Description
Description
Active ingredient: Ganciclovir
Each vial contains 500 mg of ganciclovir (as ganciclovir sodium).
Powder for concentrate for solution for infusion
CYMEVENE is the brand innovator for ganciclovir – FDA approved.
Indications:
Cymevene is indicated in adults and adolescents ≥ 12 years of age for the:
– treatment of cytomegalovirus (CMV) disease in immunocompromised patients
– prevention of CMV disease using pre-emptive therapy in patients with drug- induced immunosuppression (for example following organ transplantation or cancer chemotherapy).
Cymevene is also indicated from birth for the:
– prevention of CMV disease using universal prophylaxis in patients with drug- induced immunosuppression (for example following organ transplantation or cancer chemotherapy).
Consideration should be given to official guidance on the appropriate use of antiviral agents.
Dosage and route of administration
Posology
Treatment of CMV disease
Adults and paediatric population ≥ 12 years of age with normal renal function:
– Induction treatment: 5 mg/kg given as an intravenous infusion over one hour, every 12 hours for 14 – 21 days.
– Maintenance treatment: For immunocompromised patients at risk of relapse maintenance therapy may be given. 5 mg/kg given as an intravenous infusion over one hour, once daily on 7 days per week or 6 mg/kg once daily on 5 days per week. The duration of maintenance treatment should be determined on an individual basis, local treatment guidelines should be consulted.
– Treatment of disease progression: Any patient, in whom CMV disease progresses, either while on maintenance treatment or because treatment with ganciclovir has been withdrawn, may be re-treated using the induction treatment regimen.
Paediatric population from birth to < 12 years of age:
Currently available paediatric data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made.
Prevention of CMV disease using pre-emptive therapy
Adults and paediatric population ≥ 12 years of age with normal renal function:
Induction therapy: 5 mg/kg given as an intravenous infusion over one hour, every 12 hours for 7 – 14 days.
Maintenance therapy: 5 mg/kg given as an intravenous infusion over one hour, once daily on 7 days per week or 6 mg/kg once daily on 5 days per week. The duration of maintenance therapy is based on the risk of CMV disease, local treatment guidelines should be consulted.
Paediatric population from birth to < 12 years of age:
Currently available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made.
Prevention of CMV disease using universal prophylaxis
Adults and paediatric population > 16 years of age:
5 mg/kg given as an intravenous infusion over one hour, once daily on 7 days per week or 6 mg/kg once daily on 5 days per week. The duration is based on the risk of CMV disease, local treatment guidelines should be consulted.
Paediatric population from birth to ≤ 16 years of age:
The recommended once daily dose of ganciclovir given as an intravenous infusion over one hour is based on Body Surface Area (BSA) using the Mosteller BSA formula and creatinine clearance derived from Schwartz formula (CrCLS) and is calculated using the equations below. The duration of universal prophylaxis is based on the risk of CMV disease and should be determined on an individual basis.
Paediatric dose (mg) = 3 x BSA x CrCLS (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:
where k = 0.33 for patients < 1 year of age with low birth weight, 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.
It is recommended that serum creatinine levels, height and weight are reviewed regularly, and the dose amended as appropriate.
Special dosage instructions
Renal impairment
Paediatric patients (from birth to ≤ 16 years of age) with renal impairment receiving a prophylactic dose of ganciclovir calculated using the 3 x BSA x CrCLS dosing algorithm do not require further dose modification because this dose is already adjusted for creatinine clearance.
For patients 12 years and older with renal impairment, treated on a mg/kg bodyweight basis for pre-emptive therapy and treatment of CMV disease, the mg/kg dose of ganciclovir should be modified according to creatinine clearance as shown in the table below .
Dose modifications for patients with renal impairment receiving mg/kg dosing
For females: 0.85 x male value
As dosage modifications are recommended in patients with renal impairment, serum creatinine or estimated creatinineclearance levels should be monitored.
Hepatic impairment
The safety and efficacy of Cymevene have not been studied in patients with hepatic impairment .
Severe leukopenia, neutropenia, anaemia, thrombocytopenia and pancytopenia
If the blood cell counts are significantly reduced during therapy with ganciclovir, treatment with haematopoietic growth factors and/or discontinuation of treatment should be considered .
Elderly
No studies on the efficacy or safety of ganciclovir in the elderly have been conducted. Since renal function decreases with age, ganciclovir should be administered to the elderly with special consideration for their renal status .
Method of administration
Caution:
Ganciclovir must be administered by intravenous infusion over 1 hour at a concentration not exceeding 10 mg/mL. Do not administer by rapid or bolus intravenous injection because the resulting excessive plasma levels may increase the toxicity of ganciclovir.
Do not administer by intramuscular or subcutaneous injection because this may result in severe tissue irritation due to the high pH (~11) of ganciclovir solutions .
The recommended dosage, frequency and infusion rates should not be exceeded.
Cymevene is a powder for solution for infusion. After reconstitution Cymevene is a colourless to slightly yellowish solution, practically free from visible particles.
The infusion should be given into a vein with adequate blood flow, preferably via a plastic cannula.
Precautions to be taken before handling or administering the medicinal product:
Since ganciclovir is considered a potential teratogen and carcinogen in humans, caution should be taken in its handling
