Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/855
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Cytovene-IV (Injection, Powder, Lyophilized, For Solution)
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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).<br/>Dosage: THE RECOMMENDED DOSE FOR CYTOVENE-IV SOLUTION SHOULD NOT BE EXCEEDED. THE RECOMMENDED INFUSION RATE FOR CYTOVENE-IV SOLUTION SHOULD NOT BE EXCEEDED.<br/>For Treatment of CMV Retinitis in Patients With Normal Renal Function:<br/>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.<br/>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.<br/>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 .<br/>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: (140 - age[yrs]) (body wt [kg])Creatinine clearance for males = (72) (serum creatinine [mg/dL]) Creatinine clearance for females = 0.85��male value 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%.<br/>Patient Monitoring: Due to the frequency of granulocytopenia, anemia and thrombocytopenia in patients receiving ganciclovir , 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 .<br/>Reduction of Dose: Dosage reductions in renally impaired patients are required for CYTOVENE-IV (see Renal Impairment). Dosage reductions should also be considered for those with neutropenia, anemia and/or thrombocytopenia . Ganciclovir should not be administered in patients with severe neutropenia (ANC less than 500/��L) or severe thrombocytopenia (platelets less than 25,000/��L).<br/>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:<br/>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. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
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Ganciclovir is a synthetic guanine derivative active against cytomegalovirus (CMV). CYTOVENE-IV is the brand name for ganciclovir sodium for injection. CYTOVENE-IV is available as sterile lyophilized powder in strength of 500 mg per vial for intravenous administration only. Each vial of CYTOVENE-IV contains the equivalent of 500 mg ganciclovir as the sodium salt (46 mg sodium). Reconstitution with 10 mL of Sterile Water for Injection, USP, yields a solution with pH 11 and a ganciclovir concentration of approximately 50 mg/mL. Further dilution in an appropriate intravenous solution must be performed before infusion . Ganciclovir is a white to off-white crystalline powder with a molecular formula of CHNand a molecular weight of 255.23. The chemical name for ganciclovir is 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl]guanine. 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 pKs for ganciclovir are 2.2 and 9.4. Ganciclovir, when formulated as monosodium salt in the IV dosage form, is a white to off-white lyophilized powder with the molecular formula of CHNNa0, and a molecular weight of 277.22. The chemical name for ganciclovir sodium is 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl]guanine, monosodium salt. 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. The chemical structures of ganciclovir sodium and ganciclovir are: All doses in this insert are specified in terms of ganciclovir.
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Pharmacokinetics: BECAUSE THE MAJOR ELIMINATION PATHWAY FOR GANCICLOVIR IS RENAL, DOSAGE REDUCTIONS ACCORDING TO CREATININE CLEARANCE ARE REQUIRED FOR CYTOVENE-IV. FOR DOSING INSTRUCTIONS IN PATIENTS WITH RENAL IMPAIRMENT, REFER TO DOSAGE AND ADMINISTRATION.<br/>Absorption: At the end of a 1-hour intravenous infusion of 5 mg/kg ganciclovir, total AUC ranged between 22.1��3.2 (n=16) and 26.8��6.1��g���hr/mL (n=16) and Cranged between 8.27��1.02 (n=16) and 9.0��1.4��g/mL (n=16).<br/>Distribution: The steady-state volume of distribution of ganciclovir after intravenous administration was 0.74��0.15 L/kg (n=98). Cerebrospinal fluid concentrations obtained 0.25 to 5.67 hours postdose in 3 patients who received 2.5 mg/kg ganciclovir intravenously q8h or q12h ranged from 0.31 to 0.68��g/mL representing 24% to 70% of the respective plasma concentrations. Binding to plasma proteins was 1% to 2% over ganciclovir concentrations of 0.5 and 51��g/mL.