Viekirax

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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This medicinal product is subject to additional monitoring. This will allow quick identification of new 
safety information. Healthcare professionals are asked to report any suspected adverse reactions. See 
section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

Viekirax 12.5 mg/75 mg/50 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 12.5 mg of ombitasvir, 75 mg of paritaprevir and 50 mg of ritonavir.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

Pink, oblong, biconvex, film-coated tablets of dimensions 18.8 mm x 10.0 mm, debossed on one side with 
‘AV1’.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Viekirax 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 Viekirax should be initiated and monitored by a physician experienced in the management 
of chronic hepatitis C.

Posology

The recommended oral dose of Viekirax is two 12.5 mg / 75 mg / 50 mg tablets once daily with food.

Viekirax should be used in combination with other medicinal products for the treatment of HCV (see 
Table 1).



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

Patient population Treatment* Duration

Genotype 1b, without cirrhosis or 
with compensated cirrhosis

Viekirax + dasabuvir

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

Viekirax + dasabuvir + ribavirin* 12 weeks

Genotype 1a,
with compensated cirrhosis

Viekirax + dasabuvir + ribavirin* 24 weeks (see section 5.1.)

Genotype 4, without cirrhosis or 
with compensated cirrhosis

Viekirax + ribavirin 12 weeks

*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.

For specific dosage instructions for dasabuvir and ribavirin, including dose modification, refer to the 
respective Summaries of Product Characteristics.

Missed doses
In case a dose of Viekirax is missed, the prescribed dose can be taken within 12 hours. If more than 12 
hours have passed since Viekirax 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 
Viekirax and dasabuvir in combination with ribavirin is recommended for 24 weeks in liver transplant 
recipients with genotype 1 HCV infection. Viekirax in combination with ribavirin is recommended in
genotype 4 infection. 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 see section 4.5. 

Elderly
No dose adjustment of Viekirax is warranted in elderly patients (see section 5.2).

Renal impairment
No dose adjustment of Viekirax 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 



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ribavirin Summary of Product Characteristics for information regarding use in patients with renal 
impairment.

Hepatic impairment
No dose adjustment of Viekirax is required in patients with mild hepatic impairment (Child-Pugh A). 
Viekirax is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C)
(see sections 4.3 and 5.2).

Paediatric population
The safety and efficacy of Viekirax 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, Viekirax tablets should be 
taken with food, without regard to fat and calorie content (see section 5.2).

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

Patients with 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).

Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma 
levels are associated with serious events must not be co-administered with Viekirax (see section 4.5).
Examples are provided below.

CYP3A4 substrates:

 alfuzosin hydrochloride
 amiodarone, disopyramide, dronedarone, quinidine, ranolazine
 astemizole, terfenadine
 cisapride
 colchicine in patients with renal or hepatic impairment
 ergotamine, dihydroergotamine, ergonovine, methylergometrine
 fusidic acid
 lomitapide
 lovastatin, simvastatin, atorvastatin
 lurasidone
 oral midazolam, triazolam
 pimozide
 quetiapine
 salmeterol
 sildenafil (when used for the treatment of pulmonary arterial hypertension)
 ticagrelor

Co-administration of Viekirax with or without dasabuvir with medicinal products that are strong or 
moderate enzyme inducers is expected to decrease ombitasvir, paritaprevir, and ritonavir plasma 



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concentrations and reduce their therapeutic effect and must not be co-administered (see section 4.5). 
Examples of contraindicated strong or moderate enzyme inducers are provided below. 

Enzyme inducers:

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

Co-administration of Viekirax with or without dasabuvir with medicinal products that are strong inhibitors 
of CYP3A4 is expected to increase paritaprevir plasma concentrations and must not be co-administered 
with Viekirax (see section 4.5). Examples of contraindicated strong CYP3A4 inhibitors are provided 
below.

CYP3A4 inhibitors:

 cobicistat
 indinavir, lopinavir/ritonavir, saquinavir, tipranavir, 
 itraconazole, ketoconazole, posaconazole, voriconazole
 clarithromycin, telithromycin
 conivaptan

4.4 Special warnings and precautions for use

General

Viekirax 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 sections 4.2 and 5.1).

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 postmarketing in patients treated with Viekirax with and without dasabuvir and 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.

Viekirax is contraindicated 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.



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ALT elevations

During clinical trials with Viekirax and dasabuvir 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 Viekirax and dasabuvir 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 Viekirax with or without
dasabuvir therapy (see sections 4.3 and 4.5).

Although ALT elevations associated with Viekirax and dasabuvir 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 Viekirax is taken in combination with ribavirin, see section 4.6 and refer to the Summary of Product 
Characteristics for ribavirin for additional information.

Use with tacrolimus, sirolimus and everolimus

Co-administration of Viekirax and dasabuvir 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 Viekirax and 
dasabuvir with systemic tacrolimus, and a similar risk can be expected with sirolimus and everolimus.

Avoid concomitant use of tacrolimus or sirolimus with Viekirax and dasabuvir unless the benefits 
outweigh the risks. If tacrolimus or sirolimus are used together with Viekirax and dasabuvir, 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 Viekirax and dasabuvir 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.



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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 Viekirax has not been established in patients with HCV genotypes 2, 3, 5 and 6; therefore 
Viekirax should not be used to treat patients infected with these genotypes.

Co-administration with other direct-acting antivirals against HCV

Viekirax safety and efficacy have been established in combination with dasabuvir and/or ribavirin. Co-
administration of Viekirax with other antivirals has not been studied and, therefore, cannot be 
recommended.

Retreatment

The efficacy of Viekirax in patients previously exposed to Viekirax, or to medicinal products of the same 
classes as those of Viekirax (NS3/4A inhibitors or NS5A inhibitors), has not been demonstrated. 
Concerning cross-resistance, see also section 5.1.

Use with glucocorticoids metabolised by CYP3A (e.g. fluticasone)

Caution should be used when administering Viekirax with fluticasone or other glucocorticoids that are 
metabolised by CYP3A4. Concomitant use of inhaled glucocorticoids metabolised with CYP3A can 
increase systemic exposures of the glucocorticoids, and cases of Cushing’s syndrome and subsequent 
adrenal suppression have been reported with ritonavir-containing regimens. Concomitant use of Viekirax
and glucocorticoids, particularly long-term use, should only be initiated if the potential benefit of 
treatment outweighs the risk of systemic corticosteroid effects (see section 4.5).

Use with colchicine

The interaction between Viekirax with or without dasabuvir and colchicine has not been evaluated. A 
reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with 
normal renal or hepatic function if treatment with Viekirax with or without dasabuvir is required (see 
section 4.5). In patients with renal or hepatic impairment, use of colchicine with Viekirax with or without 
dasabuvir is contraindicated (see sections 4.3 and 4.5).

Use with statins 

Simvastatin, lovastatin and atorvastatin are contraindicated (see sections 4.3 and 4.5).

Rosuvastatin
Viekirax with dasabuvir 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).The increase in rosuvastatin when combined with Viekirax 
without dasabuvir is less pronounced. In this combination, the maximum daily dose of rosuvastatin should 
be 10 mg (see section 4.5, Table 2).

Pitavastatin and fluvastatin
The interactions between pitavastatin and fluvastatin and Viekirax have not been investigated. 
Theoretically, Viekirax with and without dasabuvir is expected to increase the exposure to pitavastatin and 
fluvastatin. A temporary suspension of pitavastatin/fluvastatin is recommended for the duration of 



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treatment with Viekirax. 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

Low dose ritonavir, which is part of the fixed dose combination Viekirax, 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 Viekirax.

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 Viekirax and dasabuvir, 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 Viekirax. 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 Viekirax and dasabuvir, 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 Viekirax.

HIV protease inhibitors other than atazanavir and darunavir (e.g., indinavir, saquinavir, tipranavir, 
lopinavir/ritonavir) are contraindicated (see section 4.3).

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 
Viekirax and dasabuvir, 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 medicinal products. 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.

Depression or psychiatric illness

Cases of depression and more rarely of suicidal ideation and suicide attempt have been reported with 
Viekirax with or without dasabuvir 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 Viekirax with or without dasabuvir 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.



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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. 

4.5 Interaction with other medicinal products and other forms of interaction

Viekirax may be administered with or without dasabuvir. 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 increase the risk of adverse reactions and ALT elevations 
(see Table 2). Coadministration with ethinyloestradiol may increase the risk of ALT elevations (see 
sections 4.3 and 4.4). Examples of contraindicated enzyme inducers are provided in section 4.3.

Pharmacokinetic interactions

Potential for Viekirax 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 
Viekirax with or without dasabuvir. See Table 2 for guidance regarding potential interactions with other 
medicinal products and dosing recommendations.

Medicinal products metabolised by CYP3A4
Ritonavir is a strong inhibitor of CYP3A. Co-administration of Viekirax with or without dasabuvir with 
medicinal products primarily metabolized by CYP3A may result in increased plasma concentrations of 
these medicinal products. Medicinal products that are highly dependent on CYP3A for clearance and for 
which elevated plasma levels are associated with serious events are contraindicated (see section 4.3 and 
Table 2). 

CYP3A substrates evaluated in drug interaction studies which may require dose adjustment and/or clinical 
monitoring include (see Table 2) ciclosporin, sirolimus, tacrolimus, amlodipine, rilpivirine and
alprazolam. Examples of other CYP3A4 substrates which may require dose adjustment and/or clinical 
monitoring include calcium channel blockers (e.g. nifedipine), and trazodone. Although buprenorphine 
and zolpidem are also metabolized by CYP3A, drug interaction studies indicate that no dose adjustment is 
needed when co-administering these medicinal products with Viekirax with or without dasabuvir (see 
Table 2). 

Medicinal products transported by the OATP family and OCT1
Paritaprevir is an inhibitor of the hepatic uptake transporters OATP1B1 and OATP1B3, and paritaprevir 
and ritonavir are inhibitors of OATP2B1. Ritonavir is an in vitro inhibitor of OCT1, but the clinical 
relevance is unknown. Co-administration of Viekirax with or without dasabuvir with medicinal products 
that are substrates of OATP1B1, OATP1B3, OATP2B1 or OCT1 may increase plasma concentrations of 
these transporter substrates, potentially requiring dose adjustment/clinical monitoring. Such medicinal 
products include some statins (see Table 2), fexofenadine, repaglinide and angiotensin II receptor 
antagonists (e.g., valsartan).



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OATP1B1/3 substrates evaluated in drug interaction studies include pravastatin and rosuvastatin (see 
Table 2). 

Medicinal products transported by BCRP
Paritaprevir, ritonavir and dasabuvir are inhibitors of BCRP in vivo. Co-administration of Viekirax with or 
without dasabuvir 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).

BCRP substrates evaluated in drug interaction studies include rosuvastatin (see Table 2).

Medicinal products transported by P-gp in the intestine
While paritaprevir, ritonavir and dasabuvir are in vitro inhibitors of P-gp, no significant change was 
observed in the exposure of the P-gp substrate digoxin when administered with Viekirax and dasabuvir. 
However, co-administration of digoxin with Viekirax without dasabuvir may result in increased plasma 
concentrations (see Table 2). Viekirax may increase the plasma exposure to medicinal products that are 
sensitive for changed intestinal P-gp activity (such as dabigatran etexilate).

Medicinal products metabolised by glucuronidation (UGT1A1)
Paritaprevir, ombitasvir and dasabuvir are inhibitors of UGT1A1. Co-administration of Viekirax with or 
without 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 buprenorphine, which have been evaluated in drug interaction studies.

Medicinal products metabolised by CYP2C19
Co-administration of Viekirax with or without dasabuvir 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 (see Table 2).

Medicinal products metabolised by CYP2C9
Viekirax administered with or without dasabuvir 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
Viekirax administered with or without dasabuvir 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
Ombitasvir, paritaprevir, and ritonavir do not inhibit organic anion transporter (OAT1) in vivo as shown 
by the lack of interaction with tenofovir (OAT1 substrate). In vitro studies show that ombitasvir, 
paritaprevir, and ritonavir are not inhibitors of organic cation transporters (OCT2), organic anion 
transporters (OAT3), or multidrug and toxin extrusion proteins (MATE1 and MATE2K) at clinically 
relevant concentrations. 

Therefore, Viekirax with or without dasabuvir is not expected to affect medicinal products which are 
primarily excreted by the renal route via these transporters (see section 5.2). 



