Comprehensive Guide to Adefovir: Uses, Dosage, Side Effects, and More

What is Adefovir?

Overview of Adefovir

Generic Name: Adefovir (Adefovir dipivoxil, prodrug form)

Brand Name: Hepsera, generics

Drug Group: Antiviral; nucleotide analog reverse transcriptase inhibitor

The drug is used to

• Treat chronic hepatitis B with active viral replication and evidence of liver damage or compensated cirrhosis.
• Manage lamivudine-resistant HBV infections.
• Off-label uses include treatment of HBV in specific populations (e.g., HIV/HBV co-infection) under specialist guidance.

Key Characteristics

Form: Oral tablets (10 mg).

Mechanism: Inhibits HBV DNA polymerase, preventing viral DNA synthesis.

Approval: FDA-approved (2002 for Hepsera) and EMA-approved for chronic hepatitis B.

Indications and Uses of Adefovir

Adefovir is indicated for

Chronic Hepatitis B: Treats adults with chronic HBV infection, evidenced by elevated HBV DNA levels, alanine aminotransferase (ALT), or histological liver damage.

Lamivudine-Resistant HBV: Manages HBV strains resistant to lamivudine, reducing viral load.

Compensated Cirrhosis: Used in HBV patients with stable liver function to prevent disease progression.

Off-Label Uses: May be used in HIV/HBV co-infection or post-liver transplant HBV recurrence under specialist supervision.

Dosage of Adefovir

Dosage for Adults

Chronic Hepatitis B:

• Standard: 10 mg orally once daily, with or without food.
• Duration: Long-term, often years, based on viral suppression and liver function.

Lamivudine-Resistant HBV: Same as standard dosing, with monitoring for resistance.

Dosage for Children

Not approved for pediatric use; limited data exist for off-label use in adolescents under specialist oversight.

Dosage for Pregnant Women

Pregnancy Category C: Limited data; use only if benefits outweigh risks, as animal studies suggest potential fetal harm. Consult a hepatologist.

Dosage Adjustments

Renal Impairment:

• CrCl 20–49 mL/min: 10 mg every 48 hours.
• CrCl 10–19 mL/min: 10 mg every 72 hours.
• Hemodialysis: 10 mg every 7 days post-dialysis.

Hepatic Impairment: No adjustment needed for compensated liver disease; monitor closely in decompensated cirrhosis.

Resistance: Switch or combine with other antivirals (e.g., tenofovir) if resistance develops.

Additional Considerations

• Monitor renal function (creatinine clearance) and HBV DNA levels every 3–6 months.
• Take consistently at the same time daily to maintain steady-state levels.

How to Use Adefovir

Administration: Take the medication orally as a 10 mg tablet, with or without food. Swallow whole with water.

Timing: Administer once daily (or as adjusted for renal impairment) at a consistent time to optimize efficacy.

Missed Dose: Take as soon as remembered unless it’s nearly time for the next dose; do not double doses. Consult your doctor if multiple doses are missed.

Additional Tips:

• Continue therapy even if feeling well, as stopping prematurely may lead to HBV flare or resistance.
• Report symptoms like fatigue, nausea, or dark urine immediately, as they may indicate liver or kidney issues.

Contraindications for Adefovir

The drug is contraindicated in:

Patients with hypersensitivity to Adefovir or its components.

Those with severe renal impairment (CrCl <10 mL/min) unless on dialysis.

Patients with untreated HIV/HBV co-infection, as Adefovir monotherapy may cause HIV resistance.

Warnings & Precautions for Adefovir

General Warnings

Nephrotoxicity: Risk of renal impairment, including proximal renal tubulopathy; monitor creatinine clearance and serum creatinine regularly.

HBV Resistance: Prolonged use may lead to resistant HBV strains; monitor HBV DNA levels and consider combination therapy.

Hepatic Flares: Stopping the medication abruptly may cause severe HBV exacerbation; taper under medical supervision.

Lactic Acidosis and Hepatomegaly: Rare but serious; associated with steatosis, particularly in patients with risk factors.

HIV Resistance: In HIV/HBV co-infected patients, test for HIV before starting therapy to avoid resistance.

Use in Specific Populations

Pregnancy: Category C; avoid unless essential due to limited data. Use contraception during therapy.

Breastfeeding: Unknown if excreted in breast milk; avoid breastfeeding to prevent infant exposure.

Elderly: Increased risk of renal impairment; monitor renal function closely.

Children: Not approved; safety data are limited.

HIV/HBV Co-Infection: Use with effective HIV therapy to prevent resistance.

Additional Precautions

• Inform your doctor about kidney disease, HIV status, or other antiviral treatments.
• Avoid alcohol to reduce liver stress during HBV treatment.