<br/>Elimination: When administered intravenously, ganciclovir exhibits linear pharmacokinetics over the range of 1.6 to 5.0 mg/kg and when administered orally, it exhibits linear kinetics up to a total daily dose of 4 g/day. Renal excretion of unchanged drug by glomerular filtration and active tubular secretion is the major route of elimination of ganciclovir. In patients with normal renal function, 91.3��5.0% (n=4) of intravenously administered ganciclovir was recovered unmetabolized in the urine. Systemic clearance of intravenously administered ganciclovir was 3.52��0.80 mL/min/kg (n=98) while renal clearance was 3.20��0.80 mL/min/kg (n=47), accounting for 91��11% of the systemic clearance (n=47). Half-life was 3.5��0.9 hours (n=98) following IV administration and 4.8��0.9 hours (n=39) following oral administration.<br/>Special Populations:<br/>Renal Impairment: The pharmacokinetics following intravenous administration of CYTOVENE-IV solution were evaluated in 10 immunocompromised patients with renal impairment who received doses ranging from 1.25 to 5.0 mg/kg. Based on these observations, it is necessary to modify the dosage of ganciclovir in patients with renal impairment . Hemodialysis reduces plasma concentrations of ganciclovir by about 50% after intravenous administration.<br/>Race/Ethnicity and Gender: The effects of race/ethnicity and gender were studied in subjects receiving a dose regimen of 1000 mg every 8 hours. Although the numbers of blacks (16%) and Hispanics (20%) were small, there appeared to be a trend towards a lower steady-state Cand AUCin these subpopulations as compared to Caucasians. No definitive conclusions regarding gender differences could be made because of the small number of females (12%); however, no differences between males and females were observed.<br/>Pediatrics: Ganciclovir pharmacokinetics were studied in 27 neonates, aged 2 to 49 days. At an intravenous dose of 4 mg/kg (n=14) or 6 mg/kg (n=13), the pharmacokinetic parameters were, respectively, Cof 5.5��1.6 and 7.0��1.6��g/mL, systemic clearance of 3.14��1.75 and 3.56��1.27 mL/min/kg, and tof 2.4 hours (harmonic mean) for both. Ganciclovir pharmacokinetics were also studied in 10 pediatric patients, aged 9 months to 12 years. The pharmacokinetic characteristics of ganciclovir were the same after single and multiple (q12h) intravenous doses (5 mg/kg). The steady-state volume of distribution was 0.64��0.22 L/kg, Cwas 7.9��3.9��g/mL, systemic clearance was 4.7��2.2 mL/min/kg, and twas 2.4��0.7 hours. The pharmacokinetics of intravenous ganciclovir in pediatric patients are similar to those observed in adults.<br/>Elderly: No studies have been conducted in adults older than 65 years of age.
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CYTOVENE-IV is contraindicated in patients with hypersensitivity to ganciclovir or acyclovir.
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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).<br/>Storage: Store vials at temperatures below 40��C (104��F).
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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 .
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General: In clinical studies with CYTOVENE-IV, the maximum single dose administered was 6 mg/kg by intravenous infusion over 1 hour. Larger doses have resulted in increased toxicity. It is likely that more rapid infusions would also result in increased toxicity . Administration of CYTOVENE-IV solution should be accompanied by adequate hydration. Initially reconstituted solutions of CYTOVENE-IV have a high pH (pH 11). Despite further dilution in intravenous fluids, phlebitis and/or pain may occur at the site of intravenous infusion. Care must be taken to infuse solutions containing CYTOVENE-IV only into veins with adequate blood flow to permit rapid dilution and distribution . Since ganciclovir is excreted by the kidneys, normal clearance depends on adequate renal function. IF RENAL FUNCTION IS IMPAIRED, DOSAGE ADJUSTMENTS ARE REQUIRED FOR CYTOVENE-IV. Such adjustments should be based on measured or estimated creatinine clearance values .<br/>Information for Patients: All patients should be informed that the major toxicities of ganciclovir are granulocytopenia (neutropenia), anemia and thrombocytopenia and that dose modifications may be required, including discontinuation. The importance of close monitoring of blood counts while on therapy should be emphasized. Patients should be informed that ganciclovir has been associated with elevations in serum creatinine. Patients should be advised that ganciclovir has caused decreased sperm production in animals and may cause infertility in humans. Women of childbearing potential should be advised that ganciclovir causes birth defects in animals and should not be used during pregnancy. Women of childbearing potential should be advised to use effective contraception during treatment with CYTOVENE-IV. Similarly, men should be advised to practice barrier contraception during and for at least 90 days following treatment with CYTOVENE-IV. Patients should be advised that ganciclovir causes tumors in animals. Although there is no information from human studies, ganciclovir should be considered a potential carcinogen.