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Potential for other medicinal products to affect the pharmacokinetics of ombitasvir, paritaprevir, and 
dasabuvir

Medicinal products that inhibit CYP3A4
Co-administration of Viekirax with or without dasabuvir with strong inhibitors of CYP3A may increase 
paritaprevir concentrations (see section 4.3 and Table 2).

Enzyme inducers
Co-administration of Viekirax and dasabuvir with medicinal products that are moderate or strong enzyme 
inducers is expected to decrease ombitasvir, paritaprevir, ritonavir and dasabuvir plasma concentrations 
and reduce their therapeutic effect. Contraindicated enzyme inducers are provided in section 4.3 and Table 
2.

Medicinal products that inhibit CYP3A4 and transport proteins
Paritaprevir is eliminated via CYP3A4 mediated metabolism and biliary excretion (substrate of the hepatic 
transporters OATP1B1, P-gp and BCRP). Caution is advised if co-administering Viekirax with medicinal 
products that are both moderate inhibitors of CYP3A4 and inhibitors of multiple transporters (P-gp, BCRP 
and/or OATP1B1/ OATP1B3). These medicinal products may show clinically relevant increases in 
exposures of paritaprevir (e.g., ritonavir with atazanavir, erythromycin, diltiazem or verapamil).

Medicinal products that inhibit transport proteins
Potent inhibitors of P-gp, BCRP, OATP1B1 and/or OATP1B3 have the potential to increase the exposure 
to paritaprevir. Inhibition of these transporters is not expected to show clinically relevant increases in 
exposures of ombitasvir and dasabuvir.

Patients treated with vitamin K antagonists

As liver function may change during treatment with Viekirax administered with or without dasabuvir, a 
close monitoring of International Normalised Ratio (INR) values is recommended.

Drug interaction studies

Recommendations for co-administration of Viekirax with and without dasabuvir 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 
Viekirax with or without dasabuvir 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 Viekirax or 
Viekirax with dasabuvir, doses should be re-adjusted after administration of Viekirax or Viekirax with
dasabuvir is completed.

Table 2 provides the Least Squares Means Ratio (90% Confidence Interval) effect on concentration of 
Viekirax with or without dasabuvir and concomitant medicinal products. 

The magnitude of interaction when administered with medicinal products listed in Table 2 are similar 
(≤25% difference in the Least Square Means ratio) for Viekirax with or without dasabuvir, unless 
otherwise noted. Drug interactions were evaluated for the Viekirax and dasabuvir regimen, but not for the 
Viekirax without dasabuvir, with carbamazepine, furosemide, zolpidem, darunavir twice daily, darunavir 
(evening administration), atazanavir (evening administration), rilpivirine, abacavir/lamivudine, 
dolutegravir, metformin, sulfamethoxazole/trimethoprim, cyclobenzaprine, carisoprodol, hydrocodone/



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paracetamol or diazepam. Thus, for these medicinal products, results and dosing recommendations of the 
Viekirax and dasabuvir regimen can be extrapolated to Viekirax without dasabuvir.

The direction of the arrow indicates the direction of the change in exposures (Cmax, and AUC) in 
paritaprevir, ombitasvir, dasabuvir and the co-administered medicinal product (↑ = increase (more than 
20%), ↓ = decrease (of more than 20%), ↔ = no change or change less than 20%). This is not an 
exclusive list.

Table 2. Interactions between Viekirax with or without dasabuvir and other medicinal products

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

ALPHA 1-ADRENORECEPTOR ANTAGONIST
Alfuzosin

Mechanism: 
CYP3A 
inhibition by 
ritonavir

Viekirax 
with or 
without  
dasabuvir

Not studied. Expected 

↑ alfuzosin

Concomitant use is 
contraindicated (see section 
4.3).

AMINOSALICYLATE
Sulfasalazine

Mechanism: 
BCRP 
inhibition by 
paritaprevir, 
ritonavir and 
dasabuvir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ sulfasalazine

Caution should be used 
when sulfasalazine is co-
administered with Viekirax
with or without dasabuvir.

.

ANGIOTENSIN RECEPTOR BLOCKER
Valsartan
Losartan
Candesartan

Mechanism: 
CYP3A4 
and/or
OATP1B 
inhibition by 
paritaprevir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ valsartan
↑ losartan
↑ candesartan

Clinical monitoring and 
dose reduction is 
recommended for 
angiotensin receptor 
blockers when co-
administered with Viekirax 
with or without dasabuvir.

ANTIANGINA/ANTIARRYTHMICS
Amiodarone
Disopyramide
Dronedarone
Quinidine
Ranolazine 
Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ amiodarone
↑ disopyramide
↑ dronedarone
↑ quinidine
↑ ranolazine

Concomitant use is 
contraindicated (see section 
4.3).

Digoxin Viekirax + 
dasabuvir

↔ 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 ↔ 

ombitasvir 
1.03

(0.97-1.10)
1.00

(0.98-1.03)
0.99

(0.96-1.02)



13

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

0.5 mg single 
dose 

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

↔ 
paritaprevir

0.92
(0.80-1.06)

0.94
(0.81-1.08)

0.92
(0.82-1.02)

serum digoxin levels is 
recommended.

↔ dasabuvir 0.99
(0.92-1.07)

0.97
(0.91-1.02)

0.99
(0.92-1.07)

Viekirax 
without 
dasabuvir

↑ digoxin 1.58
(1.43-1.73)

1.36
(1.21-1.54)

1.24
(1.07-1.43)

Decrease digoxin dose by 
30-50%. Appropriate 
monitoring of serum 
digoxin levels is 
recommended.

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
paritaprevir

ANTIBIOTICS (SYSTEMIC ADMINISTRATION)
Clarithromycin

Telithromycin

Mechanism: 
CYP3A4/P-
gp inhibition 
by 
clarithromyci
n and 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ clarithromycin
↑ telithromycin

↑ paritaprevir
↑ dasabuvir

Concomitant use is 
contraindicated (see 
section 4.3).

Erythromycin

Mechanism: 
CYP3A4/P-
gp inhibition 
by 
erythromycin, 
paritaprevir, 
ritonavir and 
dasabuvir. 

Viekirax 
with or  
without 
dasabuvir

Not Studied. Expected:

↑ erythromycin

↑ paritaprevir
↑ dasabuvir

Administration of Viekirax 
with or without dasabuvir 
with erythromycin may 
result in increased 
concentrations of 
erythromycin and 
paritaprevir. Caution is 
advised.

Fusidic Acid

Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax
with or 
without 
dasabuvir

Not studied. Expected:

↑ fusidic acid

Concomitant use is 
contraindicated (see 
section 4.3).

Sulfameth-
oxazole, 
Trimethoprim

800/160 mg 
twice daily

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

Viekirax + 
dasabuvir

↑ 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 Viekirax with or 
without dasabuvir. ↑ trimetho-

prim
1.17

(1.12-1.22)
1.22

(1.18-1.26)
1.25

(1.19-1.31)
↔ 
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

↑ dasabuvir 1.15
(1.02-1.31)

1.33
(1.23-1.44)

NA

Viekirax
without 
dasabuvir

Not studied: 
Similar effect is expected as observed with Viekirax + 

dasabuvir.



14

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

ANTICANCER AGENTS/KINASE INHIBITORS
Encorafenib

Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ encorafenib

Co-administration may 
result in increased risk for 
adverse events. Refer to 
the prescribing information 
of encorafenib for details 
on co-administration with 
strong CYP3A inhibitors.

Apalutamide

Enzalutamide

Mitotane

Mechanism: 
CYP3A4 
induction 
apalutamide
enzalutamide 
or mitotane.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↓ombitasvir
↓ paritaprevir
↓ dasabuvir

Concomitant use is 
contraindicated (see 
section 4.3).

Fostamatinib

Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected

↑ fostamatinib

Co-administration may 
result in increased risk for 
adverse events. Refer to 
the prescribing information 
of fostamatinib for details 
on co-administration with 
strong CYP3A inhibitors.

Ibrutinib

Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ ibrutinib

Co-administration may 
result in increased risk for 
adverse events. Refer to 
the prescribing information 
of ibrutinib for details on 
co-administration with 
strong CYP3A inhibitors.

Imatinib

Mechanism: 
BCRP 
inhibition by 
paritaprevir, 
ritonavir and 
dasabuvir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ imatinib

Clinical monitoring and 
lower doses of imatinib are 
recommended.

ANTICOAGULANTS
Warfarin

5 mg single 
dose and 
other vitamin 
K antagonists

Viekirax + 
dasabuvir

↔ 
R-warfarin

1.05
(0.95-1.17)

0.88
(0.81-0.95)

0.94
(0.84-1.05)

While no change to the 
pharmacokinetics of 
warfarin is expected, close 
monitoring of INR is 
recommended with all 
vitamin K antagonists. This 
is due to liver function 

↔ 
S-warfarin

0.96
(0.85-1.08)

0.88
(0.81-0.96)

0.95
(0.88-1.02)

↔ 
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)

↔ 0.97 0.98 1.03



15

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

dasabuvir (0.89-1.06) (0.91-1.06) (0.94-1.13) changes during treatment 
with Viekirax ± dasabuvir.Viekirax 

without 
dasabuvir

↔ 
R-warfarin

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
S-warfarin
↔ 
paritaprevir
↔ 
ombitasvir

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

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ dabigatran etexilate

Viekirax without dasabuvir 
may increase the plasma 
concentrations of dabigatran 
etexilate. Use with caution.

ANTICONVULSANTS
Carbamaze-
pine

200 mg once 
daily followed 
by 200 mg 
twice daily

Mechanism: 
CYP3A4 
induction by 
carbamazepine

Viekirax + 
dasabuvir

↔ 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 
section 4.3).↓ carbamaze 

pine 10, 11-
epoxide

0.84
(0.82-0.87)

0.75
(0.73-0.77)

0.57 
(0.54-0.61)

↓ 
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

↓ 
dasabuvir

0.45
(0.41-0.50)

0.30
(0.28-0.33)

NA

Viekirax 
without 
dasabuvir

Not studied: similar effect expected as observed with 
Viekirax + dasabuvir.

Phenobarbital

Mechanism:
CYP3A4 
induction by 
phenobarbital.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↓ ombitasvir
↓ paritaprevir
↓ dasabuvir

Concomitant use is 
contraindicated (see 
section 4.3).

Phenytoin

Mechanism:
CYP3A4 
induction by 
phenytoin.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↓ ombitasvir
↓ paritaprevir
↓ dasabuvir

Concomitant use is 
contraindicated (see 
section 4.3).

S-
mephenytoin

Mechanism: 
CYP2C19 
induction by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↓ S-mephenytoin

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



16

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

ANTIDEPRESSANTS
Escitalopram

10 mg single 
dose

Viekirax + 
dasabuvir

↔ 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

↔ 
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)

↔ 
dasabuvir

1.10
(0.95-1.27)

1.01
(0.93-1.10)

0.89
(0.79-1.00)

Viekirax 
without 
dasabuvir

↓ es-
citalopram

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ S-
Desmethyl 
citalopram

1.17
(1.08-1.26)

1.07
(1.01-1.13)

NA

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
paritaprevir

Duloxetine
60 mg single 
dose

Viekirax + 
dasabuvir

↓ 
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 Viekirax with or 
without dasabuvir.

↔ 
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)

↔ 
dasabuvir

0.94
(0.81-1.09)

0.92
(0.81-1.04)

0.88
(0.76-1.01)

Viekirax 
without 
dasabuvir

↔
duloxetine

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
paritaprevir

1.07
(0.63-1.81)

0.96
(0.70-1.32)

0.93
(0.76-1.14)

Trazodone
Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied.  Expected:

↑ trazodone

Trazodone should be used 
with caution and a lower 
dose of trazodone may be 
considered.



17

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

ANTI-DIURETIC HORMONE
Conivaptan

Mechanism: 
CYP3A4/P-
gp inhibition 
by conivaptan 
and 
paritaprevir/ 
ritonavir/ombi
tasvir

Viekirax 
with or 
without 
dasabuvir

Not studied.  Expected:

↑conivaptan
↑ paritaprevir
↑ dasabuvir

Concomitant use is 
contraindicated (see section 
4.3).

