INDICATION

HARVONI is indicated with or without ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection.

INDICATION

HARVONI is indicated with or without ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection.

HCV cure can start with you
and a once-daily, single-tablet regimen

The goal of HCV therapy is cure, or sustained virologic response (SVR12), which is defined as undetectable HCV RNA at 12 or more weeks after the end of treatment.1,2 Click here to learn more about results from HARVONI clinical studies. Scroll below to review the dosing recommendations for HARVONI.

References:
  1. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.
  2. AASLD, IDSA, IAS-USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed January 10, 2017.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

HARVONI OVERVIEW

HARVONI delivered high cure (SVR12) rates in a broad range of GT 1 subjects1

  • In the ION-1, ION-2, and ION-3 clinical trials, HARVONI delivered overall cure (SVR12) rates of 94%-99% across HCV GT 1 subjects1
  • These high cure rates were observed in GT 1 subjects, including those with cirrhosis, previous treatment experience, advanced age, and high BMI1-4

Study Designs: randomized, open-label trials in GT 1 subjects1

ION-1: TN subjects (N=865) without cirrhosis or with compensated cirrhosis received HARVONI for 12 weeks, HARVONI + RBV for 12 weeks, HARVONI for 24 weeks, or HARVONI + RBV for 24 weeks.

ION-2: TE subjects (N=440) without cirrhosis or with compensated cirrhosis received HARVONI for 12 weeks, HARVONI + RBV for 12 weeks, HARVONI for 24 weeks, or HARVONI + RBV for 24 weeks.

ION-3: TN subjects (N=647) without cirrhosis received HARVONI for 8 weeks, HARVONI + RBV for 8 weeks, or HARVONI for 12 weeks.

These studies did not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients.

 
SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR is considered a virologic cure.5

Compensated cirrhosis = Child-Pugh A, RBV = ribavirin, TE = treatment-experienced (patients who have failed a peginterferon alfa + RBV-based regimen with or without an HCV protease inhibitor), TN = treatment-naïve

HARVONI is the only HCV treatment that offers an 8-week course of therapy1

Pill not actual size
  • The dosing information listed here does not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients
  • 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 HARVONI
  • 97% (n=119/123) overall cure rate among TN GT 1 subjects without cirrhosis who had baseline HCV RNA <6 million IU/mL and who received HARVONI for 8 weeks1
  • Many patients may qualify for an 8-week HARVONI regimen
    • In the ION-3 clinical trial, 59% of subjects taking HARVONI had baseline HCV RNA <6 million IU/mL1
    • In an independent chart review, more than half (56%) of GT 1 patients (n=3428) were TN without cirrhosis and had baseline HCV RNA <6 million IU/mL6,b
 
These data are derived from a study conducted by Ipsos. The study consisted of 2100 patient chart reviews per quarter by approximately 150 HCV-treating physicians from January–December 2016.
  • HARVONI has been prescribed to more than 350,000 patients8,d
 
IMS Weekly NPA™ Market Dynamics™ from week-ending 11/14/14–10/1/16.
 
This information is derived from IMS NPA, IMS NSP™, and IntegriChain® data; data reflect estimated patient starts for HARVONI from October 2014–September 2016.

HARVONI was safe with low rates of discontinuations and adverse events (AEs) across clinical trials1

  • Adverse reactions (all grades) reported in ≥5% of GT 1 subjects receiving 8, 12, or 24 weeks of treatment with HARVONI (in ION–3, ION–1, and ION–2): fatigue (13%–18%), headache (11%–17%), nausea (6%–9%), diarrhea (3%–7%), and insomnia (3%–6%)1

