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GT 3 Efficacy & Study Design

ALLY 3 Study Design: Genotype 3

ALLY 3 was a phase 3, open-label, two-cohort study of 152 patients, including treatment-naive and treatment-experienced, treated for 12 weeks with Daklinza (daclatasvir) plus sofosbuvir.1*

ALLY 3 was a phase 3, open-label, two-cohort study of 152 patients, including treatment-naive (n=101) and treatment-experienced (n=51), treated for 12 weeks with Daklinza (daclatasvir) (60 mg) plus sofosbuvir (400 mg).1*

The ALLY 3 study was conducted without the use of ribavirin.

Study Design

Co-primary endpoints: Sustained viral response at post-treatment Week 12 (SVR12) for treatment-naive and treatment-experienced patients.

*Subjects were monitored for 24 weeks after the end of treatment.
HCV RNA < Lower Limit of Quantitation (LLOQ) (25 IU/mL).2

Selected secondary endpoints: SVR12 rates by baseline cirrhosis status and IL28B status.

Selected inclusion criteria: Age ≥18 years, genotype 3 infection, HCV RNA ≥10,000 IU/mL, treatment-naive (no prior exposure to any interferon formulation, ribavirin, or any HCV direct-acting antiviral agent) or treatment-experienced (prior therapy with interferon alfa [with or without ribavirin], sofosbuvir plus ribavirin, or other anti-HCV agents [such as inhibitors of cyclophilin or microRNA] excluding prior exposure to NS5A inhibitors).1

90% of treatment-naive patients, including cirrhotics, achieved SVR12 with 12 weeks of treatment with Daklinza plus sofosbuvir1

86% in treatment-experienced patients (including 7 prior sofosbuvir failures)

SVR12 rates were comparable regardless of gender, age, baseline HCV RNA levels, or IL28B status.2

Sixteen patients experienced relapse after the end of treatment; 1 patient had detectable HCV RNA at the final on-treatment visit. Of these 17 patients, 12 were cirrhotic.1

Efficacy regardless of treatment history Efficacy regardless of treatment history

19% of treatment-naive patients (n=19) and 25% of treatment-experienced (n=13) were cirrhotic at baseline.1
aHCV RNA < Lower Limit Of Quantitation (LLOQ) (25 IU/mL).2

Efficacy with and without cirrhosis

96% SVR12 rate achieved with 12 weeks of treatment for treatment-naive and treatment-experienced GT 3 patients without cirrhosis,§ including F3 fibrosis (n=17; including patients with missing or inconclusive cirrhosis status).1-3

In difficult-to-treat GT 3 patients with cirrhosis, a 63% SVR12 rate was achieved with 12 weeks of treatment1,2

The study was conducted without the use of ribavirin.

Efficacy in cirrhotics Efficacy in cirrhotics

§Includes 11 subjects with missing or inconclusive cirrhosis status2
aHCV RNA < Lower Limit Of Quantitation (LLOQ) (25 IU/mL).2

Daklinza-based regimens have been studied in a variety of chronic HCV GT 3 patient populations1,2,4,5,6

In three phase 3 studies, 179 GT 3 patients have been studied using Daklinza plus sofosbuvir (+/- ribavirin)

  • ALLY 3 – Genotype 3 patients (N=152)1,2
  • ALLY 2 – Chronic HCV/HIV-coinfected patients (n=10 in GT 3)2,5
  • ALLY 1 – Advanced cirrhotic and post-transplant patients, with ribavirin (n=17 in GT 3)2,6

ALLY 2 Study Design: Daklinza plus sofosbuvir for 12 weeks in chronic HCV patients coinfected with HIV2,4,5

A phase 3, open-label, two-cohort, 12-week study that included 153 chronic HCV patients (treatment-naive and treatment-experienced GT 1-4**) coinfected with human immunodeficiency virus-1 (HIV-1).

  • Primary endpoint: Sustained virologic response, defined as HCV RNA below the LLOQ at post-treatment week 12 (SVR12)†† in genotype 1 treatment-naive patients (96% SVR12 n=83)4
  • Subgroup efficacy analysis included: SVR12 rates by genotype; race; baseline HCV RNA; baseline cirrhosis status; concomitant HAART regimen (by class)

For additional information on ALLY 2 study design and baseline characteristics, please see links below.

Subjects were monitored for 24 weeks after the end of treatment.
**Genotypes 1-6 were allowed to enroll in the study.
††SVR defined as HCV RNA <25 IU per milliliter.

