An HCV treatment for

VIEKIRA XR—A once-daily treatment taken with a meal for GT1 chronic HCV infection that may provide a virologic cure* for patients like yours.

* Cure (virologic cure): sustained virologic response (SVR12).1

* Cure (virologic cure): sustained virologic response (SVR12); HCV RNA <25 IU/mL 12 weeks after the end of treatment.1

No dose adjustment is required for patients with mild, moderate, or severe renal impairment, including those on dialysis. VIEKIRA XR is contraindicated with colchicine in patients with renal and/or hepatic impairment due to the potential for serious and/or life-threatening reactions.

VIEKIRA XR reduces omeprazole concentrations. Monitor patients for decreased efficacy of omeprazole and consider increasing the dose if symptoms are not well controlled. Avoid use of omeprazole >40 mg/day.

GT = genotype. | PPI = proton pump inhibitor.

SAFETY CONSIDERATIONS1
  • Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VIEKIRA XR. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • When VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • ALT elevations >5x upper limit of normal (ULN) occurred in 1% of all subjects and were significantly more frequent in females using ethinyl estradiol-containing medications, which are contraindicated. Perform hepatic lab testing on all patients.
  • Due to risk of HIV-1 protease inhibitor drug resistance, HCV/HIV-1 coinfected patients should be on a suppressive antiretroviral drug regimen.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Individualized approaches
GT1b

An individualized approach for patients like Victor—with GT1b

Clinically proven results in GT1b patients, in an extended-release formulation1

* Cure (virologic cure): sustained virologic response (SVR12).1

  • Patients received the components of VIEKIRA XR administered as 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets QD and 1 dasabuvir (250 mg) tablet BID (VIEKIRA)
  • In multiple clinical trials, 100% of GT1b patients reached SVR12 with 12 weeks of VIEKIRA therapy (n=360/360)1-4
  • Patients were either treatment-naive or failed to respond to prior pegylated interferon/ribavirin (pegIFN/RBV) treatment
  • VIEKIRA XR must be taken with a meal because administration under fasting conditions may result in reduced virologic response and possible development of resistance1

AE = adverse event; BID = twice daily; QD: once daily; RBV = ribavirin.


In phase III clinical trials, VIEKIRA cured* GT1b patients regardless of presence or absence of compensated cirrhosis1-4

SVR12 rate in GT1b patients with and without compensated cirrhosis (Child-Pugh A) after 12 weeks of therapy


Study designs:

PEARL II was an open-label trial of VIEKIRA +/- RBV in treatment-experienced non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: prior failed triple therapy with pegIFN/RBV + a protease inhibitor, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV or VIEKIRA alone, of which 88 and 91 subjects were included in the intent-to-treat efficacy population, respectively. Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,3

PEARL III was a controlled trial of VIEKIRA +/- RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=210) or VIEKIRA + matching placebo for RBV (n=209). Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,4

TURQUOISE III was an open-label, single-arm, multicenter phase IIIb study of VIEKIRA for 12 weeks in 60 GT1b chronic HCV infected adults with compensated cirrhosis who were either treatment-naïve or did not achieve sustained virologic response (SVR) with prior pegIFN/RBV treatment. Eligible patients had documented cirrhosis by means of liver biopsy (Metavir score >3 or Ishak score of >4) or transient elastography (FibroScan score ≥12.5 kPa within 6 months of screening or during screening), and a Child-Pugh score of 5 or 6 with no evidence of decompensation or hepatocellular carcinoma. Primary endpoint: SVR12. Secondary efficacy endpoints included virologic failure during treatment and post-treatment relapse.1,2

SAFETY CONSIDERATIONS1
  • VIEKIRA XR is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis prior to initiating therapy. Reported cases typically occurred within 1 to 4 weeks of initiating therapy.
  • For patients with cirrhosis: monitor for clinical signs and symptoms of hepatic decompensation; perform hepatic lab testing, including direct bilirubin levels, at baseline and during the first 4 weeks of starting treatment and as clinically indicated; discontinue treatment in patients who develop evidence of hepatic decompensation.
  • VIEKIRA XR without RBV most common adverse events (≥5% of subjects): nausea, pruritus, and insomnia.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Individualized approaches
Renal impairment

An individualized approach for patients like Michael—with renal impairment

In the United States, approximately 300,000 of all chronic HCV patients* have also been diagnosed with chronic kidney disease (CKD), including those on dialysis5†

* Includes all HCV genotypes.

Based on IMS Health, Rapid Weekly (12/6/2013 – 7/1/2016), IMS LifeLink™ LRx (1/2008 – 6/2016), IMS Dx Medical Claims (10/2013 – 4/2016).

KDIGO guidelines: renal function should be taken into account when prescribing medications6
  • Some renally excreted drugs may accumulate systemically, and must be administered at a modified dose
  • Others should be avoided due to potential nephrotoxicity

KDIGO = Kidney Disease: Improving Global Outcomes.


VIEKIRA XR is primarily hepatically cleared1

No dose adjustment needed in patients with impaired renal function

Mild renal impairment
Moderate renal impairment
Severe renal impairment
HCV patients on dialysis

GT1b—No RBV is required

VIEKIRA XR is approved for use without RBV for 12 weeks in GT1b chronic HCV patients.

GT1a—RBV is recommended

  • VIEKIRA XR with RBV for 12 or 24 weeks is the recommended regimen for use in GT1a chronic HCV patients
  • RBV is primarily renally cleared and may require dose modifications consistent with its prescribing information as recommended by the American Association for the Study of Liver Diseases (AASLD) guidelines7

Additional dosing considerations1

Regardless of GT1 subtype, in liver transplant recipients with normal hepatic function and mild fibrosis (Metavir fibrosis score ≤2), the recommended duration of VIEKIRA XR with ribavirin is 24 weeks.

Drug-Drug Interactions (DDIs)
for VIEKIRA XR (VIEKIRA)
SAFETY CONSIDERATIONS1
  • VIEKIRA XR is contraindicated with colchicine in patients with renal and/or hepatic impairment due to the potential for serious and/or life-threatening reactions.
  • VIEKIRA XR increases the concentration of angiotensin-receptor blockers (ARB) (valsartan, losartan, candesartan) and calcium-channel blockers (CCB) (amlodipine, nifedipine, diltiazem, verapamil). Decrease the dose of the ARB or CCB and monitor patients for signs and symptoms of hypotension and/or worsening renal function and edema.
  • If VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Individualized approaches
PPI user

An individualized approach for patients like Beth—who need a PPI

Nearly 1/3 of HCV patients are on a prescription acid-reducing therapy, primarily a PPI8*

In addition to prescription PPIs, many patients may be using over-the-counter formulations

PPIs may compromise the bioavailability of some chronic HCV therapies7

* Based on IMS diagnosis data from Jan 2012–Dec 2013.


A DDI may result when HCV therapy is used concomitantly with a PPI

  • The PPI may affect the bioavailability of HCV therapy7
  • HCV therapy may affect the bioavailability of the PPI1

DDI = drug-drug interaction.


