DailyMed Label: Ganciclovir

DailyMed Label: Ganciclovir

2021

DailyMed Prescription

Ganciclovir

ganciclovir sodium

Slate Run Pharmaceuticals, LLC

NDC: 70436-089

NDC: 70436-089

Ganciclovir for injection contains ganciclovir, in the form of the sodium salt for intravenous injection. Ganciclovir is a synthetic guanine derivative active against cytomegalovirus (CMV). Chemically, ganciclovir is 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl]guanine and ganciclovir sodium is 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl]guanine, monosodium salt. The chemical structures of ganciclovir sodium and ganciclovir are: Ganciclovir is a white to off-white crystalline powder. Ganciclovir is a polar hydrophilic compound with a solubility of 2.6 mg/mL in water at 25°C and an n-octanol/water partition coefficient of 0.022. The pK a s for ganciclovir are 2.2 and 9.4. Ganciclovir for injection (ganciclovir), formulated as monosodium salt, using sodium hydroxide as a salt forming agent, is a sterile white to off-white lyophilized powder. The lyophilized powder has an aqueous solubility of greater than 50 mg/mL at 25°C. At physiological pH, ganciclovir sodium exists as the un-ionized form with a solubility of approximately 6 mg/mL at 37°C. Each vial contains 543 mg ganciclovir sodium equivalent to 500 mg ganciclovir. Inactive ingredients may include hydrochloric acid (QS) and sodium hydroxide (QS) added to adjust the pH. All doses in this package insert are specified in terms of ganciclovir

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 ) Prevention of CMV disease in adult transplant recipients at risk for CMV disease. ( 1.2 )

Ganciclovir for Injection, USP is administered only intravenously. ( 2.1 ) 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 )

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 Dosage and Administration (2.6) ].

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.

Renal Impairment: Increased serum creatinine levels have been observed with the use of ganciclovir, particularly in elderly patients and transplant recipients receiving concomitant nephrotoxic drugs. Monitor renal function during therapy with ganciclovir for injection, particularly in elderly patients and in patients taking other nephrotoxic drugs, and reduce dosage in patients with renal impairment. ( 5.2 )

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

Drug-drug interaction studies were conducted in patients with normal renal function. Patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug following concomitant administration of ganciclovir for injection and drugs excreted by the same pathway as ganciclovir. Therefore, these patients should be closely monitored for toxicity of ganciclovir and the coadministered drug. Established and other potentially significant drug interactions conducted with ganciclovir are listed in Table 6 [see Clinical Pharmacology (12.3) ]. Table 6. Established and Other Potentially Significant Drug Interactions with Ganciclovir Name of the Concomitant Drug Change in the Concentration of Ganciclovir or Concomitant Drug Clinical Comment Imipenem-cilastatin Unknown Coadministration with imipenem-cilastatin is not recommended because generalized seizures have been reported in patients who received ganciclovir and imipenem-cilastatin. Cyclosporine or amphotericin B Unknown Monitor renal function when ganciclovir for injection is coadministered with cyclosporine or amphotericin B because of potential increase in serum creatinine [see Warnings and Precautions (5.2) ]. Mycophenolate mofetil (MMF) ↔Ganciclovir (in patients with normal renal function) ↔MMF (in patients with normal renal function) Based on increased risk, patients should be monitored for hematological and renal toxicity. Other drugs associated with myelosuppresion or nephrotoxicity (e.g., dapsone, doxorubicin, flucytosine, hydroxyurea, pentamidine, tacrolimus, trimethoprim/sulfamethoxazole, vinblastine, vincristine and zidovudine) Unknown Because of potential for higher toxicity, coadministration with ganciclovir for injection should be considered only if the potential benefits are judged to outweigh the risks Didanosine ↔ Ganciclovir ↑ Didanosine Patients should be closely monitored for didanosine toxicity (e.g., pancreatitis). Probenecid ↑ Ganciclovir Ganciclovir for injection dose may need to be reduced. Monitor for evidence of ganciclovir toxicity.

Lactation: Breastfeeding is not recommended with use of Ganciclovir for Injection, USP. ( 8.2 )

How Supplied Ganciclovir for Injection, USP is supplied in 10 mL sterile single-dose vials, each containing 543 mg ganciclovir sodium equivalent to 500 mg of ganciclovir as a white to off-white powder. The concentration of ganciclovir in the reconstituted solution is 50 mg/mL. 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. Ganciclovir for Injection, USP is supplied in cartons of 25 vials (NDC 70436-089-55).