ALLY 1 Study Design: Daklinza plus sofosbuvir and ribavirin for 12 weeks in chronic HCV patients with advanced cirrhosis or post-liver transplant2,6

A phase 3, open-label, two-cohort (60 advanced cirrhosis in GT 1-4 and 53 post-transplant with GT 1, 3, 6), 12-week study‡‡ to assess the efficacy of treatment in 113 chronic HCV patients.§§

  • Primary endpoint: Sustained viral response at post-treatment Week 12 (SVR12)¶¶ in each cohort of patients with genotype 1 infection treated for 12 weeks (82% SVR12 in advanced cirrhotics and 95% in post-transplants)
  • Selected secondary endpoints included: SVR12 for each individual GT 2, 3, 4, 5, 6 in both cohorts***

For additional information on ALLY 1 study design and baseline characteristics, please see links below.

‡‡Subjects were monitored for 24 weeks after the end of treatment.
§§Patients with chronic HCV GT 1-6 were allowed to enroll in both cohorts.
¶¶SVR defined as HCV RNA <25 IU per milliliter.
***Available data from ALLY 1 on GT 2 (n=5) and 4 (n=4) in the advanced cirrhosis cohort, and GT 6 (n=1) in the post-transplant cohort, were insufficient to provide treatment recommendations, and efficacy results for these genotypes are not included in the Daklinza PI.

12-week, all-oral Daklinza-based regimens: SVR12 in a broad range of GT 3 patients2,6

SVR12 in genotype 3 SVR12 in genotype 3

aHCV RNA < Lower Limit of Quantitation (LLOQ) (25 IU/mL).
bChild-Pugh B & C.

IMPORTANT SAFETY INFORMATION

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 Daklinza. 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 management for HBV infection as clinically indicated.

CONTRAINDICATIONS

  • When used in combination with other agents, the contraindications applicable to those agents are applicable to the combination regimen; refer to the respective prescribing information.
  • Drugs contraindicated with Daklinza: strong inducers of CYP3A that may lead to loss of efficacy of Daklinza include, but are not limited to: phenytoin, carbamazepine, rifampin, St. John's wort (Hypericum perforatum).

WARNINGS AND PRECAUTIONS

  • Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV (additional information): HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation may be increased in these patients.
  • Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of Daklinza and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of Daklinza and possible development of resistance, dosage adjustments for other agents or Daklinza, possible clinically significant adverse events from greater exposure for the other agents or Daklinza.
  • Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported with ledipasvir/sofosbuvir.
    • Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.3 of the prescribing information.
    • Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.
    • Bradycardia generally resolved after discontinuation of HCV treatment.
  • Risks Associated with Ribavirin Combination Treatment: If ribavirin is used as part of the regimen, the warnings and precautions for ribavirin, particularly the pregnancy avoidance warning, apply. See the ribavirin full prescribing information for complete information.

ADVERSE REACTIONS

  • In clinical trials (ALLY 2, 3) with the Daklinza and sofosbuvir regimen, the most common adverse reactions (≥5%) were, respectively: headache (8%, 14%), fatigue (15%, 14%), nausea (9%, 8%), diarrhea (7%, 5%).
  • In clinical trials (ALLY 1) with Daklinza, in combination with sofosbuvir and ribavirin, the most common adverse reactions (≥5%) were, in the cirrhosis cohort and the post-liver transplantation cohort, respectively: headache (12%, 30%), anemia (20%, 19%), fatigue (15%, 17%), nausea (15%, 6%), rash (8%, 2%), diarrhea (3%, 6%), insomnia (3%, 6%), dizziness (0, 6%), somnolence (5%, 0).

DRUG INTERACTIONS

  • CYP3A: Daklinza is a substrate. Moderate or strong inducers may decrease plasma levels and effect of Daklinza. Strong inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir) may increase plasma levels of Daklinza.
  • P–gp, OATP 1B1 and 1B3, and BCRP: Daklinza is an inhibitor, and may increase exposure to substrates, potentially increasing or prolonging their adverse effect.

See Sections 4, 7, and 12.3 of the Daklinza Full Prescribing Information for additional established and other potentially significant drug interactions and related dose modification recommendations. Refer to the prescribing information for other agents in the regimen for drug interaction information.

DAKLINZA IN PREGNANCY

  • No adequate human data are available to determine whether or not Daklinza poses a risk to pregnancy outcomes. Animal studies of Daklinza at exposure above the recommended human dose have shown maternal and embryofetal toxicity.
  • If Daklinza and sofosbuvir are administered with ribavirin, the information for ribavirin with regard to pregnancy testing, contraception, and infertility also applies to this combination regimen. Refer to the ribavirin prescribing information.

LACTATION

  • It is not known whether Daklinza is present in human milk, affects human milk production, or has effects on the breastfed infant. Daklinza was present in the milk of lactating rats. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Daklinza and any potential adverse effects on the breastfed child from Daklinza or from the underlying condition.
  • When Daklinza is administered with ribavirin, the nursing mothers' information for ribavirin also applies to this combination regimen. Refer to the nursing mothers' information in the ribavirin prescribing information.

