Tell your doctor if you have a history of depression or psychiatric illness. Depression, including 
suicidal thoughts and behaviours, has been reported in some patients taking this medicine, particularly 
in patients with a prior history of depression or psychiatric illness or in patients taking ribavirin with 
this medicine. You or your caregiver should also immediately inform your doctor of any changes in 
behaviour or mood and of any suicidal thoughts you may have. 
 
Blood tests 
Your doctor will test your blood before, during and after your treatment with Exviera. This is so that 
your doctor can: 
• Decide what other medicines you should take with Exviera and for how long. 
• Confirm if your treatment has worked and if you are free of the hepatitis C virus. 
• Check for side effects of Exviera or other antiviral medicines your doctor has prescribed for you to 

use with Exviera (such as “ombitasvir/paritaprevir/ritonavir” and “ribavirin”). 
 
Children and adolescents 
Do not give Exviera to children and adolescents under 18 years of age. The use of Exviera in children 
and adolescents has not yet been studied. 



59 
 

 
Other medicines and Exviera 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
There are some medicines you must not take with Exviera - see the previous table “Medicines you 
must not take with Exviera”. 
 
Tell your doctor or pharmacist before taking Exviera, if you are taking any of the medicines in the 
table below. The doctor may need to change your dose of these medicines. Tell your doctor or 
pharmacist before taking Exviera if you are also using hormonal contraceptives. See the section on 
contraception below. 
 

Medicines you must tell your doctor about before taking Exviera 
Medicine or active substance Purpose of the medicine 
alprazolam, diazepam for anxiety, panic attacks and trouble 

sleeping 
ciclosporin, everolimus, sirolimus, tacrolimus to suppress the immune system 
cyclobenzaprine, carisoprodol for muscle spasms 
dabigatran to thin the blood 
deferasirox to help reduce iron levels in the blood  
digoxin, amlodipine for heart problems or high blood 

pressure 
furosemide for the build-up of too much fluid in 

the body 
hydrocodone for pain 
imatinib for the treatment of some cancers of 

the blood 
levothyroxine for thyroid problems 
darunavir/ritonavir, atazanavir/ritonavir, rilpivirine for HIV infection  
omeprazole, lansoprazole, esomeprazole for stomach ulcers and other stomach 

problems 
rosuvastatin, pravastatin, fluvastatin, pitavastatin  to lower blood cholesterol 
s-mephenytoin for epilepsy 
teriflunomide for multiple sclerosis 
sulfasalazine to treat and manage inflammatory 

bowel disease or to treat rheumatoid 
arthritis 

warfarin and other similar medicines called vitamin 
K antagonists* 

to thin the blood 

*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 
Exviera. 
 
Pregnancy and contraception  
 
The effects of Exviera during pregnancy are not known. Exviera should not be used during pregnancy 
or in women of childbearing potential not using effective contraception. 
 
• You or your partner must use an effective method of contraception during treatment. 

Contraceptive medicines that contains ethinyloestradiol cannot be used in combination with 
Exviera. Ask your doctor about the best contraception for you. 

  



60 
 

Extra precautions are needed if Exviera is taken together with ribavirin. Ribavirin may cause severe 
birth defects. Ribavirin stays for a long time in the body after treatment is stopped, and effective 
contraception is therefore needed both during treatment and for some time afterwards. 
 

• There is a risk for birth defects when ribavirin is given to a female patient that becomes 
pregnant.  

 
• There may also be a risk for birth defects if ribavirin is taken by a male patient, whose female 

partner becomes pregnant.  
 
• Read the “Contraception” section of the package leaflet for ribavirin very carefully. It is 

important that both men and women read the information. 
 
• If you or your partner becomes pregnant during treatment with Exviera and ribavirin or in the 

months that follow, you must contact your doctor immediately. 
 
Breastfeeding 
You should not breastfeed during treatment with Exviera. It is not known whether the active substance 
in Exviera (dasabuvir), passes into breast milk. 
 
Driving and using machines 
Some patients have reported feeling very tired when taking Exviera with other medicines for their 
hepatitis C infection. If you feel tired, do not drive or use any machines. 
 
Exviera contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
 
3. How to take Exviera 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
Exviera tablets do not work on their own. They are always taken with other antiviral medicines such as 
ombitasvir/paritaprevir/ritonavir. Your doctor may also give you an antiviral medicine called ribavirin. 
 