No baseline resistance testing is required with HARVONI1

  • HARVONI is RBV free for the majority of TN and TE patients without cirrhosis or with compensated cirrhosis, regardless of GT 1a or 1b subtype1
  • In patients without evidence of HBV infection, no hepatic or hematologic monitoring is required when HARVONI is used alone1
References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. February 2017.
  2. Afdhal N, Zeuzem S, Kwo P, et al; for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898.
  3. Kowdley KV, Gordon SC, Reddy KR, et al; for the ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888.
  4. Afdhal N, Reddy KR, Nelson DR, et al; for the ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.
  5. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.
  6. Data on file. Ipsos Healthcare. Ipsos HCV USA. January–December 2016.
  7. Data on file. IMS Weekly National Prescription Audit (NPA) Market Dynamics, 11/14/14–10/1/16. Gilead Sciences, Inc.
  8. Data on file. HARVONI Patient Starts from October 2014–September 2016. Gilead Sciences, Inc.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

STUDY RESULTS AND HYPOTHETICAL CASES

HARVONI delivered high cure (SVR12) rates across a broad range of genotype 1 patients, including those with compensated cirrhosis, previous treatment experience, advanced age, and high BMI1-4

These hypothetical profiles of patients may help you identify patients in your own practice who could be evaluated by an HCV specialist for HARVONI treatment.

Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ (25 IU/mL) at 12 weeks after the end of treatment.1 Achieving SVR12 is considered a virologic cure.5

Click the photos below to learn more about each type of HCV genotype 1 patient and the corresponding results from HARVONI ION-1, ION-2, and ION-3 clinical trials.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

HARVONI is the only HCV treatment that offers an 8-week course of therapy1

WENDYa: A 43-year-old female who was diagnosed with chronic HCV

aNot an actual patient. Profile is based on published data from clinical studies.


Let's explore the clinical trial data that support the use of HARVONI in a patient like Wendy.

The ION-3 study was a randomized, open-label trial evaluating 8 weeks of treatment with HARVONI with or without ribavirin (RBV) and 12 weeks of treatment with HARVONI in treatment-naïve, non-cirrhotic subjects (N=647) with HCV genotype 1.1 For more information on HARVONI clinical trials, including the ION-3 study, click here.

Treatment for 8 weeks can be considered for treatment-naïve genotype 1 patients without cirrhosis and with baseline HCV RNA <6 million IU/mL1
% SVR12 among treatment-naïve HCV GT 1 subjects without cirrhosis who had a baseline HCV RNA <6 million IU/mL in ION-31
  • Many treatment-naïve genotype 1 patients without cirrhosis may qualify for an 8-week HARVONI regimen1,6
  • 59% of subjects taking HARVONI in ION-3 had baseline HCV RNA <6 million IU/mL1
  • Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ (25 IU/mL) at 12 weeks after the end of treatment.1 Achieving SVR12 is considered a virologic cure5
  • HARVONI for 12 weeks is the recommended treatment duration for treatment-naïve genotype 1 patients without cirrhosis or with compensated cirrhosis.1 The information listed above does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
Relapse rates among subjects with baseline HCV RNA <6 million IU/mL in ION-31,a

aHCV RNA values were determined using the Roche TaqMan® Assay; a subject's HCV RNA may vary from visit to visit.

  • Among patients with baseline HCV RNA ≥6 million IU/mL, relapse rates were 10% (n=9/92) with 8 weeks of HARVONI and 1% (n=1/85) with 12 weeks1
  • Relapse was a secondary endpoint, which was defined as HCV RNA ≥25 IU/mL with 2 consecutive measurements or last available post-treatment measurement taken after achieving HCV RNA <25 IU/mL at the end of treatment1
Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

HARVONI consistently delivered high cure (SVR12) rates across a wide range of treatment-naïve HCV genotype 1 subjects1

MARIAa: A 56-year-old female who was diagnosed with chronic HCV and compensated cirrhosis

aNot an actual patient. Profile is based on published data from clinical studies.


Let's explore the clinical trial data that support the use of HARVONI in a patient like Maria.

The ION-1 study was a randomized, open-label trial evaluating 12 and 24 weeks of treatment with HARVONI with or without ribavirin (RBV) in treatment-naïve subjects (N=865) with HCV genotype 1 without cirrhosis or with compensated cirrhosis.1 For more information on HARVONI clinical trials, including the ION-1 study, click here.