Please see
Full Prescribing Information, including Boxed WARNING.

References: 1. Daklinza [package insert]. Princeton, NJ; Bristol-Myers Squibb Company. 2. Ampuero J, Romero-Gomez J-M, Reddy KR. HCV genotype 3: the new treatment challenge. Aliment Pharmacol Ther. 2014;39(7):686-698. 3. Kanwal F, Kramer JR. Ilyas J, et al. HCV genotype 3 is associated with an Increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. veterans with HCV. Hepatology. 2014;60:98-105. 4. Tapper EB, Afdhal NH. Is 3 the new 1: perspectives on virology, natural history and treatment for hepatitis C genotype 3. J Virol Hepat. 2013;20:669-677. 5. Rockstroh JK, Bhagani S. Managing HIV/hepatitis C co-infection in the era of direct acting antivirals. BMC Medicine. 2013;11:234-243. 6. Thein H-H, Yi Q, Dore GJ, Krahn MD. Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS. 2008;22:1979 -1991. 7. Gambato M, Lens S, Navasa M, Forns X. Treatment options in patients with decompensated cirrhosis, pre- and post-transplantation. Journal of Hepatology. 2014;61:S120 -S131. 8. Berenguer M, Schuppan D. Progression of liver fibrosis in post-transplant hepatitis C: mechanisms, assessment and treatment. Journal of Hepatology. 2013;58:1028 -41. 9. Demetris A. Evolution of hepatitis C virus in liver allografts. Liver Transplantation. 2009;15(2):S35-S41

Reference: 1. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb.

References: 1. Guedj J, Dahari H, Rong L, et al. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci. 2013;110(10):3991-3996. 2. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.

References: 1. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral, 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61(4):1127-1135.

References: 1. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral, 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase 3 study. Hepatology. 2015;61(4):1127-1135. doi:10.1002/hep.27726. 2. Daklinza (daclatasvir) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 3. Data on file, DACL 032, Bristol-Myers Squibb Company. 4. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725. 5. Supplementary Appendix to Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725. 6. Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir, Sofosbuvir, and Ribavirin Combination for HCV Patients with Advanced Cirrhosis or Post-transplant Recurrence: ALLY-1 Phase 3 Study. Presented at The International Liver Congress 2015, 50th Annual Meeting of the European Association for the Study of the Liver: April 22-26, 2015; Vienna, Austria.

References: 1. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral, 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase 3 study. Hepatology. 2015;61(4):1127-1135. doi:10.1002/hep.27726. 3. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725. 4. Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir, Sofosbuvir, and Ribavirin Combination for HCV Patients with Advanced Cirrhosis or Post-transplant Recurrence: ALLY-1 Phase 3 Study. Presented at The International Liver Congress 2015, 50th Annual Meeting of the European Association for the Study of the Liver: April 22-26, 2015; Vienna, Austria.

References: 1. Daklinza [package insert]. Princeton, NJ; Bristol-Myers Squibb. 2. Eley T, You X, Wang R, et al. Daclatasvir: Overview of drug-drug interactions with antiretroviral agents and other common concomitant drugs. HIV DART: Frontiers in Drug Development for Antiretroviral Therapies. Miami, FL; December 9-12, 2014. Poster 63. 3. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725.

References: 1. Daklinza [package insert]. Princeton, NJ; Bristol-Myers Squibb. 2. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725. 3. Supplement to Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725. 4. Eley T, You X, Wang R, et al. Daclatasvir: Overview of drug-drug interactions with antiretroviral agents and other common concomitant drugs. HIV DART: Frontiers in Drug Development for Antiretroviral Therapies. Miami, FL; December 9-12, 2014. Poster 63.

References: 1. Daklinza [package insert]. Princeton, NJ; Bristol-Myers Squibb. 2. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725.

References: 1. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir with sofosbuvir and ribavirin for HCV infection with advanced cirrhosis or post-liver transplant recurrence. Hepatology. In press. doi:10.1002/hep.28446.

References: 1. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir with sofosbuvir and ribavirin for HCV infection with advanced cirrhosis or post-liver transplant recurrence. Hepatology. In press. doi:10.1002/hep.28446.

Reference: 1. Daklinza [package insert]. Princeton, NJ; Bristol-Myers Squibb.

References: 1. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. Sovaldi [package insert]. Foster City, CA: Gilead Sciences, Inc. 3. Rebetol [package insert]. Whitehouse Station, NJ: Merck & Co. 4. Eley T, You X, Wang RL, et al. Daclatasvir: Overview of drug-drug interactions with antiretroviral agents and other common concomitant drugs. HIV DART: Frontiers in Drug Development for Antiretroviral Therapies. Miami, FL; December 9-12, 2014. Poster 63. 5. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725.

