Version July 2025
Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti–hepatitis B therapy, including adefovir. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who discontinue anti–hepatitis B therapy. If appropriate, resumption of anti–hepatitis B therapy may be warranted.
In patients at risk of or having underlying renal dysfunction, long-term administration of adefovir may result in nephrotoxicity. Closely monitor renal function in these patients; they may require dose adjustment.
HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection treated with anti–hepatitis B therapies that may have activity against HIV (eg, adefovir).
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals.
Chronic hepatitis B: Note: Adefovir is not preferred due to high rate of resistance with long-term use; antivirals with a higher barrier to drug resistance are preferred (Ref).
Children 2 to <7 years: Limited data available: Oral: 0.3 mg/kg/dose once daily; maximum dose: 10 mg/dose (Ref).
Children 7 to <12 years: Limited data available: Oral: 0.25 mg/kg/dose once daily; maximum dose: 10 mg/dose (Ref).
Children ≥12 years and Adolescents: Oral: 10 mg once daily (Ref).
Duration of therapy: Optimal duration of treatment not established; oral antiviral therapy was continued for 1 to 4 years in trials; hepatitis B e antigen (HBeAg) seroconversion has been suggested as a therapeutic end point followed by an additional 12 months of consolidation (Ref).
Children ≥12 years and Adolescents: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling (has not been studied); based on experience in adults, dosage adjustment should be considered.
Children ≥12 years and Adolescents: No dosage adjustments necessary.
(For additional information see "Adefovir: Drug information")
Hepatitis B virus infection, treatment:
Note: Adefovir is not preferred in the management of hepatitis B due to high rate of resistance with long-term use (Ref); other guidelines do not recommend adefovir therapy (Ref). Other antiviral agents with a high barrier to drug resistance are preferred (eg, tenofovir, entecavir) (Ref).
Oral: 10 mg once daily; may be used as part of a combination regimen (avoid concurrent use with tenofovir) (Ref).
Treatment duration: Treatment duration is variable and influenced by hepatitis B e antigen (HBeAg) status, duration of HBV suppression, and presence of cirrhosis/decompensation (Ref):
Patients without cirrhosis:
HBeAg-positive-immune active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged duration of therapy is often required in patients treated with nucleos(t)ide analogues. Optimal duration is unknown; however, consolidation therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion (Ref).
HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is competing rationale for discontinuation (risk/benefit decision); treatment discontinuation may be considered in patients with loss of HBsAg; however, there is insufficient evidence to guide decisions in these patients (Ref).
Patients with cirrhosis:
HBeAg-positive immune-active chronic hepatitis: In patients who seroconvert on therapy, continue antiviral therapy indefinitely due to concerns with decompensation and death, unless there is a strong competing rationale for discontinuation (Ref).
HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data) (Ref).
Viral breakthrough: Patients with confirmed viral breakthrough (HBV DNA ≥100 IU/mL with previously undetectable levels [<10 IU/mL] or >1 log increase in HBV DNA compared to nadir) should either be switched to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or receive a second antiviral agent with a complementary resistance profile; consult current clinical practice guidelines for recommended agents (Ref).
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 49 mL/minute: 10 mg every 48 hours.
CrCl 10 to 29 mL/minute: 10 mg every 72 hours.
CrCl <10 mL/minute (nonhemodyalisis): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Hemodialysis: Dialyzable (~35%): 10 mg every 7 days (following dialysis)
No dosage adjustment necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Gastrointestinal: Dyspepsia (3%)
Renal: Increased serum creatinine (≥0.5 mg/dL: 2% to 3%)
Frequency not defined: Renal: Nephrotoxicity
Postmarketing:
Endocrine & metabolic: Hypophosphatemia (Song 2020), lactic acidosis
Gastrointestinal: Pancreatitis
Hepatic: Severe hepatomegaly with steatosis
Neuromuscular & skeletal: Myopathy, osteomalacia (Song 2020)
Renal: Fanconi syndrome (Song 2020), nephrolithiasis (Lin 2017), proximal tubular nephropathy, renal failure syndrome (Xiang 2020)
Hypersensitivity to adefovir or any component of the formulation.