<br/>All HIV+ Patients: These patients may be receiving zidovudine. Patients should be counseled that treatment with both ganciclovir and zidovudine simultaneously may not be tolerated by some patients and may result in severe granulocytopenia (neutropenia). Patients with AIDS may be receiving didanosine. Patients should be counseled that concomitant treatment with both ganciclovir and didanosine can cause didanosine serum concentrations to besignificantly increased.<br/>HIV+ Patients With CMV Retinitis: Ganciclovir is not a cure for CMV retinitis, and immunocompromised patients may continue to experience progression of retinitis during or following treatment. Patients should be advised to have ophthalmologic follow-up examinations at a minimum of every 4 to 6 weeks while being treated with CYTOVENE-IV. Some patients will require more frequent follow-up.<br/>Transplant Recipients: Transplant recipients should be counseled regarding the high frequency of impaired renal function in transplant recipients who received CYTOVENE-IV solution in controlled clinical trials, particularly in patients receiving concomitant administration of nephrotoxic agents such as cyclosporine and amphotericin B. Although the specific mechanism of this toxicity, which in most cases was reversible, has not been determined,the higher rate of renal impairment in patients receiving CYTOVENE-IV solution compared with those who received placebo in the same trials may indicate that CYTOVENE-IV played a significant role.<br/>Laboratory Testing: Due to the frequency of neutropenia, anemia and thrombocytopenia in patients receiving CYTOVENE-IV , 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 leukopenia, or in whom neutrophil counts are less than 1000 cells/��L at the beginning of treatment. Increased serum creatinine levels have been observed in trials evaluating both CYTOVENE-IV. Patients should have serum creatinine or creatinine clearance values monitored carefully to allow for dosage adjustments in renally impaired patients .<br/>Drug Interactions:<br/>Didanosine: When the standard intravenous ganciclovir induction dose (5 mg/kg infused over 1 hour every 12 hours) was coadministered with didanosine at a dose of 200 mg orally every 12 hours, the steady-state didanosine AUCincreased 70��40% (range: 3% to 121%, n=11) and Cincreased 49��48% (range: -28% to 125%). In a separate study, when the standard intravenous ganciclovir maintenance dose (5 mg/kg infused over 1 hour every 24 hours) was coadministered with didanosine at a dose of 200 mg orally every 12 hours, didanosine AUCincreased 50��26% (range: 22% to 110%, n=11) and Cincreased 36��36% (range: -27% to 94%) over the first didanosine dosing interval. Didanosine plasma concentrations (AUC) were unchanged during the dosing intervals when ganciclovir was not coadministered. Ganciclovir pharmacokinetics were not affected by didanosine. In neither study were there significant changes in the renal clearance of either drug.<br/>Zidovudine: At an oral dose of 1000 mg of ganciclovir every 8 hours, mean steady-state ganciclovir AUCdecreased 17��25% (range: -52% to 23%) in the presence of zidovudine, 100 mg every 4 hours (n=12). Steady-state zidovudine AUCincreased 19��27% (range: -11% to 74%) in the presence of ganciclovir. No drug-drug interaction studies have been conducted with IV ganciclovir and zidovudine. Since both zidovudine and ganciclovir have the potential to cause neutropenia and anemia, some patients may not tolerate concomitant therapy with these drugs at full dosage.<br/>Probenecid: At an oral dose of 1000 mg of ganciclovir every 8 hours (n=10), ganciclovir AUCincreased 53��91% (range: -14% to 299%) in the presence of probenecid, 500 mg every 6 hours. Renal clearance of ganciclovir decreased 22��20% (range: -54% to -4%), which is consistent with an interaction involving competition for renal tubular secretion. No drug-drug interaction studies have been conducted with IV ganciclovir and probenecid.<br/>Imipenem-cilastatin: Generalized seizures have been reported in patients who received ganciclovir and imipenem-cilastatin. These drugs should not be used concomitantly unless the potential benefits outweigh the risks.