Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ADEFOVIR DIPIVOXIL vs ACYCLOVIR SODIUM
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Adefovir dipivoxil is a prodrug of adefovir, an acyclic nucleotide analog of adenosine monophosphate. It is phosphorylated intracellularly to adefovir diphosphate, which inhibits hepatitis B virus (HBV) DNA polymerase by competing with the natural substrate deoxyadenosine triphosphate and causing DNA chain termination after incorporation into viral DNA.
Acyclovir is a synthetic nucleoside analogue with activity against herpes simplex virus (HSV) types 1 and 2, and varicella-zoster virus (VZV). It is converted to acyclovir monophosphate by viral thymidine kinase, then further phosphorylated to acyclovir triphosphate, which competitively inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination.
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.,Treatment of chronic hepatitis B in pediatric patients aged 12 years and older.
Treatment of initial and recurrent genital herpes in immunocompetent patients,Treatment of herpes simplex encephalitis,Treatment of neonatal herpes simplex virus infection,Treatment of varicella-zoster (shingles) in immunocompetent and immunocompromised patients,Treatment of mucocutaneous herpes simplex in immunocompromised patients,Prophylaxis of herpes simplex in immunocompromised patients (off-label)
10 mg orally once daily on an empty stomach.
Dosing is indication-specific. For herpes simplex encephalitis: 10 mg/kg IV every 8 hours for 10–14 days (adults and children ≥12 years) or 20 mg/kg IV every 8 hours (3 months–12 years). For severe genital herpes: 5 mg/kg IV every 8 hours for 5 days. For mucocutaneous HSV in immunocompromised: 5 mg/kg IV every 8 hours for 7–14 days. For varicella zoster in immunocompromised: 10 mg/kg IV every 8 hours for 7 days. For neonatal HSV: 20 mg/kg IV every 8 hours for 14–21 days (disseminated/CNS) or 14 days (skin/eyes/mouth).
Terminal elimination half-life is 7.5 hours (range 5–10 h); clinically, supports once-daily dosing with dose adjustment for renal impairment.
Terminal elimination half-life: 2.5-3.3 hours in adults with normal renal function; up to 20 hours in anuria/end-stage renal disease.
Adefovir dipivoxil is rapidly converted to adefovir by esterases. Adefovir is not significantly metabolized; it is eliminated renally by a combination of glomerular filtration and active tubular secretion. No CYP450-mediated metabolism.
Acyclovir is primarily excreted unchanged in the urine via glomerular filtration and tubular secretion. Hepatic metabolism is minimal, with less than 15% metabolized to 9-carboxymethoxymethylguanine via alcohol dehydrogenase and aldehyde dehydrogenase.
Renal (90% as unchanged drug via active tubular secretion); biliary/fecal (<5%)
Primarily renal excretion via glomerular filtration and tubular secretion: 62-91% of dose excreted unchanged in urine within 24 hours; minor biliary/fecal elimination (<2%).
≤4% (low binding; negligible affinity for serum proteins)
9-33% bound primarily to albumin.
0.4 L/kg (392 L in adults); indicates extensive tissue distribution (including liver).
0.6-1.0 L/kg; approximates total body water, indicating wide distribution including into vesicles and CSF (CSF concentrations ~50% of plasma).
Oral: 59% (range 40–70%); prodrug adefovir dipivoxil is rapidly converted to adefovir.
Oral: 10-20% (dose-dependent, saturable absorption); topical: negligible systemic absorption.
Cr Cl ≥50 m L/min: 10 mg every 24 hours; Cr Cl 30-49 m L/min: 10 mg every 48 hours; Cr Cl 10-29 m L/min: 10 mg every 72 hours; Hemodialysis: 10 mg every 7 days after dialysis.
Adjust dosing interval based on creatinine clearance (Cr Cl): Cr Cl >50 m L/min: standard dose every 8 hours. Cr Cl 25–50 m L/min: standard dose every 12 hours. Cr Cl 10–25 m L/min: standard dose every 24 hours. Cr Cl 0–10 m L/min: reduce dose by 50% and administer every 24 hours. Hemodialysis: administer after dialysis; typically 50% of standard dose every 24 hours, with a supplemental dose post-dialysis.