ANTIFUNGALS
Ketoconazole
400 mg once 
daily 

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

Viekirax 
with 
dasabuvir

↑ keto-
conazole

1.15
(1.09-1.21)

2.17
(2.05-2.29)

NA Concomitant use is 
contraindicated (see 
section 4.3).↔ 

ombitasvir
0.98

(0.90-1.06)
1.17

(1.11-1.24)
NA

↑ 
paritaprevir

1.37
(1.11-1.69)

1.98
(1.63-2.42)

NA

↑ 
dasabuvir

1.16
(1.03-1.32)

1.42
(1.26-1.59)

NA

Viekirax 
without 
dasabuvir

↑ keto-
conazole

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↑ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↑ 
paritaprevir

1.72
(1.32-2.26)

2.16
(1.76-2.66)

NA

Itraconazole
Posaconazole

Mechanism: 
CYP3A4 
and/or P-gp 
inhibition by 
itraconazole,  
posaconazole 
and 
paritaprevir/ 
ritonavir/ombi
tasvir 

Viekirax + 
dasabuvir

Not Studied. Expected:

↑ itraconazole
↑ posaconazole
↑ paritaprevir
↑ dasabuvir

Concomitant use is 
contraindicated (see 
section 4.3).

Viekirax 
without 
dasabuvir

Voriconazole 

Mechanism: 
CYP2C19 
induction and 
CYP3A4 
inhibition by 
ritonavir

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected in CYP2C19 Extensive 
Metabolisers:

↓ voriconazole
↑ paritaprevir
↑ dasabuvir

Not studied. Expected in CYP2C19 Poor Metabolisers:

↑ voriconazole
↑ dasabuvir
↑ paritaprevir

Concomitant use is 
contraindicated (see section 
4.3).



18

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

ANTI-GOUT
Colchicine
Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ colchicine

A reduction in colchicine 
dosage or an interruption of 
colchicine treatment is 
recommended in patients 
with normal renal or hepatic 
function if treatment with 
Viekirax with or without 
dasabuvir is required. Use of 
colchicine is contraindicated 
with Viekirax with or 
without dasabuvir in 
patients with renal or 
hepatic impairment (see 
sections 4.3 and 4.4).

ANTIHISTAMINES
Astemizole
Terfenadine
Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ astemizole/terfenadine

Concomitant use is 
contraindicated (see section 
4.3).

Fexofenadine

Mechanism: 
OATP1B1 
inhibition by 
paritaprevir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ fexofenadine

Caution should be used 
when Viekirax with or 
without dasabuvir is 
coadministered with 
fexofenadine.

ANTIHYPERLIPIDAEMICS
Gemfibrozil
600  mg twice 
daily 

Mechanism: 
Increase in 
dasabuvir 
exposure is 
possibly due 
to CYP2C8 
inhibition and 
increase in 
paritaprevir 
possibly due 
to OATP1B1 
inhibition by 
gemfibrozil.

Paritaprevir/
ritonavir + 
dasabuvir

↑ 
paritaprevir

1.21 
(0.94-1.57)

1.38
(1.18-1.61)

NA Concomitant use of 
Viekirax with dasabuvir is 
contraindicated (see 
section 4.3).

↑ dasabuvir 2.01
(1.71-2.38)

11.25
(9.05-13.99)

NA

Viekirax 
without 
dasabuvir

Not studied; 
No interaction expected when gemfibrozil is used in 

combination with Viekirax without dasabuvir.

No dose adjustment of 
gemfibrozil is necessary.

No dose adjustment 
needed for Viekirax.



19

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Lomitapide

Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

lomitapide

Concomitant use is 
contraindicated (see 
section 4.3).

ANTIMYCOBACTERIALS
Rifampicin

Mechanism:
CYP3A4 
induction by 
rifampicin.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↓ ombitasvir
↓ paritaprevir
↓ dasabuvir

Concomitant use is 
contraindicated (see section 
4.3).

ANTIPSYCHOTICS
Lurasidone
Pimozide
Quetiapine

Mechanism:
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ pimozide
↑ quetiapine
↑ lurasidone

Concomitant use is 
contraindicated (see section 
4.3).

ANTITPLATELET AGENTS
Ticagrelor

Mechanism:
CYP3A4 
inhibition by 
ritonavir

Viekirax 
with or 
without 
dasabuvir 

Not studied. Expected:

↑ ticagrelor

Concomitant use is 
contraindicated (see section 
4.3).

BIGUANIDE ORAL  ANTIHYPERGLYCEMICS
Metformin 

500 mg single 
dose

Viekirax + 
dasabuvir

↓ metformin 0.77
(0.71-0.83)

0.90
(0.84-0.97) NA

No dose adjustment 
needed for metformin
when co-administered with 
Viekirax with and without 
dasabuvir. 

↔ 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)

↔ dasabuvir 0.83
(0.74-0.93)

0.86
(0.78-0.94)

0.95
(0.84-1.07)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.

CALCIUM CHANNEL BLOCKERS
Amlodipine

5 mg single 
dose 

Mechanism: 
CYP3A4 

Viekirax + 
dasabuvir

↑ 
amlodipine

1.26
(1.11-1.44)

2.57
(2.31-2.86)

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

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)
↔ dasabuvir 1.05

(0.97-1.14)
1.01

(0.96-1.06)
0.95

(0.89-1.01)



20

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

inhibition by 
ritonavir.

Viekirax 
without 
dasabuvir

Not studied: 
Similar effect expected as observed with Viekirax + 

dasabuvir.

Diltiazem
Verapamil

Mechanism:
CYP3A4/P-
gp inhibition.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ diltiazem, verapamil

↑ paritaprevir
↑/↔ dasabuvir

Caution is advised due to 
the expected increase in 
paritaprevir exposures. 

Dose decrease and clinical 
monitoring of calcium 
channel blockers is 
recommended when co-
administered with Viekirax 
with and without 
dasabuvir.

Nifedipine

Mechanism:
CYP3A4 
inhibition

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ nifedipine

Dose decrease and clinical 
monitoring of calcium 
channel blockers is 
recommended when co-
administered with Viekirax 
with and without 
dasabuvir.

CONTRACEPTIVES
Ethinyloestra
diol/ 
norgestimate

0.035/0.25 mg 
once daily 

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

Viekirax 
with or 
without 
dasabuvir

↔ 
ethinyloestra

diol

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-

elgestromine
2.01

(1.77-2.29)
2.60

(2.30-2.95)
3.11

(2.51-3.85)
↔ 

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)

↓ dasabuvir 0.51
(0.22-1.18)

0.48
(0.23-1.02)

0.53
(0.30-
0.95)

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

Viekirax + 
dasabuvir

↔ 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 Viekirax 
with or without dasabuvir.

↔ 
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)

↔ dasabuvir 1.01
(0.90-1.14)

0.96
(0.85-1.09)

0.95
(0.80-1.13)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.

DIURETICS



21

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Furosemide

20 mg single 
dose 

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

Viekirax + 
dasabuvir

↑ 
furosemide

1.42
(1.17-1.72)

1.08
(1.00-1.17)

NA Patients should be 
monitored for clinical 
effects; a decrease in 
furosemide dose of up to 
50% may be required.

No dose adjustment 
needed for Viekirax with 
or without dasabuvir.

↔ 
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)

↔ dasabuvir 1.12
(0.96-1.31)

1.09
(0.96-1.23)

1.06
(0.98-1.14)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.

ERGOT ALKALOIDS
Ergotamine
Dihydroergot
amine
Ergonovine
Methylergom
etrine
Mechanism:
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ ergot derivatives

Concomitant use is 
contraindicated (see section 
4.3).

GLUCOCORTICOIDS (INHALED)
Fluticasone

Mechanism:
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ fluticasone

Concomitant use of 
fluticasone can increase 
systemic exposures of 
fluticasone. Concomitant 
use of Viekirax and 
fluticasone particularly 
long-term use, should only 
be initiated if the potential 
benefit of treatment 
outweighs the risk of 
systemic corticosteroid 
effects (see section 4.4).

GASTROINTESTINAL PRODUCTS (PROPULSIVE)
Cisapride
Mechanism:
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ cisapride

Concomitant use is 
contraindicated (see section 
4.3).

HCV ANTIVIRALS
Sofosbuvir

400 mg once 
daily

Viekirax + 
dasabuvir

↑ sofosbuvir 1.61
(1.38-1.88)

2.12
(1.91-2.37)

NA No dose adjustment 
needed for sofosbuvir 
when administered with ↑ GS-331007 1.02

(0.90-1.16)
1.27

(1.14-1.42)
NA

↔ ombitasvir 0.93
(0.84-1.03)

0.93
(0.87-0.99)

0.92
(0.88-0.96)



22

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

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

↔ 
paritaprevir

0.81
(0.65-1.01)

0.85
(0.71-1.01)

0.82
(0.67-1.01)

Viekirax with or without 
dasabuvir.

↔ dasabuvir 1.09
(0.98-1.22)

1.02
(0.95-1.10)

0.85
(0.76-0.95)

Viekirax 
without 
dasabuvir

The magnitude of interaction was similar to that observed 
with Viekirax + dasabuvir.

HERBAL PRODUCTS
St. John's Wort (hypericum 
perforatum)

Mechanism:
CYP3A4 induction by St. 
John's Wort

Viekirax with or without 
dasabuvir

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).
Atazanavir

300 mg once 
daily (given at 
the same 
time)

Mechanism: 
Increase in 
paritaprevir 
exposures 
may be due to 
inhibition of 
OATP1B1/B3 
and CYP3A 
by atazanavir.

Viekirax + 
dasabuvir

↔ 
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 Viekirax 
with dasabuvir. Atazanavir 
must be administered at 
the same time as Viekirax 
with dasabuvir. Ritonavir 
dose in Viekirax will 
provide atazanavir 
pharmacokinetic 
enhancement). 

No dose adjustment 
needed for Viekirax with 
dasabuvir.

Treatment with atazanavir 
+ Viekirax without 
dasabuvir is not 
recommended-(↑ 
paritaprevir).

The combination of 
atazanavir and Viekirax + 
dasabuvir increase 
bilirubin levels, in 
particular when ribavirin is 
part of the hepatitis C 
regimen (see sections 4.4 
and 4.8).

↓ ombitasvir 0.77
(0.70-0.85)

0.83
(0.74-0.94)

0.89
(0.78-1.02)

↑ 
paritaprevir

1.46
(1.06-1.99)

1.94
(1.34-2.81)

3.26
(2.06-5.16)

↔ dasabuvir 0.83
(0.71-0.96)

0.82
(0.71-0.94)

0.79
(0.66-0.94)

↔ 
atazanavir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.



23

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Viekirax 
without 
dasabuvir

↑ 
paritaprevir

2.74
(1.76-4.27)

2.87
(2.08-3.97)

3.71
(2.87-4.79)

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

Atazanavir/ 
ritonavir

300/100 mg
once daily 
(administered 
12 hours 
apart)

Mechanism: 
Increase in 
paritaprevir 
exposures 
may be due to 
inhibition of 
OATP1B1/B3 
and CYP3A 
by atazanavir 
and CYP3A 
by the 
additional 
dose of 
ritonavir.

Viekirax + 
dasabuvir

↔ 
atazanavir

1.02
(0.92-1.13)

1.19
(1.11-1.28)

1.68
(1.44-1.95)

↔ 
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)

↔ dasabuvir 0.81
(0.73-0.91)

0.81
(0.71-0.92)

0.80
(0.65-0.98)

Viekirax 
without 
dasabuvir

Not studied:
Similar effect expected as observed with Viekirax + 

dasabuvir.

Darunavir

800 mg once 
daily (given at 
the same 
time)

Mechanism: 
Unknown

Viekirax + 
dasabuvir

↓ 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 Viekirax + 
dasabuvir (ritonavir dose 
in Viekirax 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.

No dose adjustment 
needed for Viekirax with 
dasabuvir.

Darunavir combined with 
Viekirax + dasabuvir is not 
recommended in patients 

↔
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)

↔ dasabuvir 1.10
(0.88-1.37)

0.94
(0.78-1.14)

0.90
(0.76-1.06)

Viekirax 
without 
dasabuvir

↔ darunavir 0.99
(0.92-1.08)

0. 92
(0.84-1.00)

0.74
(0.63-0.88)

↔
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↑
paritaprevir

2.09
(1.35-3.24)

1.94
(1.36-2.75)

1.85
(1.41-2.42)



24

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

with extensive PI 
resistance.

Treatment with darunavir 
+ Viekirax without 
dasabuvir is not 
recommended-(↑ 
paritaprevir).

