Posology : מינונים

4.2    Posology and method of administration
Therapy should be initiated by a physician experienced in the management of HIV infection and/or treatment of chronic hepatitis B.
Posology
HIV-1
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.

Chronic hepatitis B
Adults
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.

Duration of therapy in adults 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 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.

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
Paediatric population: Viread is not recommended for use in children below the age of 12 years due to insufficient data on safety and efficacy (see section 5.2). The recommended dose for the treatment of HIV-1 in paediatric patients (12 years of age and older with body weight ≥35 kg) is 245 mg (one tablet) once daily taken orally.

The safety of Viread in paediatric patients aged 12 to <18 years is supported by data from one randomized study in which Viread was administered to HIV-1 infected treatment-experienced subjects. In this study, the pharmacokinetic profile of Viread was similar to that found to be safe and effective in adult clinical trials. In study GS-US-104-0321, 87 treatment-experienced subjects 12 to <18 years of age were treated with Viread (N=45) or placebo (N=42) in combination with an optimized background regimen (OBR) for 48 weeks. The mean baseline CD4 cell count was 374 cells/mm3, and the mean baseline plasma HIV-1 RNA was 4.6 log10 copies/ml. At baseline, 90% of subjects harboured NRTI resistance-associated substitutions in their HIV-1 isolates. Overall, the trial failed to show a difference in virologic response between the Viread and placebo treatment groups.
Subgroup analyses suggest the lack of difference in virologic response may be attributable to imbalances between treatment arms in baseline viral susceptibility to Viread and OBR.
Although changes in HIV-1 RNA in these highly treatment-experienced subjects were less than anticipated, the comparability of the pharmacokinetic and safety data to that observed in adults 

supports the use of Viread in paediatric patients ≥12 years of age who weigh ≥35 kg and whose HIV-1 isolate is expected to be sensitive to Viread (see sections 4.4, 4.8 and 5.2).

No data are currently available in paediatric patients infected with chronic hepatitis B.

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. Dose interval adjustments are recommended for patients with creatinine clearance < 50 ml/min.

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)
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 Viread 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 12 years of age and older 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.

Patients should be instructed not to chew or split the tablets as it may impact the absorption of Viread.
However, in exceptional circumstances Viread can be administered following disintegration of the tablet in at least 100 ml of water, orange juice or grape juice.