OVERVIEW

 

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

97% icon [97% overall cure rate (SVR12) in GT 1 subjects across three HARVONI Phase 3 trials (n=1042/1079; ION-1, -2, -3)]
  • The HARVONI clinical trial program enrolled the most challenging subjects, regardless of GT 1a or 1b subtype, prior experience with HCV therapy, or presence of compensated cirrhosis1

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

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

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

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

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

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

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

HARVONI is an established 8-week option that can be considered for eligible 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]
  • The dosing information listed here does not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients
  • 97% (n=119/123) overall cure rate among TN GT 1 subjects without cirrhosis who had baseline HCV RNA <6 million IU/mL and who received HARVONI for 8 weeks1
  • Many patients may qualify for an 8-week HARVONI regimen
    • In the ION-3 clinical trial, 59% of subjects taking HARVONI had baseline HCV RNA <6 million IU/mL1
    • In an independent chart review, more than half (56%) of GT 1 patients (n=3428) were TN without cirrhosis and had baseline HCV RNA <6 million IU/mL6,b
These data are derived from a study conducted by IPSOS. The study consisted of over 2100 patient chart reviews per quarter by approximately 150 HCV-treating physicians from January-December 2016.

IMPORTANT SAFETY INFORMATION

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

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

Contraindications

  • If HARVONI is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.
#1 icon [HARVONI is the #1 prescribed HCV treatment for GT 1 patients in the US]
  • HARVONI has been prescribed to more than 350,000 patients8,d
IMS Weekly NPA™ Market Dynamics™ from week-ending 11/14/14–10/1/16.
This information is derived from IMS NPA, IMS NSP™, and IntegriChain® data; data reflect estimated patient starts for HARVONI from October 2014–September 2016.

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

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

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

No baseline resistance testing is required with HARVONI1

  • HARVONI is RBV-free for the majority of TN and TE patients without cirrhosis or with compensated cirrhosis, regardless of GT 1a or 1b subtype1
  • In patients without 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. February 2017.
  2. Afdhal N, Zeuzem S, Kwo P, et al; for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898.
  3. Kowdley KV, Gordon SC, Reddy KR, et al; for the ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888.
  4. Afdhal N, Reddy KR, Nelson DR, et al; for the ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.
  5. US Department of Health and Human Services, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.
  6. Data on file. IPSOS Healthcare. IPSOS HCV USA, January-December 2016.
  7. Data on file. IMS Weekly National Prescription Audit (NPA) Market Dynamics, 11/14/14–10/1/16. Gilead Sciences, Inc.
  8. Data on file. HARVONI Patient Starts from October 2014–September 2016. Gilead Sciences, Inc.

IMPORTANT SAFETY INFORMATION

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

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

Contraindications

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

Warnings and Precautions

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

Adverse Reactions

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

Drug Interactions

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

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

References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. February 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, 11/14/14–10/1/16. 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 (SVR12) 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 with or without ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection.

HARVONI delivered high cure (SVR12) 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 with or without ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection.

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

HARVONI delivered high cure (SVR12) rates in treatment-naïve and treatment-experienced subjects with HCV/HIV-1 co-infection1,a

% SVR12 in HCV GT 1 or 4 subjects with HCV/HIV-1 co‑infection 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 co-infected 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 co-infection, 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. February 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

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

Adverse Reactions

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

Drug Interactions

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

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

References:
  1. HARVONI US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. February 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 with or without ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection.

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

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

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

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. February 2017.
  2. Afdhal N, Zeuzem S, Kwo P, et al; for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(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

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

Adverse Reactions

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

Drug Interactions

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

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

REAL-WORLD DATA

INDICATION

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

The HCV-TARGET study was supported by Gilead Sciences, Inc. Real-world experience data were derived from patient medical records. Such data are longitudinal and observational in nature, and are not based on controlled clinical studies. Results from this cohort may differ from results seen in clinical practice.

HARVONI real-world results support clinical trial data1,2

In clinical trials and HCV-TARGET, HARVONI delivered high cure (SVR12) rates in a broad range of GT 1 subjects1,2
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.

In the HCV-TARGET study, HARVONI delivered high cure rates in the most challenging of patients regardless of GT 1a or 1b subtype, prior experience with HCV therapy, or presence of compensated cirrhosis1
  • In the HCV-TARGET study, HARVONI was safe with low rates of discontinuations and AEs1
    • The overall discontinuation rate was 3% (n=63/2019)1
    • The most common AEs were fatigue and headache1
 

HARVONI Study Designs: randomized, open-label trials in GT 1 subjects2

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

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

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

These studies did not include patients with decompensated cirrhosis (Child-Pugh B or C) or liver transplant recipients. SVR12 was the primary endpoint and was defined as HCV RNA <25 IU/mL at 12 weeks after the end of treatment.2 Achieving SVR is considered a virologic cure.6

 

HCV-TARGET Study Design1:

The HCV-TARGET study evaluated the safety and efficacy of 8, 12, or 24 weeks of HARVONI in real-world GT 1 patients in academic or community settings. HCV-TARGET included GT 1 TN and TE patients without cirrhosis or with compensated cirrhosis (N=2099). SVR12 rates in HCV-TARGET excluded patients lost to follow-up. The HARVONI regimen was selected and administered at clinician's discretion according to local standards of care.

