HARVONI OVERVIEW

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

  • These high cure rates were observed in GT 1 subjects, including those with compensated 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. The overall SVR12 for subjects receiving HARVONI for 12 weeks was 99% (n=210/213).

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. The overall SVR12 for subjects receiving HARVONI for 12 or 24 weeks was 96% (n=210/218).

ION-3: TN subjects (N=647) without cirrhosis received HARVONI for 8 weeks, HARVONI + RBV for 8 weeks, or HARVONI for 12 weeks. The overall SVR12 for subjects receiving HARVONI for 8 weeks (including those with HCV RNA >6 million IU/mL) was 94% (n=202/215).

Compensated cirrhosis = Child-Pugh A, TN = treatment-naïve, RBV = ribavirin, TE = treatment-experienced

These studies did not include subjects 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 cessation of treatment.1 Achieving SVR is considered a virologic cure.7

The only 8-week, once-daily, single-tablet regimen for eligible HCV GT 1 patients1

  • The dosing information listed here does not include patients who have received liver transplants
  • 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
  • For patients with HCV/HIV-1 coinfection, follow the dosage recommendations above. Refer to the Drug Interactions section of the HARVONI Prescribing Information for dosage recommendations for concomitant HIV-1 antiviral drugs
  • HARVONI has been prescribed to more than 400,000 patients5,c
 
IMS Weekly NPA Market Dynamics from week-ending 11/14/14–3/1/17.
 
This information is derived from IMS NPA, IMS NSP, and IntegriChain® data; data reflect estimated patient starts for HARVONI from October 2014–March 2017.
 
These data were derived from a study conducted by Ipsos. The study consisted of over 2100 patient chart reviews per quarter by approximately 150 HCV-treating physicians from April 2016 through March 2017.

HARVONI demonstrated a favorable safety profile with low rates of discontinuations and adverse events (AEs) across the ION-1, ION-2, and ION-3 clinical trials1

  • Across the ION-1, ION-2, and ION-3 clinical trials, adverse reactions (all grades) reported in ≥5% of subjects receiving 8, 12, or 24 weeks of treatment with HARVONI were fatigue (13%–18%), headache (11%–17%), nausea (6%–9%), diarrhea (3%–7%), and insomnia (3%–6%)1
References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  2. 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.
  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. 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. Data on file. IMS Weekly National Prescription Audit (NPA) Market Dynamics, 11/14/14-3/1/17. Gilead Sciences, Inc.
  6. Data on file. Ipsos Healthcare. Ipsos HCV USA, April 2016-March 2017.
  7. HHS/FDA/CDER. Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. November 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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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 rates (SVR12) 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 treatment provider for HARVONI treatment.

Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than 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.

HARVONI is the only 8-week, once-daily, single-tablet regimen for eligible HCV GT 1 patients

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
  • In an independent chart review, 75% of GT 1 TN non-cirrhotic patients qualified for an 8-week regimen of HARVONI6,b
  • Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than 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
b
These data were derived from a study conducted by Ipsos. The study consisted of over 2100 patient chart reviews per quarter by approximately 150 HCV-treating physicians from April 2016 through March 2017.
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 posttreatment 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

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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 rates (SVR12) 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 25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR12 is considered a virologic cure.5
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

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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 rates (SVR12) 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 rates (SVR12) 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 25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR12 is considered a virologic cure.5
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

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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 rates (SVR12) 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 compensated cirrhosis in ION-21
  • Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than 25 IU/mL at 12 weeks after the end of treatment.1 Achieving SVR12 is considered a virologic cure.5
  • 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 compensated 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
References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 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. HHS/FDA/CDER. Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. November 2017.
  6. Data on file. Ipsos Healthcare. Ipsos HCV USA. April 2016–March 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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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


Connecting patients to cure starts with screening and diagnosis

The first step toward cure is to identify patients who are at risk for HCV. Screening recommendations for HCV in the United States have been updated to focus on both age-based and risk-based cohorts.1-3

The CDC, USPSTF, and AASLD recommend screening all high-risk populations, including a one-time screening of all baby boomers.1-3

  • Baby boomers

    Approximately 75% of all HCV patients are baby boomers (born 1945–1965), and 60% of them don't know they are infected.3-4

    Other high-risk populations

    Besides the one-time screening of all baby boomers, the CDC, USPSTF, and AASLD recommend screening other high-risk groups, including persons who ever injected illegal drugs, HIV-infected patients, and people who received a blood transfusion before July 1992.1-3

  • Screen all high-risk patients with an HCV antibody test

    If the antibody test is positive, your patient has been exposed to HCV, but you must confirm the diagnosis with an HCV RNA test.

    If the antibody test is negative, it is highly unlikely your patient has been exposed to HCV. However, if exposure is suspected in the past 6 months, consider re-testing for HCV antibodies or ordering an HCV RNA test.

