TAP FOR IMPORTANT SAFETY
INFORMATION, including BOXED
WARNING on Hepatitis B reactivation.

OVERVIEW

 

HARVONI provides the simplicity of an 8-week once-daily single-tablet regimen (STR) for eligible GT 1 patients1

Dosing chart [8 weeks can be considered in GT 1 TN patients without cirrhosis who have pre-treatment HCV RNA <6 million IU/mL; 12 weeks is the recommended treatment duration for TN patients with or without cirrhosis]

Compensated cirrhosis = Child-Pugh A, TN = treatment-naïve

  • The dosing information listed here does not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients

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.

Many of your HCV GT 1 patients may be eligible for an 8-week HARVONI regimen

In an independent chart review, 75% of GT 1 TN non-cirrhotic (NC) adult patients qualified for an 8-week regimen of HARVONI2,a
  • In an independent chart review, the majority of patients initiating HCV treatment today are GT 1, TN, and NC2
These data are derived from a study conducted by IPSOS. The study consisted of over 2100 patient chart reivews per quarter by approximately 150 HCV-treating physicians from April 2016-March 2017.

HARVONI is an established choice for your GT 1 patients, backed by real-world data1,3

In clinical trials and HCV-TARGET, HARVONI delivered high cure rates in a broad range of GT 1 subjects1,3,b
97% icon [97% overall cure rate across three HARVONI Phase 3 trials (n=1042/1079; ION-1, -2, -3)]
96% icon [96% overall cure rate in the real-world HCV-TARGET study (n=1638/1702; HCV-TARGET)]

Click to see HARVONI Clinical Study Designs and HCV-TARGET Study Design.

 

HARVONI Clinical 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).

RBV = ribavirin, TE = treatment-experienced

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

bSVR12 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.7

 

HCV-Target Study Design3:

HCV-TARGET is a prospective, longitudinal, observational study that evaluated the safety and efficacy of HARVONI, with or without ribavirin, in GT 1 adults treated for 8, 12, or 24 weeks in academic or community settings. HCV-TARGET included TN and TE patients with or without cirrhosis (N=2099). SVR12 rates in HCV-TARGET were reported for 1702 patients who received HARVONI monotherapy and excluded patients lost to follow-up.3

Real-world data are observational in nature and are not based on controlled clinical studies. Results from the HCV-TARGET study may differ from those observed in clinical practice and are not presented in the HARVONI Prescribing Information. The HCV-TARGET study was supported by Gilead Sciences, Inc.

#1 icon [HARVONI is the #1 prescribed HCV treatment for GT 1 patients in the US]

More than 400,000 patients have been prescribed HARVONI in the US9,d

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.

HARVONI demonstrated a favorable safety profile with low rates of discontinuations and adverse events (AEs) across clinical trials1

≤1% icon [≤1% discontinuations due to AEs]
  • 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 a history of HBV infection, no hepatic monitoring is required when HARVONI is used alone1
  • No hematologic monitoring is required when HARVONI is used alone1

HARVONI demonstrated a favorable safety profile 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 a history of HBV infection, no hepatic monitoring is required when HARVONI is used alone1
  • No hematologic monitoring is required when HARVONI is used alone1
References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  2. Data on file. IPSOS Healthcare. IPSOS HCV USA, April 2016-March 2017.
  3. Terrault NA, Zeuzem S, Di Biceglie AM, et al; for the HCV-TARGET Study Group. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated with sustained virologic response. Gastroenterology. 2016;151(6):1131-1140.
  4. 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.
  5. 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.
  6. 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.
  7. US Department of Health and Human Services, Center for Drug Evaluation and Research. Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. November 2017.
  8. Data on file. IMS Weekly National Prescription Audit (NPA) Market Dynamics, 11/14/14–3/1/17. Gilead Sciences, Inc.
  9. Data on file. HARVONI Patient Starts from October 2014–March 2017. 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

  • 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.

References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  2. 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.
  3. Data on file. IPSOS Healthcare. IPSOS HCV USA, January 2016-December 2016.
  4. Data on file. IMS Weekly National Prescription Audit (NPA) Market Dynamics, 11/14/14–3/1/17. Gilead Sciences, Inc.
  5. Data on file. HCV Weekly Sales Reports, 11/14/14–1/1/16. Gilead Sciences, Inc.
  6. Data on file. HARVONI Patient Starts from October 2014–February 2016. Gilead Sciences, Inc.

