Hepiral (adefovir dipivoxil): Uses, Dosage & Side Effects

What it's for (Indications)

Adefovir dipivoxil is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adult patients with evidence of active viral replication and persistent elevations in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, or histologically active disease.
The primary goal of treatment is to suppress HBV DNA replication, reduce liver inflammation, and prevent progression of liver fibrosis, cirrhosis, and hepatocellular carcinoma.
Efficacy has been demonstrated in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients with compensated and decompensated liver disease.
Careful assessment of the patient's HBV status, liver function, and renal function is crucial before initiating therapy to ensure appropriate patient selection and management, aiming to achieve sustained virological response and improve long-term outcomes.

Dosage Information

Type	Guideline
Standard	The recommended oral dose of adefovir dipivoxil for the treatment of chronic hepatitis B in adults is 10 mg once daily, administered without regard to food. For patients with renal impairment, dose adjustment is necessary based on creatinine clearance (CrCl). For those with a CrCl between 20-49 mL/min, the dose should be 10 mg every 48 hours. For CrCl 10-19 mL/min, the dose should be 10 mg every 72 hours. Patients on hemodialysis should receive 10 mg every 7 days, administered after dialysis. No dosage adjustment is required for patients with hepatic impairment. Treatment duration typically extends for many months or years, depending on the patient's virological and biochemical response and clinical status, and discontinuation should be carefully managed to prevent severe exacerbations, often requiring prolonged monitoring.

Type

Guideline

Standard

The recommended oral dose of adefovir dipivoxil for the treatment of chronic hepatitis B in adults is 10 mg once daily, administered without regard to food. For patients with renal impairment, dose adjustment is necessary based on creatinine clearance (CrCl). For those with a CrCl between 20-49 mL/min, the dose should be 10 mg every 48 hours. For CrCl 10-19 mL/min, the dose should be 10 mg every 72 hours. Patients on hemodialysis should receive 10 mg every 7 days, administered after dialysis. No dosage adjustment is required for patients with hepatic impairment. Treatment duration typically extends for many months or years, depending on the patient's virological and biochemical response and clinical status, and discontinuation should be carefully managed to prevent severe exacerbations, often requiring prolonged monitoring.

Safety & Warnings

Common Side Effects

The most common adverse effects associated with adefovir dipivoxil therapy include renal impairment, which can manifest as elevated serum creatinine, hypophosphatemia, and phosphaturia, potentially leading to osteomalacia or bone pain with prolonged use.
Gastrointestinal disturbances such as nausea, abdominal pain, and diarrhea are also frequently reported.
Other systemic side effects may include headache, asthenia (weakness or lack of energy), fever, and pruritus.
Less common but serious adverse events include lactic acidosis, severe hepatomegaly with steatosis, and severe acute exacerbations of hepatitis B upon discontinuation of treatment.
Regular monitoring of renal function, serum electrolytes (especially phosphate), and liver function tests is essential throughout the treatment period to identify and manage these potential side effects promptly, thereby mitigating the risk of serious complications.

Serious Warnings

Black Box Warning: **WARNING: Lactic Acidosis and Severe Hepatomegaly with Steatosis, Severe Acute Exacerbations of Hepatitis B, and HIV Resistance** * **Lactic Acidosis and Severe Hepatomegaly with Steatosis:** Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including adefovir dipivoxil, alone or in combination with other antiretrovirals. The risk of lactic acidosis is increased in patients with decompensated liver disease, obesity, or prolonged nucleoside exposure. Adefovir dipivoxil should be discontinued if clinical or laboratory findings suggestive of lactic acidosis (e.g., unexplained fatigue, myalgia, dyspnea, abdominal pain, weight loss) or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations) occur. Close monitoring for these serious adverse events is critical during therapy. * **Severe Acute Exacerbations of Hepatitis B:** Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including adefovir dipivoxil. These exacerbations can be severe and potentially fatal. Hepatic function should be monitored closely with both clinical assessment and laboratory follow-up (e.g., ALT, AST, bilirubin, HBV DNA levels) for at least several months in patients discontinuing adefovir dipivoxil. If appropriate, resumption of anti-hepatitis B therapy may be warranted to manage severe exacerbations. * **HIV Resistance in HBV/HIV Co-infected Patients:** Due to the risk of development of human immunodeficiency virus (HIV) resistance, adefovir dipivoxil should not be used as monotherapy for the treatment of chronic hepatitis B in patients with unrecognized or untreated HIV infection. HIV antibody testing should be offered to all HBV-infected patients before initiating adefovir dipivoxil. If HIV co-infection is confirmed, adefovir dipivoxil therapy should be accompanied by appropriate anti-HIV treatment to prevent the emergence of adefovir-resistant HIV strains.
Several significant warnings are associated with adefovir dipivoxil.
Patients should be closely monitored for renal toxicity, as adefovir can cause or worsen renal impairment, particularly in those with pre-existing renal dysfunction or those receiving concomitant nephrotoxic agents.
Regular assessment of serum creatinine, phosphorus, and urinalysis is imperative.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogs, requiring immediate cessation of treatment if suspected.
Severe acute exacerbations of hepatitis B have occurred in patients discontinuing anti-HBV therapy, necessitating close monitoring of liver function for several months post-treatment.
Furthermore, in HIV/HBV co-infected patients, adefovir dipivoxil monotherapy for HBV can lead to the development of HIV resistance, underscoring the importance of concurrent effective anti-HIV therapy in such individuals.
Bone mineral density should also be considered, as adefovir may contribute to bone loss.

How it Works (Mechanism of Action)

Adefovir dipivoxil is an orally administered prodrug of adefovir. Upon absorption from the gastrointestinal tract, adefovir dipivoxil is rapidly converted to adefovir by esterase hydrolysis within the body. Intracellularly, adefovir is then phosphorylated by cellular kinases to its active metabolite, adefovir diphosphate. Adefovir diphosphate acts as a potent competitive inhibitor of the hepatitis B virus (HBV) DNA polymerase (reverse transcriptase), specifically targeting the enzyme responsible for viral replication. It competes effectively with the natural substrate deoxyadenine triphosphate. Its subsequent incorporation into the nascent viral DNA chain results in premature chain termination, thereby inhibiting HBV DNA synthesis and replication. This targeted interference with the viral replication machinery effectively reduces viral load in patients with chronic hepatitis B infection, contributing to clinical improvement and disease management by suppressing viral propagation.