    Choose a lab's "reflex-testing" option at the screening stage, so an HCV RNA test will be run automatically if the antibody test is positive

    Confirm diagnosis of chronic HCV with an HCV RNA test

    If HCV RNA is detected, your patient should be connected to an HCV treatment provider for an evaluation. Further testing includes a genotype test and may include a liver biopsy and/or liver ultrasound to determine disease progression.

    If HCV RNA is not detected, your patient has been exposed to HCV but is not chronically infected. About 20%-50% of patients clear the virus spontaneously within the first few months following initial infection.2 Such patients do not need further medical evaluation for HCV infection. However, once a person has been infected with HCV, he/she will always test positive for HCV antibodies.5

    Of those who tested positive for HCV antibodies, 1/3 have not had their diagnosis confirmed
  • Counsel patients and connect them to cure
    • Explain to patients why you want to run an HCV antibody test, discussing the shift in recommendations that focus on age- and risk-based factors
    • Counsel patients on the risk of HCV and the advances in treatment that have made treatment shorter and more effective, with high cure rates

Screen and diagnose all of your at-risk patients to connect them to cure.

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

Register to Learn More About HARVONI and Receive an Info Packet

You can connect patients to treater 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 treatment provider for further evaluation.

  • Help referred patients follow through

    Between 25%–50% of referred patients miss their first treater appointment or never see the treater at all.6 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 treatment provider
    • Communicate that for most 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 an HCV treatment provider who is accepting new patients and has a convenient location. For tools to help find a treatment provider 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 treatment provider
    • After the appointment with the treatment provider has taken place, record the referral, and stay in touch with the patient and treatment provider as co-management needs arise
Register to Learn More About HARVONI and Receive an Info Packet

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 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 treatment provider
    • What to expect at the treatment provider'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.

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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.

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

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 treatment provider. 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 treatment provider, her primary care physician:

    • Found a conveniently located provider experienced in treating HCV
    • After the HCV treatment provider prescribed HARVONI for Laura, her primary care physician followed up with her to monitor progress and answer questions while she was on HARVONI treatment
Register to Learn More About HARVONI and Receive an Info Packet

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

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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.

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 treatment provider 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 treatment provider

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

    • Explained to Carlos the cure 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

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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.

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 (born 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 treatment provider
    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 treatment provider for evaluation.

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

    • Selected a provider experienced in treating HCV and had her staff call to make the appointment for Robert
    • Explained that the treatment provider would likely conduct more tests and discuss treatment options with him
    • Told Robert about HARVONI, which offers simple dosing and is taken once daily for 12 weeks in most patients1
    • Made herself available after the HCV treatment provider's evaluation and during treatment to answer Robert's questions
Register to Learn More About HARVONI and Receive an Info Packet
References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 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 September 21, 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.

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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.

DOSAGE AND ADMINISTRATION

HARVONI is a once-daily, single-tablet regimen for the majority of HCV GT 1 adult patients1

  • For GT 1 TEa patients with compensated cirrhosis, 24 weeks of HARVONI is recommended, and 12 weeks of HARVONI + RBVb can be considered
  • 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
  • For patients with HCV/HIV-1 coinfection, follow the dosage recommendations above. Refer to the Drug Interactions section of the HARVONI Prescribing Information for dosage recommendations for concomitant HIV-1 antiviral drugs
  • No dosage recommendation can be given for patients with severe renal impairment (estimated glomerular filtration rate [eGFR] less than 30 mL/min/1.73 m2) or with end-stage renal disease (ESRD) due to higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite
  • Each HARVONI tablet contains 90 mg of ledipasvir and 400 mg of sofosbuvir1

TE = treatment-experienced

aTreatment-experienced patients who have failed treatment with either peginterferon (Peg-IFN) alfa + ribavirin (RBV) or an HCV protease inhibitor (PI) + Peg-IFN alfa + RBV

bThe daily dose of RBV is weight-based (1000 mg for patients <75 kg and 1200 mg for those ≥75 kg) administered orally in two divided doses with food. Refer to the RBV prescribing information.


Reference:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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

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 posttreatment 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

  • 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 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.

HARVONI demonstrated a favorable safety profile with low rates of adverse events across clinical trials1

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

Fluctuations in international normalized ratio (INR) may occur in patients on concomitant warfarin; frequent monitoring of INR is recommended during HARVONI treatment and post-treatment follow-up.

