Gilead Sciences Ltd

Section 4.2

• The information on renal insufficiency has been updated. The first paragraph has been replaced with the following wording:        

Emtricitabine and tenofovir are eliminated by renal excretion and the exposure to emtricitabine and tenofovir increases in patients with renal dysfunction.  There are limited data on the safety and efficacy of Truvada in 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 patients with renal impairment Truvada should only be used if the potential benefits of treatment are considered to outweigh the potential risks.  Patients with renal impairment may require close monitoring of renal function (see section 4.4).  Dose interval adjustments are recommended for patients with creatinine clearance between 30 and 49 ml/min.  These dose adjustments have not been confirmed in clinical studies and the clinical response to treatment should be closely monitored in these patients (see sections 4.4 and 5.2).

• The table has been deleted and the information relating to mild, moderate and severe renal impairment and its associated creatinine clearance has been made clearer.

Section 4.4

• The section on renal impairment has been updated to include the sentence

In patients at risk for renal impairment, including patients who have previously experienced renal events while receiving adefovir dipivoxil, consideration should be given to more frequent monitoring of renal function.

The paragraph immediately below this statement has been replaced with the following text:

Patients with renal impairment (creatinine clearance < 80 ml/min), including haemodialysis patients: Renal safety with Truvada has only been studied to a very limited degree in patients with impaired renal function (creatinine clearance < 80 ml/min).  Dose interval adjustments are recommended for patients with creatinine clearance 30‑49 ml/min (see section 4.2).  Limited clinical study data suggest that the prolonged dose interval is not optimal and could result in increased toxicity and possibly inadequate response.  Furthermore, in a small clinical study, a subgroup of patients with creatinine clearance between 50 and 60 ml/min who received tenofovir disoproxil fumarate in combination with emtricitabine every 24 hours had a 2‑4‑fold higher exposure to tenofovir and worsening of renal function (see section 5.2).  Therefore, a careful benefit-risk assessment is needed when Truvada is used in patients with creatinine clearance < 60 ml/min, and renal function should be closely monitored.  In addition, the clinical response to treatment should be closely monitored in patients receiving Truvada at a prolonged dosing interval.  The use of Truvada is not recommended in patients with severe renal impairment (creatinine clearance < 30 ml/min) and in patients who require haemodialysis since appropriate dose reductions cannot be achieved with the combination tablet (see sections 4.2 and 5.2).

The statement on dose interval adjustment has been deleted.

Section 5.2

·         The information on renal impairment has been updated to include information from a sub-group of patients with creatinine clearance between 50 and 60ml/min from a small clinical trial.

Section 10 – date updated to December 2008