VIEKIRA +/- RBV demonstrated comparable cure rates, with or without PPIs, in 7 phase III clinical trials—based on a post hoc analysis1,9

Drug-Drug Interactions (DDIs)
for VIEKIRA XR (VIEKIRA)

Cure = Cure (virologic cure): sustained virologic response (SVR12).1

Across patient populations, pooled by recommended regimen (n=1076), VIEKIRA +/- RBV delivered consistently high cure rates ranging from 95%-100%.

§ High doses were defined as >20 mg omeprazole, esomeprazole, and rabeprazole, >30 mg for dexlansoprazole, >15 mg for lansoprazole, and >40 mg for pantoprazole.9


  • VIEKIRA XR reduces omeprazole concentrations. Monitor patients for decreased efficacy of omeprazole and consider increasing the dose if symptoms are not well controlled. Avoid use of omeprazole >40 mg/day1
  • Patients received 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets QD and 1 dasabuvir (250 mg) tablet BID +/- RBV for 12 or 24 weeks
SAFETY CONSIDERATIONS1
  • VIEKIRA XR is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events; moderate or strong inducers of CYP3A and strong inducers of CYP2C8, which may lead to reduced efficacy of VIEKIRA XR; and strong CYP2C8 inhibitors, which may increase dasabuvir levels and the risk of QT prolongation.
  • VIEKIRA XR is contraindicated with the following drugs: alfuzosin HCL; ranolazine; dronedarone; carbamazepine; phenytoin; phenobarbital; colchicine (in patients with renal and/or hepatic impairment); gemfibrozil; rifampin; lurasidone; pimozide; ergotamine; dihydroergotamine; methylergonovine; ethinyl estradiol-containing medicines, such as combined oral contraceptives; cisapride; St. John’s Wort (Hypericum perforatum); lovastatin, simvastatin; efavirenz; sildenafil (when dosed as Revatio for pulmonary arterial hypertension); triazolam and oral midazolam.
  • When VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Individualized approaches
Compensated cirrhotic

An individualized approach for patients like Carl—who have compensated cirrhosis

According to the Ipsos Healthcare HCV Monitor from Q2 201610*

of GT1 HCV patients tested for fibrosis were considered cirrhotic
of those with cirrhosis were compensated cirrhotics

* Data were provided on 1158 GT1 HCV-infected patients with an identified fibrosis score.


VIEKIRA has 2 dedicated phase III studies in GT1 chronic HCV patients with compensated cirrhosis [Child-Pugh A]1

High SVR12 rates in GT1 chronic HCV-compensated cirrhotic patients, regardless of subgenotypes or prior pegIFN/RBV treatment experience

Drug-Drug Interactions (DDIs)
for VIEKIRA XR (VIEKIRA)
SAFETY CONSIDERATIONS1
  • VIEKIRA XR is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity.
  • VIEKIRA XR is contraindicated with colchicine in patients with renal and/or hepatic impairment due to the potential for serious and/or life-threatening reactions.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis prior to initiating therapy. Reported cases typically occurred within 1 to 4 weeks of initiating therapy.
  • For patients with cirrhosis: monitor for clinical signs and symptoms of hepatic decompensation; perform hepatic lab testing, including direct bilirubin levels, at baseline and during the first 4 weeks of starting treatment and as clinically indicated; discontinue treatment in patients who develop evidence of hepatic decompensation.
  • Elevations of ALT to >5x the upper limit of normal (ULN) occurred in 1% of all subjects in clinical trials and were significantly more frequent in females using ethinyl estradiol-containing medications. In female patients, discontinue ethinyl estradiol-containing medications prior to starting therapy and use alternative methods of contraception during therapy. Use caution when co-administering VIEKIRA XR with estrogens other than ethinyl estradiol, such as estradiol and conjugated estrogens.
  • Perform hepatic lab testing on all patients during the first 4 weeks of treatment and as clinically indicated thereafter. If ALT is elevated above baseline levels, repeat testing and monitor closely. Patients should be instructed to consult their doctor without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, or discolored feces. Consider discontinuing VIEKIRA XR if ALT levels remain persistently >10x the ULN. Discontinue VIEKIRA XR if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing direct bilirubin, alkaline phosphatase, or INR.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Efficacy
Overview

Consistently high cure* rates in multiple GT1 chronic HCV patient types

VIEKIRA +/- RBV was studied in 7 phase III clinical trials that included >2300 adult patients with GT1 chronic HCV1

SVR12 rate of 97% across patient populations, pooled by recommended treatment regimens for 12 or 24 weeks (n=1046/1076)

* Cure (virologic cure): sustained virologic response (SVR12).1

Patients received 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets QD and 1 dasabuvir (250 mg) tablet BID +/- RBV for 12 or 24 weeks.1 Review each trial for additional detailed study design information.1


VIEKIRA + RBV was also studied in additional populations of GT1 chronic HCV patient types in 2 open-label phase II clinical trials1

VIEKIRA + RBV SVR12 rate in phase II clinical trials

BID = twice daily; GT = genotype; QD = once daily.


Study drugs:

Patients received the components of VIEKIRA XR administered as 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets once daily and 1 dasabuvir (250 mg) tablet twice daily.1

Phase III study background information2-4,11-15

SAFETY ASSESSMENTS: AEs were assessed at each study visit and were collected from the start of study drug administration until 30 days after last dose.

HCV RNA MEASUREMENT: Plasma HCV RNA levels were measured using an assay with a lower limit of detection 15 IU/mL and the lower limit of quantification of 25 IU/mL.

ON-TREATMENT VIROLOGIC FAILURE was defined as confirmed HCV RNA ≥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.

POST-TREATMENT RELAPSE was defined as confirmed HCV RNA ≥25 IU/mL between the final visit during the treatment period and 12 weeks after the last dose of study drug, for subjects assigned to 12 or 24 weeks of treatment, respectively.

TREATMENT-NAÏVE SUBJECTS were defined as not having received any prior therapy for HCV infection.

TREATMENT-EXPERIENCED SUBJECTS (SAPPHIRE-I/II, PEARL-II/III/IV, TURQUOISE-II) were defined as either: prior relapsers (subjects with HCV RNA undetectable at or after the end of at least 36 weeks of pegIFN/RBV treatment, but HCV RNA was detectable within 52 weeks of treatment follow-up) or prior partial responders (received at least 20 weeks of pegIFN/RBV and achieved ≥2 log10 IU/mL reduction in HCV RNA at Week 12, but not achieving HCV RNA undetectable at end of treatment) or prior null responders (received at least 12 weeks of pegIFN/RBV treatment and failed to achieve a 2 log10 IU/mL reduction in HCV RNA at Week 12 or received at least 4 weeks of pegIFN/RBV treatment and achieved a <1 log10 IU/mL reduction in HCV RNA at Week 4).

TREATMENT-EXPERIENCED SUBJECTS (TURQUOISE-III) were defined as either: prior null-responders (failed to achieve a 1 log10 IU/mL reduction in HCV RNA by Week 4 or a 2 log10 IU/mL reduction in HCV RNA by Week 12 during a prior pegIFN/RBV treatment course), or prior partial responders (achieved at least a 2 log10 IU/mL reduction in HCV RNA by Week 12 during a prior pegIFN/RBV treatment course but failed to achieve HCV RNA undetectable at the end of treatment), or prior relapsers (achieved HCV RNA unquantifiable [detected or undetected] at end of a prior treatment course but HCV RNA was quantifiable following cessation of therapy).