HARVONI is not recommended with the following medications1,a

Concomitant
Drug Class
and Drug Names

Coadministration
Is Not
Recommended

Clinical Considerations

Antiarrhythmics

amiodarone

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

Antimycobacterials

rifabutin, rifapentine, rifampinb

May significantly decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Herbal Supplements

St. John's wort

May significantly decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

HCV Protease Inhibitors

simeprevirb

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

Anticonvulsants

carbamazepine, phenytoin, phenobarbital, oxcarbazepine

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

HIV Antiretrovirals

STRIBILD® (elvitegravir/cobicistat/ emtricitabine/tenofovir DF)

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Statins

rosuvastatin

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

HARVONI use with HIV antiretrovirals1,a

Concomitant Drug
Class and
Drug Names

Coadministration
Is Not
Recommended

Potentially Significant Interaction

No Clinically Significant Interaction

Clinical Considerations

HIV Antiretrovirals

STRIBILD® (elvitegravir/
cobicistat/emtricitabine/​tenofovir DF)

   

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir

   

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Regimens containing tenofovir DF and an HIV protease inhibitor/ritonavir or cobicistat:

  • atazanavir/ritonavir or cobicistat + emtricitabine/​tenofovir DFb
  • darunavir/ritonavir or cobicistat + emtricitabine/​tenofovir DFb
  • lopinavir/ritonavir + emtricitabine/tenofovir DF

   

The safety of increased tenofovir concentrations in this setting has not been established. Consider alternative HCV or antiretroviral therapy. If coadministration is required, monitor for tenofovir-associated adverse reactions. Refer to VIREAD® or TRUVADA® prescribing information for recommendations on renal monitoring.

Regimens containing tenofovir DF without an HIV protease inhibitor/ritonavir or cobicistat

   

Monitor for tenofovir-associated adverse reactions. Refer to VIREAD or TRUVADA prescribing information for recommendations on renal monitoring.

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir® (darunavir/ritonavir),
Tivicay® (dolutegravir),
Sustiva® (efavirenz),
GENVOYA® (elvitegravir/ cobicistat/emtricitabine/​tenofovir alafenamide),
EMTRIVA® (emtricitabine),
Epivir® (lamivudine),
Isentress® (raltegravir),
Edurant® (rilpivirine)

   

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI may be coadministered with acid-reducing agents1,a

Concomitant
Drug Class
and Drug Names

Potentially
Significant

Interaction

Clinical Considerations

Acid-Reducing Agents

 

Ledipasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of ledipasvir.

Antacids (eg, aluminum and magnesium hydroxide)

It is recommended to separate antacid and HARVONI administration by 4 hours.

H2-receptor antagonistsb (eg, 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 daily.

Proton-pump inhibitorsb (eg, omeprazole)

Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with HARVONI under fasted conditions.

HARVONI use with antiarrhythmics and statins1,a

Concomitant
Drug Class
and Drug Names

Coadministration
Is Not
Recommended

Potentially Significant Interaction

No Clinically Significant Interaction

Clinical Considerations

Antiarrhythmics

amiodarone

   

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

digoxin

   

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

Statins

rosuvastatin

   

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

atorvastatin

   

May be associated with increased risk of myopathy, including rhabdomyolysis. Monitor closely for HMG-CoA reductase inhibitor-associated adverse reactions, such as myopathy and rhabdomyolysis.

pravastatin

   

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI does not have clinically significant interactions with the following medications1,a

Concomitant
Drug Class
and Drug Names

No Clinically
Significant

Interaction

Clinical Considerations

Immunosuppressants

cyclosporine, tacrolimus

Opioids

methadone

Oral Contraceptives

oral contraceptives

Calcium Channel Blockers

verapamil

HIV Antiretrovirals

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir® (darunavir/ritonavir),
Tivicay® (dolutegravir),
Sustiva® (efavirenz),
GENVOYA® (elvitegravir/ cobicistat/emtricitabine/
tenofovir alafenamide),
EMTRIVA® (emtricitabine),
Epivir® (lamivudine),
Isentress® (raltegravir),
Edurant® (rilpivirine)

No clinically significant drug interactions have been observed or are expected with HARVONI.


See "HARVONI use with HIV antiretrovirals" table, above, for additional information on the use of HARVONI with certain HIV antiretroviral regimens.

Statins

pravastatin

Fluctuations in international normalized ratio (INR) may occur in patients on concomitant warfarin; frequent monitoring of INR is recommended during HARVONI treatment and post-treatment follow-up.

HARVONI is not recommended with the following medications1,a

Coadministration Is Not Recommended

amiodarone - Antiarrhythmics

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

rifabutin, rifapentine, rifampinb - Antimycobacterials

May significantly decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

St. John's wort - Herbal Supplements

May significantly decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

simeprevirb - HCV Protease Inhibitors

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

carbamazepine, phenytoin, phenobarbital, oxcarbazepine - Anticonvulsants

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

STRIBILD® (elvitegravir/cobicistat/ emtricitabine/tenofovir DF) - HIV Antiretrovirals

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir - HIV Antiretrovirals

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

rosuvastatin - Statins

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

HARVONI use with HIV antiretrovirals1,a

Coadministration Is Not Recommended

STRIBILD® (elvitegravir/
cobicistat/emtricitabine/tenofovir DF)
- HIV Antiretrovirals

The safety of increased tenofovir concentrations in the setting of HARVONI and STRIBILD coadministration has not been established.

tipranavir/ritonavir - HIV Antiretrovirals

Expected to decrease the concentration of HARVONI, leading to a reduced therapeutic effect.

