Posology : מינונים

2    DOSAGE AND ADMINISTRATION
CAUTION - DO NOT ADMINISTER CYMEVENE 500 MG SOLUTION BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF CYMEVENE 500 MG MAY BE INCREASED AS A RESULT OF EXCESSIVE PLASMA LEVELS.

CAUTION - INTRAMUSCULAR OR SUBCUTANEOUS INJECTION OF RECONSTITUTED CYMEVENE 500 MG SOLUTION MAY RESULT IN SEVERE TISSUE IRRITATION DUE TO HIGH pH (11).

Dosage
THE RECOMMENDED DOSE FOR CYMEVENE 500 MG SOLUTION SHOULD NOT BE EXCEEDED. THE RECOMMENDED INFUSION RATE FOR CYMEVENE 500 MG SOLUTION SHOULD NOT BE EXCEEDED.
For Treatment of CMV Retinitis in Patients with Normal Renal Function 
Induction Treatment
The recommended initial dosage for patients with normal renal function is 5 mg/kg (given intravenously at a constant rate over 1 hour) every 12 hours for 14 to 21 days.

Maintenance Treatment
Following induction treatment, the recommended maintenance dosage of CYMEVENE 500 MG solution is 5 mg/kg given as a constant-rate intravenous infusion over 1 hour once daily, 7 days per week, or 6 mg/kg once daily, 5 days per week.

For patients who experience progression of CMV retinitis while receiving maintenance treatment with CYMEVENE 500 MG, reinduction treatment is recommended.

For the Prevention of CMV Disease in Transplant Recipients with Normal Renal Function The recommended initial dosage of CYMEVENE 500 MG solution for patients with normal renal function is 5 mg/kg (given intravenously at a constant rate over 1 hour) every 12 hours for 7 to 14 days, followed by 5 mg/kg once daily, 7 days per week or 6 mg/kg once daily, 5 days per week.

The duration of treatment with CYMEVENE 500 MG solution in transplant recipients is dependent upon the duration and degree of immunosuppression. In controlled clinical trials in bone marrow allograft recipients, treatment with CYMEVENE 500 MG was continued until day 100 to 120 post transplantation. CMV disease occurred in several patients who discontinued treatment with CYMEVENE 500 MG solution prematurely. In heart allograft recipients, the onset of newly diagnosed CMV disease occurred after treatment with CYMEVENE 500 MG was stopped at day 28 posttransplant, suggesting that continued dosing may be necessary to prevent late occurrence of CMV disease in this patient population (see INDICATIONS AND USAGE section for a more detailed discussion).

Renal Impairment
For patients with impairment of renal function, refer to Table 8 for recommended doses of CYMEVENE 500 MG solution and adjust the dosing interval as indicated:

Table 1             Dosing for Patients with Renal Impairment
Creatinine CYMEVENE 500                 Dosing           CYMEVENE 500                Dosing Clearance*          MG                   Interval                 MG                  Interval (mL/min)        Induction               (hours)             Maintenance              (hours) Dose (mg/kg)                                 Dose (mg/kg)
70             5.0                     12                    5.0                    24 50–69             2.5                     12                    2.5                    24 25–49             2.5                     24                    1.25                   24
10–24             1.25                    24                   0.625                   24 <10             1.25           3 times per week,             0.625           3 times per week, following hemodialysis                        following hemodialysis
* Creatinine clearance can be related to serum creatinine by the formulas given below.

(140 - age[yrs]) (body wt [kg])
Creatinine clearance for males = —————————————— (72) (serum creatinine [mg/dL])
Creatinine clearance for females = 0.85 x male value

Hemodialysis
Dosing for patients undergoing hemodialysis should not exceed 1.25 mg/kg 3 times per week, following each hemodialysis session. CYMEVENE 500 MG should be given shortly after completion of the hemodialysis session, since hemodialysis has been shown to reduce plasma levels by approximately 50%.

Patient Monitoring
Due to the frequency of granulocytopenia, anemia and thrombocytopenia in patients receiving ganciclovir (see ADVERSE EVENTS), it is recommended that complete blood counts and platelet counts be performed frequently, especially in patients in whom ganciclovir or other nucleoside analogues have previously resulted in cytopenia, or in whom neutrophil counts are less than 1000 cells/L at the beginning of treatment. Patients should have serum creatinine or creatinine clearance values followed carefully to allow for dosage adjustments in renally impaired patients (see DOSAGE AND ADMINISTRATION).

Reduction of Dose
Dosage reductions in renally impaired patients are required for CYMEVENE 500 MG (see Renal Impairment).
Dosage reductions should also be considered for those with neutropenia, anemia and/or thrombocytopenia (see ADVERSE EVENTS). Ganciclovir should not be administered in patients with severe neutropenia (ANC less than 500/L) or severe thrombocytopenia (platelets less than 25,000/L).

Method of Preparation of CYMEVENE 500 MG Solution
Each 10 mL clear glass vial contains ganciclovir sodium equivalent to 500 mg of ganciclovir and 46 mg of sodium.
The contents of the vial should be prepared for administration in the following manner: 
1. Reconstituted Solution:
 a. Reconstitute lyophilized CYMEVENE 500 MG by injecting 10 mL of Sterile Water for Injection, USP, into the vial.
DO NOT USE BACTERIOSTATIC WATER FOR INJECTION CONTAINING PARABENS. IT IS INCOMPATIBLE WITH CYMEVENE 500 MG AND MAY CAUSE PRECIPITATION.
b. Shake the vial to dissolve the drug.
c. Visually inspect the reconstituted solution for particulate matter and discoloration prior to proceeding with infusion solution. Discard the vial if particulate matter or discoloration is observed.
d. Reconstituted solution in the vial is stable at room temperature for 12 hours. It should not be refrigerated.

2. Infusion Solution:

Based on patient weight, the appropriate volume of the reconstituted solution (ganciclovir concentration 50 mg/mL) should be removed from the vial and added to an acceptable infusion fluid (typically 100 mL) for delivery over the course of 1 hour. Infusion concentrations greater than 10 mg/mL are not recommended. The following infusion fluids have been determined to be chemically and physically compatible with CYMEVENE 500 MG solution: 0.9% Sodium Chloride, 5% Dextrose, Ringer’s Injection and Lactated Ringer’s Injection, USP.

CYMEVENE 500 MG, when reconstituted with sterile water for injection, further diluted with 0.9% sodium chloride injection, and stored refrigerated at 2-8°C in polyvinyl chloride (PVC) bags, remains physically and chemically stable for 24 hours.
Because CYMEVENE 500 MG is reconstituted with nonbacteriostatic sterile water, it is recommended that the infusion solution be used within 24 hours of dilution to reduce the risk of bacterial contamination. The infusion should be refrigerated. Do not Freeze.


Handling and Disposal
Caution should be exercised in the handling and preparation of solutions of CYMEVENE 500 MG. Solutions of CYMEVENE 500 MG are alkaline (pH 11). Avoid direct contact of the skin or mucous membranes with CYMEVENE 500 MG solution. If such contact occurs, wash thoroughly with soap and water; rinse eyes thoroughly with plain water. Wearing disposable gloves is recommended.
Because ganciclovir shares some of the properties of antitumor agents (i.e., carcinogenicity and mutagenicity), consideration should be given to handling and disposal according to guidelines issued for antineoplastic drugs.