VALGANCICLOVIR Film-coated tablets Ref.[8518] Active ingredients: Valganciclovir

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 Valganciclovir 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).

Maintenance treatment of CMV retinitis:

Following induction treatment, or in patients with inactive CMV retinitis, the recommended dose is 900 mg valganciclovir (two Valganciclovir 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 valganciclovir 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

Adult patients

For kidney transplant patients, the recommended dose is 900 mg (two Valganciclovir 450 mg tablets) once daily, starting within 10 days post-transplantation and continuing until 100 days post-transplantation. Prophylaxis may be continued until 200 days post-transplantation (see sections 4.4, 4.8 and 5.1).

For patients who have received a solid organ transplant other than kidney, the recommended dose is 900 mg (two Valganciclovir 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.

Paediatric population

In paediatric solid organ transplant patients, aged from birth, who are at risk of developing CMV disease, the recommended once daily dose of valganciclovir is based on body surface area (BSA) and creatinine clearance (Clcr) derived from Schwartz formula (ClcrS), and is calculated using the equation below:

Paediatric Dose (mg) = 7 x BSA x ClcrS (see Mosteller BSA formula and Schwartz Creatinine Clearance formula below).

If the calculated Schwartz creatinine clearance exceeds 150 mL/min/1.73m², then a maximum value of 150 mL/min/1.73m² should be used in the equation:

Mosteller BSA (m²) =

Schwartz Creatinine Clearance (ml/min/1,73m²) =

Where k = 0.45* for patients aged <2 years, 0.55 for boys aged 2 to <13 years and girls aged 2 to 16 years, and 0.7 for boys aged 13 to 16 years. Refer to adult dosing for patients older than 16 years of age.

The k values provided are based on the Jaffe method of measuring serum creatinine and may require correction when enzymatic methods are used.

* For appropriate sub-populations a lowering of k value may also be necessary (e.g. in paediatric patients with low birth weight).

For paediatric kidney transplant patients, the recommended once daily mg dose (7 x BSA x ClcrS) should start within 10 days post-transplantation and continue until 200 days post-transplantation.

For paediatric patients who have received a solid organ transplant other than kidney, the recommended once daily mg dose (7x BSA x ClcrS) should start within 10 days post transplantation and continue until 100 days post-transplantation.

All calculated doses should be rounded to the nearest 25 mg increment for the actual deliverable dose. If the calculated dose exceeds 900 mg, a maximum dose of 900 mg should be administered. The oral solution is the preferred formulation since it provides the ability to administer a dose calculated according to the formula above; however, valganciclovir film-coated tablets may be used if the calculated doses are within 10% of available tablet doses, and the patient is able to swallow tablets. For example, if the calculated dose is between 405 mg and 495 mg, one 450 mg tablet may be taken.

It is recommended to monitor serum creatinine levels regularly and consider changes in height and body weight and adapt the dose as appropriate during the prophylaxis period.

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 ages. Since renal clearance decreases with age, valganciclovir 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]) X (body weight [kg]) / (72) X (0.011 X serum creatinine [μmol/l])

For females = 0.85 X male value

Patients undergoing haemodialysis

For patients on haemodialysis (Clcr < 10 ml/min) a dose recommendation cannot be given. Thus Valganciclovir 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 valganciclovir tablets have not been established in patients with hepatic impairment (see section 5.2).

Patients with severe leukopenia, 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 valganciclovir, treatment with haematopoietic growth factors and/or dose interruption should be considered (see section 4.4).

Method of administration

Valganciclovir is administered orally, and whenever possible, should be taken with food (see section 5.2).

Valganciclovir is also available as an oral suspension for use in patients who are unable to swallow tablets (please refer to the Summary of Product Characteristics for oral suspension containing valganciclovir).

Precautions to be taken before handling or administering the medicinal product

The tablets should not be broken or crushed. Since valganciclovir 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.

Overdose experience with valganciclovir and intravenous ganciclovir

It is expected that an overdose of valganciclovir could possibly result in increased renal toxicity (see sections 4.2 and 4.4).

Reports of overdoses with intravenous ganciclovir, some with fatal outcomes, have been received from clinical trials and during post-marketing experience. In some of these cases no adverse events were reported. The majority of patients experienced one or more of the following adverse events:

• Haematological toxicity: myelosuppression including pancytopenia, bone marrow failure, leukopenia, neutropenia, granulocytopenia.
• Hepatotoxicity: hepatitis, liver function disorder.
• Renal toxicity: worsening of haematuria in a patient with pre-existing renal impairment, acute kidney injury, elevated creatinine.
• Gastrointestinal toxicity: abdominal pain, diarrhoea, vomiting.
• Neurotoxicity: generalised tremor, seizure.

Haemodialysis and hydration may be of benefit in reducing blood plasma levels in patients who receive an overdose of valganciclovir (see section 5.2).

Shelf life: 24 months.

This medicinal product does not require any special storage conditions.

High density polyethylene (HDPE) bottles and child resistant polypropylene (PP) screw cap with induction heat sealing (with aluminum foil). The screw cap has a tamper evident.

Pack size: One bottle containing 60 film coated tablets.

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