No adjustment required for mild-moderate hepatic impairment (Child-Pugh A or B). Not studied in severe (Child-Pugh C).
No dosage adjustment required in isolated hepatic impairment; caution if concomitant renal dysfunction.
Approved for age ≥12 years: 10 mg orally once daily. For age <12 years, use is not established.
Indicated in neonates and children. Neonates: 20 mg/kg/dose IV every 8 hours. Infants >3 months: 10–20 mg/kg/dose every 8 hours based on indication. For HSV encephalitis: children 3 months–12 years: 20 mg/kg/dose every 8 hours; ≥12 years: 10 mg/kg/dose every 8 hours. Doses are based on ideal body weight in obese patients.
Monitor renal function; adjust dose based on Cr Cl. No specific dose adjustment solely for age.
No age-specific dose adjustment; dose adjustments are based on renal function, which is often reduced in the elderly. Monitor renal function closely and consider risk of neurotoxic side effects.
WARNING: SEVERE ACUTE EXACERBATION OF HEPATITIS B, NEPHROTOXICITY, HIV RESISTANCE, and LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS. See full prescribing information for complete boxed warning.
None.
Severe acute exacerbation of hepatitis B upon discontinuation of therapy,Nephrotoxicity: monitor renal function, especially in patients at risk or with pre-existing renal impairment,HIV resistance: test for HIV before initiation in patients with unknown HIV status,Lactic acidosis and severe hepatomegaly with steatosis,Use with caution in elderly, renal impairment, or concomitant nephrotoxic agents
Renal impairment: Dose adjustment required in patients with decreased renal function.,Neurotoxicity: May cause tremors, seizures, hallucinations, or confusion, particularly in elderly patients or those with renal impairment.,Hydration: Ensure adequate hydration during administration to prevent renal tubule crystallization.,Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) reported in immunocompromised patients.,Do not administer by intramuscular or subcutaneous injection due to tissue irritation.
Hypersensitivity to adefovir dipivoxil or any component of the formulation
Hypersensitivity to acyclovir or valacyclovir
No clinically significant food interactions; can be taken with or without food. Avoid high-fat meals if gastrointestinal intolerance occurs.
No significant food interactions. Maintain adequate fluid intake to prevent renal precipitation.
Adefovir dipivoxil is an FDA Pregnancy Category C drug. Animal studies have shown teratogenicity (malformations, embryo-fetal toxicity) at doses 23 times the human therapeutic dose. There are no adequate and well-controlled studies in pregnant women. In first trimester, risk cannot be excluded; use only if benefit outweighs risk. In second and third trimesters, potential for fetal harm exists; consider alternative therapy.
Pregnancy Category B. No evidence of teratogenicity in humans; fetal risks not established in first trimester. Use during pregnancy only if clearly needed.
It is unknown whether adefovir is excreted in human breast milk. Animal studies indicate it is present in rat milk. The M/P ratio is not established. Given the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy or for 2 weeks after last dose.
Acyclovir is excreted in breast milk; M/P ratio 0.6-4.1. Typically compatible with breastfeeding; monitor infant for rash or gastrointestinal disturbances.
Pregnancy may increase renal clearance; however, specific pharmacokinetic data are lacking. Dose adjustment is not routinely recommended but may be necessary if renal function changes. Use standard dose of 10 mg once daily with monitoring of renal function and HBV DNA levels.
No routine dose adjustment; pharmacokinetic changes in pregnancy may require increased dosing due to increased clearance and volume of distribution, especially in third trimester. Monitor clinical response.
Monitor renal function closely; dose adjust for Cr Cl <50 m L/min. Check LFTs and HBV DNA every 3 months. Avoid in decompensated cirrhosis. HIV co-infected patients require concomitant antiretroviral therapy due to risk of HIV resistance. Prolonged therapy may lead to adefovir-resistant HBV mutations (rt A181V/T, rt N236T).
Monitor renal function closely; adjust dose in renal impairment. Ensure adequate hydration to prevent crystalluria. Infuse over at least 1 hour to avoid phlebitis. Use with caution in elderly and those with pre-existing renal disease. Neurotoxicity may occur at high doses or in renal failure. Not effective for EBV or CMV treatment.
