Adefovir dipivoxil is a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. The approximate oral bioavailability of adefovir from HEPSOVIR is 59%, and it is not affected by the consumption of food. Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. Adefovir binding to human plasma or human serum proteins is ≤4%, and forty-five percent of the dose is recovered as adefovir in the urine over 24 hours following 10 mg oral doses of  HEPSOVIR.

 

HEPSOVIR is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases or histologically active disease.

This indication is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg+ and HBeAg- chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function.

For patients 12 to <18 years of age, the indication is based on virological and biochemical responses in patients with HBeAg+ chronic hepatitis B virus infection with compensated liver function.

 

HEPSOVIR is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product.

 

The recommended dose of HEPSOVIR in chronic hepatitis B patients for patients ≥12 years of age with adequate renal function is 10 mg, once daily, taken orally, without regard to food.

Dosing and dosing interval should be monitored depending on creatinine clearance.

 

 

- Severe acute exacerbation of hepatitis has been reported in patients who have discontinued HEPSOVIR therapy. Hepatic function should be monitored at repeated intervals with both clinical and laboratory follow-up for at least several months in patients who discontinue HEPSOVIR. These exacerbations generally occurred in the absence of HBeAg seroconversion, and presented as serum ALT elevations in addition to re-emergence of viral replication.  

- Treatment with HEPSOVIR could result in nephrotoxicity characterized by a delayed onset of gradual increases in serum creatinine and decreases in serum phosphorus, so It is important to monitor renal function for all patients during treatment with HEPSOVIR every three month.

- Prior to initiating HEPSOVIR therapy, HIV antibody testing should be offered to all patients. Treatment with anti-hepatitis B therapies, such as HEPSOVIR, that have activity against HIV in a chronic hepatitis B patient with unrecognized or untreated HIV infection may result in emergence of HIV resistance.

- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues such as Adefovir. Obesity and prolonged nucleoside exposure may be risk factors. Treatment with HEPSOVIR should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

- Resistance to adefovir dipivoxil can result in viral load rebound which may result in exacerbation of hepatitis B and, in the setting of diminished hepatic function, lead to liver decompensation and possible fatal outcome.

- In order to reduce the risk of resistance in patients with lamivudine resistant HBV, adefovir dipivoxil should be used in combination with lamivudine and not as adefovir dipivoxil monotherapy.

- In order to reduce the risk of resistance in all patients receiving adefovir dipivoxil monotherapy, a modification of treatment should be considered if serum HBV DNA remains above 1000 copies/mL with continued treatment.

 

The most common adverse effects reported from adefovir have been gastrointestinal effects including nausea, flatulence, diarrhea, dyspepsia, and abdominal pain. Other common adverse effects are headache and asthenia. There have been also reported pruritus and rash. Increased in serum creatinine may occur and there have been instances of renal impairment and acute renal failure. Raised liver enzymes concentration may occur and exacerbation of hepatitis has been reported after cessation of treatment with adefovir.

Lactic acidosis, usually associated with hepatomegaly and steatosis, has been associated with treatment with nucleoside adverse transcriptase inhibitor.

 

Since Adefovir is eliminated by the kidney, co-administration of HEPSOVIR with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either adefovir and/or these co-administered drugs

HEPSOVIR should not be used concurrently with tenofovir disoproxil fumarate or tenofovir disoproxil fumarate-containing products.

Patients taking concomitant nephrotoxic agents such as cyclosporine, tacrolimus, aminoglycosides, vancomycin and non-steroidal anti-inflammatory drugs may have risk of nephrotoxicity.

 

HEPSOVIR should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits.

Decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother.

 

HEPSOVIR is not recommended for use in children below 12 years of age.

 

Caution should be exercised when prescribing to elderly patients since they have greater frequency of decreased renal or cardiac function due to concomitant disease or other drug therapy.

 

HEPSOVIR Tablets: Packet with one blister contains 10 tablets or plastic package contains 30 tablets. Each tablet contains 10 mg of Adefovir Dipivoxil.

 

Store at temperature between (15-30)°C.