STUDY RESULTS

HARVONI delivered high cure rates in GT 1 treatment-naïve adult subjects without cirrhosis or with compensated cirrhosis1,a

% SVR12 in treatment-naïve GT 1 subjects in ION-11
ION-1 chart [% SVR12 in treatment-naïve GT 1 subjects in ION-1]

RBV was not shown to increase the response rates observed with HARVONI in ION-1. Therefore, the HARVONI + RBV arm is not presented.1

aSVR12 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.2

One tablet taken once daily without IFN or RBV1

  • The recommended treatment duration for adult treatment-naïve patients without cirrhosis or with compensated cirrhosis is HARVONI once daily for 12 weeks. HARVONI for 8 weeks can be considered in adult GT 1 treatment-naïve patients without cirrhosis with pre-treatment HCV RNA <6 million IU/mL1
    • The dosing information listed above does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
  • No on-treatment virologic failure occurred in subjects treated with HARVONI for 12 weeks in ION-11

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

HARVONI delivered high cure rates in GT 1 treatment-naïve adult subjects without cirrhosis1,a

% SVR12 in treatment-naïve GT 1 subjects without cirrhosis in ION-31,b
ION-3 chart [% SVR12 in treatment-naïve GT 1 subjects without cirrhosis in ION-3]

RBV was not shown to increase the response rates observed with HARVONI in ION-3. Therefore, the HARVONI + RBV arm is not presented.1

aSVR12 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.2

bThe treatment difference between the 8-week treatment of HARVONI and 12-week treatment of HARVONI was -2.3% (97.5% confidence interval [-7.2% to 2.5%]).1

One tablet taken once daily without IFN or RBV

  • The recommended treatment duration for adult treatment-naïve patients without cirrhosis or with compensated cirrhosis is HARVONI once daily for 12 weeks. HARVONI for 8 weeks can be considered in adult GT 1 treatment-naïve patients without cirrhosis with pre-treatment HCV RNA <6 million IU/mL1
    • The dosing information listed above does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
  • No on-treatment virologic failure occurred in ION-31

Relapse rates are affected by baseline host and viral factors and differ between durations for certain subgroups1

Relapse rates by baseline viral load in ION‑31
Relapse rates in ION-3 chart [Relapse rates by baseline viral load in ION-3]

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

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

HARVONI delivered high cure (SVR12) rates in GT 1 treatment-experienced adult subjects1,a

% SVR12 in GT 1 treatment-experienced subjects in ION‑21
ION-2 chart [% SVR12 in GT 1 treatment-experienced subjects in ION-2]

RBV was not shown to increase the response rates observed with HARVONI in ION-2. Therefore, the HARVONI + RBV arms are not presented.1

aSVR12 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.2

One tablet taken once daily without IFN or RBV

  • The recommended treatment duration for adult treatment-experienced patients without cirrhosis is 12 weeks1
  • The recommended treatment duration for adult GT 1 treatment-experienced patients with compensated cirrhosis is 24 weeks1
    • HARVONI + RBV for 12 weeks can be considered in treatment-experienced adult GT 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 information1
  • The dosing information listed above does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients
  • No on-treatment virologic failure occurred in subjects receiving HARVONI alone for 12 or 24 weeks1
  • SVR rates in other subgroups were 86% in subjects with compensated cirrhosis treated with HARVONI for 12 weeks (n=22) and 99% in subjects without cirrhosis treated with HARVONI for 24 weeks (n=86)1
  • Among subjects with available SVR12 and SVR24 data (206/218), all subjects who achieved SVR12 in the ION-2 study also achieved SVR241
  • In subjects with compensated cirrhosis, relapse rates were 14% with HARVONI for 12 weeks (n=22) and 0% with HARVONI for 24 weeks (n=22)1

Relapse rates are affected by baseline host and viral factors and differ between durations for certain subgroups1

Relapse rates for selected subgroups in ION-21
Relapse rates in ION-2 chart [Relapse rates for selected subgroups in ION-2]

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

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

cNS5A resistance-associated polymorphisms include any change at NS5A positions 24, 28, 30, 31, 58, 92, or 93.