SVR12 was defined as HCV RNA below the lower limit of quantification (<25 IU/mL) 12 weeks after the end of treatment. Subjects who achieved SVR12 were considered virologically cured.

Baseline characteristics1

Subjects with HCV GT1a infection treated with VIEKIRA + RBV in SAPPHIRE I and SAPPHIRE II and in PEARL IV had a median age of 53 years (range: 18 to 70); 63% were male; 90% were White; 7% were Black/African American; 8% were Hispanic or Latino; 19% had a BMI ≥30 kg/m2; 55% were enrolled in US sites; 72% had IL28B non-CC genotype; 85% had baseline HCV RNA levels ≥800,000 IU/mL.

Subjects with HCV GT1b infection treated with VIEKIRA +/- RBV in PEARL II and PEARL III had a median age of 52 years (range: 22 to 70); 47% were male; 93% were White; 5% were Black/African American; 2% were Hispanic or Latino; 21% had a BMI ≥30 kg/m2; 21% were enrolled in US sites; 83% had IL28B non-CC genotype; 77% had baseline HCV RNA levels ≥800,000 IU/mL.

In TURQUOISE II, treated subjects had a median age of 58 years (range: 21 to 71); 70% were male; 95% were White; 3% were Black/ African American; 12% were Hispanic or Latino; 28% had a BMI ≥30 kg/m2; 43% were enrolled in US sites; 82% had IL28B non-CC genotype; 86% had baseline HCV RNA levels ≥800,000 IU per mL; 69% had GT1a infection; 31% had GT1b infection; 42% were treatment-naïve, 36% were prior pegIFN/RBV null responders; 8% were prior pegIFN/RBV partial responders; 14% were prior pegIFN/RBV relapsers; 15% had platelet counts <90 x 109/L; 50% had albumin <4.0 mg/dL.

In TURQUOISE III, treated subjects had a median age of 61 years (range: 26 to 78); including 45% treatment-naïve and 55% pegIFN/RBV treatment-experienced; 25% were ≥65 years; 62% were male; 12% were Black; 5% were Hispanic or Latino; 28% had a body mass index of at least 30 kg per m2; 40% of patients were enrolled in US sites; 92% had baseline HCV RNA levels of at least 800,000 IU per mL; 83% had IL28B non-CC genotype.

Non-cirrhotic phase III trials

The clinical trial program included 5 randomized, global, multicenter, phase III trials conducted to evaluate the safety and efficacy of VIEKIRA +/- RBV in different non-cirrhotic patient populations described below. In each study, RBV dose adjustments were performed according to the RBV labeling.1

SAPPHIRE I was a placebo-controlled trial of VIEKIRA + RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1a or GT1b chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 3:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=473) or matching placebos (n=158). Primary endpoint: SVR12 for subjects initially randomized to active treatment. Secondary efficacy endpoints included SVR12 according to HCV genotype (1a or 1b), virologic failure during treatment, and post-treatment relapse. Subjects randomized to the placebo arm for the first 12 weeks then received open-label VIEKIRA + RBV for the subsequent 12 weeks.1,11

SAPPHIRE II was a placebo-controlled trial of VIEKIRA + RBV in treatment-experienced non-cirrhotic adults, 18 to 70 years of age, with GT1a or GT1b chronic HCV infection. Exclusion criteria included: prior failed triple therapy with pegIFN/RBV + a protease inhibitor, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 3:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=297) or matching placebos (n=97). Primary endpoint: SVR12 for subjects initially randomized to active treatment. Secondary efficacy endpoints included SVR12 according to HCV genotype (1a or 1b), virologic failure during treatment, and post-treatment relapse. Subjects randomized to the placebo arm for the first 12 weeks then received open-label VIEKIRA + RBV for the subsequent 12 weeks.1,12

PEARL II was an open-label trial of VIEKIRA +/- RBV in treatment-experienced non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: prior failed triple therapy with pegIFN/RBV + a protease inhibitor, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV or VIEKIRA alone, of which 88 and 91 subjects were included in the intent-to-treat efficacy population, respectively. Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,3

PEARL III was a controlled trial of VIEKIRA +/- RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=210) or VIEKIRA + matching placebo for RBV (n=209). Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,4

PEARL IV was a controlled trial of VIEKIRA +/- RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1a chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:2 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=100) or VIEKIRA + matching placebo for RBV (n=205). Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,4

Cirrhotic phase III trials

TURQUOISE II was a randomized, global, multicenter, open-label phase III trial conducted to evaluate the safety and efficacy of VIEKIRA + RBV exclusively in treatment-experienced or treatment-naïve adults with compensated cirrhosis (Child-Pugh A), 18 to 70 years of age, with GT1a or GT1b chronic HCV infection. Eligible subjects had documentation of cirrhosis by means of liver biopsy (Metavir score >3 or Ishak score >4) or FibroScan result (≥14.6 kPa within 6 months before screening or during screening), a Child-Pugh Class A score of <7 at screening, and no current or past clinical evidence of Child-Pugh Class B or C disease. Key eligibility criteria were a platelet count ≥60,000/mm3, a serum albumin level ≥2.8 g/dL, a total bilirubin level <3 mg/dL, an INR ≤2.3, and a serum alpha-fetoprotein level ≤100 ng/mL. Exclusion criteria included: subjects with prior failed therapy with a treatment regimen that included VIEKIRA or other DAA agents, HBV or HIV coinfection, a recent history of drug or alcohol abuse, or hepatocellular carcinoma. Subjects were randomly assigned in a ratio of approximately 1:1 to 12 weeks (n=208) or 24 weeks (n=172) of treatment with VIEKIRA + RBV and stratified based on whether or not they received previous pegIFN/RBV treatment. RBV dose adjustments were performed according to the RBV labeling. Primary endpoint: SVR12. The key secondary efficacy endpoint was the percentage of subjects with a SVR12 in the 24-week group as compared with the 12-week group. Other secondary efficacy endpoints included SVR12 according to HCV genotype (1a or 1b), virologic failure during treatment, and post-treatment relapse.1,13

TURQUOISE III was an open-label, single-arm, multicenter phase IIIb study of VIEKIRA for 12 weeks in 60 GT1b chronic HCV infected adults with compensated cirrhosis who were either treatment-naïve or did not achieve sustained virologic response (SVR) with prior pegIFN/RBV treatment. Eligible patients had documented cirrhosis by means of liver biopsy (Metavir score >3 or Ishak score of >4) or transient elastography (FibroScan score ≥12.5 kPa within 6 months of screening or during screening), and a Child-Pugh score of 5 or 6 with no evidence of decompensation or hepatocellular carcinoma. Primary endpoint: SVR12. Secondary efficacy endpoints included virologic failure during treatment and post-treatment relapse.1,2

Additional Populations:

