Adefovir For Hepatitis B: Complete Guide And Key Facts
Comprehensive guide to Adefovir (Hepsera): uses, dosage, side effects, and management of chronic hepatitis B virus infection.
Adefovir dipivoxil (brand name: Hepsera) is a medication specifically designed to treat chronic hepatitis B virus (HBV) infection. It belongs to a class of drugs known as nucleotide analogues, which work by inhibiting the HBV DNA polymerase enzyme, thereby preventing viral replication.
About adefovir tablets
Adefovir dipivoxil is an oral prodrug that is converted in the body to its active form, adefovir diphosphate. This active metabolite competes with the natural substrate deoxyadenosine triphosphate and causes DNA chain termination after incorporation into viral DNA, effectively halting HBV replication.
Hepsera tablets are typically supplied as 10 mg oral tablets taken once daily. The medication was first approved by the U.S. Food and Drug Administration (FDA) in September 2002 as the first nucleotide analogue for chronic hepatitis B treatment. It is indicated for patients with evidence of active viral replication and either elevated serum aminotransferases (ALT or AST) or histologically active disease.
The FDA label extends its use to patients 12 years of age and older, based on virological, biochemical, histological, and serological responses observed in clinical trials. Unlike some antivirals, adefovir demonstrates efficacy against both HBeAg-positive and HBeAg-negative chronic HBV, as well as lamivudine-resistant strains.
Key facts about adefovir
- Dosage form: 10 mg oral tablet, taken once daily without regard to meals.
- Approved for: Chronic HBV in adults and adolescents ≥12 years with compensated liver function; also lamivudine-resistant HBV with compensated or decompensated liver function.
- Mechanism: Nucleotide analogue reverse transcriptase inhibitor specific to HBV DNA polymerase.
- Resistance profile: Low resistance emergence in initial 48-96 weeks; effective against lamivudine-resistant HBV.
- Monitoring required: Renal function (serum creatinine, CrCl), liver enzymes, HBV DNA levels, and HIV status.
- Duration: Long-term therapy often required; exact duration unknown and depends on response.
About chronic hepatitis B
Chronic hepatitis B is a liver infection caused by the hepatitis B virus (HBV) that persists for more than six months. Globally, it affects over 250 million people and can lead to cirrhosis, liver failure, or hepatocellular carcinoma if untreated. HBV is transmitted via blood, semen, or other body fluids, often perinatally or through contaminated needles.
Key markers include HBeAg status: HBeAg-positive indicates high viral replication and infectivity; HBeAg-negative (precore mutant) often shows fluctuating ALT but persistent viremia. Active disease is confirmed by elevated ALT/AST, high HBV DNA, and liver biopsy showing inflammation or fibrosis.
Treatment goals: Suppress viral replication, normalize ALT, achieve histological improvement, and promote HBeAg seroconversion (loss of HBeAg with anti-HBe appearance). Nucleotide/nucleoside analogues like adefovir provide sustained suppression but rarely cure due to cccDNA persistence in hepatocytes.
How adefovir works in hepatitis B
Adefovir dipivoxil is rapidly absorbed and hydrolyzed by esterases to adefovir, then phosphorylated by cellular kinases to adefovir diphosphate. This diphosphate form selectively inhibits HBV DNA polymerase (by competition with dATP) and reverse transcriptase, causing premature chain termination.
Its broad activity covers wild-type HBV, lamivudine-resistant mutants (rtM204V/I ± rtL180M), and both HBeAg+ and HBeAg- strains. Unlike nucleoside analogues, nucleotide prodrugs like adefovir require fewer phosphorylation steps, providing potent activity at low concentrations.
How and when to take adefovir
The recommended dose is one 10 mg tablet once daily, swallowed whole with water, with or without food. No dose adjustment for mild hepatic impairment, but renal dosing is required:
| Creatinine Clearance (mL/min) | Dose |
|---|---|
| ≥50 | 10 mg once daily |
| 30–49 | 10 mg every 48 hours |
| 10–29 | 10 mg every 72 hours |
| Hemodialysis | 10 mg every 7 days post-dialysis |
Miss a dose? Take as soon as remembered unless near next dose; do not double. Store at room temperature. Discontinue if no virologic response after 48 weeks or upon HBeAg seroconversion with undetectable HBV DNA.
Dosage for adefovir
Adults (≥18 years): 10 mg orally once daily.
Adolescents (12–<18 years): 10 mg once daily, based on virological suppression data (mean HBV DNA reduction 3.1 log10 copies/mL at week 48).