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

HARVONI delivered high cure rates in treatment-naïve and treatment-experienced subjects with HCV/HIV-1 coinfection1,a

% SVR12 in HCV GT 1 or 4 subjects with HCV/HIV-1 coinfection in ION‑41
ION-4 chart [% SVR12 in HCV GT 1 or 4 subjects with HCV/HIV-1 co-infection in ION-4]

aSVR12 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.2

  • HARVONI delivered consistently high cure rates regardless of prior HCV treatment experience or cirrhosis status (94% in subjects with compensated cirrhosis and 98% in treatment-experienced subjects with compensated cirrhosis)1
  • No subjects had HIV-1 rebound during this study1
  • The relapse rate in Black subjects was 9% (10/115) and all 10 were IL28B non-C/C genotype. The relapse rate in non-Black subjects was 0% (0/220). In the ION-1, ION-2, and ION-3 HCV mono-infection studies, relapse rates were 3% (10/305) in Black subjects and 2% (26/1637) in non-Black subjects1
  • The safety profile in HCV/HIV-1 coinfected subjects was similar to that observed in HCV mono-infected subjects. See the Drug Interactions section of the HARVONI Prescribing Information for potentially significant drug interactions with HIV antiretrovirals1
  • For patients with HCV/HIV-1 coinfection, follow the dosage recommendations listed in the Dosage and Administration section. Refer to the Drug Interactions section of the HARVONI Prescribing Information for dosage recommendations for concomitant HIV-1 antiviral drugs1
References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  2. 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.

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

  • 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.

References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  2. U.S. 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. Published October 2013.

STUDY DESIGNS

ION-1: GT 1 treatment-naïve adults without cirrhosis or with compensated cirrhosis1

ION-1: GT 1 treatment-naïve adults without cirrhosis or with compensated cirrhosis1

A Phase 3, randomized, open-label clinical trial (N=865)1
ION-1 Study Design chart [ION-1: GT 1 treatment-naïve adults with or without cirrhosis]

Subjects were randomized in a 1:1:1:1 ratio for each treatment arm, and randomization was stratified by the presence or absence of cirrhosis and HCV genotype (1a vs 1b).1

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA ≥25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • 16% had compensated cirrhosis
  • Median age: 54 years (range: 18 to 80)
  • 59% were male; 41% were female
  • 85% were White; 12% were Black; 12% were Hispanic or Latino
  • Mean BMI was 27 kg/m2 (range: 18 to 48 kg/m2)
  • 79% had baseline HCV RNA levels ≥ 800,000 IU/mL
  • 67% had HCV GT 1a
  • 70% had IL28B non-C/C alleles (CT or TT)

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

ION-3: GT 1 treatment-naïve adults without cirrhosis1

ION-3: GT 1 treatment-naïve adults without cirrhosis1

A Phase 3, randomized, open-label clinical trial (N=647)1
ION-3 Study Design chart [ION-3: GT 1 treatment-naïve adults without cirrhosis]

Subjects were randomized in a 1:1:1 ratio to 1 of the 3 treatment groups and stratified by HCV genotype (1a vs 1b).1

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • Median age: 55 years (range: 20 to 75)
  • 58% were male; 42% were female
  • 78% were White; 19% were Black; 6% were Hispanic or Latino
  • Mean BMI was 28 kg/m2 (range: 18 to 56 kg/m2)
  • 81% had baseline HCV RNA levels ≥ 800,000 IU/mL
  • 80% had HCV GT 1a
  • 73% had IL28B non-C/C alleles (CT or TT)

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

ION-2: GT 1 previously treated adults without cirrhosis or with compensated cirrhosis1

ION-2: GT 1 previously treated adults without cirrhosis or with compensated cirrhosis1

A Phase 3, randomized, open-label clinical trial (N=440)1
ION-2 Study Design chart [ION-2: GT 1 previously treated adults with or without cirrhosis]

Subjects were randomized in a 1:1:1:1 ratio to each of the treatment arms, and randomization was stratified by the presence or absence of cirrhosis, HCV genotype (1a vs 1b), and response to prior HCV therapy (relapse/breakthrough vs nonresponse).1