HARVONI was effective in treatment-naïve HCV genotype 1 subjects with compensated cirrhosis1
% SVR12 among treatment-naïve HCV genotype 1 subjects without cirrhosis or with compensated cirrhosis in ION-11
  • Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ (25 IU/mL) at 12 weeks after the end of treatment1
Relapse rates were low among subjects without cirrhosis or with compensated cirrhosis receiving HARVONI in ION-11

aExcluding one subject with genotype 4 infection.

bRelapse was a secondary endpoint.

cThe denominator for relapse is the number of subjects with HCV RNA <25 IU/mL at their last on-treatment assessment.

Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

HARVONI delivered high cure (SVR12) rates in genotype 1 subjects who failed prior therapy1

KEVINa: A 55-year-old male who was diagnosed with chronic HCV in 2009 and previously received treatment.

aNot an actual patient. Profile is based on published data from clinical studies.


Let's explore the clinical trial data that support the use of HARVONI in a patient like Kevin.

The ION-2 study was a randomized, open-label trial evaluating 12 and 24 weeks of treatment with HARVONI with or without ribavirin (RBV) in genotype 1 HCV-infected subjects without cirrhosis or with compensated cirrhosis (N=440) who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor.1 For more information on HARVONI clinical trials, including the ION-2 study, click here.

HARVONI delivered high cure (SVR12) rates in HCV genotype 1 treatment-experienced adult subjects1
% SVR12 among treatment-experienced HCV GT 1 subjects without cirrhosis in ION-21
  • Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ (25 IU/mL) at 12 weeks after the end of treatment.1 Achieving SVR12 is considered a virologic cure5
Relapse rates were low for treatment-experienced non-cirrhotic HCV genotype 1 ION-2 subjects1

aThe denominator for relapse is the number of subjects with HCV RNA <25 IU/mL at their last on-treatment assessment.

bRelapse was a secondary endpoint.

cSubjects with missing cirrhosis status were excluded from this subgroup analysis.

dThese 4 non-cirrhotic relapsers all had baseline NS5A resistance–associated polymorphisms.

Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

HARVONI produced consistently high cure (SVR12) rates among HCV genotype 1 treatment-experienced subjects1

JOEa: A 62-year-old male, diagnosed with chronic HCV, who has prior treatment experience and compensated cirrhosis.

aNot an actual patient. Profile is based on published data from clinical studies.


Let's explore the clinical trial data that support the use of HARVONI in a patient like Joe.

The ION-2 study was a randomized, open-label trial evaluating 12 and 24 weeks of treatment with HARVONI with or without ribavirin (RBV) in genotype 1 HCV-infected subjects without cirrhosis or with compensated cirrhosis (N=440) who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor.1 For more information on HARVONI clinical trials, including the ION-2 study, click here.

100% of treatment-experienced genotype 1 subjects with compensated cirrhosis receiving HARVONI alone for 24 weeks achieved cure (SVR12)1
% SVR12 among treatment-experienced HCV GT 1 subjects with cirrhosis in ION-21
  • Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ (25 IU/mL) at 12 weeks after the end of treatment.1 Achieving SVR12 is considered a virologic cure5
  • HARVONI + RBV for 12 weeks can be considered in treatment-experienced genotype 1 patients with compensated cirrhosis who are eligible for RBV. The daily dosage of RBV is weight-based (1000 mg for patients <75 kg and 1200 mg for those ≥75 kg) administered orally in 2 divided doses with food. Refer to the RBV prescribing information.1
Relapse rates for treatment-experienced HCV genotype 1 subjects with cirrhosis in ION-21

aThe denominator for relapse is the number of subjects with HCV RNA <25 IU/mL at their last on-treatment assessment.

bRelapse was a secondary endpoint.

cSubjects with missing cirrhosis status were excluded from this subgroup analysis.

Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579
References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. February 2017.
  2. Afdhal N, Zeuzem S, Kwo P, et al; for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 Infection. N Engl J Med. 2014;370(20):1889-1898.
  3. Kowdley KV, Gordon SC, Reddy KR, et al; for the ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888.
  4. Afdhal N, Reddy KR, Nelson DR, et al; for the ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.
  5. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.
  6. Data on file. Ipsos Healthcare. Ipsos HCV USA. January–December 2016.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

YOUR ROLE IN HCV MANAGEMENT


HCV cure can start with you. Begin by screening your patients.

The initial action you can take toward HCV cure is to identify patients who are chronically infected with the disease. Screening recommendations in the US have changed in recent years, and treatment options have demonstrated cure rates above 90%.1 Be the one to take action today. Your patients' cure can start with you.

  • Discover which patients have been exposed to HCV

    Screening based upon several risk factors, such as past or current injection drug use and HIV infection, was the standard for many years. However, identifying all potential patients through these risk factors alone was only partially successful.

    Baby boomers
    People born between 1945 and 1965, also known as baby boomers, account for approximately 75% of all HCV patients, and they may have been infected for over 20 years.2

    That's why the Centers for Disease Control and Prevention (CDC), US Preventive Services Task Force (USPSTF), and American Association for the Study of Liver Diseases (AASLD) issued updated HCV screening recommendations that include both age- and risk-based criteria.3-5

    Other high-risk populations
    Besides the one-time screening of all baby boomers, the CDC, USPSTF, and AASLD recommend screening other high-risk populations.3-5

  • A simple blood test can reveal the presence of HCV antibodies

    Order a simple one-time antibody test for the patient. The American Medical Association provides CPT billing codes to order the appropriate screening test for your patient. The Centers for Medicare and Medicaid Services provide ICD-10 billing codes to indicate why you are ordering the HCV test.

    Once the screening test is performed, a negative HCV antibody test result means it is unlikely your patient has been exposed to the hepatitis C virus. If, however, you believe your patient may have been exposed in the past 6 months, consider testing for HCV antibodies again or ordering an HCV RNA test.

    Once the screening test is performed, a positive HCV antibody test result means your patient has been exposed to hepatitis C and a diagnosis of chronic HCV will need to be confirmed using an HCV RNA test.

    At this point, you can refer your patient to an HCV specialist, or take the next step to confirm the diagnosis.

  • Counseling

    When a patient presents who falls within the screening recommendations:

    • Discuss screening with him/her
    • Counsel him/her on HCV
    • Explain why you want to run an HCV screening (antibody) test
    • Tell a patient who is potentially infected with HCV about viable treatment options, to help allay any anxieties, concerns, or resistance he/she may have about being screened

To help you counsel your patients about screening, download the Hepatitis C Discussion Guide.

Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

To determine if an HCV infection is chronic, confirm the diagnosis

  • A blood test that detects the presence of HCV RNA is needed to verify that your patient is chronically infected with HCV.

    You or an HCV specialist can order an HCV RNA quantification/viral load test to confirm the diagnosis. Order the test yourself to potentially accelerate the specialist's evaluation and possible treatment of the patient.

    If HCV RNA is not detected, your patient is not chronically infected, even though he/she has been exposed to HCV. (About 20%-50% of patients clear the virus spontaneously within the first few months following initial infection.5) However, once a person has been infected with HCV, he/she will always test positive for HCV antibodies.

    If HCV RNA is present, your patient should be referred to an HCV specialist for assessment and treatment evaluation.

  • Automate screening and diagnosis with reflex testing

    If your patient's antibody test result is positive, many lab services can perform an HCV RNA test on the sample automatically, through a "reflex-testing" option. You can enhance the speed and efficiency of patient care by selecting this option on the lab order form when available. When ordering the antibody test, look for "Reflex" or "w/Reflex" in the test name.

Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

You can connect patients to specialist care

  • Patient referral can take place either once there is a positive antibody screening or once the patient is diagnosed with chronic HCV following a positive HCV RNA test. It is helpful to confirm the diagnosis, as no viral load would indicate that a referral is not needed.

