Hepsera 10 mg tablets Ref.[2461] Active ingredients: Adefovir dipivoxil

Therapy should be initiated by a physician experienced in the management of chronic hepatitis B.

Posology

Adults: The recommended dose of Hepsera is 10 mg (one tablet) once daily taken orally with or without food.

Higher doses must not be administered.

The optimum duration of treatment is unknown. The relationship between treatment response and long-term outcomes such as hepatocellular carcinoma or decompensated cirrhosis is not known.

Patients should be monitored every six months for hepatitis B biochemical, virological and serological markers.

Treatment discontinuation may be considered as follows:

• In HBeAg positive patients without cirrhosis, treatment should be administered for at least 6-12 months after HBe seroconversion (HBeAg loss and HBV DNA loss with anti-HBe detection) is confirmed or until HBs seroconversion or there is loss of efficacy (see section 4.4). Serum ALT and HBV DNA levels should be followed regularly after treatment discontinuation to detect any late virological relapse.
• In HBeAg negative patients without cirrhosis, treatment should be administered at least until HBs seroconversion or there is evidence of loss of efficacy. With prolonged treatment for more than 2 years, regular reassessment is recommended to confirm that continuing the selected therapy remains appropriate for the patient.

In patients with decompensated liver disease or cirrhosis, treatment cessation is not recommended (see section 4.4).

Special populations

Elderly: No data are available to support a dose recommendation for patients over the age of 65 years (see section 4.4).

Renal impairment: Adefovir is eliminated by renal excretion and adjustments of the dosing interval are required in patients with a creatinine clearance < 50 ml/min or on dialysis. The recommended dosing frequency according to renal function must not be exceeded (see sections 4.4 and 5.2). The proposed dose interval modification is based on extrapolation of limited data in patients with end stage renal disease (ESRD) and may not be optimal.

Patients with creatinine clearance between 30 and 49 ml/min: It is recommended to administer adefovir dipivoxil (one 10 mg tablet) every 48 hours in these patients. There are only limited data on the safety and efficacy of this dosing interval adjustment guideline. Therefore, clinical response to treatment and renal function should be closely monitored in these patients (see section 4.4).

Patients with creatinine clearance < 30 ml/min and dialysis patients: There are no safety and efficacy data to support the use of adefovir dipivoxil in patients with a creatinine clearance < 30 ml/min or on dialysis. Therefore, use of adefovir dipivoxil is not recommended in these patients and should only be considered if the potential benefits outweigh the potential risks. In that case, the limited data available suggest that for patients with creatinine clearance between 10 and 29 ml/min, adefovir dipivoxil (one 10 mg tablet) may be administered every 72 hours; for haemodialysis patients, adefovir dipivoxil (one 10 mg tablet) may be administered every 7 days following 12 hours continuous dialysis (or 3 dialysis sessions, each of 4 hours duration). These patients should be closely monitored for possible adverse reactions and to ensure efficacy is maintained (see sections 4.4 and 4.8). No dosing interval recommendations are available for other dialysis patients (e.g. ambulatory peritoneal dialysis patients) or non-haemodialysed patients with creatinine clearance less than 10 ml/min.

Hepatic impairment: No dose adjustment is required in patients with hepatic impairment (see section 5.2).

Clinical resistance: Lamivudine-refractory patients and patients harbouring HBV with evidence of resistance to lamivudine (mutations at rtL180M, rtA181T and/or rtM204I/V) should not be treated with adefovir dipivoxil monotherapy in order to reduce the risk of resistance to adefovir. Adefovir may be used in combination with lamivudine in lamivudine-refractory patients and in patients harbouring HBV with mutations at rtL180M and/or rtM204I/V. However, for patients harbouring HBV that contains the rtA181T mutation, consideration should be given to alternative treatment regimens due to the risk of reduced susceptibility to adefovir (see section 5.1).

In order to reduce the risk of resistance in patients receiving adefovir dipivoxil monotherapy, a modification of treatment should be considered if serum HBV DNA remains above 1,000 copies/ml at or beyond 1 year of treatment.

Paediatric population: Hepsera is not recommended for use in children below the age of 18 years due to limitations of the available data on safety and efficacy (see section 5.1).

Method of administration

Hepsera tablets should be taken once daily, orally with or without food.

Administration of 500 mg adefovir dipivoxil daily for 2 weeks and 250 mg daily for 12 weeks has been associated with the gastrointestinal disorders listed above and anorexia.

If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.

Adefovir can be removed by haemodialysis; the median haemodialysis clearance of adefovir is 104 ml/min. The elimination of adefovir by peritoneal dialysis has not been studied.

2 years.

Do not store above 30°C. Store in the original package in order to protect from moisture. Keep the bottle tightly closed.

Hepsera is supplied in high-density polyethylene (HDPE) bottles with a child-resistant closure. Each bottle contains 30 tablets, silica gel desiccant and fibre packing material.

The following pack sizes are available: outer cartons containing 1 × 30 tablet and 3 × 30 tablet bottles. Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.