1392US1502415-03-02 05/16

More Important Safety Information 

SELECTED IMPORTANT SAFETY INFORMATION

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 Daklinza. 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 management for HBV infection as clinically indicated.

DRUG INTERACTIONS

  • CYP3A: Daklinza is a substrate. Moderate or strong inducers may decrease plasma levels and effect of Daklinza. Strong inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir) may increase plasma levels of Daklinza.
  • P-gp, OATP 1B1 and 1B3, and BCRP: Daklinza is an inhibitor, and may increase exposure to substrates, potentially increasing or prolonging their adverse effect.

See Sections 4, 7, and 12.3 of the Daklinza Full Prescribing Information for additional established and other potentially significant drug interactions and related dose modification recommendations. Refer to the prescribing information for other agents in the regimen for drug interaction information.

DAKLINZA IN PREGNANCY

  • No adequate human data are available to determine whether or not Daklinza poses a risk to pregnancy outcomes. Animal studies of Daklinza at exposure above the recommended human dose have shown maternal and embryofetal toxicity.
  • If Daklinza and sofosbuvir are administered with ribavirin, the information for ribavirin with regard to pregnancy testing, contraception, and infertility also applies to this combination regimen. Refer to the ribavirin prescribing information.

LACTATION

  • It is not known whether Daklinza is present in human milk, affects human milk production, or has effects on the breastfed infant. Daklinza was present in the milk of lactating rats. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Daklinza and any potential adverse effects on the breastfed child from Daklinza or from the underlying condition.
  • When Daklinza is administered with ribavirin, the nursing mothers' information for ribavirin also applies to this combination regimen. Refer to the nursing mothers' information in the ribavirin prescribing information.

WARNINGS AND PRECAUTIONS (continued)

  • Risks Associated with Ribavirin Combination Treatment: If ribavirin is used as part of the regimen, the warnings and precautions for ribavirin, particularly the pregnancy avoidance warning, apply. See the ribavirin full prescribing information for complete information.

WARNINGS AND PRECAUTIONS

  • Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of Daklinza and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of Daklinza and possible development of resistance, dosage adjustments for other agents or Daklinza, possible clinically significant adverse events from greater exposure for the other agents or Daklinza.

ADVERSE REACTIONS

  • In clinical trials (ALLY 2, 3) with the Daklinza and sofosbuvir regimen, the most common adverse reactions (≥5%) were, respectively: headache (8%, 14%), fatigue (15%, 14%), nausea (9%, 8%), diarrhea (7%, 5%).
  • In clinical trials (ALLY 1) with Daklinza, in combination with sofosbuvir and ribavirin, the most common adverse reactions (≥5%) were, in the cirrhosis cohort and the post-liver transplantation cohort, respectively: headache (12%, 30%), anemia (20%, 19%), fatigue (15%, 17%), nausea (15%, 6%), rash (8%, 2%), diarrhea (3%, 6%), insomnia (3%, 6%), dizziness (0, 6%), somnolence (5%, 0).

WARNINGS AND PRECAUTIONS (continued)

  • Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of Daklinza and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of Daklinza and possible development of resistance, dosage adjustments for other agents or Daklinza, possible clinically significant adverse events from greater exposure for the other agents or Daklinza.

WARNINGS AND PRECAUTIONS

  • Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV (additional information): HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation may be increased in these patients.

CONTRAINDICATIONS

  • When used in combination with other agents, the contraindications applicable to those agents are applicable to the combination regimen; refer to the respective prescribing information.
  • Drugs contraindicated with Daklinza: strong inducers of CYP3A that may lead to loss of efficacy of Daklinza include, but are not limited to: phenytoin, carbamazepine, rifampin, St. John’s wort (Hypericum perforatum).

WARNINGS and PRECAUTIONS

  • Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported with ledipasvir/sofosbuvir.
    • Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.2 of the prescribing information.
    • Bradycardia generally resolved after discontinuation of HCV treatment.
    • Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.

CONTRAINDICATIONS

  • When used in combination with other agents, the contraindications applicable to those agents are applicable to the combination regimen; refer to the respective prescribing information.
  • Drugs contraindicated with Daklinza: strong inducers of CYP3A that may lead to loss of efficacy of Daklinza include, but are not limited to: phenytoin, carbamazepine, rifampin, St. John’s wort (Hypericum perforatum).

WARNINGS AND PRECAUTIONS (continued)

  • Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported with ledipasvir/sofosbuvir.
    • Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.3 of the prescribing information.
    • Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.
    • Bradycardia generally resolved after discontinuation of HCV treatment.

ADVERSE REACTIONS

  • The most common adverse reactions were (≥5%): headache (14%), fatigue (14%), nausea (8%), and diarrhea (5%).