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA 25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • 20% of subjects had compensated cirrhosis
  • Median age: 57 years (range: 24 to 75)
  • 65% were male; 35% were female
  • 81% were White; 18% were Black; 9% were Hispanic or Latino
  • Mean BMI was 28 kg/m2 (range: 19 to 50 kg/m2)
  • 89% had baseline HCV RNA levels ≥ 800,000 IU/mL
  • 79% had HCV GT 1a
  • 88% had IL28B non-C/C alleles (CT or TT)
  • 53% failed prior therapy with an HCV protease inhibitor + Peg-IFN + RBV regimen (62% were relapse/breakthrough; 38% were nonresponder)
  • 47% of subjects failed prior therapy with Peg-IFN + RBV (49% were relapse/breakthrough; 51% were nonresponder)

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

ION-4: GT 1 or 4 treatment-naïve and treatment-experienced subjects with HCV/HIV-1 co-infection1

ION-4: GT 1 or 4 treatment-naïve and treatment-experienced subjects with HCV/HIV-1 co-infection1

A Phase 3, open-label clinical trial (N=335)1
ION-4 Study Design chart [ION-4: GT 1 or 4 treatment-naïve and treatment- experienced subjects with HCV/HIV-1 co-infection]

SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.1

Relapse was a secondary endpoint, which was defined as HCV RNA ≥25 IU/mL with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA <25 IU/mL at the end of treatment.1

Baseline Characteristics1

  • Median age: 52 years (range: 26 to 72)
  • 82% of the subjects were male; 18% were female
  • 61% were White; 34% were Black
  • Mean BMI was 27 kg/m2 (range: 18 to 66 kg/m2)
  • 75% had HCV GT 1a infection
  • 76% had non-C/C IL28B alleles (CT or TT)
  • 20% had compensated cirrhosis
  • 55% of subjects were treatment-experienced; 45% of subjects were treatment-naïve

Subjects were on stable HIV-1 antiretroviral therapy that included emtricitabine + tenofovir disoproxil fumarate, administered with efavirenz, rilpivirine, or raltegravir.

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

HARVONI was studied in a range of subjects1

Select baseline characteristics in HCV HARVONI clinical trials (ION‑1, ION‑3, ION‑2, ION‑4)1-7
Baseline characteristic chart [Select baseline characteristics in HCV HARVONI clinical trials (ION-1, -3, -2, and -4)]
References:
  1. HARVONI US full 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(16):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(16):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. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16)(suppl).
  6. Naggie S, Cooper C, Saag M, et al; for the ION-4 Investigators. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):705-713.
  7. Naggie S, Cooper C, Saag M, et al; for the ION-4 Investigators. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8)(suppl).

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

  • 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.

REAL-WORLD DATA

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

Real-world data support the efficacy of 8 weeks of HARVONI1-3

8 weeks of HARVONI delivered high cure rates in a clinical trial and real-world studies1-3,a
% SVR12 in GT 1, TN adults without cirrhosis who had pre-treatment HCV RNA <6 million IU/mL
97%, 98%, and 96% icons 97%, 98%, and 96% icons

TN = treatment-naïve

Sustained virologic response (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.4
  • 8 weeks of HARVONI can be considered in adult GT 1, TN patients without cirrhosis who have pre-treatment HCV RNA <6 million IU/mL1
  • 12 weeks of HARVONI is the recommended duration for GT 1 TN adults without cirrhosis or with compensated cirrhosis1
  • ION-3 common adverse events ([AEs] ≥5%) among patients taking HARVONI for 8 weeks: fatigue (21%), headache (14%), nausea (7%), diarrhea (7%), insomnia (5%); discontinuations due to AEs (0%)5
  • In HARVONI clinical trials, the most common adverse reactions (≥10%, all grades) were fatigue, headache, and asthenia1
  • The pooled real-world analysis did not provide safety results
  • HCV-TARGET most common (≥10%) AEs (among patients taking 8, 12, or 24 weeks of HARVONI): fatigue (23%), headache (21%); discontinuations due to AEs (3%)3

Click for ION-3 Clinical Study Design, Pooled Real-world Analysis Study Design, and HCV-TARGET Study Design.

