Usage
- Adefovir dipivoxil is prescribed for the treatment of chronic hepatitis B (HBV) infection in adults and adolescents 12 years of age and older with evidence of active viral replication and either persistently elevated serum aminotransferases (ALT or AST) or histologically active liver disease.
- Pharmacological Classification: Antiviral, specifically a nucleotide analogue reverse transcriptase inhibitor.
- Mechanism of Action: Adefovir dipivoxil is a prodrug of adefovir. After conversion to adefovir, it is phosphorylated intracellularly to its active form, adefovir triphosphate. Adefovir triphosphate inhibits HBV DNA polymerase (reverse transcriptase), thereby suppressing HBV replication.
Alternate Names
- International Nonproprietary Name (INN): Adefovir dipivoxil
- Brand name: Hepsera
How It Works
- Pharmacodynamics: Adefovir triphosphate competes with deoxyadenosine triphosphate for incorporation into viral DNA, resulting in chain termination and inhibition of viral replication. It reduces HBV DNA levels in serum and liver, as well as serum ALT levels.
- Pharmacokinetics:
- Absorption: Adefovir dipivoxil is orally administered and well-absorbed. Bioavailability is approximately 59%. Peak plasma concentrations occur within 0.58-4 hours. Food does not significantly affect absorption.
- Metabolism: Adefovir dipivoxil is rapidly converted to adefovir. Adefovir is not significantly metabolized by CYP450 enzymes.
- Elimination: Adefovir is primarily eliminated by renal excretion, with a half-life of approximately 7.2 hours. Hemodialysis removes approximately 35% of the drug.
Dosage
Standard Dosage
Adults:
- 10 mg orally once daily, with or without food.
Children (12 years and older):
- 10 mg orally once daily, with or without food.
Special Cases:
- Elderly Patients: Use with caution due to potential age-related decline in renal function. Monitor renal function closely.
- Patients with Renal Impairment: Dose adjustment is required based on creatinine clearance (CrCl).
- CrCl 30–49 mL/minute: 10 mg every 48 hours
- CrCl 10–29 mL/minute: 10 mg every 72 hours
- Hemodialysis patients: 10 mg every 7 days following dialysis.
- Patients with Hepatic Dysfunction: No dosage adjustment is necessary.
Clinical Use Cases
Adefovir is not typically used in acute medical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is chronic HBV infection management.
Side Effects
Common Side Effects:
- Weakness/Asthenia
- Headache
- Nausea
- Abdominal pain
- Diarrhea
- Flatulence
Rare but Serious Side Effects:
- Nephrotoxicity (renal impairment): manifested by increased serum creatinine and decreased serum phosphorus.
- Lactic acidosis (buildup of lactic acid in the blood)
- Severe hepatomegaly with steatosis (enlarged liver with fat accumulation)
- Acute exacerbation of hepatitis B after discontinuation of therapy
Long-Term Effects:
- Chronic kidney disease may develop with prolonged use, particularly in patients with pre-existing renal dysfunction or risk factors.
Contraindications
- Hypersensitivity to adefovir dipivoxil or any component of the formulation.
- Co-administration with tenofovir-containing products.
Drug Interactions
- Drugs that reduce renal function (e.g., aminoglycosides, NSAIDs) can increase the risk of adefovir nephrotoxicity.
- Tenofovir: Co-administration is contraindicated due to increased risk of nephrotoxicity.
- Other nephrotoxic drugs: Caution is advised when using adefovir concomitantly.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Adefovir should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Adefovir is contraindicated during breastfeeding. It is not known if adefovir is excreted in human milk.
Drug Profile Summary
- Mechanism of Action: Nucleotide analogue reverse transcriptase inhibitor.
- Side Effects: Weakness, headache, nausea, abdominal pain, diarrhea, nephrotoxicity, lactic acidosis, hepatomegaly with steatosis, exacerbation of hepatitis B upon discontinuation.
- Contraindications: Hypersensitivity, co-administration with tenofovir.
- Drug Interactions: Nephrotoxic drugs, tenofovir.
- Pregnancy & Breastfeeding: Category C; contraindicated during breastfeeding.
- Dosage: Adults and children 12 years and older: 10 mg orally once daily. Adjustments required for renal impairment.
- Monitoring Parameters: Renal function (serum creatinine, phosphorus), liver function tests (ALT, AST), HBV DNA levels.
Popular Combinations
Adefovir may be used in combination with other antiviral agents in cases of decompensated liver disease due to HBV. The choice of combination therapy depends on various factors including resistance patterns and individual patient characteristics.
Precautions
- General Precautions: Monitor renal function closely, especially in patients at risk for renal impairment. Assess HIV status prior to initiation. Monitor for signs and symptoms of lactic acidosis and hepatic steatosis.
- Specific Populations: Use with caution in elderly patients.
- Pregnant Women: Use only if clearly needed.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Monitor renal function closely.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Adefovir?
A: The standard dose is 10 mg orally once daily for adults and children 12 years and older. Dosage adjustments are required for patients with renal impairment.
Q2: What are the most common side effects of Adefovir?
A: Common side effects include asthenia, headache, nausea, abdominal pain, and diarrhea.
Q3: How is Adefovir eliminated from the body?
A: Adefovir is predominantly eliminated through renal excretion.
Q4: Is Adefovir safe to use during pregnancy?
A: Adefovir is Pregnancy Category C. Use only if the potential benefit justifies the potential risk to the fetus.
Q5: Can Adefovir be used with Tenofovir?
A: No, co-administration with tenofovir is contraindicated due to increased risk of nephrotoxicity.
Q6: What should be monitored in patients taking Adefovir?
A: Renal function (serum creatinine, phosphorus), liver function (ALT, AST), and HBV DNA levels should be monitored regularly.
Q7: What is the mechanism of action of Adefovir?
A: Adefovir inhibits HBV DNA polymerase (reverse transcriptase), thus blocking viral replication.
Q8: Is Adefovir a cure for hepatitis B?
A: No, Adefovir is not a cure for hepatitis B. It suppresses viral replication but does not eradicate the virus.
Q9: What happens if a patient stops taking Adefovir abruptly?
A: Acute exacerbation of hepatitis B can occur if Adefovir is discontinued abruptly. Patients should be closely monitored after discontinuation.
Q10: What are the signs of Adefovir nephrotoxicity?
A: Nephrotoxicity is characterized by elevated serum creatinine and decreased serum phosphorus.