PHASE II – CORAL I was an open-label study conducted to evaluate the safety and efficacy of VIEKIRA + RBV in 34 liver transplant recipients who were ≥12 months post transplantation with recurrent HCV GT1-infection. All subjects had not received treatment for HCV after transplantation and had normal hepatic function and a Metavir fibrosis score of F2 or lower. All subjects were taking a stable immunosuppressant regimen based on either tacrolimus or cyclosporine. Exclusion criteria included: use of everolimus or sirolimus within 2 months of screening visit, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. All subjects received 24 weeks of treatment with VIEKIRA + RBV. Primary endpoint: SVR12. Secondary assessments included the percentage of patients with a SVR at post-treatment Week 24, virologic failure during treatment, and post-treatment relapse.1,14

PHASE II – TURQUOISE I was an open-label clinical trial conducted to evaluate the safety and efficacy of 12 or 24 weeks of treatment with VIEKIRA + RBV in 63 subjects coinfected with GT1 HCV and HIV-1. Subjects were on a stable HIV-1 ART regimen that included tenofovir disoproxil fumarate plus emtricitabine or lamivudine, administered with ritonavir-boosted atazanavir or raltegravir. Subjects on atazanavir stopped the ritonavir component of their HIV-1 ART regimen upon initiating treatment with VIEKIRA + RBV. Atazanavir was taken with the morning dose of VIEKIRA. The ritonavir component of the HIV-1 ART regimen was restarted after completion of treatment with VIEKIRA + RBV. Exclusion criteria included: HBV coinfection, subjects with prior therapy with a DAA for the treatment of HCV, or a recent history of drug or alcohol abuse. Primary endpoint: SVR12. Secondary efficacy endpoints included virologic failure during treatment and post-treatment relapse.1,15

SAFETY CONSIDERATIONS1
  • Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VIEKIRA XR. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment followup. Initiate appropriate patient management for HBV infection as clinically indicated.
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • When VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
  • Due to risk of HIV-1 protease inhibitor drug resistance, HCV/HIV-1 co-infected patients should be on a suppressive antiretroviral drug regimen.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Efficacy
GT1b

In phase III clinical trials, VIEKIRA cured* GT1b patients regardless of presence or absence of compensated cirrhosis1-4

SVR12 rate in GT1b patients with and without compensated cirrhosis (Child-Pugh A) after 12 weeks of therapy

Patients received 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets QD and 1 dasabuvir (250 mg) tablet BID.


AE-related discontinuations
Post-treatment relapse
On-treatment virologic failure

* Cure (virologic cure): sustained virologic response (SVR12).1

Study designs:

TURQUOISE III was an open-label, single-arm, multicenter phase IIIb study of VIEKIRA for 12 weeks in 60 GT1b chronic HCV infected adults with compensated cirrhosis who were either treatment-naive or did not achieve sustained virologic response (SVR) with prior pegIFN/RBV treatment. Eligible patients had documented cirrhosis by means of liver biopsy (Metavir score >3 or Ishak score of >4) or transient elastography (FibroScan score ≥12.5 kPa within 6 months of screening or during screening), and a Child-Pugh score of 5 or 6 with no evidence of decompensation or hepatocellular carcinoma. Primary endpoint: SVR12. Secondary efficacy endpoints included virologic failure during treatment and post-treatment relapse.1,2

PEARL II was an open-label trial of VIEKIRA +/- RBV in treatment-experienced non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: prior failed triple therapy with pegIFN/RBV + a protease inhibitor, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV or VIEKIRA alone, of which 88 and 91 subjects were included in the intent-to-treat efficacy population, respectively. Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,3

PEARL III was a controlled trial of VIEKIRA +/- RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=210) or VIEKIRA + matching placebo for RBV (n=209). Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,4

Post-treatment relapse was defined as confirmed HCV RNA ≥25 IU/mL between the final visit during the treatment period and 12 weeks after the last dose of study drug, for subjects assigned to 12 or 24 weeks of treatment, respectively.2-4,11-15

On-treatment virologic failure was defined as confirmed HCV RNA ≥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.

GT1 = genotype 1; RBV = ribavirin; SVR = sustained virologic response.

SAFETY CONSIDERATIONS1
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • Perform hepatic lab testing on all patients during the first 4 weeks of treatment and as clinically indicated thereafter. If ALT is elevated above baseline levels, repeat testing and monitor closely. Patients should be instructed to consult their doctor without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, or discolored feces. Consider discontinuing VIEKIRA XR if ALT levels remain persistently >10x the ULN. Discontinue VIEKIRA XR if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing direct bilirubin, alkaline phosphatase, or INR.
Efficacy
GT1a

Consistently high cure* rates achieved in non-cirrhotic and compensated cirrhotic (Child-Pugh A) chronic HCV GT1a patients1

Patients received 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets QD and 1 dasabuvir (250 mg) tablet BID + RBV for 12 or 24 weeks.

GT1a 12- vs 24-week efficacy

VIEKIRA XR + RBV for 24 weeks is recommended in GT1a patients with compensated cirrhosis. VIEKIRA XR administered with ribavirin for 12 weeks may be considered for some patients based on prior treatment history.

SAFETY CONSIDERATIONS1
  • If VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis prior to initiating therapy. Reported cases typically occurred within one to four weeks of initiating therapy.
  • ALT elevations >5x ULN occurred in 1% of all subjects and were significantly more frequent in females using ethinyl estradiol-containing medications, which are contraindicated. Perform hepatic lab testing on all patients.
  • Most common adverse reactions observed for VIEKIRA with RBV (>10% of subjects): fatigue, nausea, pruritus, other skin reactions, insomnia, and asthenia.
Efficacy
HCV/HIV-1 coinfected

VIEKIRA + RBV cured* GT1 chronic HCV in HCV/HIV-1 coinfected patients1

Patients received 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets QD and 1 dasabuvir (250 mg) tablet BID + RBV for 12 or 24 weeks.

Per the prescribing information, GT1b HCV/HIV-1 coinfected patients do not require RBV.


Post-treatment relapse (n=1/62)
On-treatment virologic failure (n=1/63)

  • Out of the 5 patients who were non-responders, 1 experienced virologic failure, 1 discontinued treatment, 1 experienced relapse, and 2 had evidence of HCV reinfection post treatment
  • 19% of patients had compensated cirrhosis, 33% were treatment-experienced§ (pegIFN/RBV), and 24% were Black
  • No patients switched their ART regimen due to loss of plasma HIV-1 RNA suppression

* Cure (virologic cure): sustained virologic response (SVR12).1

Study designs:

PHASE II – TURQUOISE I was an open-label clinical trial conducted to evaluate the safety and efficacy of 12 or 24 weeks of treatment with VIEKIRA + RBV in 63 subjects coinfected with GT1 HCV and HIV-1. Subjects were on a stable HIV-1 ART regimen that included tenofovir disoproxil fumarate plus emtricitabine or lamivudine, administered with ritonavir-boosted atazanavir or raltegravir. Subjects on atazanavir stopped the ritonavir component of their HIV-1 ART regimen upon initiating treatment with VIEKIRA + RBV. Atazanavir was taken with the morning dose of VIEKIRA. The ritonavir component of the HIV-1 ART regimen was restarted after completion of treatment with VIEKIRA + RBV. Exclusion criteria included: HBV coinfection, subjects with prior therapy with a DAA for the treatment of HCV, or a recent history of drug or alcohol abuse. Primary endpoint: SVR12. Secondary efficacy endpoints included virologic failure during treatment and post-treatment relapse.1,15

Post-treatment relapse was defined as confirmed HCV RNA ≥25 IU/mL between the final visit during the treatment period and 12 weeks after the last dose of study drug, for subjects assigned to 12 or 24 weeks of treatment, respectively.2-4,11-15

On-treatment virologic failure was defined as confirmed HCV RNA ≥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.