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

INDICATION

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

The HCV-TARGET study was supported by Gilead Sciences, Inc. Real-world experience data were derived from patient medical records. Such data are longitudinal and observational in nature, and are not based on controlled clinical studies. Results from this cohort may differ from results seen in clinical practice.

Real-world results support clinical trial use of HARVONI in a broad range of GT 1 patients1

Real-world use of HARVONI has been observed in a large retrospective study that included more than 2000 GT 1 treatment-naïve and treatment-experienced patients without cirrhosis or with compensated cirrhosis1
% SVR12 in GT 1 patients1-5
GT 1 chart

Click to see HARVONI clinical study designs, dosage and administration, and safety information.

The HCV-TARGET study evaluated the safety and efficacy of 8, 12, or 24 weeks of HARVONI in real-world GT 1 patients in academic or community settings. HCV-TARGET included GT 1 TN and TE patients without cirrhosis or with compensated cirrhosis (N=2099). SVR12 rates in HCV-TARGET excluded patients lost to follow-up. The HARVONI regimen was selected and administered at clinician's discretion according to local standards of care.1

C = cirrhotic (compensated [Child-Pugh A] or decompensated), NC = non-cirrhotic, TE = treatment-experienced, TN = treatment-naïve

  • HCV-TARGET results support clinical trial data for use of HARVONI in the majority of GT 1 patients for 8, 12, or 24 weeks1,2
    • HARVONI for 8 weeks can be considered in GT 1 adult treatment-naïve patients without cirrhosis with pre-treatment HCV RNA <6 million IU/mL2

AEs in the HCV-TARGET study were similar to those observed in the HARVONI Phase 3 trials1,2

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. February 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.

IMPORTANT SAFETY INFORMATION

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

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

Contraindications

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

Warnings and Precautions

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect of HARVONI Due to P-gp Inducers:
    Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended:
    HARVONI is not recommended for use with other products containing sofosbuvir.
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. February 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 with or without ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, 5, or 6 infection.

HARVONI is a once-daily single-tablet regimen for the majority of HCV GT 1, 4, 5, or 6 patients built on a sofosbuvir backbone1

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.

aHARVONI + RBV for 12 weeks can be considered in TE 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 information.

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

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

IMPORTANT SAFETY INFORMATION (continued)

Adverse Reactions

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

Drug Interactions

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

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

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

  • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:
    Amiodarone is not recommended for use with HARVONI due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

To learn more about counseling and the cardiac monitoring of patients, as well as the signs and symptoms of bradycardia, click here.

  • Risk of Reduced Therapeutic Effect Due to P-gp Inducers: Rifampin and St. John's wort are not recommended for use with HARVONI as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
  • Related Products Not Recommended: HARVONI is not recommended for use with other products containing sofosbuvir.

HARVONI demonstrated tolerability with low discontinuation rates and does not require IFN or RBV1

Adverse reactions (all grades) reported in ≥5% of subjects receiving 8, 12, or 24 weeks of treatment with HARVONI (ION-1, -3, -2)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 with compensated liver disease 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 co-infected 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 for HARVONI were 1% or less1

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

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

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, rifampin,b rifapentine

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

Herbal Supplements

St. John's wort

Expected to 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

   

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

pravastatin

   

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

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

Concomitant
Drug Class
and Drug Names

No Clinically
Significant

Interaction

Clinical Considerations

Immunosuppressants

cyclosporine, tacrolimus

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

Opioids

methadone

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

Oral Contraceptives

oral contraceptives

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

Calcium Channel Blockers

verapamil

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

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

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

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, rifampin,b rifapentine - Antimycobacterials

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

St. John's wort - Herbal Supplements

Expected to 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

Coadministration 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.

No Clinically Significant Interaction

pravastatin - Statins

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

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

No Clinically Significant Interaction

cyclosporine, tacrolimus - Immunosuppressants

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

methadone - Opioids

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

oral contraceptives - Oral Contraceptives

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

verapamil - Calcium Channel Blockers

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

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

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

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

ACCESS AND RESOURCES

Support Path can help your patients start HARVONI and move toward treatment completion

Support Path: Getting Started icons [Support Path: Getting Started]

Help your commercially insured patients lower their out-of-pocket costs

With the HARVONI co-pay coupon, an eligible patient's co-pay may be no more than $5 per fill.

Co-pay icon and $5 icon [With the HARVONI co-pay coupon, an eligible patient's co-pay may be no more than $5 per fill.]

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

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

Help along the way

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

  • Ongoing support for access and reimbursement, including help with refill authorization

Enroll


Resources to help you in the treatment of patients with HCV

Centers for Disease Control and Prevention: Hepatitis C information for health professionals

US Preventive Services Task Force: Screening for hepatitis C virus infection in adults

American College of Gastroenterology: Hepatitis C treatment resources

AASLD/IDSA HCV Guidelines

IMPORTANT SAFETY INFORMATION (continued)

Adverse Reactions

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

Drug Interactions

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

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

PRESCRIBING INFORMATION

Review the HARVONI full Prescribing Information as a PDF.

This information is intended for US healthcare professionals

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