Overdose and Management of Adefovir

Overdose Symptoms

Overdose is rare but may cause:

• Severe nausea, vomiting, or diarrhea.
• Renal dysfunction (e.g., elevated creatinine, decreased urine output).
• Liver toxicity (e.g., jaundice, elevated ALT).

Immediate Actions

Contact Healthcare Provider: Seek medical advice immediately.

Supportive Care: Manage symptoms (e.g., fluids for dehydration, dialysis for renal failure).

Monitor: Check renal and liver function tests for toxicity.

Additional Notes

• Overdose risk is low with proper dosing; store securely to prevent misuse.
• Report persistent symptoms promptly.

Side Effects of Adefovir

Common Side Effects

• Asthenia (fatigue; 13%)
• Headache (9%)
• Nausea (5%)
• Abdominal pain (9%)
• Elevated creatinine (2–4%)

These effects are usually mild and may decrease with continued use.

Serious Side Effects

Seek immediate medical attention for:

Renal Toxicity: Decreased urine output, swelling, or fatigue.

Hepatic Flares: Jaundice, dark urine, or right-sided abdominal pain.

Lactic Acidosis: Muscle pain, weakness, or rapid breathing.

Allergic Reactions: Rare; rash, hives, or difficulty breathing.

Additional Notes

• Regular monitoring of renal and liver function is critical, especially in long-term use.
• Report any new or worsening symptoms promptly.

Drug Interactions with Adefovir

The medication may interact with:

Nephrotoxic Drugs (e.g., NSAIDs, Aminoglycosides): Increase risk of renal impairment; monitor renal function closely.

Tenofovir: Concurrent use may increase nephrotoxicity; avoid unless necessary.

Lamivudine, Entecavir: No significant interactions; often used in combination for resistant HBV.

Probenecid: May increase Adefovir levels; monitor for toxicity.

Patient Education or Lifestyle

Pharmacokinetics of Adefovir

Absorption: Adefovir dipivoxil is a prodrug, rapidly converted to Adefovir; bioavailability ~59%. Peak plasma concentration at 0.6–4 hours.

Distribution: Volume of distribution ~0.4 L/kg; minimal protein binding.

Metabolism: Minimal hepatic metabolism; converted to active Adefovir via esterases.

Excretion: Primarily renal (45% as unchanged drug); clearance reduced in renal impairment.

Half-Life: ~7 hours (prolonged in renal impairment).

Pharmacodynamics of Adefovir

The drug exerts its effects by:

Inhibiting HBV DNA polymerase, blocking viral DNA synthesis and replication.

Reducing HBV viral load, improving liver histology in chronic hepatitis B.

Exhibiting activity against lamivudine-resistant HBV mutants.

Having minimal impact on human DNA polymerases, reducing host toxicity.

Storage of Adefovir

Temperature: Store at room temperature (20–25°C or 68–77°F); avoid moisture and heat.

Protection: Keep in original container to protect from light.

Safety: Store out of reach of children to prevent accidental ingestion.

Disposal: Follow local regulations or consult a pharmacist for safe disposal of unused or expired medication.

Frequently Asked Questions (FAQs)

Q: What does Adefovir treat?
A: The drug treats chronic hepatitis B with active viral replication or lamivudine resistance.

Q: Can Adefovir cure hepatitis B?
A: No, the medication suppresses HBV but does not cure it.

Q: Is Adefovir safe for kidney disease patients?
A: Requires dose adjustments; avoid in severe renal impairment unless on dialysis.

Q: How long is Adefovir treatment needed?
A: Often long-term (years) to maintain viral suppression; follow your doctor’s guidance.

Q: Can Adefovir cause kidney problems?
A: Yes, nephrotoxicity is a risk; regular renal monitoring is essential.

Regulatory Information

The medication is approved by:

U.S. Food and Drug Administration (FDA): Approved in 2002 (Hepsera) for chronic hepatitis B.

European Medicines Agency (EMA): Approved for chronic hepatitis B with active replication.

Other Agencies: Approved globally for similar indications; consult local guidelines.

References

1. U.S. Food and Drug Administration (FDA). (2023). Hepsera (Adefovir Dipivoxil) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety for hepatitis B.
2. European Medicines Agency (EMA). (2023). Hepsera (Adefovir Dipivoxil) Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Adefovir: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Adefovir.
   • WHO’s inclusion of Adefovir as an essential medicine for hepatitis B.
5. Hepatology. (2018). Adefovir in the Management of Chronic Hepatitis B.
   • Peer-reviewed article on the medication’s efficacy in HBV (note: access may require a subscription).