Ganciclovir is an antiviral drug with activity against CMV [see Microbiology (12.4) ].

Ganciclovir was carcinogenic in mice at the same mean drug exposure in humans as at the RHD (5 mg/kg). At the dose of 1000 mg/kg/day (1.4 times the exposure at the RHD), there was a significant increase in the incidence of tumors of the preputial gland in males, forestomach (nonglandular mucosa) in males and females, and reproductive tissues (ovaries, uterus, mammary gland, clitoral gland and vagina) and liver in females. At the dose of 20 mg/kg/day (0.1 times the exposure at the RHD), a slightly increased incidence of tumors was noted in the preputial and harderian glands in males, forestomach in males and females, and liver in females. No carcinogenic effect was observed in mice administered ganciclovir at 1 mg/kg/day (exposure estimated as 0.01 times the RHD). Except for histiocytic sarcoma of the liver, ganciclovir-induced tumors were generally of epithelial or vascular origin. Although the preputial and clitoral glands, forestomach and harderian glands of mice do not have human counterparts, ganciclovir should be considered a potential carcinogen in humans. Ganciclovir increased mutations in mouse lymphoma cells and DNA damage in human lymphocytes in vitro at concentrations between 50 to 500 and 250 to 2000 µg/mL, respectively. In the mouse micronucleus assay, ganciclovir was clastogenic at doses of 150 and 500 mg/kg (2.8 to 10 times the exposure at the RHD) but not at doses of 50 mg/kg (exposure approximately comparable to the RHD). Ganciclovir was not mutagenic in the Ames Salmonella assay at concentrations of 500 to 5000 µg/mL.

In a retrospective, non-randomized, single-center analysis of 41 patients with AIDS and CMV retinitis diagnosed by ophthalmologic examination between August 1983 and April 1988, treatment with intravenous ganciclovir resulted in a delay in mean (median) time to first retinitis progression compared to untreated controls [105 (71) days from diagnosis vs. 35 (29) days from diagnosis]. Patients in this series received induction treatment of intravenous ganciclovir 5 mg/kg twice daily for 14 to 21 days followed by maintenance treatment with either 5 mg/kg once daily, 7 days per week or 6 mg/kg once daily, 5 days per week. In a controlled, randomized study conducted between February 1989 and December 1990, immediate treatment with intravenous ganciclovir was compared to delayed treatment in 42 patients with AIDS and peripheral CMV retinitis; 35 of 42 patients (13 in the immediate-treatment group and 22 in the delayed-treatment group) were included in the analysis of time to retinitis progression. Based on masked assessment of fundus photographs, the mean [95% CI] and median [95% CI] times to progression of retinitis were 66 days [39, 94] and 50 days [40, 84], respectively, in the immediate-treatment group compared to 19 days [11, 27] and 13.5 days [8, 18], respectively, in the delayed-treatment group. Data from trials ICM 1653, ICM 1774, and AVI 034, which were performed comparing intravenous ganciclovir to oral ganciclovir for treatment of CMV retinitis in patients with AIDS, are shown in Table 12 , and Figures 1 , 2 , and 3 , and are discussed below. Table 12. Population Characteristics in Studies ICM 1653, ICM 1774, and AVI 034 Demographics ICM 1653 (n=121) ICM 1774 (n=225) AVI 034 (n=159) Median age (years) Range 38 37 39 24-62 22-56 23-62 Sex Males 116 (96%) 222 (99%) 148 (93%) Females 5 (4%) 3 (1%) 10 (6%) Ethnicity Asian 3 (3%) 5 (2%) 7 (4%) Black 11 (9%) 9 (4%) 3 (2%) Caucasian 98 (81%) 186 (83%) 140 (88%) Other 9 (7%) 25 (11%) 8 (5%) Median CD 4 Count Range 9.5 0-141 7.0 0-80 10.0 0-320 Mean (SD) Observation Time (days) 107.9 (43.0) 97.6 (42.5) 80.9 (47.0)

NDC 70436-089-55 Ganciclovir for Injection, USP, 500 mg per vial