Stability data:
|
| Drug |
Stability
Refrigerated |
Stability
Room Temp. |
Reconstituted
Vial/Powder |
Notes |
| Ganciclovir - Cytovene |
|
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F)
Reconstituted solution in the vial is stable at room temperature for 12 hours. |
Powder |
Solution: CYTOVENE-IV, when reconstituted with sterile water for injection, further diluted with 0.9% sodium chloride injection, and stored refrigerated at 5°C in polyvinyl chloride (PVC) bags, remains physically and chemically stable for 14 days.
However, because CYTOVENE-IV 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. Freezing is not recommended. |
EXP: 1 DAY (REF).
Reconstitute vial with 10 ml of Sterile Water for Injection (do not use bacteriostatic water), and shake well to dissolve drug. Vial stability: stable at room temperature for 12 hours (Do not refrigerate). Remember when further diluted with NS or D5W, final solution should be refrigerated until ready for use.
Label: Refrigerate.
Maximum concentration: 10 mg/ml.
Follow chemotherapy handling precautions when preparing.
Must adjust dose in renal failure.
| WARNING
THE CLINICAL TOXICITY OF CYTOVENE-IV INCLUDES GRANULOCYTOPENIA, ANEMIA AND THROMBOCYTOPENIA. IN ANIMAL STUDIES GANCICLOVIR WAS CARCINOGENIC, TERATOGENIC AND CAUSED ASPERMATOGENESIS.
CYTOVENE-IV IS INDICATED FOR USE ONLY IN THE TREATMENT OF CYTOMEGALOVIRUS (CMV) RETINITIS IN IMMUNOCOMPROMISED PATIENTS AND FOR THE PREVENTION OF CMV DISEASE IN TRANSPLANT PATIENTS AT RISK FOR CMV DISEASE |
INDICATIONS AND USAGE
CYTOVENE-IV is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). CYTOVENE-IV is also indicated for the prevention of CMV disease in transplant recipients at risk for CMV disease.
SAFETY AND EFFICACY OF CYTOVENE-IV HAS NOT BEEN ESTABLISHED FOR CONGENITAL OR NEONATAL CMV DISEASE; NOR FOR THE TREATMENT OF ESTABLISHED CMV DISEASE OTHER THAN RETINITIS; NOR FOR USE IN NON-IMMUNOCOMPROMISED INDIVIDUALS.
DOSAGE AND ADMINISTRATION
CAUTION - DO NOT ADMINISTER CYTOVENE-IV SOLUTION BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF CYTOVENE-IV MAY BE INCREASED AS A RESULT OF EXCESSIVE PLASMA LEVELS.
CAUTION - INTRAMUSCULAR OR SUBCUTANEOUS INJECTION OF RECONSTITUTED CYTOVENE-IV SOLUTION MAY RESULT IN SEVERE TISSUE IRRITATION DUE TO HIGH pH (11).
Dosage------------------------
THE RECOMMENDED DOSE FOR CYTOVENE-IV SOLUTION SHOULD NOT BE EXCEEDED. THE RECOMMENDED INFUSION RATE FOR CYTOVENE-IV 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 CYTOVENE-IV 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 CYTOVENE-IV, reinduction treatment is recommended.
For the Prevention of CMV Disease in Transplant Recipients With Normal Renal Function
The recommended initial dosage of CYTOVENE-IV 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 CYTOVENE-IV solution in transplant recipients is dependent upon the duration and degree of immunosuppression. In controlled clinical trials in bone marrow allograft recipients, treatment with CYTOVENE-IV was continued until day 100 to 120 posttransplantation. CMV disease occurred in several patients who discontinued treatment with CYTOVENE-IV solution prematurely. In heart allograft recipients, the onset of newly diagnosed CMV disease occurred after treatment with CYTOVENE-IV 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 above section for a more detailed discussion).
Renal Impairment
For patients with impairment of renal function, refer to Table 8 for recommended doses of CYTOVENE-IV solution and adjust the dosing interval as indicated:
Dosing for Patients with Renal Impairment
Creatinine
Clearance*
(mL/min) |
CYTOVENE-IV
Induction
Dose (mg/kg) |
Dosing
Interval
(hours) |
CYTOVENE-IV
Maintenance
Dose (mg/kg) |
Dosing
Interval
(hours) |
| *Creatinine clearance can be related to serum creatinine by the formulas given below. |
| ≥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,
following hemodialysis |
0.625 |
3 times per week,
following hemodialysis |
| Creatinine clearance for males = |
[140-age (years)]× [body wt (kg)]
72 × [serum creatinine (mg/dL)] |
| Creatinine clearance for females = |
[140-age (years)]× [body wt (kg)]× 0.85
72 × [serum creatinine (mg/dL)] |
Dosing for patients undergoing hemodialysis should not exceed 1.25 mg/kg 3 times per week, following each hemodialysis session. CYTOVENE-IV 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 package insert for 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/µL 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 above).
Reduction of Dose
Dosage reductions in renally impaired patients are required for CYTOVENE-IV (see Renal Impairment above). Dosage reductions should also be considered for those with neutropenia, anemia and/or thrombocytopenia (see package insert for ADVERSE EVENTS). Ganciclovir should not be administered in patients with severe neutropenia (ANC less than 500/µL) or severe thrombocytopenia (platelets less than 25,000/µL).
Method of Preparation of CYTOVENE-IV 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:
Reconstituted Solution:
1. Reconstitute lyophilized CYTOVENE-IV 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 CYTOVENE-IV AND MAY CAUSE PRECIPITATION.
2. Shake the vial to dissolve the drug.
3. 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.
4. Reconstituted solution in the vial is stable at room temperature for 12 hours. It should not be refrigerated.
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 CYTOVENE-IV solution: 0.9% Sodium Chloride, 5% Dextrose, Ringer's Injection and Lactated Ringer's Injection, USP.
Stability: CYTOVENE-IV, when reconstituted with sterile water for injection, further diluted with 0.9% sodium chloride injection, and stored refrigerated at 5°C in polyvinyl chloride (PVC) bags, remains physically and chemically stable for 14 days.
However, because CYTOVENE-IV 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. Freezing is not recommended.
Handling and Disposal
Caution should be exercised in the handling and preparation of solutions of CYTOVENE-IV. Solutions of CYTOVENE-IV are alkaline (pH 11). Avoid direct contact of the skin or mucous membranes with CYTOVENE-IV solutions. If such contact occurs, wash thoroughly with soap and water; rinse eyes thoroughly with plain water.
Because ganciclovir shares some of the properties of antitumor agents (ie, carcinogenicity and mutagenicity), consideration should be given to handling and disposal according to guidelines issued for antineoplastic drugs. Several guidelines on this subject have been published.7-9
There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
HOW SUPPLIED
CYTOVENE®-IV (ganciclovir sodium for injection) is supplied in 10 mL sterile vials, each containing ganciclovir sodium equivalent to 500 mg of ganciclovir, in cartons of 25 (NDC 0004-6940-03).
Storage
Store vials at temperatures below 40°C (104°F).
January 2006
Copyright ©1999-2006 by Roche Laboratories Inc. All rights reserved.
Source: [package insert]
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