No pediatric data under 12 years. Adjust for renal impairment as above; monitor CrCl every 3 months. Avoid in severe renal failure (CrCl <10 mL/min) without adjustment.
Getting the most benefit from adefovir
- Adhere strictly to daily dosing to prevent resistance.
- Monitor HBV DNA, ALT, and renal function regularly (q3 months).
- Test for HIV before and during therapy; adefovir may select HIV resistance if untreated.
- Combine with lamivudine in naive patients to delay resistance, though monotherapy effective.
- Lifestyle: Avoid alcohol, maintain healthy weight, vaccinate contacts against HBV.
Side-effects of adefovir
Adefovir 10 mg/day is generally well-tolerated, with adverse events similar to placebo in 48-week trials. Common (>1%): asthenia, headache, abdominal pain, nausea, flatulence, rash.
Serious risks:
- Nephrotoxicity: Proximal tubulopathy, Fanconi syndrome, creatinine increase ≥0.5 mg/dL (2–8% over 96 weeks). Risk factors: baseline renal impairment, elderly, co-meds. Monitor CrCl; discontinue if confirmed rise.
- Lactic acidosis/Hepatic steatosis: Rare, but discontinue if suspected.
- Exacerbation of HBV: Upon discontinuation, ALT flares in up to 30%; monitor 6 months post-stop.
- HIV superinfection: Masked progression if undiagnosed.
No HBV resistance in initial trials; low rtN236T emergence long-term.
Who can and cannot take adefovir tablets
Can take: Adults/adolescents ≥12 years with compensated chronic HBV (HBeAg+/-), lamivudine-resistant HBV (compensated/decompensated).
Cannot take/Avoid:
- Hypersensitivity to adefovir.
- CrCl <10 mL/min without dialysis adjustment.
- Pregnancy/lactation (Category C; limited data, use if benefit outweighs risk).
- Decompensated cirrhosis without lamivudine resistance (limited data).
Pregnancy and breastfeeding with adefovir
Limited human data; animal studies show no teratogenicity. Register in Antiretroviral Pregnancy Registry. HBV perinatal transmission risk high; treat mothers if active disease. Unknown if excreted in breast milk; caution advised.
Common questions about adefovir
Frequently Asked Questions (FAQs)
How effective is adefovir for chronic hepatitis B?
In pivotal trials, 10 mg/day led to undetectable HBV DNA (21–51%), ALT normalization (48–72%), histological improvement (53–64%), and HBeAg seroconversion (12–29%) at 48 weeks—superior to placebo.
Does adefovir cure hepatitis B?
No, it suppresses replication but does not eradicate cccDNA; lifelong therapy often needed. HBeAg seroconversion allows possible discontinuation.
Is adefovir better than lamivudine?
Similar efficacy in naive patients, but adefovir superior for lamivudine-resistant HBV and no resistance emergence in 48 weeks. Combo delays resistance.
What are the main side effects to watch for?
Renal toxicity (monitor creatinine); discontinue if CrCl falls 20% from baseline. Also lactic acidosis, HBV flares on discontinuation.
How long do I take adefovir?
Indefinitely until seroconversion or switch; monitor response at 48 weeks.
Can children take adefovir?
Yes, approved ≥12 years based on viral suppression (not histology).
References
- Adefovir dipivoxil: a review of its use in chronic hepatitis B — PubMed/Drugs. 2002. https://pubmed.ncbi.nlm.nih.gov/14498759/
- Adefovir (Hepsera) for Chronic Hepatitis B Infection — American Academy of Family Physicians (AAFP). 2003-12-15. https://www.aafp.org/pubs/afp/issues/2003/1215/p2429.html
- Hepsera (adefovir dipivoxil) Pharmacy Policy — Federal Employee Program (FEPBlue). 2024-06. https://www.fepblue.org/-/media/PDFs/Medical-Policies/2024/June/June-2024-Pharmacy-Policies/Remove–Replace/501057-Hepsera-adefovir.pdf
- FDA Approves Gilead’s Hepsera(TM) for the Treatment of Chronic Hepatitis B — Gilead Sciences. 2002-09-23. https://www.gilead.com/news/news-details/2002/fda-approves-gileads-hepseratm-for-the-treatment-of-chronic-hepatitis-b
- HEPSERA® (adefovir dipivoxil) Tablets Prescribing Information — U.S. FDA. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021449s024lbl.pdf
- Adefovir dipivoxil: Uses, Interactions, Mechanism of Action — DrugBank. Accessed 2026. https://go.drugbank.com/drugs/DB00718
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