    If the diagnosis is confirmed, referral needs to take place regardless of viral load levels, liver enzyme levels, or absence or presence of symptoms. Studies show that none of these indicates or predicts disease severity or progression.6 Therefore, you should refer all HCV patients to a specialist for further evaluation.

  • Help referred patients follow through

    Between 25%–50% of referred patients miss their first specialist appointment or never see the specialist at all.7 Below are some suggestions that can make a difference:

    • When possible, confirm your patient's chronic HCV diagnosis with an HCV RNA quantification/viral load test
    • If HCV RNA is present, the patient has a chronic HCV infection
    • If HCV RNA is not detected, your patient is not chronically infected, even though he/she has been exposed to HCV
    • Consider ordering an additional blood test to determine the HCV genotype so treatment can be expedited once the patient reaches the specialist
    • Communicate that for HCV genotype 1 patients, a once-daily, single-tablet regimen with HARVONI is available. To help you counsel your patients about HARVONI, download the Hepatitis C Discussion Guide
    • Refer to a specialist who treats HCV, is accepting new patients, and has a convenient location. For tools to help find a specialist in your area, click here
    • Be hands-on. Assist with scheduling the appointment for the patient and call to check if he/she went to the specialist
    • After the specialist appointment has taken place, record the referral, and stay in touch with the patient and specialist as co-management needs arise
Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Help prepare your patients for success by counseling at every stage

When patients fully understand HCV, the screening steps, and treatment options, they are more informed and less likely to be anxious or resistant about taking steps toward possible cure. That's why counseling and guidance are so important at all stages. Key areas to cover with your patients are:

  • Screen
    • Who should be screened
    • Why they should be screened
    • The treatment options like HARVONI that exist for patients who test positive for HCV genotype 1
  • Diagnose
    • Confirming for a chronic hepatitis C infection if the screening test is positive
    • What a positive diagnosis means
    • The importance of being evaluated for treatment
  • Connect
    • Finding an HCV specialist
    • What to expect at the specialist's office

At each stage, make sure patient questions have been answered.

To assist in your conversations with patients, the Hepatitis C Discussion Guide is available here to download.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

From screening to referral, be the one to put it into practice

The hypothetical patient profiles in this section illustrate the types of patients with HCV you may encounter in your practice and reflect common issues that can arise when addressing a patient's HCV at each of the screening, diagnosis, and referral steps. Click the photos below to read each profile.

LAURAa

Overcoming treatment hesitation in a previously diagnosed, treatment-
naïve patient

Hypothetical Patient: Laura

CARLOSa

Convincing the treatment-experienced patient to consider
retreatment

Hypothetical Patient: Carlos

   

Adhering to
at-risk screening recommendations

Hypothetical Patient: Robert

aNot an actual patient. Profile is based on published data from clinical studies.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

LAURAa

Overcoming treatment hesitation in a previously diagnosed, treatment-
naïve patient

aNot an actual patient. Profile is based on published data from clinical studies.

PATIENT CHARACTERISTICS

Screening and Diagnosis

  • 1990

    Laura received a blood transfusion.

  • 2011

    Laura's primary care physician diagnosed her with chronic HCV genotype 1 infection when the RNA viral load test was positive. Laura did not seek treatment because of:

    • Lack of symptoms
    • Fear of potential treatment side effects
    Referral
  • 2014

    After Laura's primary care physician learned about treatments like HARVONI, he suggested Laura see an HCV specialist. Her primary care physician counseled her on these points:

    • Most patients remain asymptomatic until serious liver complications arise8
    • HCV is curable
    • Treatments are shorter, with fewer side effects

    To help Laura feel comfortable in her decision to seek treatment with an HCV specialist, her primary care physician:

    • Found a conveniently located specialist experienced in treating HCV
    • After the HCV specialist prescribed HARVONI for Laura, her primary care physician followed up with her to monitor progress and answer questions while she was on HARVONI treatment
    • Told Laura about Support Path®, which offers tools and guidance for patients taking HARVONI
Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

CARLOSa

Convincing the treatment-experienced patient to consider
retreatment

aNot an actual patient. Profile is based on published data from clinical studies.