Darunavir/ 
ritonavir

600/100 mg 
twice daily

Mechanism: 
Unknown

Viekirax + 
dasabuvir

↔ darunavir 0.87
(0.79-0.96)

0.80
(0.74-0.86)

0.57
(0.48-0.67)

↓ 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)

↓ dasabuvir 0.84
(0.67-1.05)

0.73
(0.62-0.86)

0.54
(0.49-0.61)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.

darunavir/ 
ritonavir

800/100 mg 
once daily

(administered 
12 hours 
apart)

Mechanism: 
Unknown

Viekirax + 
dasabuvir

↑ darunavir 0.79
(0.70-0.90)

1.34
(1.25-1.43)

0.54
(0.48-0.62)

↔
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)

↓ dasabuvir 0.75
(0.64-0.88)

0.72
(0.64-0.82)

0.65
(0.58-0.72)

Viekirax 
without 
dasabuvir

Not studied: 
Similar effect expected as observed with Viekirax + 

dasabuvir.

Lopinavir / 
ritonavir

400/100 mg 
twice daily1

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

Viekirax + 
dasabuvir

↔ lopinavir 0.87
(0.76-0.99)

0.94
(0.81-1.10)

1.15
(0.93-1.42)

Concomitant use is 
contraindicated (see 
section 4.3).↔ 

ombitasvir
1.14

(1.01-1.28)
1.17

(1.07-1.28)
1.24

(1.14-1.34)
↑

paritaprevir
2.04

(1.30-3.20)
2.17

(1.63-2.89)
2.36

(1.00-5.55)
↔ 

dasabuvir
0.99

(0.75-1.31)
0.93

(0.75-1.15)
0.68

(0.57-0.80)
Viekirax 
without 
dasabuvir

↔ lopinavir The magnitude of interaction was similar to 
that observed with Viekirax + dasabuvir.

↑
ombitasvir

The magnitude of interaction was similar to 
that observed with Viekirax + dasabuvir.

↑
paritaprevir

4.76
(3.54-6.39)

6.10
(4.30-8.67)

12.33
(7.30-20.84)



25

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Indinavir
Saquinavir
Tipranavir

Mechanism:
CYP3A4 
inhibition by 
protease 
inhibitors.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected

↑ paritaprevir

Concomitant use is 
contraindicated (see 
section 4.3).

HIV ANTIVIRALS: NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS 
Rilpivirine2

25 mg once 
daily 
administered 
in the 
morning, with 
food
\

Mechanism: 
CYP3A4 
inhibition by 
ritonavir.

Viekirax + 
dasabuvir

↑ rilpivirine 2.55
(2.08-3.12)

3.25
(2.80-3.77)

3.62
(3.12-4.21)

Co-administration of 
Viekirax with rilpivirine
once daily should only be 
considered in patients 
without known QT-
prolongation, and without 
other QT-prolongation co-
medications. If the 
combination is used, 
repeated ECG-monitoring 
should be done, see section 
4.4. No dose adjustment 
needed for Viekirax with 
or without dasabuvir.

↔ 
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)

↔ dasabuvir 1.18
(1.02-1.37)

1.17
(0.99-1.38)

1.10
(0.89-1.37)

Viekirax
without 
dasabuvir

Not studied:  
Similar effect expected as observed with Viekirax + 

dasabuvir.

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

Mechanism: 
possible 
CYP3A4 
induction by 
efavirenz.

Viekirax
with or 
without 
dasabuvir

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 is 
contraindicated (see 
section 4.3).

Nevirapine
etravirine

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↓ ombitasvir
↓ paritaprevir
↓ dasabuvir

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

HIV ANTIVIRALS: INTEGRASE STRAND TRANSFER INHIBITOR
Dolutegravir Viekirax + 

dasabuvir
↑ 
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 coadministered with 
Viekirax with or without 
dasabuvir.

↔ 
ombitasvir

0.96
(0.89-1.03)

0.95
(0.90-1.00)

0.92
(0.87-0.98)



26

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

50 mg once 
daily

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

↔ 
paritaprevir

0.89
(0.69-1.14)

0.84
(0.67-1.04)

0.66
(0.59-0.75)

↔ dasabuvir 1.01
(0.92-1.11)

0.98
(0.92-1.05)

0.92
(0.85-0.99)

Viekirax 
without 
dasabuvir

Not studied.
Similar effect expected as observed with Viekirax + 

dasabuvir.

Raltegravir

400 mg twice 
daily 

Mechanism: 
Increase in 
raltegravir
exposures 
may be due to 
UGT1A1 
inhibition by 
paritaprevir, 
ombitasvir. 
and dasabuvir

Viekirax + 
dasabuvir

↑ 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 
Viekirax with or without 
dasabuvir.

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

historical data) were observed during co-administration.

Viekirax 
without 
dasabuvir

↑ raltegravir 1.22
(0.78-1.89)

1.20
(0.74-1.95)

1.13
(0.51-2.51)

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

historical data) were observed during co-administration.



27

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

HIV ANTIVIRALS: NUCLEOSIDE INHIBITORS 
Abacavir/ 
lamivudine

600/300 mg 
once daily

Viekirax + 
dasabuvir

↔ abacavir 0.87
(0.78-0.98)

0.94
(0.90-0.99)

NA No dose adjustment 
needed for abacavir or 
lamivudine when co-
administered with Viekirax
with or without dasabuvir.

↓ 
lamivudine

0.78
(0.72-0.84)

0.88
(0.82-0.93)

1.29
(1.05-1.58)

↔ 
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)

↔ dasabuvir 0.94
(0.86-1.03)

0.91
(0.86-0.96)

0.95
(0.88-1.02)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.
Em-
tricitabine/ 
tenofovir

200 mg once 
daily/300 mg 
once daily

Viekirax + 
dasabuvir

↔ 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 
Viekirax with or without 
dasabuvir.

↔ tenofovir 1.07
(0.93-1.24)

1.13
(1.07-1.20)

1.24
(1.13-1.36)

↔ 
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)

↔ dasabuvir 0.85
(0.74-0.98)

0.85
(0.75-0.96)

0.85
(0.73-0.98)

Viekirax 
without 
dasabuvir

↔ em-
tricitabine

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ tenofovir 0.80
(0.71-0.90)

1.01
(0.96-1.07)

1.13
(1.06-1.21)

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
paritaprevir

1.02
(0.63-1.64)

1.04
(0.74-1.47)

1.09
(0.88-1.35)

HIV ANTIVIRALS: PHARMACOKINETIC ENHANCER
Cobicistat-
containing 
regimens
Mechanism: 
CYP3A4 
inhibition by 
cobicistat

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ ombitasvir
↑ paritaprevir
↑ dasabuvir

Concomitant use is 
contraindicated (See section 
4.3).

HMG CoA REDUCTASE INHIBITOR
Viekirax + 
dasabuvir

↑ 
rosuvastatin

7.13
(5.11-9.96)

2.59
(2.09-3.21)

0.59
(0.51-0.69)

↔ 
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)



28

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Rosuvastatin

5 mg once 
daily 

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

↔ dasabuvir 1.07
(0.92-1.24)

1.08
(0.92-1.26)

1.15
(1.05-1.25)

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

No dose adjustment 
needed for Viekirax with 
dasabuvir

Viekirax 
without 
dasabuvir

↑ 
rosuvastatin

2.61
(2.01-3.39)

1.33
(1.14-1.56)

0.65
(0.57-0.74)

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

No dose adjustment 
needed for Viekirax.

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↑ 
paritaprevir

1.40
(1.12-1.74)

1.22
(1.05-1.41)

1.06
(0.85-1.32)

Pravastatin

10 mg once 
daily 

Mechanism: 
OATP1B1 
inhibition by 
paritaprevir.

Viekirax+ 
dasabuvir

↑ pravastatin 1.37
(1.11-1.69)

1.82
(1.60-2.08)

NA Reduce pravastatin dose by 
50%.

No dose adjustment 
needed for Viekirax with 
or without dasabuvir.

↔ 
ombitasvir

0.95
(0.89-1.02)

0.89
(0.83-0.95)

0.94
(0.89-0.99)

↔ dasabuvir 1.00
(0.87-1.14)

0.96
(0.85-1.09)

1.03
(0.91-1.15)

↔ 
paritaprevir

0.96
(0.69-1.32)

1.13
(0.92-1.38)

1.39
(1.21-1.59)

Viekirax
without 
dasabuvir

↑ pravastatin The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↑ 
paritaprevir

1.44
(1.15-1.81)

1.33
(1.09-1.62)

1.28
(0.83-1.96)

Fluvastatin

Mechanism:
OATP1B/BC
RP inhibition 
by 
paritaprevir

Pitavastatin
Mechanism:
OATP1B 
inhibition by 
paritaprevir

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ fluvastatin

↑ pitavastatin

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 with 
Viekirax. If statin 
treatment is required 
during the treatment 
period, a switch to dose 
reduced pravastatin or 
rosuvastatin is possible.



29

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Lovastatin
Simvastatin
atorvastatin

Mechanism:
CYP3A4/OA
TP1B 
inhibition 

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ lovastatin, simvastatin, atorvastatin

Concomitant use is 
contraindicated (see 
section 4.3).

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.

Viekirax + 
dasabuvir

↑ 
ciclosporin

1.01
(0.85-1.20)

5.82
(4.73-7.14)

15.8
(13.8-
18.09)

When starting co-
administration with 
Viekirax, give one fifth of 
the total daily dose of 
ciclosporin once daily with 
Viekirax. Monitor 
ciclosporin levels and 
adjust dose and/or dosing 
frequency as needed.

No dose adjustment 
needed for Viekirax with 
or without dasabuvir.

↔ 
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)

↓ dasabuvir 0.66
(0.58-0.75)

0.70
(0.65-0.76)

0.76
(0.71-0.82)

Viekirax 
without 
dasabuvir

↑ 
ciclosporin

0.83
(0.72-0.94)

4.28
(3.66-5.01)

12.8
(10.6-15.6)

↔ 
ombitasvir

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↑ 
paritaprevir

1.39
(1.10-1.75)

1.46
(1.29-1.64)

1.18
(1.08-1.30)

Everolimus

0.75 mg 
single dose

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

Viekirax + 
dasabuvir

↑ 
everolimus

4.74
(4.29-5.25)

27.1
(24.5-30.1)

16.1
(14.5-
17.9)4

Co-administration of 
Viekirax with everolimus 
is not recommended 
because of a significant 
increase in everolimus
exposures which cannot be 
properly dose adjusted 
with available dose 
strengths (see section 4.4).

↔
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)

↔
dasabuvir

1.03
(0.90-1.18)

1.08
(0.98-1.20)

1.14
(1.05-1.23)

Viekirax 
without 
dasabuvir

Not studied: 
Similar effect is expected as observed with Viekirax + 
dasabuvir.

Sirolimus

0.5 mg single 
dose5

Viekirax + 
dasabuvir

↑ 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 Viekirax
and dasabuvir is not
recommended unless the
benefits outweigh the risks

↔ 
ombitasvir

1.03
(0.93-1.15)

1.02
(0.96-1.09)

1.05
(0.98-1.12)

↔ 
paritaprevir

1.18
(0.91-1.54)

1.19
(0.97-1.46)

1.16
(1.00-1.34)



30

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Mechanism: 
Effect on 
sirolimus is 
due to 
CYP3A4 
inhibition by 
ritonavir

↔ dasabuvir 1.04
(0.89-1.22)

1.07
(0.95-1.22)

1.13
(1.01-1.25) (see section 4.4). If 

sirolimus is used together 
with Viekirax + dasabuvir, 
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 
Viekirax + dasabuvir 
treatment, the sirolimus 
dose and dosing frequency 
prior to receiving Viekirax 
should be resumed, along 
with routine monitoring of 
sirolimus blood 
concentrations.

Viekirax 
without 
dasabuvir

Not studied:
Similar effect is expected as observed with Viekirax + 
dasabuvir

Tacrolimus

2 mg single 
dose7

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

Viekirax + 
dasabuvir

↑ tacrolimus 3.99
(3.21-4.97)

57.1
(45.5-71.7)

16.6
(13.0-21.2)

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

↔ 
ombitasvir

0.93
(0.88-0.99)

0.94
(0.89-0.98)

0.94
(0.91-0.96)

↓ 
paritaprevir

0.57
(0.42-0.78)

0.66
(0.54-0.81)

0.73
(0.66-0.80)

↔ dasabuvir 0.85
(0.73-0.98)

0.90
(0.80-1.02)

1.01
(0.91-1.11)

Viekirax 
without 
dasabuvir

↑ tacrolimus 4.27
(3.49-5.22)

85.8
(67.9-108)

24.6
(19.7-30.8)

↔ 
ombitasvir 

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↓ 
paritaprevir



31

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

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

INHALED BETA AGONISTS
Salmeterol
Mechanism:
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ salmeterol

Concomitant use is 
contraindicated (see section 
4.3).