How much to take 
The recommended dose is one tablet, twice a day. Take one tablet in the morning and one tablet in the 
evening. 
 
How to take 
• Take the tablets with food. The type of food is not important. 
• Swallow the tablets whole with water.  
• Do not chew, crush or break the tablets as they may have a bitter taste. 
 
How long to take Exviera for 
You will take Exviera for 8, 12 or 24 weeks. Your doctor will tell you how long your treatment will 
last. Do not stop taking Exviera unless your doctor tells you to. It is very important that you complete 
the full course of treatment. This will give the medicines the best chance to clear the hepatitis C virus 
infection. 
 



61 
 

If you take more Exviera than you should 
If you accidentally take more than the recommended dose, you should contact your doctor or go to the 
nearest hospital straight away. Keep the medicine pack with you so you can easily describe what you 
have taken. 
 
If you forget to take Exviera 
It is important not to miss a dose of this medicine. If you do miss a dose and it is: 
• More than 6 hours until your next dose - take the missed dose with food as soon as possible. 
• Less than 6 hours until your next dose - do not take the missed dose, take your next dose as usual 

with food. 
Do not take a double dose to make up for a forgotten dose. 

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. 
 
Stop taking Exviera and talk to your doctor or get medical help immediately if any of the 
following occur:  
 
Side effects when taking Exviera with ombitasvir/paritaprevir/ritonavir with or without 
ribavirin: 
Frequency not known: cannot be estimated based on available data 
• Serious allergic reactions, signs may include: 

o Difficulty breathing or swallowing 
o Dizziness or light-headedness, which may be due to low blood pressure 
o Swelling of the face, lips, tongue or throat 
o Rash and itching of the skin 

• Worsening liver problems. Symptoms include: 
o Feel sick (nauseous), are sick (vomit) or lose your appetite 
o Notice yellowing of your skin or eyes 
o Your urine is darker than normal  
o Confusion 
o Notice swelling of your stomach area 

 
Tell your doctor or pharmacist if you notice any of the following side effects: 
 
Side effects when taking Exviera with ombitasvir/paritaprevir/ritonavir: 
Common: may affect up to 1 in 10 people 
• Itching. 
Rare: may affect up to 1 in 1,000 people 
• Swelling of the layers of skin which can affect any part of the body including the face, tongue or 

throat and may cause difficulty swallowing or breathing (angioedema) 
 
Side effects when taking Exviera and ombitasvir/paritaprevir/ritonavir with ribavirin: 
Very common: may affect more than 1 in 10 people 
• Feeling very tired (fatigue) 
• Feeling sick (nausea) 
• Itching  
• Trouble sleeping (insomnia) 
• Feeling weak or lack of energy (asthenia). 
• Diarrhoea  
Common: may affect up to 1 in 10 people 
• Anaemia (low number of red blood cells). 
• Vomiting 



62 
 

Uncommon: may affect up to 1 in 100 people 
• Dehydration 
Rare: may affect up to 1 in 1,000 people 
• Swelling of the layers of skin which can affect any part of the body including the face, tongue or 

throat and may cause difficulty swallowing or breathing (angioedema) 
 
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 Exviera 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use the medicine after the expiry date which is stated on the carton after ‘EXP’. The expiry 
date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
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 to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Exviera contains  
• Each tablet contains 250 mg of dasabuvir (as sodium monohydrate). 
• The other ingredients are: 

− Tablet core: microcrystalline cellulose (E 460(i)), lactose monohydrate, copovidone, 
croscarmellose sodium, colloidal anhydrous silica (E 551), magnesium stearate (E 470b). 

− Tablet film-coating: poly(vinyl alcohol) (E 1203), titanium dioxide (E 171), macrogol (3350), 
talc (E 553b), iron oxide yellow (E 172), iron oxide red (E 172) and iron oxide black (E 172). 

 
What Exviera looks like and contents of the pack 
Exviera tablets are beige, ovaloid film-coated tablets, of dimensions of 14.0 mm x 8.0 mm, marked 
with “AV2”. Exviera tablets are packed into foil blisters containing 2 tablets. Each carton contains 56 
tablets (multipack carton containing 4 inner cartons of 14 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 

България 
АбВи ЕООД 

Luxembourg/Luxemburg 
AbbVie SA 

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


63 
 

Тел.: +359 2 90 30 430 
 

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. 
Tel: +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 
 



64 
 

 
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. 

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

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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