Disease-related concerns:
• Kidney impairment: Dosage adjustment is required in adult patients with kidney dysfunction or in patients who develop kidney dysfunction during therapy; no data available for use in children ≥12 years of age or adolescents with kidney impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as dipivoxil:
Hepsera: 10 mg [DSC]
Generic: 10 mg
Yes
Tablets (Adefovir Dipivoxil Oral)
10 mg (per each): $37.89
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as dipivoxil:
Hepsera: 10 mg [DSC]
Generic: 10 mg
Oral: May be administered without regard to food.
Oral: Administer without regard to food.
Store controlled room temperature of 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).
Treatment of chronic hepatitis B with evidence of active viral replication and either persistent elevations of ALT or AST or histologically active disease (FDA approved in ages ≥12 years and adults).
Substrate of OAT1/3; Inhibits MRP2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Ataluren: May increase serum concentration of Adefovir. Risk C: Monitor
Atidarsagene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Atidarsagene Autotemcel. Risk X: Avoid
Cabozantinib: MRP2 Inhibitors may increase serum concentration of Cabozantinib. Risk C: Monitor
Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid
Fexinidazole: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider Therapy Modification
Leflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Nitisinone: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Orlistat: May decrease serum concentration of Antiretroviral Agents. Risk C: Monitor
Pivmecillinam: Pivalate-Conjugated Medications may increase adverse/toxic effects of Pivmecillinam. Specifically, the risk for carnitine deficiency may be increased. Management: Use of pivmecillinam with other pivalate-conjugated medications should be avoided due to the risk of carnitine depletion. If use of the combination cannot be avoided, monitor closely for adverse reactions that could be evidence of carnitine depletion. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Tacrolimus (Systemic): Adefovir may increase nephrotoxic effects of Tacrolimus (Systemic). Risk C: Monitor
Taurursodiol: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid
Tenofovir Products: Adefovir may decrease therapeutic effects of Tenofovir Products. Adefovir may increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Adefovir. Risk X: Avoid
Teriflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Vaborbactam: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Vadadustat: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Valproic Acid and Derivatives: Pivalate-Conjugated Medications may increase adverse/toxic effects of Valproic Acid and Derivatives. Specifically, the risk for decreased carnitine concentrations is increased. Risk C: Monitor
Food does not have a significant effect on adefovir absorption. Management: Administer without regard to meals.
Treatment for hepatitis B infection should be evaluated prior to pregnancy. Adefovir is not recommended for use in pregnant patients (AASLD [Terrault 2018]; EASL 2017). Algorithms are available for assessing antiviral prophylaxis and treatment of hepatitis B infection in persons who could become pregnant (WHO 2024).
Outcome data following maternal or paternal use of adefovir during pregnancy are limited (Funk 2021; Gao 2022; Gu 2014; Yang 2022; Yi 2012). Agents other than adefovir are recommended when hepatitis B treatment is needed in pregnant patients. Patients who become pregnant while taking adefovir should be switched to the preferred agent (AASLD [Terrault 2018]; EASL 2017). Algorithms are available for assessing antiviral prophylaxis and treatment of hepatitis B infection in pregnant patients (WHO 2024).
Data collection to monitor pregnancy and infant outcomes following exposure to adefovir is ongoing. Health care providers are encouraged to enroll patients exposed to adefovir during pregnancy in the pregnancy registry (800-258-4263).
HIV status (prior to initiation of therapy); serum creatinine (prior to initiation and during therapy); LFTs for several months following discontinuation of adefovir; HBV DNA (every 3 to 6 months during therapy); HBeAg and anti-HBe; if at risk for renal impairment, also consider serum phosphate, urinalysis (glucose/protein); bone density for individuals at risk for fracture or history of osteopenia (AASLD [Terrault 2016]).
Acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Note: Pharmacokinetic data reported in pediatric patients (12-18 years) similar to reported adult data.
Distribution: 0.35 to 0.39 L/kg
Protein binding: ≤4%
Metabolism: Prodrug; rapidly converted to adefovir (active metabolite) in intestine
Bioavailability: 59%
Half-life elimination: 7.5 hours; prolonged in renal impairment
Time to peak: Median: 1.75 hours (range: 0.58 to 4 hours)
Excretion: Urine (45% as active metabolite within 24 hours); Dialysis: ~35% of dose (10 mg) removed during 4 hours hemodialysis session
Altered kidney function: Cmax and AUC increased in those with moderate or severe renal function impairment or with end-stage renal disease.