INSULIN SECRETAGOGUES
Repaglinide
Mechanism: 
OATP1B1 
inhibition by 
paritaprevir.

Viekirax 
with or 
without 
dasabuvir

Not Studied. Expected:

↑ repaglinide

Caution should be used and 
dose decrease maybe 
needed for repaglinide 
when administered with 
Viekirax with or without 
dasabuvir.

MUSCLE RELAXANTS
Carisoprodol 
250 mg single 
dose

Mechanism: 
CYP2C19 
induction by 
ritonavir

Viekirax 
with 
dasabuvir

↓ 
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.↔ 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)

↔ dasabuvir 0.96
(0.91-1.01)

1.02
(0.97-1.07)

1.00
(0.92-1.10)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.



32

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Cyclobenzapr
ine 5 mg 
single dose

Mechanism: 
decrease 
possibly due 
to CYP1A2 
induction by 
ritonavir

Viekirax 
with 
dasabuvir

↓ cycloben-
zaprine

0.68
(0.61-0.75)

0.60
(0.53-0.68)

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

(0.90-1.07)
1.01

(0.96-1.06)
1.13

(1.07-1.18)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.
NARCOTIC ANALGESICS
Paracetamol 
(as given in a 
fixed-dose 
hydrocodone/
paracetamol)

300 mg single 
dose

Viekirax 
+ 
dasabuvir

↔ 
paracetamol

1.02
(0.89-1.18)

1.17
(1.09-1.26)

NA No dose adjustment 
necessary for paracetamol 
when administered with 
Viekirax with or without 
dasabuvir.

↔ 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)

↔ dasabuvir 1.13
(1.01-1.26)

1.12
(1.05-1.19)

1.16
(1.08-1.25)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

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

5 mg single 
dose

Mechanism: 
CYP3A4 
inhibition by 
ritonavir

Viekirax 
+ 
dasabuvir

↑ hydrocodo
ne

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 Viekirax 
with or without dasabuvir .

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

Viekirax 
without 
dasabuvir

Not studied.
Similar effect expected as observed with Viekirax + 

dasabuvir.

OPIOIDS
Methadone

20-120 mg 
once daily8

Viekirax + 
dasabuvir

↔ 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 Viekirax with or 
without dasabuvir.

↔ S-
Methadone

0.99
(0.91-1.08)

0.99
(0.89-1.09)

0.86
(0.76-0.96)

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

Viekirax 
without 
dasabuvir

The magnitude of interaction was similar to that observed 
with Viekirax + dasabuvir.



33

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Buprenorphine
/ naloxone

4-24 mg/1-
6 mg once 
daily8

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

Viekirax + 
dasabuvir

↑ 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/naloxone 
and Viekirax with or 
without dasabuvir.↑ 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/dasabuvir (based on the cross-
study comparison)

Viekirax 
without 
dasabuvir

↑ bu-
prenorphine

1.19
(1.01-1.40)

1.51
(1.27-1.78)

1.65
(1.30-2.08)

↑ norbu-
prenorphine

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ naloxone
↔ ombitasvir/paritaprevir (based on the cross-study 

comparison)

PHOSPHODIESTERASE-(PDE-5) INHIBITORS
Sildenafil 
(when used 
for treatment 
of pulmonary 
hypertension)
Mechanism:
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with and 
without 
dasabuvir

Not studied. Expected:

↑ sildenafil

Concomitant use is 
contraindicated (see section 
4.3).

PROTON PUMP INHIBITORS
Omeprazole

40 mg once 
daily 

Mechanism: 
CYP2C19 
induction by 
ritonavir.

Viekirax + 
dasabuvir

↓ 
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 Viekirax with 
or without dasabuvir.

↔ 
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)

↔ dasabuvir 1.13
(1.03-1.25)

1.08
(0.98-1.20)

1.05
(0.93-1.19)

Viekirax 
without 
dasabuvir

↓ 
omeprazole

0.48
(0.29-0.78)

0.46
(0.27-0.77)

NA

↔ 
ombitasvir 

The magnitude of interaction was similar 
to that observed with Viekirax + dasabuvir.

↔ 
paritaprevir

Esomeprazole
Lansoprazole
Mechanism: 
CYP2C19 
induction by 
ritonavir.

Viekirax  
with and 
without 
dasabuvir

Not studied. Expected:
↓ esomeprazole, lansoprazole

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

SEDATIVES / HYPNOTICS
↔ zolpidem 0.94 0.95 NA



34

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Zolpidem

5 mg single 
dose

Viekirax + 
dasabuvir

(0.76-1.16) (0.74-1.23) No dose adjustment is 
necessary for zolpidem.

No dose adjustment 
needed for Viekirax with 
or without dasabuvir.

↔ 
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)

↔ dasabuvir 0.93
(0.84-1.03)

0.95
(0.84-1.08)

0.92
(0.83-1.01)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.

Alprazolam

0.5 mg single 
dose  

Mechanism: 
CYP3A4 
inhibition by 
ritonavir

Viekirax + 
dasabuvir

↑ 
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 Viekirax with 
or without dasabuvir.

↔ 
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)

↔ dasabuvir 0.93
(0.83-1.04)

0.98
(0.87-1.11)

1.00
(0.87-1.15)

Viekirax 
without 
dasabuvir

Not studied.  
Similar effect expected as observed with Viekirax + 

dasabuvir.

Oral 
midazolam
Triazolam

Mechanism:
CYP3A4 
inhibition by 
ritonavir.

Viekirax 
with or 
without 
dasabuvir

Not studied. Expected:

↑ midazolam or triazolam

Concomitant use is 
contraindicated (see 
section 4.3).

If parenteral midazolam is 
co-administered with
Viekirax with or without 
dasabuvir, close clinical 
monitoring for respiratory 
depression and/or 
prolonged sedation should 
be exercised and dosage 
adjustment should be 
considered.

Diazepam

2 mg single 
dose

Mechanism: 
CYP2C19 
induction by 
ritonavir

Viekirax + 
dasabuvir

↓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

↔ 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)

↔ dasabuvir 1.05
(0.98-1.13)

1.01
(0.94-1.08)

1.05
(0.98-1.12)

Viekirax 
without 
dasabuvir

Not studied. 
Similar effect expected as observed with Viekirax + 

dasabuvir.

THYROID HORMONES



35

Medicinal 
Product/Poss

ible 
Mechanism 

of 
Interaction

GIVEN 
WITH

EFFECT Cmax AUC Ctrough Clinical Comments

Levothyroxine

Mechanism:
UGT1A1 
inhibition by 
paritaprevir, 
ombitasvir
and 
dasabuvir.

Viekirax 
with or 
without 
dasabuvir

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 
Viekirax with or without dasabuvir. 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 Viekirax 
with or without dasabuvir.

2. Rilpivirine was also administered in the evening with food and at night 4 hours after dinner with 
Viekirax + dasabuvir in other two arms in the study. The effect on rilpivirine exposures was similar 
to that observed when rilpivirine was administered in the morning with food with Viekirax + 
dasabuvir (shown in the table above).

3. Ciclosporin 100 mg dosed alone, 10 mg administered with Viekirax and 30 mg administered with 
Viekirax + dasabuvir. Dose normalized cyclosporine ratios are shown for interaction with Viekirax 
with or without dasabuvir. 

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

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

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

7. Tacrolimus 2 mg was dosed alone, 0.5 mg administered with Viekirax and 2 mg was administered 
with Viekirax + dasabuvir. Dose normalized tacrolimus ratios are shown for interaction with 
Viekirax with or without dasabuvir.

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

Note: Doses used for Viekirax and dasabuvir 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. Viekirax with or without dasabuvir was 
administered as multiple doses in all the drug interaction studies except the drug interaction studies with 
carbamazepine, gemfibrozil, ketoconazole, and sulfamethoxazole/trimethoprim..

Paediatric population

Drug interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation



36

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 Viekirax is taken in combination 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.
Ethinyloestradiol is contraindicated in combination with Viekirax (see sections 4.3 and 4.4).

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. 

Pregnancy

There are very limited data from the use of Viekirax in pregnant women. Studies with ombitasvir and 
paritaprevir/ritonavir in animals have shown malformations (see section 5.3). The potential risk for 
humans is unknown. Viekirax should not be used during pregnancy or in women of childbearing potential 
not using effective contraception.

If ribavirin is co-administered with Viekirax, 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 paritaprevir /ritonavir or ombitasvir and their metabolites are excreted in human 
breast milk. Available pharmacokinetic data in animals have shown excretion of active substance and 
metabolite 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 breast-feeding or discontinue 
treatment with Viekirax, taking into account the importance of the therapy to the mother. For patients co-
administered ribavirin refer to the Summary of Product Characteristics of ribavirin.

Fertility

No human data on the effect of Viekirax 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

Viekirax 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 Viekirax in combination with dasabuvir and 
ribavirin (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile

In subjects receiving Viekirax and dasabuvir with ribavirin, the most commonly reported adverse 
reactions (greater than 20% of subjects) were fatigue and nausea. The proportion of subjects who 



37

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 
Viekirax and dasabuvir with or without ribavirin. The majority of adverse reactions presented in Table 3 
were of grade 1 severity in Viekirax and dasabuvir-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 drug reactions identified with Viekirax in combination with dasabuvir with and 
without ribavirin

Frequency
Viekirax + dasabuvir + 

ribavirin*
N = 2,044

Viekirax + dasabuvir
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
*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



38

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 shown to 
simplify presentation; direct comparison across trials should not be made due to differing 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)

Viekirax and dasabuvir
+ ribavirin

12 weeks
N = 770
n (%)

Viekirax and dasabuvir

12 weeks
N = 509
n (%)

Viekirax and dasabuvir
+ 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 according to testing laboratory.

Serum ALT elevations

In a pooled analysis of clinical trials with Viekirax and dasabuvir 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 medicinal product, such medicinal products are contraindicated with Viekirax
with or without dasabuvir. No increase in incidence of ALT elevations was observed with other types of 
estrogens commonly used for hormone replacement therapy (e.g. oestradiol and conjugated estrogens). 
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 
Viekirax and dasabuvir due to elevated ALT, including one on ethinyloestradiol. Three interrupted 
Viekirax and dasabuvir for one to seven days, including one on ethinyloestradiol. The majority of these 
ALT elevations were transient and assessed as drug-related. 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 
Viekirax and dasabuvir with ribavirin, related to the inhibition of the bilirubin transporters OATP1B1/1B3 
by paritaprevir and ribavirin-induced haemolysis. Bilirubin elevations occurred after initiation of 



39

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 Viekirax and 
dasabuvir and ribavirin (in addition to their immunosuppressant medications) was similar to subjects 
treated with Viekirax and dasabuvir 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)
Viekirax and dasabuvir 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. Viekirax 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 Viekirax 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 administered to healthy volunteers was 400 mg for paritaprevir (with 
100 mg ritonavir), 200 mg for ritonavir (with 100 mg paritaprevir) and 350 mg for ombitasvir. No study 

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


40

related adverse reactions with paritaprevir, ritonavir, or ombitasvir were observed. Transient increases in 
indirect bilirubin were observed at the highest doses of paritaprevir/ritonavir. 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: J05AP53

Mechanism of action

Viekirax, when co-administered with dasabuvir, 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 dasabuvir for its 
pharmacological properties.

Ritonavir
Ritonavir is not active against HCV. Ritonavir is a CYP3A inhibitor that increases the systemic exposure 
of the CYP3A substrate paritaprevir. 

Ombitasvir
Ombitasvir is an inhibitor of HCV NS5A which is essential for viral replication. 

Paritaprevir
Paritaprevir is an inhibitor of HCV NS3/4A protease which is necessary for the proteolytic cleavage of the 
HCV encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and 
is essential for viral replication.

Activity in cell culture and/or biochemical studies

Ombitasvir
The EC50 of ombitasvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture assays 
was 14.1 and 5 pM, respectively. The activity of ombitasvir was attenuated 11- to 13-fold in the presence 
of 40% human plasma. The mean EC50 of ombitasvir against replicons containing NS5A from a panel of 
treatment-naïve genotype 1a and 1b isolates in the HCV replicon cell culture assay was 0.66 pM (range 
0.35 to 0.88 pM; n=11) and 1.0 pM (range 0.74 to 1.5 pM; n=11), respectively. Ombitasvir has EC50
values of 12, 4.3, 19, 1.7, 3.2, and 366 pM against replicon cell lines constructed with NS5A from single 
isolates representing genotypes 2a, 2b, 3a, 4a, 5a, and 6a, respectively.

