Ganciclovir Sodium - Ganciclovir Sodium injection, Powder, Lyophilized, For Solution
(Ganciclovir Sodium)Ganciclovir Sodium - Ganciclovir Sodium injection, Powder, Lyophilized, For Solution Prescribing Information
- Hematologic Toxicity: Granulocytopenia, anemia, thrombocytopenia, and pancytopenia have been reported in patients treated with ganciclovir[see.]
5.1 Hematologic ToxicityGranulocytopenia (neutropenia), anemia, thrombocytopenia and pancytopenia, have been observed in patients treated with ganciclovir. The frequency and severity of these events vary widely in different patient populations [see Adverse Reactions (6.1)]. Ganciclovir for injection is not recommended if the absolute neutrophil count is less than 500 cells/μL, hemoglobin is less than 8 g/dL, or the platelet count is less than 25,000 cells/μL. Ganciclovir for injection should also be used with caution in patients with pre-existing cytopenias and in patients receiving myelosuppressive drugs or irradiation. Granulocytopenia (neutropenia) usually occurs during the first or second week of treatment but may occur at any time during treatment. Cell counts usually begin to recover within 3 to 7 days after discontinuing drug. Colony-stimulating factors have been shown to increase neutrophil and white blood cell counts in patients receiving ganciclovir solution for treatment of CMV retinitis.
Due to the frequency of neutropenia, anemia and thrombocytopenia in patients receiving ganciclovir for injection [see Adverse Reactions (6.1)], complete blood counts with differential and platelet counts should be performed frequently in all patients, especially in patients with renal impairment and in patients in whom ganciclovir or other nucleoside analogues have previously resulted in leukopenia, or in whom neutrophil counts are less than 1000 cells/µL at the beginning of treatment [see Dosage and Administration (2.2)].
- Impairment of Fertility: Based on animal data and limited human data, Ganciclovir for Injection, USP may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females[see.]
5.3 Impairment of FertilityBased on animal data and limited human data, ganciclovir for injection at the recommended human dose (RHD) may cause temporary or permanent inhibition of spermatogenesis in males, and may cause suppression of fertility in females. Advise patients that fertility may be impaired with the use of ganciclovir for injection [see Use in Specific Population (8.1, 8.3), Nonclinical Toxicology (13.1)].
- Fetal Toxicity: Based on animal data, Ganciclovir for Injection, USP has the potential to cause birth defects in humans[see.]
5.4 Fetal ToxicityGanciclovir for injection may cause fetal toxicity when administered to pregnant women based on findings in animal studies. Systemic exposure of ganciclovir in animals at approximately 2 times the RHD caused fetal growth retardation, embryolethality, teratogenicity, and/or maternal toxicity. Teratogenic changes in animals included cleft palate, anophthalmia/microphthalmia, aplastic organs (kidney and pancreas), hydrocephaly and brachygnathia. Women of childbearing potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with ganciclovir for injection. Similarly, men should be advised to practice barrier contraception during and for at least 90 days following treatment with ganciclovir for injection [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].
- Mutagenesis and Carcinogenesis: Based on animal data, Ganciclovir for Injection, USP has the potential to cause cancers in humans[see.]
5.5 Mutagenesis and CarcinogenesisAnimal data indicate that ganciclovir is mutagenic and carcinogenic. Ganciclovir for injection should therefore be considered a potential carcinogen in humans [see Dosage and Administration (2.7), Nonclinical Toxicology (13.1)].
Ganciclovir for Injection, USP is a deoxynucleoside analogue cytomegalovirus (CMV) DNA polymerase inhibitor indicated for the:
- Treatment of CMV retinitis in immunocompromised adult patients, including patients with acquired immunodeficiency syndrome (AIDS). ()
1.1 Treatment of CMV RetinitisGanciclovir for Injection, USP is indicated for the treatment of cytomegalovirus (CMV) retinitis in immunocompromised adult patients, including patients with acquired immunodeficiency syndrome (AIDS) [see Clinical Studies (14.1)].
- Prevention of CMV disease in adult transplant recipients at risk for CMV disease. ()
1.2 Prevention of CMV Disease in Transplant RecipientsGanciclovir for Injection, USP is indicated for the prevention of CMV disease in adult transplant recipients at risk for CMV disease [see Clinical Studies (14.2)].
- Ganciclovir for Injection, USP is administered only intravenously. ()
2.1 Important Dosing and Administration Information- To avoid phlebitis/pain at the infusion site, ganciclovir for injection must only be administered by intravenous infusion over 1 hour, preferably via plastic cannula, into a vein with adequate blood flow to permit rapid dilution and distribution.
- Do not administer ganciclovir for injection by rapid or bolus intravenous injection which may increase toxicity as a result of excessive plasma levels.
- The recommended dosage and infusion rate for ganciclovir for injection should not be exceeded.
- Do not administer the reconstituted ganciclovir for injection solution intramuscularly or subcutaneously because it may result in severe tissue irritation due to high pH [see Description 11].