PATIENT CHARACTERISTICS

Screening and Diagnosis

  • 2007

    Carlos' primary care physician screened him with an antibody test, which was positive. The physician then:

    • Ordered an HCV RNA test to confirm the diagnosis, which was positive
    • Ordered a genotype test, which indicated that Carlos had genotype 1
  • 2011

    Carlos was referred to an HCV specialist who:

    • Treated Carlos for chronic HCV with pegylated interferon, ribavirin, and an HCV protease inhibitor for 48 weeks
    • Did not attempt other options when Carlos' treatment failed
    Referral
  • 2015

    Carlos' primary care physician:

    • Learned of HARVONI for chronic HCV genotype 1 patients
    • Re-referred Carlos to an HCV specialist

    To encourage Carlos to see the specialist and be informed about HARVONI treatment, his primary care physician:

    • Explained to Carlos the SVR12 rates observed in the HARVONI clinical studies
    • Discussed how treatments offer all-oral, simple dosing
    • Told him that interferon injections are no longer needed
    • Kept in contact with Carlos throughout the course of treatment with HARVONI
Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

aNot an actual patient. Profile is based on published data from clinical studies.

PATIENT CHARACTERISTICS

Screening and Diagnosis

  • 2013

    Because of updated screening recommendations for baby boomers (those born between 1945–1965), Robert's primary care physician suggested he be tested for HCV.

    After Robert agreed to be tested, his primary care physician ordered an HCV antibody test.

    After the positive antibody test result, his primary care physician counseled Robert on these key points:

    • A positive result does not prove chronic infection
    • To confirm the diagnosis, Robert needed an HCV RNA test
    • If the RNA test showed chronic infection, his primary care physician would counsel Robert on treatment options and discuss referral to an HCV specialist
    Referral
  • 2014

    Based on the positive results of his HCV RNA test, his primary care physician ordered a genotype test, which showed Robert had genotype 1. His primary care physician also began taking steps to refer Robert to a specialist for treatment evaluation.

    To help ensure he followed through with the referral and any possible treatment, Robert's primary care physician:

    • Selected a specialist experienced in treating HCV and had her staff call to make the appointment for Robert
    • Explained that the specialist would likely conduct more tests and discuss treatment options with him
    • Told the patient about HARVONI, which offers simple dosing and is taken once daily for 12 weeks in most patient types1
    • Made herself available after the HCV specialist's evaluation and during treatment to answer Robert's questions
Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579
References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. February 2017.
  2. CDC. Hepatitis C information for health professionals: statistics and surveillance. http://www.cdc.gov/​hepatitis/​HCV/​statisticsHCV.htm. Updated May 19, 2016. Accessed January 10, 2017.
  3. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61(RR-4):1-32.
  4. US Preventive Services Task Force. Screening for hepatitis C virus infection in adults: US Preventive Services Task Force recommendation statement. http://www.us​preventive​services​taskforce​.org/​uspstf12/​hepc/​hepcfinalrs.htm. Published June 25, 2013. Accessed January 10, 2017.
  5. AASLD, IDSA, IAS-USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed January 10, 2017.
  6. Heller T, Seeff LB. Viral load as a predictor of progression of chronic hepatitis C? Hepatology. 2005;42(6):1261-1263.
  7. McGowan CE, Fried MW. Barriers to hepatitis C treatment. Liver Int. 2011;32(suppl 1):151-156.
  8. Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation. Am Fam Physician. 2006;74(5):756-762.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings, and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
    To learn more about counseling and the cardiac monitoring of patients, as well as the signs and symptoms of bradycardia, click here.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers: Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended: HARVONI is not recommended for use with other products containing sofosbuvir.