Paritaprevir
The EC50 of paritaprevir against genotype 1a-H77 and 1b-Con1 strains in the HCV replicon cell culture 
assay was 1.0 and 0.21 nM, respectively. The activity of paritaprevir was attenuated 24 to 27 -fold in the 
presence of 40% human plasma. The mean EC50 of paritaprevir against replicons containing NS3 from a 
panel of treatment-naïve genotype 1a and 1b isolates in the HCV replicon cell culture assay was 0.86 nM 
(range 0.43 to 1.87 nM; n=11) and 0.06 nM (range 0.03 to 0.09 nM; n=9), respectively. Paritaprevir had 
an EC50 value of 5.3 nM against the 2a-JFH-1 replicon cell line, and EC50 values of 19, 0.09, and 0.68 nM 
against replicon cell lines containing NS3 from a single isolate each of genotype 3a, 4a, and 6a, 
respectively
Ritonavir did not exhibit a direct antiviral effect on the replication of HCV subgenomic replicons, and the 
presence of ritonavir did not affect the in vitro antiviral activity of paritaprevir.



41

Resistance

In cell culture

Genotype 1

Resistance to paritaprevir and ombitasvir conferred by variants in NS3 and NS5A respectively, 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 F43L, R155K, A156T, and D168A/F/H/V/Y in HCV NS3 reduced 
susceptibility to paritaprevir. In the genotype 1a replicon, the activity of paritaprevir was reduced 20-, 37-, 
and 17-fold by the F43L, R155K and A156T substitutions, respectively. The activity of paritaprevir was 
reduced 96-fold by D168V, and 50- to 219-fold by each of the other D168 substitutions. The activity of 
paritaprevir in genotype 1a was not significantly affected (less than or equal to 3-fold) by single 
substitutions V36A/M, V55I, Y56H, Q80K or E357K. Double variants including combinations of 
V36LM, F43L, Y56H, Q80K or E357K with R155K or with a D168 substitution reduced the activity of 
paritaprevir by an additional 2 to 3-fold relative to the single R155K or D168 substitution. In the genotype 
1b replicon, the activity of paritaprevir was reduced 76- and 159-and 337- fold by D168A, D168H, 
D168V, and D168Y respectively. Y56H alone could not be evaluated due to poor replication capacity, 
however, the combination of Y56H and D168A/V/Y reduced the activity of paritaprevir by 700- to 4118-
fold.

In genotype 1a, substitutions M28T/V, Q30E/R, L31V, H58D, Y93C/H/N, and M28V + Q30R in HCV 
NS5A reduced susceptibility to ombitasvir. In the genotype 1a replicon, the activity of ombitasvir was 
reduced by 896-, 58- and 243-fold against the M28T/V and H58D substitutions, respectively, and 1326-, 
800-, 155-foldand 1675- to 66740- fold by the Q30E/R, L31V and Y93C/H/N substitutions, respectively. 
Y93H, Y93N or M28V in combination with Q30R reduced the activity of ombitasvir by more than 
42,802-fold. In genotype 1b, substitutions L28T, L31F/V, as well as Y93H alone or in combination with 
L28M, R30Q, L31F/M/V or P58S in HCV NS5A reduced susceptibility to ombitasvir. In the genotype 1b 
replicon, the activity of ombitasvir was reduced by less than 10-fold by variants at amino acid positions 30 
and 31. The activity of ombitasvir was reduced by 661-, 77-, 284- and 142-fold against the genotype 1b 
substitutions L28T, Y93H, R30Q in combination with Y93H, and L31M in combination with Y93H, 
respectively. All other double substitutions of Y93H in combination with substitutions at positions 28, 31, 
or 58 reduced the activity of ombitasvir by more than 400-fold.

Genotype 4

In genotype 4a, resistance to paritaprevir or ombitasvir by variants in NS3 or NS5A, respectively, selected 
in cell culture were phenotypically characterised. Substitutions R155C, A156T/V, and D168H/V in HCV 
NS3 reduced susceptibility to paritaprevir by 40- to 323-fold. Substitution L28V in HCV NS5A reduced 
the susceptibility to ombitasvir by 21-fold.

Effect of baseline HCV substitutions/polymorphisms on treatment outcome
A pooled analysis of subjects with genotype 1 HCV infection, who were treated with ombitasvir, 
paritaprevir, and dasabuvir (a non-nucleotide NS5B inhibitor) with or without ribavirin in the 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 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. 



42

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 ombitasvir, 
paritaprevir, and dasabuvir 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 Viekirax and 
dasabuvir 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 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.



43

Persistence of resistance-associated substitutions

The persistence of paritaprevir, ombitasvir, and dasabuvir resistance-associated amino acid substitutions in 
NS3, NS5A, and NS5B, respectively, was assessed in genotype 1a-infected subjects in Phase 2b trials. 
Paritaprevir treatment-emergent variants V36A/M, R155K or D168V were observed in NS3 in 47 
subjects. Ombitasvir treatment-emergent variants M28T, M28V or Q30R in NS5A were observed in 32 
subjects. Dasabuvir treatment-emergent variants M414T, G554S, S556G, G558R or D559G/N in NS5B 
were observed in 34 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 Viekirax- and dasabuvir-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 ombitasvir, paritaprevir or dasabuvir treatment experience 
on the efficacy of other NS5A inhibitors, NS3/4A protease inhibitors, or NS5B inhibitors has not been 
studied.

Clinical efficacy and safety

Clinical studies in subjects with genotype 1 hepatitis C infection
The efficacy and safety of Viekirax in combination with dasabuvir with and without ribavirin was 
evaluated in eight Phase 3 clinical trials, including two trials exclusively in subjects with cirrhosis (Child-
Pugh A), in over 2,360 subjects with genotype 1 chronic hepatitis C infection as summarised in Table 6.



44

Table 6. Phase 3 global multicentre studies conducted with Viekirax and dasabuvir 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: Viekirax and dasabuvir + RBV
Arm B: Placebo

PEARL III 419 GT1b
Arm A: Viekirax and dasabuvir + RBV
Arm B: Viekirax and dasabuvir

PEARL IV 305 GT1a
Arm A: Viekirax and dasabuvir + RBV
Arm B: Viekirax and dasabuvir

GARNET
(open-label)

166 GT1b Viekirax and dasabuvir (8 weeks)

Peginterferon+ribavirin experienced -, without cirrhosis

SAPPHIRE II 394 GT1
Arm A: Viekirax and dasabuvir + RBV
Arm B: Placebo

PEARL II 
(open-label)

179 GT1b
Arm A: Viekirax and dasabuvir + RBV
Arm B: Viekirax and dasabuvir 

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

TURQUOISE II 
(open-label)

380 GT1

Arm A: Viekirax and dasabuvir + RBV (12 
weeks)
Arm B: Viekirax and dasabuvir + RBV (24 
weeks)

TURQUOISE III
(open-label)

60 GT1b Viekirax and dasabuvir (12 weeks)

In all eight trials, the Viekirax dose was 25 mg/150 mg/100 mg once daily and the dasabuvir dose was 
250 mg twice 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: Viekirax and dasabuvir 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 



45

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

Viekirax and dasabuvir 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.

b. Other includes early drug discontinuation not due to virologic failure 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: Viekirax and dasabuvir 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

Viekirax and dasabuvir 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

20
9/209

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: Viekirax and dasabuvir 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).



46

Table 9. SVR12 for genotype 1a-infected treatment-naïve subjects in PEARL IV

Treatment outcome

Viekirax and dasabuvir 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: Viekirax and dasabuvir 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; 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

Viekirax and dasabuvir 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: Viekirax and dasabuvir 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.



47

Table 11. SVR12 for genotype 1-infected peginterferon+ribavirin-experienced subjects in 
SAPPHIRE-II

Treatment outcome
Viekirax and dasabuvir 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.

PEARL-II – genotype 1b, pegIFN+RBV-experienced, without cirrhosis

Design: randomised, global multicentre, open-label
Treatment: Viekirax and dasabuvir 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

Viekirax and dasabuvir 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



48

Treatment: Viekirax and dasabuvir 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.

Table 13. SVR12 for genotype 1-infected subjects with compensated cirrhosis who were treatment-
naïve or previously treated with pegIFN/RBV

Treatment outcome Viekirax and dasabuvir 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.



49

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

Viekirax and 
dasabuvir with RBV

12-week arm

Viekirax and 
dasabuvir 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: Viekirax and dasabuvir without ribavirin for 12 weeks

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) with genotype 1 HCV 
infection received the recommended regimen (see section 4.2). Table 16 shows SVR rates for these 
subjects.



50

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.

Table 16. SVR12 rates for recommended treatment regimens by patient population 

HCV Genotype 1b
Viekirax and dasabuvir

HCV Genotype 1a
Viekirax and dasabuvir 

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.

Viekirax without ribavirin and without dasabuvir was also evaluated in genotype 1b infected subjects in 
Phase 2 studies M13-393 (PEARL-I) and M12-536. PEARL I was conducted in the US and Europe, M12-
536 in Japan. The treatment-experienced subjects studied were primarily pegIFN/RBV null responders. 
The doses of ombitasvir, paritaprevir, ritonavir were 25 mg 150 mg, 100 mg once daily in PEARL-I, while 
the dose of paritaprevir was 100 mg or 150 mg in study M12-536. Treatment duration was 12 weeks for 
treatment naïve subjects, 12-24 weeks for treatment experienced subjects and 24 weeks for subjects with 
cirrhosis. Overall, 107 of 113 subjects without cirrhosis and 147 of 155 subjects with cirrhosis achieved 
SVR12 after 12-24 weeks of treatment.

Viekirax with ribavirin & without dasabuvir was evaluated for 12 weeks in genotype 1 treatment naive 
and treatment experienced non-cirrhotic subjects in a phase 2 study M11-652 (AVIATOR). The doses of 
paritaprevir were 100 mg and 200 mg and ombitasvir 25 mg. Ribavirin was dosed based on weight (1000 
mg – 1200 mg per day). Overall, 72 of 79 treatment-naive subjects (45 of 52 GT1a and 27 of 27 GT1b) 
and 40 of 45 treatment-experienced subjects (21 of 26 GT1a and 19 of 19 GT1b) achieved SVR12 after 12 
weeks of treatment. 

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.



51

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: Viekirax 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. HCV GT1- or 4-infected 
subjects with HIV-1 coinfection were on a stable HIV-1 antiretroviral therapy (ART) regimen that 
included ritonavir-boosted atazanavir, 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 Viekirax and dasabuvir 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 Viekirax and dasabuvir 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 Viekirax and dasabuvir with or without ribavirin for 12 or 24 
weeks.  Subjects with HCV GT4 received Viekirax 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 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

Viekirax and dasabuvir 
with/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, loss to follow-up or subject withdrawal, and 
subjects with reinfection 



52

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, at least 3 months post liver transplant or 
12 months post renal transplant

Design: randomised, global multicentre, open-label
Treatment: Viekirax and dasabuvir 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 Viekirax and 
dasabuvir for 12-24 weeks, with and without RBV. Liver transplant subjects with cirrhosis were dosed 
with Viekirax and dasabuvir 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 Viekirax with RBV 
(non-cirrhotic for 12 weeks [n=2] and cirrhotic for 24 weeks [n=1]. The dose of ribavirin was left to the 
discretion of the investigator, with most subjects receiving 600 to 800 mg per day 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.

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 GT4 infection who were post liver transplant achieved SVR12.

Clinical trial in patients receiving 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 +/- naloxone (N=19) received 12 weeks of Viekirax and dasabuvir with 
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



53

Treatment: Viekirax and dasabuvir 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 Viekirax 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.

Clinical trials in subjects with genotype 4 chronic hepatitis C

PEARL- I– genotype 4, treatment-naïve or pegIFN + RBV experienced without cirrhosis

Design: randomised, global multicentre, open-label
Treatment: treatment naïve: Viekirax without ribavirin or with weight-based ribavirin for 12 weeks

pegIFN + RBV experienced: Viekirax with weight-based ribavirin for 12 weeks

Subjects (N=135) had a median age of 51 years (range: 19 to 70); 63,7% were treatment-naïve, 17.0% 
were prior pegIFN/RBV null responders, 6.7% were prior pegIFN/RBV partial responders, 12.6% were 
prior pegIFN/RBV relapsers; 65.2%were male; 8.9% were Black, 69.6% had baseline HCV RNA levels 
at least 800,000 IU/mL; 6.7% had bridging fibrosis (F3).