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

8 weeks of HARVONI demonstrated clinical and real-world efficacy in a broad range of GT 1 TN patients2,6

Clinical trial and pooled real-world analysis results in GT 1 TN adults without cirrhosis who have pre-treatment HCV RNA <6 million IU/mL following 8 weeks of HARVONI2,6,a-c
% SVR12 in GT 1 patients in the ION-3 clinical trial and the Pooled Real-world Analysis2,6
GT 1 chart
a
Fibrosis scores were determined by FibroTest (FibroSure™)
b
19 patients who were initially deemed F4 by FibroTest were subsequently determined to be non-cirrhotic (F0-F3) by liver biopsy
c
Fibrosis scores were determined by transient elastography, serum biomarkers, or liver biopsy within 3 years of treatment
  • The pooled real-world analysis used individual patient data from the German IFI (Institut für Interdisziplinäre Medizin), Temple University/Burman’s Pharmacy, and Kaiser Permanente Southern California2

In the ION-3 clinical trial and the pooled real-world analysis, the 8-week HARVONI option delivered high cure rates regardless of GT 1a or 1b subtype, ethnicity, or fibrosis stage2,6

  • Consistently high SVR12 rates (96%) were observed in Black patients in both clinical trial and real-world cohorts2,6

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

Treatment with HARVONI for 8 or 12 weeks demonstrated consistently high cure rates1,3

% SVR12 in ION-3 and in HCV-TARGET1,3
HARVONI Cure Rates

HARVONI real-world data have been proven consistent with clinical studies1,3

  • AEs in 8-week regimens were similar to those observed in 12-week regimens1,3
  • ION-3 common adverse events ([AEs] ≥5%) among patients taking HARVONI for 8 weeks: fatigue (21%), headache (14%), nausea (7%), diarrhea (7%), insomnia (5%); discontinuations due to AEs (0%)5
  • ION-3 common AEs (among patients taking the 12-week option only): fatigue (23%), headache (15%), nausea (11%), insomnia (7%); discontinuations due to AEs (1%)5
  • HCV-TARGET most common (≥10%) AEs (among patients taking 8, 12, or 24 weeks of HARVONI): fatigue (23%), headache (21%); discontinuations due to AEs (3%)3

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

Study Designs

ION-3 Study Design: TN subjects (N=647) without cirrhosis received HARVONI for 8 weeks, HARVONI + RBV for 8 weeks, or HARVONI for 12 weeks. SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment. The overall SVR12 for subjects receiving HARVONI for 8 weeks (including those with HCV RNA >6 million IU/mL) was 94% (n=202/215).1

Pooled Real-world Analysis Study Design: The pooled real-world cohort analysis includes pooled data captured prospectively and retrospectively from patient records or systems databases from the Institut für Interdisziplinäre Medizin (German IFI), Burman’s Pharmacy/Temple University, and Kaiser Permanente Southern California. Outcomes data, including SVR12 rates, were collected from 634 GT 1, TN, non-cirrhotic (NC) adults infected with HCV who were treated with 8 weeks of HARVONI monotherapy. 92% of patients (N=583) had a pre-treatment viral load of <6 million IU/mL. SVR12 rates from the pooled analysis excluded patients lost to follow-up. The analysis did not include liver transplant recipients, and did not examine or report adverse events or other safety-related information.2

HCV-TARGET Study Design: HCV-TARGET is a prospective, longitudinal, observational study that evaluated the safety and efficacy of HARVONI, with or without RBV, in GT 1 adults treated for 8, 12, or 24 weeks in academic or community settings. HCV-TARGET included TN and treatment-experienced (TE) patients with or without cirrhosis (N=2099). SVR12 rates in HCV-TARGET were reported for 1702 patients who received HARVONI monotherapy and excluded patients lost to follow-up.3

Real-world data are observational in nature, may be prospectively or retrospectively collected, and are not based on controlled clinical studies. Results from these cohorts may differ from those observed in clinical practice and are not presented in the HARVONI prescribing information. The HCV-TARGET study and the German IFI cohort analysis were supported by Gilead Sciences, Inc.

References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  2. Kowdley KV, Sundaram V, Jeon CY, et al. Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection. Hepatology. 2017;65(4):1094-1103.
  3. Terrault NA, Zeuzem S, Di Biceglie AM, et al; for the HCV-TARGET Study Group. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated with sustained virologic response. Gastroenterology. 2016;151(6):1131-1140.
  4. 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.
  5. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888.0(16):1483-1493.
  6. Gordon S, et. al. Patients with baseline HCV RNA <6 million IU/mL achieved high SVR rates with 8 or 12 weeks of LDV/SOF regardless of baseline characteristics. Poster 459. Presented at ACG 2015, Annual Scientific Meeting and Postgraduate Course, October 16-21, 2015, Honolulu, Hawaii.

