See viral suppression results in lamivudine-resistant chronic hepatitis B patients treated with VIREAD

Prevalence Study 121 Trial Design LAM Resistance Data
Prevalence

Prevalence of LAM Use

Lamivudine (LAM) is used globally

  • Asian and Pacific Islanders (APIs) make up less than 5% of the total population in the United States, but account for more than 50% of Americans living with chronic hepatitis B1
  • In the United States, nearly 70% of APIs were born or have parents born in countries where hepatitis B is common1
In 2012, the countries identified below reported the percentage of chronic hepatitis B patients who used lamivudine ranging from 2% (US) up to 88% (Vietnam)
  • Up to 32% of CHB patients treated with LAM developed resistance after 1 year3
  • Up to 70% of CHB patients receiving LAM developed resistance at 5 years3
Study 121 Trial Design

Study 121 Trial Design

In a randomized, double-blind, 96-week trial, the safety and efficacy of VIREAD (n=141) was compared to an unapproved antiviral regimen (n=139) in subjects with CHB, persistent viremia (HBV DNA ≥1000 IU/mL), and genotypic evidence of LAM resistance. The primary endpoint in Study 121 was defined by HBV DNA <400 copies/mL (69 IU/mL) at Week 96.1,2

LAM-R Trial Design
Baseline characteristics in LAM-resistant adult patients (n=141) with chronic hepatitis b and persistent viremia
LAM Resistance Data

Potent viral suppression at 96 weeks in patients with LAM resistance1,2

LAM-resistant VIREAD patients (Study 121) response rates

In Study 121, no HBV resistance (0%) was detected at 96 weeks in CHB patients with LAM resistance.1,2

Indication and Usage

VIREAD® is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older. The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:

  • The indication in adults is based on data from treatment of subjects who were nucleoside–treatment-naïve and treatment-experienced with documented resistance to lamivudine. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease
  • VIREAD was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease
  • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy

Important Safety Information

Warnings and Precautions

  • New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of VIREAD. In all patients, assess estimated creatinine clearance (CrCl) prior to initiating and during therapy. In patients at risk for renal dysfunction, including those who previously experienced renal events while receiving adefovir dipivoxil, additionally monitor serum phosphorus, urine glucose, and urine protein. In patients with CrCl <50 mL/min, adjust dosing interval and closely monitor renal function. Avoid concurrent or recent use with a nephrotoxic agent. Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after initiation of high dose or multiple NSAIDs in HIV-infected patients with risk factors for renal dysfunction; consider alternatives to NSAIDs in these patients.

Warnings and Precautions (cont’d)

  • New onset or worsening renal impairment (cont’d): Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function
  • Coadministration with other products:
    • Do not use in combination with other products containing tenofovir disoproxil fumarate
    • Do not administer in combination with adefovir dipivoxil
  • Patients coinfected with HIV‑1 and HBV: Due to the risk of development of HIV‑1 resistance, VIREAD should only be used in HIV‑1 and HBV coinfected patients as part of an appropriate antiretroviral combination regimen. HIV‑1 antibody testing should be offered to all HBV-infected patients before initiating therapy with VIREAD
  • Bone effects: Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia, have been seen in patients treated with VIREAD. Consider assessment of BMD in adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for bone loss. In a clinical trial conducted in pediatric subjects 12 to <18 years of age with chronic hepatitis B, total body BMD gain was less in VIREAD-treated subjects as compared to the control group. In patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms, hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered

Indication and Usage

VIREAD® (tenofovir disoproxil fumarate) is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.

The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:

  • The indication in adults is based on data from treatment of subjects who were nucleoside–treatment-naÏve and treatment-experienced with documented resistance to lamivudine. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease
  • VIREAD was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease
  • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy

Important Safety Information

TAP for Important Safety Information, including Boxed Warning on lactic acidosis, severe hepatomegaly with steatosis and post treatment exacerbation of hepatitis.

BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS

  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including VIREAD, in combination with other antiretrovirals
  • Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including VIREAD. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VIREAD. If appropriate, resumption of anti-hepatitis B therapy may be warranted

Warnings and Precautions

  • New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of VIREAD. In all patients, assess estimated creatinine clearance (CrCl) prior to initiating and during therapy. In patients at risk for renal dysfunction, including those who previously experienced renal events while receiving adefovir dipivoxil, additionally monitor serum phosphorus, urine glucose, and urine protein. In patients with CrCl <50 mL/min, adjust dosing interval and closely monitor renal function. Avoid concurrent or recent use with a nephrotoxic agent. Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after initiation of high dose or multiple NSAIDs in HIV-infected patients with risk factors for renal dysfunction; consider alternatives to NSAIDs in these patients. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function
  • Coadministration with other products:
    • Do not use in combination with other products containing tenofovir disoproxil fumarate
    • Do not administer in combination with adefovir dipivoxil
  • Patients coinfected with HIV‑1 and HBV: Due to the risk of development of HIV‑1 resistance, VIREAD should only be used in HIV‑1 and HBV coinfected patients as part of an appropriate antiretroviral combination regimen. HIV‑1 antibody testing should be offered to all HBV-infected patients before initiating therapy with VIREAD
  • Bone effects: Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia, have been seen in patients treated with VIREAD. Consider assessment of BMD in adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for bone loss. In a clinical trial conducted in pediatric subjects 12 to <18 years of age with chronic hepatitis B, total body BMD gain was less in VIREAD-treated subjects as compared to the control group. In patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms, hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered

Adverse Reactions

  • In HBV-infected subjects with compensated liver disease: Most common adverse reaction (all grades) was nausea (9%). Other treatment-emergent adverse reactions reported in >5% of patients treated with VIREAD included: abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain, and skin rash
  • In HBV-infected subjects with decompensated liver disease: Most common adverse reactions (all grades) reported in ≥10% of patients treated with VIREAD were abdominal pain (22%), nausea (20%), insomnia (18%), pruritus (16%), vomiting (13%), dizziness (13%), and pyrexia (11%)

Drug Interactions

  • Didanosine: Coadministration increases didanosine concentrations. Use with caution and monitor for evidence of didanosine toxicity (e.g., pancreatitis, neuropathy). Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. In patients weighing >60 kg, the didanosine dose should be reduced to 250 mg once daily when it is coadministered with VIREAD and in patients weighing <60 kg, the didanosine dose should be reduced to 200 mg once daily when coadministered with VIREAD
  • HIV‑1 protease inhibitors: Coadministration decreases atazanavir concentrations and increases tenofovir concentrations; use atazanavir given with ritonavir. Coadministration of VIREAD with atazanavir and ritonavir, darunavir and ritonavir, or lopinavir/ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity
  • Hepatitis C antivirals: Coadministration of VIREAD with HARVONI increases VIREAD exposure; monitor for adverse reactions associated with VIREAD. Consider an alternative HCV or HIV‑1 therapy in patients receiving VIREAD concomitantly with HARVONI and an HIV‑1 protease inhibitor with ritonavir or cobicistat
  • Drugs affecting renal function: Coadministration of VIREAD with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir

Dosage and Administration

  • Recommended dose, in adults and pediatric patients ≥12 years of age (≥35 kg), for the treatment of chronic hepatitis B: one 300 mg tablet, once daily, taken orally, without regard to food
  • In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown
  • Safety and efficacy in pediatric patients <12 years of age or weighing <35 kg with chronic hepatitis B have not been established
  • The dosing interval of VIREAD should be adjusted (using recommendations in the table below) and renal function closely monitored in patients with baseline creatinine clearance <50 mL/min

Dosage Adjustment for Patients with Altered Creatinine Clearance

Dosage Table

aCalculated using ideal (lean) body weight.

bGenerally once weekly assuming three hemodialysis sessions a week of approximately 4 hours duration. VIREAD should be administered following completion of dialysis.

  • The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance <10 mL/min; therefore, no dosing recommendation is available for these patients
  • No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50-80 mL/min). Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in these patients
  • No data are available to make dose recommendations in pediatric patients with renal impairment

Indication and Usage

VIREAD® (tenofovir disoproxil fumarate) is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.

The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:

  • The indication in adults is based on data from treatment of subjects who were nucleoside–treatment-naÏve and treatment-experienced with documented resistance to lamivudine. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease
  • VIREAD was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease
  • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy
Please click here to see full Prescribing Information, including BOXED WARNING.

References: 1. Viral Hepatitis—CDC recommendations for specific populations and settings. Asian and Pacific Islanders. http://www.cdc.gov/hepatitis/Populations/api.htm. Accessed February 2, 2016. 2. Data on file, Gilead Sciences, Inc. Gilead HBV LAM assessment, IMS MIDAS data. May 2013. 3. Lok A, McMahon B. Corrections to AASLD guidelines on chronic hepatitis B. Hepatology. 2009;50(3):661-662.

References: 1. VIREAD Prescribing Information, Foster City, CA: Gilead Sciences, Inc.; February 2016. 2. Fung S, Kwan P, Fabri M, et al. Randomized comparison of tenofovir disoproxil fumarate vs emtricitibine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology. 2014;146(4):980-988.

References: 1. VIREAD Prescribing Information, Foster City, CA: Gilead Sciences, Inc.; February 2016. 2. Fung S, Kwan P, Fabri M, et al. Randomized comparison of tenofovir disoproxil fumarate vs emtricitibine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology. 2014;146(4):980-988.

This information is intended for US healthcare professionals

You are now leaving this website.

Gilead Sciences, Inc., provides these links as a convenience; however, Gilead does not control, review, or endorse third-party Websites, and it is not responsible for the content of the Website you are about to enter.