|
Frequently Asked Questions for healthcare professionals about Hepsera® (adefovir dipivoxil)
What is the indication for Hepsera?
What is the dosing for Hepsera?
What are the efficacy data for Hepsera?
What were the most common side effects for Hepsera in clinical trials?
How many patients have participated in clinical trials for Hepsera?
Has Hepsera been associated with drug resistance?
Are there any significant drug interactions associated with Hepsera?
Is Hepsera safe for use in children?
Where can I learn more about Hepsera?
Q: What is the indication for Hepsera?
A: Hepsera is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.1
This indication is based on histological, virological, biochemical and serological responses in adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver function, and in adult patients with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function.1
 Back to top
Q: What is the dosing for Hepsera?
A: The recommended dose of Hepsera in chronic hepatitis B patients with adequate renal function is one 10 mg tablet taken once daily, without regard to food. The optimal duration of treatment is unknown. Dose interval adjustments should be made for patients with renal impairment using the suggested guidelines in the table below.1
Back to top
Q: What are the efficacy data for Hepsera?
A: The efficacy and safety of Hepsera were evaluated in two large, randomized, double-blind, placebo-controlled clinical trials of adult patients with chronic hepatitis B. In both studies, patients received Hepsera or placebo once a day for 48 weeks, with therapy extended for a second 48-week treatment period. Study results demonstrated efficacy of Hepsera in all patient types and stages of disease.1 Click here to learn more about the efficacy data for Hepsera.
Back to top
Q: What were the most common side effects for Hepsera in clinical trials?
A: The most common treatment-related adverse events occurred at rates similar to placebo. These included asthenia, headache, abdominal pain, nausea, flatulence, diarrhea and dyspepsia. Adverse events in patients receiving Hepsera beyond week 48 in Study 438 were similar in nature and severity to those reported through week 48. With increased Hepsera exposure, the incidence of adverse events related to treatment increased only slightly.1
Back to top
Q: How many patients have participated in clinical trials for Hepsera?
A: To date, nearly 1,100 people have received Hepsera in clinical trials.1
Back to top
Q: Has Hepsera been associated with drug resistance?
A: Clinical isolates with genotypic changes conferring reduced susceptibility in cell culture to nucleoside analog inhibitors for the treatment of HBV infection have been observed. Genotyping was performed for resistance surveillance annually or on the last available sample on treatment from all adefovir dipivoxil-treated patients with detectable serum HBV DNA. These analyses determined that amino acid substitutions rtN236T and rtA181 T/V have been observed in association with adefovir resistance. In cell culture, the rtN236T mutation demonstrated 4- to 14-fold, the rtA181V mutation 2.5- to 3-fold, and the rtA181T mutation 1.3- to 1.9-fold reduced susceptibility to adefovir.
In HBeAg-positive nucleoside-naïve patients, no adefovir resistance-associated mutations were observed at week 48. Sixty-five patients continued on long-term treatment after a median duration on adefovir dipivoxil of 235 weeks (range 110–279 weeks). Sixteen of 38 (42%) patients were identified with adefovir resistance-associated mutations in the setting of virologic failure. (Study 437)
In HBeAg-negative nucleoside naive patients, thirty patients were identified with adefovir resistance-associated mutations with a cumulative probability of 0%, 3%, 11%, 19%, and 30% at 48, 96, 144, 192, and 240 weeks, respectively. Of those 30 patients, 22 had a confirmed increase of ≥1 log10 HBV DNA copies/mL above nadir or never achieved HBV DNA levels below 103 copies/mL; an additional 8 patients had an adefovir resistance-associated mutation without virologic failure. (Study 438)
In an open-label study of pre- and post-liver transplantation patients, 129 patients with clinical evidence of lamivudine-resistant hepatitis B virus at baseline were evaluated for adefovir resistance-associated mutations. The incidence of adefovir resistance-associated mutations was 0% at 48 weeks. Four patients developed the rtN236T mutation after 72 weeks of adefovir dipivoxil therapy. Development of the rtN236T mutation was associated with serum HBV DNA rebound. (Study 435)
In a study of 35 HIV/HBV co-infected patients with lamivudine-resistant HBV who added adefovir dipivoxil to lamivudine, no adefovir resistance-associated mutations were observed in HBV isolates from 15/35 patients tested up to 144 weeks of therapy. (Study 460i)
Back to top
Q: Are there any significant drug interactions associated with Hepsera?
A: No significant drug interactions have been observed with Hepsera. Hepsera has been evaluated in healthy volunteers in combination with lamivudine, trimethoprim/sulfamethoxazole, acetominophen, tenofovir disoproxil fumarate or ibuprofen. Hepsera was not found to alter the pharmacokinetics of any of these agents.1
Back to top
Q: Is Hepsera safe for use in children?
A: The safety and effectiveness of Hepsera in pediatric patients have not been established.1
Back to top
Q: Where can I learn more about Hepsera?
A: To find out more about Hepsera, you can
a) review the content of www.Hepsera.com, b) read the full Prescribing Information, or c)
contact Gilead to speak with the clinical information department or set up a meeting with a Gilead Representative.
Back to top
Click here for full Prescribing Information.
|