§ Treatment-experienced subjects were defined as either: prior relapsers (subjects with HCV RNA undetectable at or after the end of at least 36 weeks of pegIFN/RBV treatment, but HCV RNA was detectable within 52 weeks of treatment follow-up) or prior partial responders (received at least 20 weeks of pegIFN/RBV and achieved ≥2 log10 IU/mL reduction in HCV RNA at Week 12, but not achieving HCV RNA undetectable at end of treatment) or prior null responders (received at least 12 weeks of pegIFN/RBV treatment and failed to achieve a 2 log10 IU/mL reduction in HCV RNA at Week 12 or received at least 4 weeks of pegIFN/RBV treatment and achieved a <1 log10 IU/mL reduction in HCV RNA at Week 4).

ART = antiretroviral therapy; GT1 = genotype 1; HCV = hepatitis C virus; pegIFN = pegylated interferon; RBV = ribavirin; RNA = ribonucleic acid; SVR = sustained virologic response.

SAFETY CONSIDERATIONS1
  • The ritonavir component of VIEKIRA XR is an HIV-1 protease inhibitor and can select for HIV-1 protease inhibitor resistance. To reduce this risk, HCV/HIV-1 co-infected patients should also be on a suppressive antiretroviral drug regimen.
  • VIEKIRA XR is contraindicated with efavirenz and is not recommended with darunavir/ritonavir, lopinavir/ritonavir, or rilpivirine
Efficacy
Post–liver transplant

VIEKIRA + RBV delivered a high cure* rate in GT1 chronic HCV non-cirrhotic patients after receiving a liver transplant1,14

Patients received 2 ombitasvir, paritaprevir, ritonavir (12.5/75/50 mg) tablets QD and 1 dasabuvir (250 mg) tablet BID + RBV. The initial dose of RBV was left to the discretion of the investigator (most commonly 600 to 800 mg/day at initiation and end of treatment).


Post-treatment relapse (n=1/34)
On-treatment virologic failure (n=0/34)

All patients had a Metavir fibrosis score of F2 or less. 44% had a Metavir score of F2.


* Cure (virologic cure): sustained virologic response (SVR12).1

Study designs:

PHASE II – CORAL I was an open-label study conducted to evaluate the safety and efficacy of VIEKIRA + RBV in 34 liver transplant recipients who were ≥12 months post transplantation with recurrent HCV GT1-infection. All subjects had not received treatment for HCV after transplantation and had normal hepatic function and a Metavir fibrosis score of F2 or lower. All subjects were taking a stable immunosuppressant regimen based on either tacrolimus or cyclosporine. Exclusion criteria included: use of everolimus or sirolimus within 2 months of screening visit, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. All subjects received 24 weeks of treatment with VIEKIRA + RBV. Primary endpoint: SVR12. Secondary assessments included the percentage of patients with a SVR at post-treatment Week 24, virologic failure during treatment, and post-treatment relapse.1,14

Post-treatment relapse was defined as confirmed HCV RNA ≥25 IU/mL between the final visit during the treatment period and 12 weeks after the last dose of study drug, for subjects assigned to 12 or 24 weeks of treatment, respectively.2-4,11-15

On-treatment virologic failure was defined as confirmed HCV RNA ≥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.

§ Treatment-experienced subjects were defined as either: prior relapsers (subjects with HCV RNA undetectable at or after the end of at least 36 weeks of pegIFN/RBV treatment, but HCV RNA was detectable within 52 weeks of treatment follow-up) or prior partial responders (received at least 20 weeks of pegIFN/RBV and achieved ≥2 log10 IU/mL reduction in HCV RNA at Week 12, but not achieving HCV RNA undetectable at end of treatment) or prior null responders (received at least 12 weeks of pegIFN/RBV treatment and failed to achieve a 2 log10 IU/mL reduction in HCV RNA at Week 12 or received at least 4 weeks of pegIFN/RBV treatment and achieved a <1 log10 IU/mL reduction in HCV RNA at Week 4).

ART = antiretroviral therapy; GT1 = genotype 1; HCV = hepatitis C virus; pegIFN = pegylated interferon; RBV = ribavirin; RNA = ribonucleic acid; SVR = sustained virologic response.

SAFETY CONSIDERATIONS1
  • Everolimus, sirolimus and tacrolimus are contraindicated. See the full prescribing information for more details.
  • When VIEKIRA XR is administered with cyclosporine dosage adjustment of cyclosporine is needed.
  • The concomitant use of VIEKIRA XR and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of VIEKIRA XR and possible development of resistance, or clinically significant adverse reactions from greater exposures of concomitant drugs or components of VIEKIRA XR.
Safety
Adverse events

The majority of AEs observed during phase III clinical trials, including placebo-controlled trials, were mild to moderate in severity1

In patients with compensated cirrhosis, the type and severity of AEs were comparable to those in patients without cirrhosis

TURQUOISE II and TURQUOISE III

In patients with compensated cirrhosis treated for 12 or 24 weeks (N=380) with VIEKIRA + RBV (TURQUOISE II)1,13

  • Fatigue, skin reactions, and dyspnea occurred at least 5% more often in patients treated for 24 weeks
  • The majority of AEs occurred during the first 12 weeks of dosing in both treatment arms
  • Most were mild to moderate in severity
  • The proportion of patients treated for 12 and 24 weeks with serious adverse events was 6% and 5%, respectively

In patients with GT1b infection and compensated cirrhosis (N=60) treated for 12 weeks with VIEKIRA without RBV (TURQUOISE III), the type and severity of adverse events and laboratory abnormalities were comparable to those of patients in other phase III trials without RBV.1,2

SAPPHIRE I and II*

Adverse
events
VIEKIRA +/- RBV
for 12 weeks (N=770)
placebo
for 12 weeks (N=255)
Fatigue34%26%
Nausea22%15%
Pruritus18%7%
Skin reactions16%9%
Insomnia14%8%
Asthenia14%7%

PEARL II, III, and IV

Adverse
events
VIEKIRA +/- RBV
for 12 weeks (N=401)
VIEKIRA – RBV
for 12 weeks (N=509)
Nausea16%8%
Pruritus13%7%
Insomnia12%5%
Asthenia9%4%

* Adverse events with ≥5% greater frequency reported in patients treated with VIEKIRA + RBV compared to placebo.

Grouped terms.

Adverse events with ≥5% greater frequency reported in patients treated with VIEKIRA + RBV compared to VIEKIRA alone.