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

  • 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.
References:
  1. Terrault NA, Zeuzem S, Di Biceglie AM, et al; for the HCV-TARGET Study Group. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated with sustained virologic response. Gastroenterology. 2016;151(6):1131-1140.
  2. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  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.

DOSAGE AND ADMINISTRATION

 

INDICATION

HARVONI is indicated for the treatment of adults with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis. HARVONI is used with ribavirin in GT 1 adults with decompensated cirrhosis and in GT 1 or 4 adult liver transplant recipients without cirrhosis or with compensated cirrhosis.

Provide the simplicity of a sofosbuvir-based, once-daily single-tablet regimen for eligible patients1

Recommended treatment duration for HARVONI1
Dosing chart [Recommended treatment duration for HARVONI]

The dosing information listed here does not include patients with decompensated cirrhosis (Child‑Pugh B or C) or liver transplant recipients.

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

  • 24 weeks of HARVONI is the recommended treatment duration for GT 1 TE adults with compensated cirrhosis.
  • HARVONI + RBV for 12 weeks can be considered in TE GT 1 adults 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.
HARVONI is IFN- and RBV-free for adult TN and TE patients without cirrhosis or with compensated cirrhosis, regardless of GT 1a or 1b subtype1

  • 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 HARVONI1
  • For patients with HCV/HIV-1 coinfection, follow the dosage recommendations listed above. Refer to the Drug Interactions section of the HARVONI Prescribing Information for dosage recommendations for concomitant HIV-1 antiviral drugs1
  • Relapse rates are affected by baseline host and viral factors and differ between treatment durations for certain subgroups1
  • No dosage adjustments are required based on advanced age, mild or moderate renal impairment, or mild, moderate, or severe hepatic impairment1
  • No dosage recommendations can be given for patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <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 metabolite1
  • Each HARVONI tablet contains 90 mg of ledipasvir and 400 mg of sofosbuvir1

Many of your HCV GT 1 patients may be eligible for an 8-week HARVONI regimen2,a

In an independent chart review, 75% of GT 1 TN non-cirrhotic (NC) adult patients qualified for an 8-week regimen of HARVONI2
Click here to learn more about the 8-week treatment option for HARVONI

These data are 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-March 2017.
References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.
  2. Data on file. IPSOS Healthcare. IPSOS HCV USA, April 2016-March 2017.

IMPORTANT SAFETY INFORMATION (continued)

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.

Reference:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. February 2017.

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 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 & 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 GT 1 subjects receiving 8, 12, or 24 weeks of treatment with HARVONI (ION-1, ION-2, ION-3)1
Adverse events chart [Adverse reactions (all grades) reported in ≥5% of subjects receiving 8, 12, or 24 weeks of HARVONI (ION-1, -3, -2)]

Direct comparison across trials should not be made due to differing trial designs.1

  • Based on pooled data from three Phase 3 clinical trials in GT 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
  • The safety profile in HCV/HIV-1 coinfected subjects was similar to that observed in HCV mono-infected subjects. See the Drug Interactions section of the HARVONI Prescribing Information for potentially significant drug interactions with HIV antiretrovirals1
    • The most common adverse reactions occurring in ≥10% of subjects in ION-4 were headache (20%) and fatigue (17%)1

Discontinuations due to adverse events were 1% or less1

Discontinuations due to adverse events in GT 1 subjects treated with HARVONI (ION-1, ION-2, ION-3)1
Discontinuation rates chart [Discontinuations due to adverse events in GT 1 subjects treated with HARVONI (ION-1, ION-2, ION-3)]

HARVONI is IFN- and RBV-free for GT 1 treatment-naïve and treatment-experienced patients without cirrhosis or with compensated cirrhosis1

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

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

Reference:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. November 2017.

ACCESS AND RESOURCES

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 (continued)

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.

PRESCRIBING INFORMATION

Review the HARVONI full Prescribing Information as a PDF.

This information is intended for US healthcare professionals

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