Posology : מינונים

4.2    Posology and method of administration

Posology
Caution – Strict adherence to dosage recommendations is essential to avoid overdose (see sections 4.4 and 4.9).

Valganciclovir is rapidly and extensively metabolised to ganciclovir after oral dosing. Oral valganciclovir 900 mg b.i.d. is therapeutically equivalent to intravenous ganciclovir 5 mg/kg b.i.d.

Treatment of cytomegalovirus (CMV) retinitis
Adult patients

Induction treatment of CMV retinitis
For patients with active CMV retinitis, the recommended dose is 900 mg valganciclovir (two Valcyte 450 mg tablets) twice a day for 21 days and, whenever possible, taken with food. Prolonged induction treatment may increase the risk of bone marrow toxicity (see section 4.4).
VALCYTE®                                                                             Valcyte PI version 3 
Maintenance treatment of CMV retinitis:
Following induction treatment, or in patients with inactive CMV retinitis, the recommended dose is 900mg valganciclovir (two Valcyte 450 mg tablets) once daily and, whenever possible, taken with food. Patients whose retinitis worsens may repeat induction treatment; however, consideration should be given to the possibility of viral drug resistance.

The duration of maintenance treatment should be determined on an individual basis.

Paediatric population
The safety and efficacy of Valcyte in the treatment of CMV retinitis have not been established in adequate and well-controlled clinical studies in paediatric patients.

Prevention of CMV disease in solid organ transplantation

For patients who have received a transplant, the recommended dose is 900 mg (two Valcyte 450 mg tablets) once daily, starting within 10 days post-transplantation and continuing until 100 days post- transplantation.

Whenever possible, the tablets should be taken with food.

Special dosage instructions
Paediatric population:
Dosing of paediatric SOT patients is individualised based on a patient’s renal function, together with body surface area.

Elderly patients:
Safety and efficacy have not been established in this patient population. No studies have been conducted in adults older than 65 years of age. Since renal clearance decreases with age, Valcyte should be administered to elderly patients with special consideration of their renal status (see table below). (See section 5.2)

Patients with renal impairment:
Serum creatinine levels or estimated creatinine clearance should be monitored carefully. Dosage adjustment is required according to creatinine clearance, as shown in the table below (see sections 4.4 and 5.2).

An estimated creatinine clearance (ml/min) can be related to serum creatinine by the following formulae:

For males =         (140 – age [years])  (body weight [kg])
(72)  (0.011  serum creatinine [micromol/l])

For females = 0.85  male value
Clcr (ml/min)           Induction dose of valganciclovir        Maintenance/Prevention dose of valganciclovir

 60                    900 mg (2 tablets) twice daily          900 mg (2 tablets) once daily 40 – 59                 450 mg (1 tablet) twice daily           450 mg (1 tablet) once daily
25 – 39                 450 mg (1 tablet) once daily            450 mg (1 tablet) every 2 days
10 – 24                 450 mg (1 tablet) every 2 days          450 mg (1 tablet) twice weekly VALCYTE®                                                                                Valcyte PI version 3 < 10                     Not recommended                          Not recommended 
Patients undergoing haemodialysis:
For patients on haemodialysis (Clcr < 10 ml/min) a dose recommendation cannot be given. Thus Valcyte film-coated tablets should not be used in these patients (see sections 4.4 and 5.2).

Patients with hepatic impairment:
Safety and efficacy of Valcyte tablets have not been established in patients with hepatic impairment (see section 5.2).

Patients with severe leucopenia, neutropenia, anaemia, thrombocytopenia and pancytopenia: See section 4.4 before initiation of therapy.

If there is a significant deterioration of blood cell counts during therapy with Valcyte, treatment with haematopoietic growth factors and/or dose interruption should be considered (see section 4.4).

Method of administration

Valcyte is administered orally, and whenever possible, should be taken with food (see section 5.2).
Precautions to be taken before handling or administering the medicinal product The tablets should not be broken or crushed. Since Valcyte is considered a potential teratogen and carcinogen in humans, caution should be observed in handling broken tablets (see section 4.4). Avoid direct contact of broken or crushed tablets with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water, rinse eyes thoroughly with sterile water, or plain water if sterile water is unavailable.