  • 2% of subjects experienced a serious adverse event

Study designs:

TURQUOISE II was a randomized, global, multicenter, open-label phase III trial conducted to evaluate the safety and efficacy of VIEKIRA + RBV exclusively in treatment-experienced or treatment-naïve adults with compensated cirrhosis (Child-Pugh A), 18 to 70 years of age, with GT1a or GT1b chronic HCV infection. Eligible subjects had documentation of cirrhosis by means of liver biopsy (Metavir score >3 or Ishak score >4) or FibroScan result (≥14.6 kPa within 6 months before screening or during screening), a Child-Pugh Class A score of <7 at screening, and no current or past clinical evidence of Child-Pugh Class B or C disease. Key eligibility criteria were a platelet count ≥60,000/mm3, a serum albumin level ≥2.8 g/dL, a total bilirubin level <3 mg/dL, an INR ≤2.3, and a serum alpha-fetoprotein level ≤100 ng/mL. Exclusion criteria included: subjects with prior failed therapy with a treatment regimen that included VIEKIRA or other DAA agents, HBV or HIV coinfection, a recent history of drug or alcohol abuse, or hepatocellular carcinoma. Subjects were randomly assigned in a ratio of approximately 1:1 to 12 weeks (n=208) or 24 weeks (n=172) of treatment with VIEKIRA + RBV and stratified based on whether or not they received previous pegIFN/RBV treatment. RBV dose adjustments were performed according to the RBV labeling. Primary endpoint: SVR12. The key secondary efficacy endpoint was the percentage of subjects with a SVR12 in the 24-week group as compared with the 12-week group. Other secondary efficacy endpoints included SVR12 according to HCV genotype (1a or 1b), virologic failure during treatment, and post-treatment relapse.1,13

TURQUOISE III was an open-label, single-arm, multicenter phase IIIb study of VIEKIRA for 12 weeks in 60 GT1b chronic HCV infected adults with compensated cirrhosis who were either treatment-naive or did not achieve sustained virologic response (SVR) with prior pegIFN/RBV treatment. Eligible patients had documented cirrhosis by means of liver biopsy (Metavir score >3 or Ishak score of >4) or transient elastography (FibroScan score ≥12.5 kPa within 6 months of screening or during screening), and a Child-Pugh score of 5 or 6 with no evidence of decompensation or hepatocellular carcinoma. Primary endpoint: SVR12. Secondary efficacy endpoints included virologic failure during treatment and post-treatment relapse.1,2

SAPPHIRE I was a placebo-controlled trial of VIEKIRA + RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1a or GT1b chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 3:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=473) or matching placebos (n=158). Primary endpoint: SVR12 for subjects initially randomized to active treatment. Secondary efficacy endpoints included SVR12 according to HCV genotype (1a or 1b), virologic failure during treatment, and post-treatment relapse. Subjects randomized to the placebo arm for the first 12 weeks then received open-label VIEKIRA + RBV for the subsequent 12 weeks.1,11

SAPPHIRE II was a placebo-controlled trial of VIEKIRA + RBV in treatment-experienced non-cirrhotic adults, 18 to 70 years of age, with GT1a or GT1b chronic HCV infection. Exclusion criteria included: prior failed triple therapy with pegIFN/RBV + a protease inhibitor, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 3:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=297) or matching placebos (n=97). Primary endpoint: SVR12 for subjects initially randomized to active treatment. Secondary efficacy endpoints included SVR12 according to HCV genotype (1a or 1b), virologic failure during treatment, and post-treatment relapse. Subjects randomized to the placebo arm for the first 12 weeks then received open-label VIEKIRA + RBV for the subsequent 12 weeks.1,12

PEARL II was an open-label trial of VIEKIRA +/- RBV in treatment-experienced non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: prior failed triple therapy with pegIFN/RBV + a protease inhibitor, HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV or VIEKIRA alone, of which 88 and 91 subjects were included in the intent-to-treat efficacy population, respectively. Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,3

PEARL III was a controlled trial of VIEKIRA +/- RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1b chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:1 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=210) or VIEKIRA + matching placebo for RBV (n=209). Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,4

PEARL IV was a controlled trial of VIEKIRA +/- RBV in treatment-naïve non-cirrhotic adults, 18 to 70 years of age, with GT1a chronic HCV infection. Exclusion criteria included: HBV or HIV coinfection, a recent history of drug or alcohol abuse, and use of specified concomitant medications, including those contraindicated for use with RBV and ritonavir. Subjects were randomized in a 1:2 ratio to 12 weeks of treatment with VIEKIRA + RBV (n=100) or VIEKIRA + matching placebo for RBV (n=205). Primary endpoint: SVR12. Secondary efficacy endpoints included assessing the noninferiority of VIEKIRA without RBV to VIEKIRA + RBV, virologic failure during treatment, and post-treatment relapse.1,4

GT1 = genotype 1; RBV = ribavirin; SVR = sustained virologic response.

SAFETY CONSIDERATIONS1
  • Skin reactions: In TURQUOISE II, 18% and 24% of subjects receiving VIEKIRA + RBV for 12 or 24 weeks reported skin reactions. The majority of events were graded as mild in severity.
Safety
Discontinuation rates

Low AE-related discontinuation rates in phase III clinical trials

Data from a pooled analysis of all patients who received VIEKIRA +/- RBV in phase III clinical trials1

Treatment completion rate VIEKIRA +/– RBV

Overall AE-related discontinuation rate VIEKIRA + RBV

Overall AE-related discontinuation rate VIEKIRA without RBV

  • 7% of patients required RBV dose adjustments because of decreased hemoglobin – 98% of those reached SVR12
  • 5 patients required erythropoietin
  • 3 received a blood transfusion
  • 1 patient discontinued because of anemia
SAFETY CONSIDERATIONS1
  • Approximately 1% of subjects treated with the components of VIEKIRA XR experienced post-baseline serum ALT levels greater than 5 times the upper limit of normal (ULN) after starting treatment. The incidence increased to 25% (4/16) among females using concomitant ethinyl-estradiol containing medications, which are contraindicated.
  • Post-baseline elevations in bilirubin at least 2x ULN were observed in 15% of subjects receiving the components of VIEKIRA XR with ribavirin compared to 2% in those receiving the components of VIEKIRA XR without ribavirin.
  • Across all phase III studies, the mean change from baseline in hemoglobin levels in subjects treated with the components of VIEKIRA XR with ribavirin was –2.4 g/dL and the mean change in subjects treated with the components of VIEKIRA XR without ribavirin was –0.5 g/dL. Decreases in hemoglobin levels occurred early in treatment (Week 1–2) with further reductions through Week 3. Hemoglobin values remained low during the remainder of treatment and returned toward baseline levels by post-treatment Week 4.
Dosing
Recommended regimen

12-week regimen without RBV for GT1b patients1

Recommended regimen for VIEKIRA XR +/- RBV

Patient Population Treatment* Weeks
GT1b with or without compensated cirrhosis VIEKIRA XR 12
GT1a without cirrhosis VIEKIRA XR + RBV 12
GT1a with compensated cirrhosis VIEKIRA XR + RBV 24 (or 12 based on prior treatment history)

* Note: Follow the GT1a dosing recommendations in patients with an unknown GT1 subtype or with mixed GT1 infection.

Cirrhotic patients with mild (Child-Pugh A) hepatic impairment; VIEKIRA XR is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C).