HARVONI demonstrated tolerability with low discontinuation rates and does not require IFN or RBV for most genotype 1 patients1

Adverse reactions (all grades) reported in ≥5% of genotype 1 subjects receiving 8, 12, or 24 weeks of treatment with HARVONI in the ION-1, ION-2, and ION-3 trials1
  • Based on pooled data from three Phase 3 clinical trials in genotype 1 subjects without cirrhosis or with compensated cirrhosis1
  • The majority of the adverse events presented in the table occurred at a severity of grade 1 (mild, transient, and did not require treatment modification)1

Discontinuation rates due to adverse events were 1% or less in genotype 1 subjects receiving HARVONI in the ION-1, ION-2, and ION-3 trials1

Discontinuations due to adverse events in genotype 1 subjects treated with HARVONI1

HARVONI drug interaction profile1

Coadministration of HARVONI with the following drugs is not recommended:

  • Antiarrhythmics: amiodaroneb
  • Anticonvulsantsc: carbamazepine, phenytoin, phenobarbital, oxcarbazepine
  • Antimycobacterialsc: rifabutin, rifampin,d rifapentine
  • HCV product: simeprevird,e
  • Herbal supplement: St. John's wortc
  • HIV antiretrovirals: elvitegravir/‌cobicistat/‌emtricitabine/‌tenofovir disoproxil fumarate (DF),f tipranavir/​ritonavirc
  • Statin: rosuvastating

aThis information is not all inclusive and is based on drug interaction studies or predicted interaction.

bCoadministration of amiodarone with HARVONI may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. If coadministration is required, cardiac monitoring is recommended.

cCoadministration of HARVONI with these medications is expected to decrease concentrations of ledipasvir and sofosbuvir, leading to a reduced therapeutic effect.

dThis interaction has been studied in healthy adults.

eConcentrations of ledipasvir and simeprevir are increased when simeprevir is coadministered with ledipasvir.

fThe safety of increased tenofovir concentrations in the setting of HARVONI and elvitegravir/​cobicistat/​emtricitabine/​tenofovir DF has not been established.

gCoadministration of HARVONI with rosuvastatin may significantly increase the concentration of
rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis.

Acid-reducing agents: Drugs that increase gastric pH are expected to decrease concentration of ledipasvir1

  • Antacids (e.g., aluminum and magnesium hydroxide): It is recommended to separate antacid and HARVONI administration by 4 hours1
  • H2-receptor antagonistsb (e.g., famotidine): H2-receptor antagonists may be administered simultaneously with or 12 hours apart from HARVONI at a dose that does not exceed doses comparable to famotidine 40 mg twice daily1
  • Proton-pump inhibitorsb (e.g., omeprazole): Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with HARVONI under fasted conditions1

Antiarrhythmic:

  • Digoxin: Coadministration of HARVONI with digoxin may increase the concentration of digoxin. Therapeutic concentration monitoring of digoxin is recommended when coadministered with HARVONI1

HIV Antiretroviralsc:

  • Regimens containing tenofovir DF without an HIV protease inhibitor/ritonavir or cobicistat: Monitor for tenofovir-associated adverse reactions in patients receiving HARVONI concomitantly with a regimen containing tenofovir DF without an HIV protease inhibitor/ritonavir or cobicistat. Refer to VIREAD or TRUVADA prescribing information for recommendations on renal monitoring1
  • Regimens containing tenofovir DF and an HIV protease inhibitor/ritonavir or cobicistat, including atazanavir/ritonavir or cobicistat + emtricitabine/tenofovir DF (TRUVADA®),b darunavir/ritonavir or cobicistat + emtricitabine/tenofovir DF,b and lopinavir/ritonavir (Kaletra®) + emtricitabine/tenofovir DF1
    • The safety of increased tenofovir concentrations in the setting of HARVONI and an HIV protease inhibitor/ritonavir or cobicistat has not been established. Consider alternative HCV or antiretroviral therapy to avoid increases in tenofovir exposures. If coadministration is necessary, monitor for tenofovir-associated adverse reactions1

aThis information is not all inclusive. Alteration in dose or regimen may be recommended based on drug interaction studies or predicted interaction.

bThese interactions have been studied in healthy adults.

cRefer to the appropriate prescribing information for recommendations on renal monitoring with these medications.

