TENOFOVIR DISOPROXIL MYLAN Film-coated tablet Ref.[7451] Active ingredients:

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

Posology

Adults

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

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 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.

For treatment of HIV-1 infection and chronic hepatitis B in adults for whom a solid dosage form is not appropriate, other suitable formulations may be checked for their availability.

Tenofovir disoproxil Mylan is available only as 245 mg film-coated tablets. Other suitable formulations may be checked for their availability.

Paediatric population

HIV-1

In adolescents aged 12 to <18 years and weighing ≥35 kg, the recommended dose of tenofovir disoproxil is 245 mg (one tablet) once daily taken orally with food (see sections 4.8 and 5.1).

Reduced doses of tenofovir disoproxil are used for treatment of HIV-1 infected paediatric patients aged 2 to <12 years. As Tenofovir disoproxil Mylan is available only as 245 mg film-coated tablets, it is not suitable for the use in paediatric patients aged 2 to <12 years. Other suitable formulations may be checked for their availability.

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

Chronic hepatitis B

In adolescents aged 12 to <18 years and weighing ≥35 kg, the recommended dose of tenofovir disoproxil is 245 mg (one tablet) once daily, taken orally with food (see sections 4.8 and 5.1). The optimal duration of treatment is currently unknown.

The safety and efficacy of tenofovir disoproxil in children with chronic hepatitis B aged 2 to <12 years or weighing <35 kg have not been established. No data are available.

For treatment of HIV-1 infection and chronic hepatitis B in adolescents aged 12 to <18 years for whom a solid dosage form is not appropriate, other suitable formulations may be checked for their availability.

Missed dose

If a patient misses a dose of tenofovir disoproxil within 12 hours of the time it is usually taken, the patient should take tenofovir disoproxil with food as soon as possible and resume their normal dosing schedule. If a patient misses a dose of tenofovir disoproxil 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 tenofovir disoproxil, another tablet should be taken. If the patient vomits more than 1 hour after taking tenofovir disoproxil 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 tenofovir disoproxil 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.

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)

Since administration of a lower dose with the 245 mg tablet is not possible, 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

Adequate dose adjustments cannot be applied due to lack of alternative tablet strengths, therefore use in this group of patients is not recommended. If no alternative treatment is available, prolonged dose intervals 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 tenofovir disoproxil 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 tenofovir disoproxil 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

Tenofovir disoproxil Mylan tablets should be taken once daily, orally with food.

However, in exceptional circumstances Tenofovir disoproxil Mylan 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.

Shelf life: 2 years.

For bottles only:

After first opening: use within 30 days.

Do not store above 25°C. Store in the original package in order to protect from light and moisture.

High density polyethylene (HDPE) bottle with polypropylene (PP) child resistant closure with wad containing aluminium induction sealing liner and desiccant (silica gel), available in the following pack sizes: 30 film-coated tablets and multipacks containing 90 (3 packs of 30) film-coated tablets.

OPA/Aluminium/PE/Desiccant/PE-Aluminium blister packs containing 10 or 30 film coated tablets. OPA/Aluminium/PE/Desiccant/PE-Aluminium perforated unit dose blister pack containing 30 × 1 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.