  • GT1 HCV/HIV coinfected: follow the dosing recommendations above
  • GT1 Post–liver transplant: recipients with normal hepatic function and mild fibrosis (Metavir fibrosis score ≤2) are recommended to receive VIEKIRA XR + RBV for 24 weeks. Everolimus, sirolimus and tacrolimus are contraindicated, cyclosporine requires dose adjustment. See the full prescribing information for more details.

Testing prior to initiation of VIEKIRA XR

  • Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with VIEKIRA XR.
  • Prior to initiation of VIEKIRA XR, assess for laboratory and clinical evidence of hepatic decompensation

VIEKIRA: Baseline polymorphisms and SVR

Baseline HCV polymorphisms are not expected to have a substantial impact on the likelihood of achieving SVR when VIEKIRA is used as recommended for HCV genotype 1a and 1b infected patients, based on the low virologic failure rates observed in clinical trials.1

  • The efficacy of VIEKIRA has not been studied in subjects who have failed prior treatment with another NS5A inhibitor, NS3/4A protease inhibitor, or NS5B inhibitor

In the 7 phase III clinical trials, 1076 subjects (including 181 with compensated cirrhosis) received the recommended regimen of VIEKIRA +/- RBV for 12, or for 24 weeks in GT1a cirrhotics. 95%-100% achieved SVR12.

A pooled analysis of subjects in the phase III clinical trials of VIEKIRA +/- RBV was conducted to explore the association between baseline HCV NS5A, NS3, or NS5B resistance-associated variants (RAVs) and treatment outcome. The NS3 Q80K polymorphism was detected in ~38% of subjects in this analysis and was enriched ~twofold in virologic failure subjects compared to SVR-achieving subjects. Ombitasvir RAVs in NS5A were detected in ~22% of subjects in this analysis and similarly were enriched ~twofold in virologic failure subjects.

  • Approximately 1 in 5 patients with GT1 chronic HCV may have baseline NS5A inhibitor resistance

Additional Safety Considerations for DAA Resistance

  • Cross-resistance is expected among NS5A inhibitors, NS3/4A protease inhibitors, and non-nucleoside NS5B palm 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
  • The long-term clinical impact of the emergence or persistence of virus containing VIEKIRA XR resistance-associated substitutions is unknown
SAFETY CONSIDERATIONS1
  • HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment followup. Initiate appropriate patient management for HBV infection as clinically indicated.
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • Due to risk of HIV-1 protease inhibitor drug resistance, HCV/HIV-1 co-infected patients should be on a suppressive antiretroviral drug regimen.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Dosing
Packaging and dosing

Each coformulated tablet contains dasabuvir, ombitasvir, paritaprevir, and ritonavir (200/8.33/50/33.33 mg).

3 tablets, once daily1
Convenient portable daily dose packs

Ribavirin (RBV) twice daily may be required for some patients. It is not included in the VIEKIRA XR packaging.

Dosing considerations for VIEKIRA XR1

The recommended dosage of VIEKIRA XR is 3 tablets taken orally once daily.

  • VIEKIRA XR must be taken with a meal because administration under fasting conditions may result in reduced virologic response and possible development of resistance
  • Swallow tablets whole. Splitting, crushing, or chewing tablets may compromise the extended-release performance, efficacy, and/or safety of VIEKIRA XR
  • For optimal release of dasabuvir, alcohol should not be consumed within 4 hours of taking VIEKIRA XR

VIEKIRA XR is used in combination with ribavirin (RBV) in certain patient populations. When administered with VIEKIRA XR, the recommended dosage of RBV is based on weight: 1000 mg/day for subjects <75 kg and 1200 mg/day for those ≥75 kg, divided and administered twice-daily with food. The starting dosage and on-treatment dosage of RBV can be decreased based on changes in hemoglobin levels and/or creatinine clearance. For ribavirin dosage modifications, refer to the ribavirin prescribing information.

SAFETY CONSIDERATIONS1
  • HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment followup. Initiate appropriate patient management for HBV infection as clinically indicated
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • Due to risk of HIV-1 protease inhibitor drug resistance, HCV/HIV-1 co-infected patients should be on a suppressive antiretroviral drug regimen.
Access & support resources
Nurse Connector

A Nurse Connector* provides personalized support for your patients

A Nurse Connector is a dedicated registered nurse who is 100% committed to supporting and educating VIEKIRA patients—before, during, and after treatment

Before
Facilitates access to helpful resources and educates patients on the approval process
Helps guide patients through important pretreatment requirements
During
Provides reminders for
– Visits & tests
– Taking medication
– Product refills
Helps educate patients about their disease, provides encouragement and motivation
Helps promote positive and productive patient-physician dialogue
After
Prompts patients to schedule their SVR12 visit
Provides patients with valuable education about reinfection prevention and post-SVR monitoring

* A Nurse Connector does not offer medical or treatment advice or replace a conversation with a medical professional.


Personalized support—for GT1 chronic HCV patients

Personalized support to help your patients navigate their treatment experience, in a way that works best for them

Two ways to enroll:

SAFETY CONSIDERATIONS1
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • When VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.
Access & support resources
Access

Consider these resources to help your prescribed patients start and stay on VIEKIRA XR

Getting started

proCeed
enrollment form

Get your patients started with proCeed and VIEKIRA XR.

Nurse Connector
enrollment form

Connect your patients to a Nurse Connector.

Patient
assistance program

Provide your eligible patients who are without prescription coverage or facing financial difficulties the ability to access medicine.

Copay cards

If needed, copay for VIEKIRA XR can be as low as $5 a month for eligible patients.


Eligibility: In Massachusetts, co-pay assistance is not available for products with certain generic equivalents (for example, any product with an AB-rated generic equivalent). Available to patients with commercial prescription insurance coverage for an FDA-approved AbbVie product for treatment of hepatitis C virus. Co-pay assistance program is not available to patients receiving prescription reimbursement under any federal, state, or government-funded insurance programs (for example, Medicare [including Part D], Medicare Advantage, Medigap, Medicaid, TRICARE, Department of Defense, or Veterans Affairs programs) or where prohibited by law. If at any time a patient begins receiving prescription drug coverage under any such federal, state, or government-funded healthcare program, the patient will no longer be able to use the AbbVie HCV Co-pay Card and the patient must call PSKW at 1-844-865-8725 to stop participation. Patients may not seek reimbursement for value received from the AbbVie HCV Co-pay Program from any third-party payers. Offer subject to change or discontinuance without notice. Restrictions, including monthly maximums, may apply. This is not health insurance.

RBV = ribavirin.

SAFETY CONSIDERATIONS1
  • Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VIEKIRA XR. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment followup. Initiate appropriate patient management for HBV infection as clinically indicated.
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • When VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
Access & support resources
Appealing coverage

Tools for appealing coverage


Medical necessity template

Use our form to create a letter to send to payers.

AbbVie is committed to helping appropriate patients obtain access to VIEKIRA by providing reimbursement and access information and resources. When using the template, please be aware that coverage policies vary by payer and change over time, so please consult with each payer directly for the most current coverage and reimbursement policies and determination processes. The template is not intended to provide reimbursement or legal advice. AbbVie does not guarantee that the use of any information provided will result in coverage or payment by any third-party payer.

SAFETY CONSIDERATIONS1
  • Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VIEKIRA XR. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment followup. Initiate appropriate patient management for HBV infection as clinically indicated.
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • When VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.