The following drugs do not have clinically significant interactions when used with HARVONI1

Antiretrovirals:

  • abacavir
  • atazanavir/ritonavir
  • darunavir/ritonavir
  • dolutegravir
  • efavirenz
  • elvitegravir/​cobicistat/​emtricitabine/​tenofovir alafenamide
  • emtricitabine
  • lamivudine
  • raltegravir
  • rilpivirine

For use of HARVONI with certain HIV antiretroviral regimens, please see the and sections.

Immunosuppressants:

  • cyclosporine
  • tacrolimus

Opioids:

  • methadone

Oral contraceptives
Statins:

  • pravastatin

Calcium channel blockers:

  • verapamil

Other drug interaction information for HARVONI

  • HARVONI is not metabolized by the CYP450 pathway1
  • Sofosbuvir is cleared renally, and ledipasvir is predominantly cleared hepatically1
  • Ledipasvir and sofosbuvir are substrates of intestinal drug transporter P-gp1
References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. February 2017.
  2. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77-87.
  3. Afdhal N, Zeuzem S, Kwo P, et al; for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898.
  4. Kowdley KV, Gordon SC, Reddy KR, et al; for the ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888.
  5. Afdhal N, Reddy KR, Nelson DR, et al; for the ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.
  6. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.

PATIENT SUPPORT AND RESOURCE CENTER

Support Path is a suite of resources designed to help patients start with HARVONI and move toward treatment completion

GETTING STARTED

Support Path helps patients access therapy and get off to an efficient start

  • Benefits investigation and prior authorization support
  • Co-pay and other financial assistance
  • A specialty pharmacy finder

CO-PAY COUPON

The HARVONI co-pay coupon may help eligible patients lower their out-of-pocket costs.

With a co-pay coupon, most eligible patients may pay no more than $5 per co-pay (restrictions apply)

To register and read full terms and conditions, click here
Or call 1-855-769-7284

  • Not valid for patients enrolled in government healthcare prescription drug programs, such as Medicare Part D and Medicaid. Patients in the coverage gap known as the "donut hole" also are not eligible
  • The HARVONI co-pay coupon program will cover the out-of-pocket costs for HARVONI prescriptions up to a maximum of 25% of the catalog price of a 12-week regimen of HARVONI

HELP ALONG THE WAY

Support Path is ready to assist patients along the way toward treatment completion

  • Educational resources, support for adherence, and progress tracking
  • A 24/7 help line with nurses on call can provide answers and assistance
  • Ongoing support for access and reimbursement, including help with refill authorization

Enroll

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.

HCV cure can start with you and these helpful tools

Register to Learn More About HARVONI and Receive an Info Packet To Speak With a Gilead Representative About
HARVONI, Call 1-877-330-5579


Adverse Reactions

Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.

Drug Interactions

  • In addition to rifampin and St. John's wort, coadministration of HARVONI is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of HARVONI.
  • Coadministration of HARVONI is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/​cobicistat/​emtricitabine/​tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for HARVONI for more information on potentially significant drug interactions, including clinical comments.

TO SPEAK WITH A REPRESENTATIVE ABOUT HARVONI, CALL 1-877-330-5579

Learning more about HARVONI can start by speaking with a Gilead representative to:


  • Receive an overview of HARVONI dosing, clinical trial information results, and important safety information, which can help in your discussions with patients
  • Sign up for a live webinar with a treating specialist

  • Receive a HARVONI Info Packet for your practice
  • Register for an educational program offering informative emails, patient brochures, and other tools and resources for HARVONI treatment

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HARVONI. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.

This information is intended for US healthcare professionals

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