Take with or without food at the same time daily.,Do not stop taking without consulting your doctor; stopping may cause severe hepatitis flare.,Report any signs of kidney problems (decreased urination, swelling) or lactic acidosis (unusual muscle pain, trouble breathing).,Regular blood tests are required to monitor liver and kidney function.,Use effective contraception during treatment if you or your partner can become pregnant.,Avoid alcohol and other medications that can damage the liver or kidneys without medical advice.
Drink plenty of water during treatment to prevent kidney problems.,Report any signs of kidney issues like decreased urine output or swelling.,Notify healthcare provider if you experience confusion, hallucinations, or seizures.,This medication is for intravenous use only and will be given in a medical setting.,Inform your doctor about all medications you are taking, especially other nephrotoxic drugs.
"Coadministration of adefovir dipivoxil and tenofovir disoproxil may reduce the antiviral efficacy of tenofovir by competing for renal tubular secretion via organic anion transporters (OATs) and potentially intracellular phosphorylation pathways. This competition can decrease tenofovir's intracellular active metabolite concentrations, leading to suboptimal viral suppression and increased risk of treatment failure in patients with chronic hepatitis B."
"The serum concentration of Teriflunomide can be increased when it is combined with Adefovir dipivoxil."
"Teriflunomide, the active metabolite of leflunomide, inhibits dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine synthesis, exerting immunomodulatory effects. Acyclovir, an antiviral nucleoside analog, may inhibit organic anion transporter 3 (OAT3)-mediated renal tubular secretion of teriflunomide, leading to increased systemic exposure. Elevated teriflunomide concentrations can potentiate hepatotoxicity, myelosuppression, and immunosuppression, increasing the risk of infections and other adverse effects."
"The serum concentration of Acyclovir can be increased when it is combined with Tizanidine."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ADEFOVIR DIPIVOXIL vs ACYCLOVIR SODIUM, answered by our medical review team.
ADEFOVIR DIPIVOXIL is a Antiviral that works by Adefovir dipivoxil is a prodrug of adefovir, an acyclic nucleotide analog of adenosine monophosphate. It is phosphorylated intracellularly to adefovir diphosphate, which inhibits hepatitis B virus (HBV) DNA polymerase by competing with the natural substrate deoxyadenosine triphosphate and causing DNA chain termination after incorporation into viral DNA.. ACYCLOVIR SODIUM is a Antiviral that works by Acyclovir is a synthetic nucleoside analogue with activity against herpes simplex virus (HSV) types 1 and 2, and varicella-zoster virus (VZV). It is converted to acyclovir monophosphate by viral thymidine kinase, then further phosphorylated to acyclovir triphosphate, which competitively inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ADEFOVIR DIPIVOXIL and ACYCLOVIR SODIUM depend on the specific clinical indication. These are both Antiviral agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ADEFOVIR DIPIVOXIL is: 10 mg orally once daily on an empty stomach.. The standard adult dose of ACYCLOVIR SODIUM is: Dosing is indication-specific. For herpes simplex encephalitis: 10 mg/kg IV every 8 hours for 10–14 days (adults and children ≥12 years) or 20 mg/kg IV every 8 hours (3 months–12 years). For severe genital herpes: 5 mg/kg IV every 8 hours for 5 days. For mucocutaneous HSV in immunocompromised: 5 mg/kg IV every 8 hours for 7–14 days. For varicella zoster in immunocompromised: 10 mg/kg IV every 8 hours for 7 days. For neonatal HSV: 20 mg/kg IV every 8 hours for 14–21 days (disseminated/CNS) or 14 days (skin/eyes/mouth).. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ADEFOVIR DIPIVOXIL and ACYCLOVIR SODIUM in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ADEFOVIR DIPIVOXIL is classified as Category C. Adefovir dipivoxil is an FDA Pregnancy Category C drug. Animal studies have shown teratogenicity (malformations, embryo-fetal toxicity) at doses 23 times the human therapeutic dose. ACYCLOVIR SODIUM is classified as Category A/B. Pregnancy Category B. No evidence of teratogenicity in humans; fetal risks not established in first trimester. Use during pregnancy only if clearly needed.. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.