Table 18. SVR12 for genotype 4-infected, subjects who were treatment-naïve or previously treated 
with pegIFN/RBV in PEARL I 

Treatment outcome

Ombitasvir + paritaprevir + ritonavir* for 12 weeks

Treatment-naïve

With RBV

Treatment-naïve

Without RBV

pegIFN + RBV-
experienced

With RBV
n/N % n/N % n/N %

Overall SVR12 42/42 100% 40/44 90.9% 49/49 100%
Outcome for subjects without SVR12

On-treatment VF 0/42 0 1/44 2.3% 0/49 0
Relapse 0/42 0 2/44 4.5% 0/49 0
Other 0/42 0 1/44 2.3% 0/49 0

* Ombitasvir tablets, paritaprevir tablets and ritonavir capsules administered separately.

AGATE-1 –treatment-naïve or pegIFN +RBV experienced patients with compensated cirrhosis

Design: randomised, global multicentre, open-label
Treatment: Viekirax with weight-based ribavirin for 12 or 16 weeks



54

Subjects had a median age of 56 years (range: 32 to 81); 50% were treatment-naïve, 28% were prior 
pegIFN/RBV null responders; 10% were prior pegIFN/RBV partial responders, 13% were prior 
pegIFN/RBV relapsers; 70% were male; 17% were Black; 73% had baseline HCV RNA levels of at least 
800,000 IU per mL; 17% had platelet counts of less than 90 x 109 per L; and 4% had albumin less than 
3.5 mg per dL.

Table 19. SVR12 for HCV Genotype 4-Infected Subjects with Compensated Cirrhosis

Ombitasvir + Paritaprevir + Ritonavir with RBV
12 Weeks 16 Weeks

SVR12 % (n/N) 97% (57/59) 98% (60/61)
Outcome for subjects without SVR12
   On-treatment virologic failure 2 (1/59) 0 (0/61)
   Post-treatment relapse 0 (0/57) 0 (0/59)
   Other 2 (1/59) 2 (1/61)

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with Viekirax
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 Viekirax with dasabuvir have been evaluated in 
healthy adult subjects and in subjects with chronic hepatitis C. Table 20 shows mean Cmax and AUC of 
Viekirax 25 mg/150 mg/100 mg once daily with dasabuvir 250 mg twice daily following multiple doses 
with food in healthy volunteers.

Table 20. Geometric mean Cmax, AUC of multiple doses of Viekirax 150 mg/100 mg/25 mg once daily 
with dasabuvir 250 mg twice daily with food in healthy volunteers

Cmax (ng/ml) (% CV) AUC (ng*hr/ml) (% CV)

Ombitasvir 127 (31) 1420 (36)

Paritaprevir 1470 (87) 6990 (96)

Ritonavir 1600 (40) 9470 (41)

Absorption

Ombitasvir, paritaprevir and ritonavir were absorbed after oral administration with mean Tmax of 
approximately 4 to 5 hours. While ombitasvir exposures increased in a dose proportional manner, 
paritaprevir and ritonavir exposures increased in a more than dose proportional manner. Accumulation is 
minimal for ombitasvir and approximately 1.5- to 2-fold for ritonavir and paritaprevir. Pharmacokinetic 
steady state for the combination is achieved after approximately 12 days of dosing.

The absolute bioavailability of ombitasvir and paritaprevir was approximately 50% when administered
with food as Viekirax.



55

Effect of paritaprevir/ritonavir on ombitasvir and dasabuvir 

In the presence of paritaprevir/ritonavir, dasabuvir exposures decreased by approximately 50% to 60% 
while ombitasvir exposures increased by 31-47%.

Effect of ombitasvir on paritaprevir/ritonavir and dasabuvir

In the presence of ombitasvir, paritaprevir exposures were minimally affected (5% to 27% change) while 
dasabuvir exposures increase by approximately 30%.

Effect of dasabuvir on paritaprevir/ritonavir and ombitasvir

In the presence of dasabuvir, paritaprevir exposures increased by 50% to 65% while there was no change 
in ombitasvir exposures.

Effects of food

Ombitasvir, paritaprevir and ritonavir should be administered with food. All clinical trials with ombitasvir, 
paritaprevir and ritonavir have been conducted following administration with food.

Food increased the exposure (AUC) of ombitasvir, paritaprevir and ritonavir by up to 82%, 211% and 
49%, respectively 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, Viekirax should be taken with food without regard to fat or calorie 
content.

Distribution

Ombitasvir, paritaprevir and ritonavir are highly bound to plasma proteins. Plasma protein binding is not 
meaningfully altered in subjects with renal or hepatic impairment. The blood to plasma concentration 
ratios in humans ranged from 0.6 to 0.8 indicating that ombitasvir and paritaprevir were preferentially 
distributed in the plasma compartment of whole blood. Ombitasvir was approximately 99.9% bound to 
human plasma proteins. Paritaprevir was approximately 97-98.6% bound to human plasma proteins. 
Ritonavir was greater than 99% bound to human plasma proteins.

In vitro data indicate that paritaprevir is a substrate for the human hepatic uptake transporters, OATP1B1 
and OATP1B3.

Biotransformation

Ombitasvir

Ombitasvir is metabolised via amide hydrolysis followed by oxidative metabolism. Following a 25 mg 
single dose of 14C-ombitasvir given alone, unchanged parent drug accounted for 8.9% of total radioactivity 
in human plasma; a total of 13 metabolites were identified in human plasma. These metabolites are not 
expected to have antiviral activity or off-target pharmacologic activity.

Paritaprevir

Paritaprevir is metabolised predominantly by CYP3A4 and to a lesser extent CYP3A5. Following 
administration of a single 200 mg/100 mg oral dose of 14C paritaprevir /ritonavir to humans, the parent 
drug was the major circulating component, accounting for approximately 90% of the plasma radioactivity. 
At least 5 minor metabolites of paritaprevir have been identified in circulation that accounted for 
approximately 10% of plasma radioactivity. These metabolites are not expected to have antiviral activity.



56

Ritonavir

Ritonavir is predominantly metabolised by CYP3A and to a lesser extent, by CYP2D6. Nearly the entire 
plasma radioactivity after a single 600 mg dose of 14C-ritonavir oral solution in humans was attributed to 
unchanged ritonavir.

Elimination

Ombitasvir

Following dosing of ombitasvir/paritaprevir/ritonavir with or without dasabuvir, mean plasma half-life of 
ombitasvir was approximately 21 to 25 hours. Following a single 25 mg dose of 14C- ombitasvir
approximately 90% of the radioactivity was recovered in faeces and 2% in urine. Unchanged parent drug 
accounted for 88% of total radioactivity recovered in faeces, indicating that biliary excretion is a major 
elimination pathway for ombitasvir. 

Paritaprevir

Following dosing of ombitasvir/paritaprevir /ritonavir with or without dasabuvir, mean plasma half-life of 
paritaprevir was approximately 5.5 hours. Following a 200 mg 14C -paritaprevir dose with 100 mg 
ritonavir, approximately 88% of the radioactivity was recovered in faeces with limited radioactivity 
(8.8%) in urine. Metabolism as well as biliary excretion of parent drug contribute to the elimination of 
paritaprevir.

Ritonavir

Following dosing of ombitasvir/paritaprevir /ritonavir, mean plasma half-life of ritonavir was 
approximately 4 hours. Following a 600 mg dose of 14C -ritonavir oral solution, 86.4% of the radioactivity 
was recovered in the faeces and 11.3% of the dose was excreted in the urine.

In vitro interaction data

Ombitasvir and paritaprevir do not inhibit organic anion transporter (OAT1) in vivo and are not expected 
to inhibit organic cation transporters (OCT1 and OCT2), organic anion transporters (OAT3), or multidrug 
and toxin extrusion proteins (MATE1 and MATE2K) at clinically relevant concentrations. Ritonavir does 
not inhibit OAT1 and is not expected to inhibit OCT2, OAT3, MATE1 and MATE2K at clinically 
relevant concentrations.

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 result in approximately 10% 
change in ombitasvir exposures, and ≤20% change in paritaprevir 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 55% higher, 100% higher and 15% higher ombitasvir, paritaprevir and 
ritonavir exposures than male subjects. However, no dose-adjustment based on gender is warranted. A 



57

10 kg change in body weight from 76 kg (median weight in the Phase 3 studies) would results in <10% 
change in ombitasvir exposures, and no change in paritaprevir exposures. Body weight is not a significant 
predictor of ritonavir exposures.

Race or ethnicity

Based on population pharmacokinetic analysis of data from Phase 3 clinical studies, Asian subjects had 
18% to 21% higher ombitasvir exposures, and 37% to 39% higher paritaprevir exposures than non-Asian 
subjects. The ritonavir exposures were comparable between Asians and non-Asians.

Renal impairment

The changes in ombitasvir, paritaprevir, and ritonavir 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 Viekirax with and without dasabuvir is required for patients with mild, moderate or 
severe renal impairment , or end-stage-renal disease on dialysis (see section 4.2). 

Pharmacokinetics of the combination of ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, 
with or without 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.

Following administration of Viekirax and dasabuvir

Compared to the subjects with normal renal function, ombitasvir exposures were comparable in subjects 
with mild, moderate and severe renal impairment. Compared to the subjects with normal renal function, 
paritaprevir Cmax values were comparable, but AUC values were 19%, 33% and 45% higher in mild, 
moderate and severe renal impairment, respectively. Ritonavir plasma concentrations increased when 
renal function was reduced: Cmax and AUC values were 26% to 42% higher, 48% to 80% higher and 66% 
to 114% higher in subjects with mild, moderate and severe renal impairment, respectively.

Following administration of Viekirax

Following administration of Viekirax, the changes in ombitasvir, paritaprevir, and ritonavir exposures in 
subjects with mild, moderate and severe renal impairment were similar to those observed when Viekirax
was administered with dasabuvir, and are not considered to be clinically significant. 

Hepatic impairment

Following administration of Viekirax and dasabuvir

Pharmacokinetics of the combination of ombitasvir 25 mg, paritaprevir 200 mg, and ritonavir 100 mg, 
with dasabuvir 400 mg were evaluated in non-HCV infected subjects with mild (Child-Pugh A), moderate 
(Child-Pugh B) and severe (Child-Pugh C) hepatic impairment.

In subjects with mild hepatic impairment, paritaprevir, ritonavir and ombitasvir mean Cmax and AUC 
values decreased by 29% to 48%, 34% to 38% and up to 8%, respectively, compared to subjects with 
normal hepatic function.

In subjects with moderate hepatic impairment, ombitasvir and ritonavir mean Cmax and AUC values 
decreased by 29% to 30% and 30 to 33%, respectively, while paritaprevir mean Cmax and AUC values
increased by 26% to 62% compared to subjects with normal hepatic function. (see sections 4.2, 4.4, and 
4.8).



58

In subjects with severe hepatic impairment, paritaprevir mean Cmax and AUC values increased by 3.2-to 
9.5-fold; ritonavir mean Cmax values were 35% lower and AUC values were 13% higher and ombitasvir
mean Cmax and AUC values decreased by 68% and 54%, respectively, compared to subjects with normal 
hepatic function, therefore, Viekirax must not be used in patients with severe hepatic impairment (see 
sections 4.2 and 4.4).

In HCV-infected subjects, in comparison to those without cirrhosis, paritaprevir AUC increased to 2.2- to 
2.4-fold for those with compensated cirrhosis (Child-Pugh A) and 3- to 4-fold for those with Child-Pugh B 
cirrhosis.

Following administration of Viekirax

Pharmacokinetics of the combination of ombitasvir 25 mg, paritaprevir 200 mg, and ritonavir 100 mg 
were not evaluated in subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and severe (Child-
Pugh C) hepatic impairment. Results from the pharmacokinetic evaluation of the combination of 
ombitasvir 25 mg, paritaprevir 200 mg, and ritonavir 100 mg, with dasabuvir 400 mg can be extrapolated 
to the combination of ombitasvir 25 mg, paritaprevir 200 mg, and ritonavir 100 mg.

Paediatric population

The pharmacokinetics of Viekirax in paediatric patients has not been established (see section 4.2).

5.3 Preclinical safety data

Ombitasvir

Ombitasvir and its major inactive human metabolites (M29, M36) were not genotoxic in a battery of in 
vitro or in vivo assays, including bacterial mutagenicity, chromosome aberration using human peripheral 
blood lymphocytes and in vivo mouse micronucleus assays.

