VIREAD Film-coated tablet Ref.[7359] Active ingredients: Tenofovir disoproxil

Therapy should be initiated by a physician experienced in the management of HIV infection and/or treatment of chronic hepatitis B.

Posology

HIV-1 and Chronic hepatitis B

Adults and adolescents aged 12 to <18 years and weighing ≥35 kg

The recommended dose of Viread for the treatment of HIV or for the treatment of chronic hepatitis B is 245 mg (one tablet) once daily taken orally with food.

Viread is also available as 33 mg/g granules for the treatment of HIV-1 infection and chronic hepatitis B in adults or adolescents for whom a solid dosage form is not appropriate.

The decision to treat paediatric patients (adolescents) should be based on careful consideration of individual patient needs and with reference to current paediatric treatment guidelines including the value of baseline histological information. The benefits of long-term virologic suppression with continued therapy must be weighed against the risk of prolonged treatment, including the emergence of resistant hepatitis B virus and the uncertainties as regards the long term impact of bone and renal toxicity (see section 4.4).

Serum ALT should be persistently elevated for at least 6 months prior to treatment of paediatric patients with compensated liver disease due to HBeAg positive chronic hepatitis B; and for at least 12 months in patients with HBeAg negative disease.

Duration of therapy in adult and adolescent patients with chronic hepatitis B

The optimal duration of treatment is unknown. Treatment discontinuation may be considered as follows:

• In HBeAg positive patients without cirrhosis, treatment should be administered for at least 12 months after HBe seroconversion (HBeAg loss and HBV DNA loss with anti-HBe detection on two consecutive serum samples at least 3-6 months apart) 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. Treatment discontinuation may also be considered after stable virological suppression is achieved (i.e. for at least 3 years) provided serum ALT and HBV DNA levels are followed regularly after treatment discontinuation to detect any late virological relapse. 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 adult patients with decompensated liver disease or cirrhosis, treatment cessation is not recommended.

Paediatric population

Viread is also available as granules for the treatment of HIV-1 infection and chronic hepatitis B in paediatric patients aged 2 to <12 years and as reduced tablet strengths for the treatment of HIV-1 infection and chronic hepatitis B in paediatric patients aged 6 to <12 years (see section 5.1). Please refer to the Summaries of Product Characteristics for Viread 33 mg/g granules and Viread 123 mg, 163 mg and 204 mg film-coated tablets.

The safety and efficacy of tenofovir disoproxil in HIV-1 infected children or children with chronic hepatitis B under 2 years of age have not been established. No data are available.

Missed dose

If a patient misses a dose of Viread within 12 hours of the time it is usually taken, the patient should take Viread with food as soon as possible and resume their normal dosing schedule. If a patient misses a dose of Viread by more than 12 hours and it is almost time for their next dose, the patient should not take the missed dose and simply resume the usual dosing schedule.

If the patient vomits within 1 hour of taking Viread, another tablet should be taken. If the patient vomits more than 1 hour after taking Viread they do not need to take another dose.

Special populations

Elderly

No data are available on which to make a dose recommendation for patients over the age of 65 years (see section 4.4).

Renal impairment

Tenofovir is eliminated by renal excretion and the exposure to tenofovir increases in patients with renal dysfunction.

Adults

There are limited data on the safety and efficacy of tenofovir disoproxil in adult patients with moderate and severe renal impairment (creatinine clearance <50 ml/min) and long-term safety data has not been evaluated for mild renal impairment (creatinine clearance 50-80 ml/min). Therefore, in adult patients with renal impairment tenofovir disoproxil should only be used if the potential benefits of treatment are considered to outweigh the potential risks. Administration of Viread 33 mg/g granules to provide a reduced daily dose of tenofovir disoproxil is recommended for adult patients with creatinine clearance <50 ml/min, including haemodialysis patients. Please refer to the Summary of Product Characteristics for Viread 33 mg/g granules.

Mild renal impairment (creatinine clearance 50-80 ml/min):

Limited data from clinical studies support once daily dosing of 245 mg tenofovir disoproxil in patients with mild renal impairment.

Moderate renal impairment (creatinine clearance 30-49 ml/min):

For patients unable to take the granule formulation of tenofovir disoproxil, prolonged dose intervals using the 245 mg film-coated tablets may be used. Administration of 245 mg tenofovir disoproxil every 48 hours can be used based on modelling of single-dose pharmacokinetic data in HIV negative and non-HBV infected subjects with varying degrees of renal impairment, including end-stage renal disease requiring haemodialysis, but has not been confirmed in clinical studies. Therefore, clinical response to treatment and renal function should be closely monitored in these patients (see sections 4.4 and 5.2).

Severe renal impairment (creatinine clearance <30 ml/min) and haemodialysis patients:

For patients unable to take the granule formulation of tenofovir disoproxil and with no alternative treatment available, prolonged dose intervals using the 245 mg film-coated tablets may be used as follows:

Severe renal impairment: 245 mg tenofovir disoproxil may be administered every 72-96 hours (dosing twice a week).

Haemodialysis patients: 245 mg tenofovir disoproxil may be administered every 7 days following completion of a haemodialysis session*.

These dose interval adjustments have not been confirmed in clinical studies. Simulations suggest that the prolonged dose interval using Viread 245 mg film-coated tablets is not optimal and could result in increased toxicity and possibly inadequate response. Therefore, clinical response to treatment and renal function should be closely monitored (see sections 4.4 and 5.2).

^* Generally, once weekly dosing assuming three haemodialysis sessions per week, each of approximately 4 hours duration or after 12 hours cumulative haemodialysis.

No dosing recommendations can be given for non-haemodialysis patients with creatinine clearance <10 ml/min.

Paediatrics

The use of tenofovir disoproxil is not recommended in paediatric patients with renal impairment (see section 4.4).

Hepatic impairment

No dose adjustment is required in patients with hepatic impairment (see sections 4.4 and 5.2).

If Viread is discontinued in patients with chronic hepatitis B with or without HIV co-infection, these patients should be closely monitored for evidence of exacerbation of hepatitis (see section 4.4).

Method of administration

Viread tablets should be taken once daily, orally with food.

A granules formulation of tenofovir disoproxil is available for patients having difficulty in swallowing film-coated tablets. However, in exceptional circumstances Viread 245 mg film-coated tablets can be administered following disintegration of the tablet in at least 100 ml of water, orange juice or grape juice.

Symptoms

If overdose occurs the patient must be monitored for evidence of toxicity (see sections 4.8 and 5.3), and standard supportive treatment applied as necessary.

Management

Tenofovir can be removed by haemodialysis; the median haemodialysis clearance of tenofovir is 134 ml/min. It is not known whether tenofovir can be removed by peritoneal dialysis.

5 years.

This medicinal product does not require any special storage conditions.

High density polyethylene (HDPE) bottle with a polypropylene child-resistant closure containing 30 film-coated tablets and a silica gel desiccant.

The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and outer cartons containing 90 (3 bottles of 30) film-coated tablets. Not all pack sizes may be marketed.

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