- Administration of ganciclovir for injection should be accompanied by adequate hydration.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Dosage in Adult Patients with Normal Renal Function | |
Treatment of CMV retinitis (2.3) | Induction: 5 mg/kg (given intravenously at a constant rate over 1 hour) every 12 hours for 14 to 21 days. Maintenance: 5 mg/kg (given intravenously at a constant rate over 1 hour) once daily for 7 days per week, or 6 mg/kg once daily for 5 days per week. |
Prevention of CMV disease in transplant recipients (2.4) | Induction: 5 mg/kg (given intravenously at a constant rate over 1 hour) every 12 hours for 7 to 14 days. Maintenance: 5 mg/kg (given intravenously at a constant rate over 1 hour) once daily for 7 days per week, or 6 mg/kg once daily for 5 days per week until 100 to 120 days post-transplantation. |
- Adults with renal impairment: Adjust dosage based on creatinine clearance. ()
2.5 Recommended Dosage in Adult Patients with Renal ImpairmentFor patients with impairment of renal function, refer to
Table 1for recommended doses of ganciclovir for injection for induction and maintenance dosage for treatment of CMV retinitis and prevention of CMV disease in recipients. Carefully monitor serum creatinine or creatinine clearance before and during treatment to allow for dosage adjustments in patients with impaired renal function.Table 1. Recommended Induction and Maintenance Dosage in Adult Patients with Renal Impairment Creatinine ClearanceCreatinine clearance can be related to serum creatinine by the formulas given below.(mL/min)Ganciclovir for Injection Induction Dose (mg/kg)Dosing Interval (hours) for InductionGanciclovir for Injection Maintenance Dose (mg/kg)Dosing Interval (hours) for MaintenanceGreater than or equal to 70
5
12
5
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
Less than 10
1.25
3 times per week, following hemodialysis
0.625
3 times per week, following hemodialysis
Patients Undergoing HemodialysisInduction dosing for ganciclovir for injection in patients undergoing hemodialysis should not exceed 1.25 mg/kg 3 times per week; and maintenance dosing should not exceed 0.625 mg/kg 3 times per week following each hemodialysis session. Ganciclovir for injection should be given shortly after completion of the hemodialysis session, since hemodialysis has been shown to reduce plasma levels by approximately 50% [see Clinical Pharmacology (12.3)].
For injection: Single-dose vial containing 500 mg of ganciclovir as a sterile lyophilized white to off-white powder for reconstitution with 10 mL of preservative-free sterile water for injection, USP for intravenous use. The concentration of ganciclovir in the reconstituted solution is 50 mg/mL [see
- Ganciclovir for Injection, USP must be reconstituted and diluted under the supervision of a healthcare provider and administered as intravenous infusion. Each 10 mL clear glass vial contains 543 mg ganciclovir sodium equivalent to 500 mg of ganciclovir. Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the vial and the table after reconstitution. The contents of the vial should be prepared for administration in the following manner:
- Reconstitution Instructions:
- Reconstitute lyophilized Ganciclovir for Injection, USP 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 Ganciclovir for Injection, USP and may cause precipitation.
- Gently swirl the vial in order to ensure complete wetting of the product. Continue swirling until a clear reconstituted solution is obtained.
- Visually inspect the reconstituted solution for particulate matter and discoloration prior to proceeding with infusion. Discard the vial if particulate matter or discoloration is observed.
- Reconstituted solution in the vial is stable at room temperature (25°C (77°F)) for 12 hours. Do not refrigerate or freeze. Discard any unused portion of the reconstituted solution.
- Infusion Instructions:
- 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 Ganciclovir for Injection, USP solution: 0.9% Sodium Chloride, 5% Dextrose, Ringer’s Injection and Lactated Ringer’s Injection, USP.
- Ganciclovir for Injection, USP, when reconstituted with Sterile Water for Injection (non-bacteriostatic) and further diluted with 0.9% sodium chloride injection or other acceptable infusion fluid as specified above, should be used within 24 hours of dilution to reduce the risk of bacterial contamination. The diluted infusion solution should be refrigerated (2°C to 8°C (36° to 46°F)). Do not freeze.
Lactation: Breastfeeding is not recommended with use of Ganciclovir for Injection, USP. (
No data are available regarding the presence of ganciclovir in human milk, the effects on the breastfed infant, or the effects on milk production. When ganciclovir was administered to lactating rats, ganciclovir was present in milk [see Data]. Advise nursing mothers that breastfeeding is not recommended during treatment with ganciclovir for injection because of the potential for serious adverse reactions in nursing infants [see Warnings and Precautions (5.1, 5.3, 5.4, 5.5), Nonclinical Toxicology (13.1)]. Furthermore, the Centers for Disease Control and Prevention recommends that HIV-infected mothers not breastfeed their infants to avoid potential postnatal transmission of HIV.
Ganciclovir administered intravenously (at 0.13 mg/h) to lactating rats (on lactation day 15) resulted in passive transfer into milk. The milk-to-serum ratio for ganciclovir at steady state was 1.6 ± 0.33.
Ganciclovir for Injection, USP is contraindicated in patients who have experienced a clinically significant hypersensitivity reaction (e.g., anaphylaxis) to ganciclovir, valganciclovir or any component of the formulation.