Ombitasvir was not carcinogenic in a 6-month transgenic mouse study up to the highest dosage tested 
(150 mg/kg/day), resulting in ombitasvir AUC exposures approximately 26-fold higher than those in 
humans at the recommended clinical dose of 25 mg.

Similarly, ombitasvir was not carcinogenic in a 2-year rat study up to the highest dose tested (30 mg per 
kg per day), resulting in ombitasvir exposures approximately 16-fold higher than those in humans at 25 
mg.

Ombitasvir has shown malformations in rabbits at maximal feasible exposures 4-fold higher than the AUC 
exposure at recommended clinical dose. Malformations at low incidence were observed mainly in the eyes 
(microphthalmia) and teeth (absent incisors). In mice, an increased incidence of open eye lid was present 
in foetuses of dams administered ombitasvir; however, the relationship to treatment with ombitasvir is 
uncertain. The major, inactive human metabolites of ombitasvir were not teratogenic in mice at exposures 
approximately 26 times higher than in humans at the recommended clinical dose. Ombitasvir had no effect 
on fertility when evaluated in mice.
Unchanged ombitasvir was the predominant component observed in the milk of lactating rats, without 
effect on nursing pups. Ombitasvir-derived material was minimally transferred through the placenta in 
pregnant rats.

Paritaprevir/ritonavir



59

Paritaprevir was positive in an in vitro human chromosome aberration test. Paritaprevir was negative in a 
bacterial mutation assay, and in two in vivo genetic toxicology assays (rat bone marrow micronucleus and 
rat liver Comet tests).

Paritaprevir /ritonavir was not carcinogenic in a 6-month transgenic mouse study up to the highest dosage 
tested (300 mg/30 mg/kg/day), resulting in paritaprevir AUC exposures approximately 38-fold higher than 
those in humans at the recommended dose of 150 mg. Similarly, paritaprevir/ritonavir was not 
carcinogenic in a 2-year rat study up to the highest dosage tested (300 mg/30 mg/kg/day), resulting in 
paritaprevir AUC exposures approximately 8-fold higher than those in humans at 150 mg.

Paritaprevir/ritonavir has shown malformations (open eye lids) at a low incidence in mice at exposures 
32/8-fold higher than the exposure in humans at the recommended clinical dose. Paritaprevir/ritonavir had 
no effects on embryo-foetal viability or on fertility when evaluated in rats at exposures 2- to 8-fold higher 
than the exposure in humans at the recommended clinical dose.
Paritaprevir and its hydrolysis product M13 were the predominant components observed in the milk of 
lactating rats, without effect on nursing pups. Paritaprevir -derived material was minimally transferred 
through the placenta in pregnant rats.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core

Copovidone
Tocofersolan
Propylene glycol monolaurate
Sorbitan monolaurate
Colloidal anhydrous silica (E 551)
Sodium stearyl fumarate

Film-coating

Poly(vinyl alcohol) (E 1203)
Macrogol (3350)
Talc (E 553b)
Titanium dioxide (E 171)
Iron oxide red (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container



60

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/1/14/982/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 15 January 2015
Date of latest renewal: 19 September 2019

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/


61

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



62

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:



63

Description Due date
In order to evaluate the recurrence of hepatocellular carcinoma associated 
withViekirax, 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: 

Q3 2021



64

ANNEX III

LABELLING AND PACKAGE LEAFLET



65

A. LABELLING



66

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

Viekirax 12.5 mg / 75 mg / 50 mg film-coated tablets
ombitasvir / paritaprevir / ritonavir 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film coated tablet contains 12.5 mg of ombitasvir, 75 mg of paritaprevir and 50 mg of ritonavir. 

3. LIST OF EXCIPIENTS

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 two tablets in the morning

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



67

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/982/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

viekirax

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



68

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

Viekirax 12.5 mg / 75 mg / 50 mg film-coated tablets
ombitasvir / paritaprevir / ritonavir 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film coated tablet contains 12.5 mg of ombitasvir, 75 mg of paritaprevir and 50 mg of ritonavir. 

3. LIST OF EXCIPIENTS

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 two tablets in the morning.

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



69

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/982/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

viekirax

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA



70

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOIL

1. NAME OF THE MEDICINAL PRODUCT

Viekirax 12.5 mg / 75 mg / 50 mg tablets
ombitasvir / paritaprevir / ritonavir

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AbbVie (as logo)

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



71

B. PACKAGE LEAFLET



72

Package leaflet: Information for the patient

Viekirax 12.5 mg/75 mg/50 mg film-coated tablets
ombitasvir/paritaprevir/ritonavir

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 Viekirax is and what it is used for
2. What you need to know before you take Viekirax
3. How to take Viekirax
4. Possible side effects
5. How to store Viekirax
6. Contents of the pack and other information

1. What Viekirax is and what it is used for

Viekirax contains the active substances ombitasvir, paritaprevir and ritonavir. It 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). 
The combined action of the three active substances stops the hepatitis C virus from multiplying and 
infecting new cells, thus clearing the virus from your blood over a period of time. Ombitasvir and
paritaprevir block two proteins essential for the virus to multiply. Ritonavir acts as a ‘booster’ to prolong 
the action of paritaprevir in the body.

Viekirax tablets are taken with other antiviral medicines such as dasabuvir and ribavirin. Your doctor will 
talk with you about which of these medicines to take with Viekirax.

It is very important that you also read the package leaflets for the other antiviral medicines that you take 
with Viekirax. If you have any questions about your medicines, please ask your doctor or pharmacist.

2. What you need to know before you take Viekirax

Do not take Viekirax
 If you are allergic to ombitasvir, paritaprevir, ritonavir, 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.



73

 If you are taking any of the medicines listed in the following table. This is because serious or life-
threatening effects can occur when Viekirax is taken with these medicines. These medicines can affect 
the way Viekirax works and Viekirax can affect the way these other medicines work.

Medicines you must not take with Viekirax
Medicine or active substance Purpose of the medicine
alfuzosin for an enlarged prostate
amiodarone, disopyramide, dronedarone used to correct irregular heartbeats
astemizole, terfenadine for allergy symptoms. These medicines may 

be available without a prescription
atorvastatin, lovastatin, simvastatin, 
lomitapide

to lower blood cholesterol

carbamazepine, phenytoin, phenobarbital for epilepsy
cisapride for relieving certain stomach problems
clarithromycin, fusidic acid, rifampicin, 
telithromycin

for bacterial infections

colchicine in patients who have severe 
problems with their liver or kidneys

for treating gout attacks

conivaptan for making the sodium levels in the blood 
normal

efavirenz, etravirine, lopinavir/ritonavir, 
saquinavir, tipranavir, nevirapine, indinavir, 
cobicistat

for HIV infection

apalutamide,enzalutamide for prostate cancer
ergotamine, dihydroergotamine for migraine headaches
ergonovine, methylergometrine used in childbirth
ethinyloestradiol-containing medicines such 
as those contained in most contraceptive pills 
and vaginal rings used for contraception

for contraception

itraconozole, ketoconozole, posaconazole, 
voriconazole 

for fungal infections

midazolam, triazolam (when taken by mouth) for anxiety or trouble sleeping
mitotane for symptoms of malignant tumours of the 

adrenal glands
pimozide, lurasidone for schizophrenia

quetiapine for schizophrenia, bipolar disorder and major 
depressive disorder

quinidine for abnormal heart rhythms or malaria

ranolazine for chronic angina (chest pain)
salmeterol for asthma
sildenafil when used to treat a heart and lung disorder 

called “pulmonary arterial hypertension”
St. John’s Wort (hypericum perforatum) a herbal medicine for anxiety and mild 

depression. This medicine is available 
without a prescription

ticagrelor stops blood from clotting

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Viekirax if you:



74

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

When taking Viekirax with dasabuvir, 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 
Viekirax.

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 Viekirax. This is so that your 
doctor can:
 Decide what other medicines you should take with Viekirax 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 Viekirax or other antiviral medicines your doctor has prescribed for you to 

use with Viekirax (such as “dasabuvir” and “ribavirin”).

Children and adolescents
Do not give Viekirax to children and adolescents under 18 years of age. The use of Viekirax in children 
and adolescents has not yet been studied.

Other medicines and Viekirax
Tell your doctor or pharmacist if you are taking, have recently taken and before starting any other 
medicines. 

There are some medicines you must not take with Viekirax see the previous table “Medicines you must 
not take with Viekirax”.

Tell your doctor or pharmacist before taking Viekirax, 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 Viekirax also if you are using hormonal contraceptives. See the section on contraception 
below.



75

Medicines you must tell your doctor about before taking Viekirax
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
colchicine for patients whose kidney and liver 
function test are normal

for treating gout attacks or familial 
Mediterranean fever

digoxin, amlodipine, nifedipine, valsartan, 
diltiazem, verapamil, candesartan, losartan

for heart problems or high blood 
pressure

encorafenib for skin cancer
furosemide for the build-up of too much fluid in 

the body
fostamatinib for low platelet counts
hydrocodone for pain
levothyroxine for thyroid problems
rilpivirine, darunavir, atazanavir for HIV infection 
omeprazole, lansoprazole, esomeprazole for stomach ulcers and other stomach 

problems
ibrutinib, imatinib for the treatment of some cancers of 

the blood
fluvastatin, pitavastatin, pravastatin, rosuvastatin to lower blood cholesterol 
dabigatran to thin the blood
fexofenadine for hay fever
s-mephenytoin for epilepsy
sulfasalazine for inflammatory bowel disease
repaglinide for lowering blood sugar
erythromycin for bacterial infections
steroid or corticosteroid medicines (such as 
fluticasone)

for many different conditions including 
serious illnesses and allergies

trazodone for anxiety and depression
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 
Viekirax.

Pregnancy and contraception 

The effects of Viekirax during pregnancy are not known. Viekirax 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 contain ethinyloestradiol cannot be used in combination with Viekirax. Ask your 
doctor about the best contraception for you.

Extra precautions are needed if Viekirax 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.



76

 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 Viekirax and ribavirin or in the 
months that follow, you must contact your doctor immediately.

Breastfeeding
You should not breast-feed during treatment with Viekirax. It is not known whether the active substances 
in Viekirax (ombitasvir, paritaprevir and ritonavir) pass into breast milk.

Driving and using machines 
Some patients have reported feeling very tired when taking Viekirax with other medicines for their hepatitis 
C infection. If you feel tired, do not drive or use machines.

3. How to take Viekirax

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure.

Viekirax tablets are usually taken with other anti-viral medicines such as “dasabuvir” and “ribavirin”.

How much to take
The recommended dose is two tablets taken together in the morning.

How to take
 Take the tablets in the morning 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 Viekirax for
You will take Viekirax for 8, 12 or 24 weeks. Your doctor will tell you how long your treatment will last.
Do not stop taking Viekirax 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.

If you take more Viekirax 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 that you can easily describe what you 
have taken.

If you forget to take Viekirax
It is important not to miss a dose of this medicine. If you do miss a dose and it is:
 More than 12 hours until your next dose - take the missed dose with food as soon as possible.
 Less than 12 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.



77

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Stop taking Viekirax and talk to your doctor or get medical help immediately if any of the following 
occur: 

Side effects when taking Viekirax with or without dasabuvir and 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

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or pharmacist if you notice any of the following side effects.

Side effects when taking Viekirax with dasabuvir:
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 Viekirax with dasabuvir and 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
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)



78

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 Viekirax

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 Viekirax contains
 Each tablet contains 12.5 mg of ombitasvir, 75 mg of paritaprevir and 50 mg of ritonavir.
 The other ingredients are:

 Tablet core: copovidone, tocofersolan, propylene glycol monolaurate, sorbitan monolaurate, 
colloidal anhydrous silica (E 551), sodium stearyl fumarate.

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

What Viekirax looks like and contents of the pack
Viekirax tablets are pink, oblong film-coated tablets of dimmensions 18.8 mm x 10.0 mm, marked with 
‘AV1’. Viekirax tablets are packed into foil blisters containing 2 tablets. Each carton contains 56 tablets 
(multipack carton containing 4 inner cartons of 14 tablets each).

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 Luxembourg/Luxemburg

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


79

АбВи ЕООД
Тел.: +359 2 90 30 430

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

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

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

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

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

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

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

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

Norge
AbbVie AS
Tlf: +47 67 81 80 00

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

Österreich
AbbVie GmbH 
Tel: +43 1 20589-0

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

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

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

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

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

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

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

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

Ísland
Vistor hf.
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



80

Latvija
AbbVie SIA 
Tel: +371 67605000

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

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