Potentially Significant Interaction

Regimens containing tenofovir DF and an HIV protease inhibitor/ritonavir or cobicistat - HIV Antiretrovirals

  • atazanavir/ritonavir or cobicistat + emtricitabine/​tenofovir DFb
  • darunavir/ritonavir or cobicistat + emtricitabine/​tenofovir DFb
  • lopinavir/ritonavir + emtricitabine/tenofovir DF

The safety of increased tenofovir concentrations in this setting has not been established. Consider alternative HCV or antiretroviral therapy. If coadministration is required, monitor for tenofovir-associated adverse reactions. Refer to VIREAD® or TRUVADA® prescribing information for recommendations on renal monitoring.

Regimens containing tenofovir DF without an HIV protease inhibitor/ritonavir or cobicistat - HIV Antiretrovirals

Monitor for tenofovir-associated adverse reactions. Refer to VIREAD or TRUVADA prescribing information for recommendations on renal monitoring.

No Clinically Significant Interaction

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir® (darunavir/ritonavir), Tivicay® (dolutegravir), Sustiva® (efavirenz), GENVOYA® (elvitegravir/ cobicistat/emtricitabine/tenofovir alafenamide), EMTRIVA® (emtricitabine), Epivir® (lamivudine), Isentress® (raltegravir), Edurant® (rilpivirine) - HIV Antiretrovirals

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI may be coadministered with acid-reducing agents1,a

Acid-Reducing Agents

Potentially Significant Interaction

Ledipasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of ledipasvir.

Antacids (eg, aluminum and magnesium hydroxide) - Acid-Reducing Agents

It is recommended to separate antacid and HARVONI administration by 4 hours.

H2-receptor antagonistsb (eg, famotidine) - Acid-Reducing Agents

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 daily.

Proton-pump inhibitorsb (eg, omeprazole) - Acid-Reducing Agents

Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with HARVONI under fasted conditions.

HARVONI use with antiarrhythmics and statins1,a

Coadministration Is Not Recommended

amiodarone - Antiarrhythmics

Coadministration may result in serious symptomatic bradycardia. If coadministration is required, cardiac monitoring is recommended.

rosuvastatin - Statins

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

Potentially Significant Interaction

digoxin - Antiarrhythmics

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

atorvastatin - Statins

May be associated with increased risk of myopathy, including rhabdomyolysis. Monitor closely for HMG-CoA reductase inhibitor-associated adverse reactions, such as myopathy and rhabdomyolysis.

No Clinically Significant Interaction

pravastatin - Statins

No clinically significant drug interactions have been observed or are expected with HARVONI.

HARVONI does not have clinically significant interactions with the following medications1,a

No Clinically Significant Interaction

cyclosporine, tacrolimus - Immunosuppressants

methadone - Opioids

oral contraceptives - Oral Contraceptives

verapamil - Calcium Channel Blockers

Ziagen® (abacavir), Reyataz®/Norvir® (atazanavir/ritonavir), Prezista®/Norvir® (darunavir/ritonavir), Tivicay® (dolutegravir), Sustiva® (efavirenz), GENVOYA® (elvitegravir/ cobicistat/emtricitabine/tenofovir alafenamide), EMTRIVA® (emtricitabine), Epivir® (lamivudine), Isentress® (raltegravir), Edurant® (rilpivirine) - HIV Antiretrovirals

No clinically significant drug interactions have been observed or are expected with HARVONI.


See "HARVONI use with HIV antiretrovirals" table, above, for additional information on the use of HARVONI with certain HIV antiretroviral regimens.

pravastatin - Statins

References:
  1. HARVONI Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 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. HHS/FDA/CDER. Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. November 2017.

PATIENT SUPPORT AND RESOURCE CENTER

Support Path® can help patients get started on therapy and move toward treatment completion.

Eligible patients may pay no more than $5 per co-pay for HARVONI

  • 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

Restrictions apply. To check your eligibility, please call 1-855-7-MYPATH (1-855-769-7284) and speak with a HARVONI Support Path® specialist, Monday through Friday from 9am to 8pm Eastern Time.

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 posttreatment 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

  • 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 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.

Adverse Reactions

  • Most common adverse reactions (≥10%, all grades) 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.

This information is intended for US healthcare professionals

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