Indication and Important Safety Information

INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.

IMPORTANT SAFETY INFORMATION1

WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VIEKIRA XR. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

Risks Associated with RBV Combination Treatment

If VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.

CONTRAINDICATIONS

VIEKIRA XR is contraindicated:

  • in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity.
  • with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events; moderate or strong inducers of CYP3A and strong inducers of CYP2C8, which may lead to reduced efficacy of VIEKIRA XR; and strong CYP2C8 inhibitors, which may increase dasabuvir levels and the risk of QT prolongation.
  • with the following drugs: alfuzosin HCL; ranolazine; dronedarone; carbamazepine, phenytoin, phenobarbital; colchicine (in patients with renal and/or hepatic impairment); gemfibrozil; rifampin; lurasidone, pimozide; ergotamine, dihydroergotamine, methylergonovine; ethinyl estradiol-containing medicines, such as combined oral contraceptives; cisapride; St. John’s Wort (Hypericum perforatum); atorvastatin, lovastatin, simvastatin; everolimus, sirolimus, tacrolimus; efavirenz; sildenafil (when dosed as Revatio* for pulmonary arterial hypertension); triazolam and oral midazolam.
  • in patients with known hypersensitivity (e.g., toxic epidermal necrolysis or Stevens-Johnson syndrome) to ritonavir.

WARNINGS AND PRECAUTIONS

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 mostly in patients with advanced cirrhosis prior to initiating therapy. Reported cases typically occurred within one to four weeks of initiating therapy.
  • For patients with cirrhosis: monitor for clinical signs and symptoms of hepatic decompensation; perform hepatic lab testing, including direct bilirubin levels, at baseline and during the first 4 weeks of starting treatment and as clinically indicated; discontinue treatment in patients who develop evidence of hepatic decompensation.

Increased Risk of ALT Elevations

  • Elevations of ALT to >5x the upper limit of normal (ULN) occurred in 1% of all subjects in clinical trials and were significantly more frequent in females using ethinyl estradiol-containing medications. In female patients, discontinue ethinyl estradiol-containing medications prior to starting therapy and use alternative methods of contraception during therapy. Use caution when co-administering VIEKIRA XR with estrogens other than ethinyl estradiol, such as estradiol and conjugated estrogens.
  • Perform hepatic lab testing on all patients during the first 4 weeks of treatment and as clinically indicated thereafter. If ALT is elevated above baseline levels, repeat testing and monitor closely. Patients should be instructed to consult their doctor without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, or discolored feces. Consider discontinuing VIEKIRA XR if ALT levels remain persistently >10x the ULN. Discontinue VIEKIRA XR if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing direct bilirubin, alkaline phosphatase, or INR.

Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions

  • The concomitant use of VIEKIRA XR and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of VIEKIRA XR and possible development of resistance, or clinically significant adverse reactions from greater exposures of concomitant drugs or components of VIEKIRA XR.

HCV/HIV-1 Coinfected Patients: Risk of HIV-1 Protease Inhibitor Drug Resistance

  • The ritonavir component of VIEKIRA XR is an HIV-1 protease inhibitor and can select for HIV-1 protease inhibitor resistance. To reduce this risk, HCV/HIV-1 coinfected patients should also be on a suppressive antiretroviral drug regimen.

ADVERSE REACTIONS

Most common adverse reactions observed:

  • VIEKIRA XR with RBV (>10% of subjects): fatigue, nausea, pruritus, other skin reactions, insomnia, and asthenia.
  • VIEKIRA XR without RBV (≥5% of subjects): nausea, pruritus, and insomnia.

*Revatio® is a trademark of its respective owner and not a trademark of AbbVie Inc. The makers of this brand are not affiliated with and do not endorse AbbVie Inc. or its products.

References:

  1. VIEKIRA XR [package insert]. North Chicago, IL: AbbVie Inc.
  2. Feld JJ, Moreno C, Trinh R, et al. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12 weeks. J Hepatol. 2016;64(2):301-307 (and supplementary appendix).
  3. Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment experienced patients with HCV genotype 1b infection. Gastroenterology. 2014;147(2):359-365.e1 (and supplementary appendix).
  4. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r–ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370(21):1983-1992 (and supplementary appendix).
  5. IMS Health. July 2016. Parsippany, NJ: IMS Health; 2016.
  6. Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
  7. American Association for the Study of Liver Diseases—Infectious Diseases Society ofAmerica. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report-view. Updated July 6, 2016. Accessed March 11, 2017.
  8. IMS Health. IMS LifeLink™ LRx. December 2013. (©IMS Health Inc., all rights reserved).
  9. Data on file. ABVRRT162642.
  10. Ipsos Healthcare HCV Monitor, 2016. New York, NY: Ipsos in North America. ©Ipsos 2016, all rights reserved.
  11. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r–ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1594-1603 (and supplementary appendix).
  12. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/r–ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1604-1614 (and supplementary appendix).
  13. Poordad F, Hezode C, Trinh R, et al. ABT-450/r–ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370:1973-1982 (and supplementary appendix).
  14. Kwo PY, Mantry PS, Coakley E, et al. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;370:1973-1982 (and supplementary appendix).
  15. Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313(12):1223-1231 (and supplementary appendix).
An HCV treatment for

VIEKIRA XR—A once-daily treatment taken with a meal for GT1 chronic HCV infection that may provide a virologic cure* for patients like yours.

* Cure (virologic cure): sustained virologic response (SVR12).1

* Cure (virologic cure): sustained virologic response (SVR12); HCV RNA <25 IU/mL 12 weeks after the end of treatment.1

No dose adjustment is required for patients with mild, moderate, or severe renal impairment, including those on dialysis. VIEKIRA XR is contraindicated with colchicine in patients with renal and/or hepatic impairment due to the potential for serious and/or life-threatening reactions.

VIEKIRA XR reduces omeprazole concentrations. Monitor patients for decreased efficacy of omeprazole and consider increasing the dose if symptoms are not well controlled. Avoid use of omeprazole >40 mg/day.

GT = genotype. | PPI = proton pump inhibitor.

SAFETY CONSIDERATIONS1
  • Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with VIEKIRA XR. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
  • VIEKIRA XR is contraindicated: in patients with moderate to severe hepatic impairment; with certain drugs that are highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A; strong inducers and inhibitors of CYP2C8; and in patients with known hypersensitivity to ritonavir.
  • When VIEKIRA XR is administered with RBV, the contraindications, warnings and precautions (particularly pregnancy avoidance), and adverse reactions for RBV also apply to this combination regimen. Refer to the RBV prescribing information.
  • Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported mostly in patients with advanced cirrhosis. Monitor for clinical signs and symptoms of hepatic decompensation.
  • ALT elevations >5x upper limit of normal (ULN) occurred in 1% of all subjects and were significantly more frequent in females using ethinyl estradiol-containing medications, which are contraindicated. Perform hepatic lab testing on all patients.
  • Due to risk of HIV-1 protease inhibitor drug resistance, HCV/HIV-1 coinfected patients should be on a suppressive antiretroviral drug regimen.
INDICATION1

VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV):

  • genotype 1b infection without cirrhosis or with compensated cirrhosis.
  • genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.