<br/>Other Medications: It is possible that drugs that inhibit replication of rapidly dividing cell populations such as bone marrow, spermatogonia and germinal layers of skin and gastrointestinal mucosa may have additive toxicity when administered concomitantly with ganciclovir. Therefore, drugs such as dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamycin, amphotericin B, trimethoprim/sulfamethoxazole combinations or other nucleoside analogues, should be considered for concomitant use with ganciclovir only if the potential benefits are judged to outweigh the risks. No formal drug interaction studies of CYTOVENE-IV and drugs commonly used in transplant recipients have been conducted. Increases in serum creatinine were observed in patients treated with CYTOVENE-IV plus either cyclosporine or amphotericin B, drugs with known potential for nephrotoxicity . In a retrospective analysis of 93 liver allograft recipients receiving ganciclovir (5 mg/kg infused over 1 hour every 12 hours) and oral cyclosporine (at therapeutic doses), there was no evidence of an effect on cyclosporine whole blood concentrations.<br/>Carcinogenesis, Mutagenesis: Ganciclovir was carcinogenic in the mouse at oral doses of 20 and 1000 mg/kg/day (approximately 0.1x and 1.4x, respectively, the mean drug exposure in humans following the recommended intravenous dose of 5 mg/kg, based on area under the plasma concentration curve [AUC] comparisons). At the dose of 1000 mg/kg/day 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, 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 (estimated as 0.01x the human dose based on AUC comparison). 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��g/mL, respectively. In the mouse micronucleus assay, ganciclovir was clastogenic at doses of 150 and 500 mg/kg (IV) (2.8 to 10x human exposure based on AUC) but not 50 mg/kg (exposure approximately comparable to the human based on AUC). Ganciclovir was not mutagenic in the Ames Salmonella assay at concentrations of 500 to 5000��g/mL.<br/>Impairment of Fertility: Ganciclovir caused decreased mating behavior, decreased fertility, and an increased incidence of embryolethality in female mice following intravenous doses of 90 mg/kg/day (approximately 1.7x the mean drug exposure in humans following the dose of 5 mg/kg, based on AUC comparisons). Ganciclovir caused decreased fertility in male mice and hypospermatogenesis in mice and dogs following daily oral or intravenous administration of doses ranging from 0.2 to 10 mg/kg. Systemic drug exposure (AUC) at the lowest dose showing toxicity in each species ranged from 0.03 to 0.1x the AUC of the recommended human intravenous dose.<br/>Pregnancy:<br/>Category C: Ganciclovir has been shown to be embryotoxic in rabbits and mice following intravenous administration and teratogenic in rabbits. Fetal resorptions were present in at least 85% of rabbits and mice administered 60 mg/kg/day and 108 mg/kg/day (2x the human exposure based on AUC comparisons), respectively. Effects observed in rabbits included: fetal growth retardation, embryolethality, teratogenicity and/or maternal toxicity. Teratogenic changes included cleft palate, anophthalmia/microphthalmia, aplastic organs (kidney and pancreas), hydrocephaly and brachygnathia. In mice, effects observed were maternal/fetal toxicity and embryolethality. Daily intravenous doses of 90 mg/kg administered to female mice prior to mating, during gestation, and during lactation caused hypoplasia of the testes and seminal vesicles in the month-old male offspring, as well as pathologic changes in the nonglandular region of the stomach (see Carcinogenesis, Mutagenesis). The drug exposure in mice as estimated by the AUC was approximately 1.7x the human AUC. Ganciclovir may be teratogenic or embryotoxic at dose levels recommended for human use. There are no adequate and well-controlled studies in pregnant women. CYTOVENE-IV should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.<br/>Nursing Mothers: It is not known whether ganciclovir is excreted in human milk. However, many drugs are excreted in human milk and, because carcinogenic and teratogenic effects occurred in animals treated with ganciclovir, the possibility of serious adverse reactions from ganciclovir in nursing infants is considered likely . Mothers should be instructed to discontinue nursing if they are receiving CYTOVENE-IV. The minimum interval before nursing can safely be resumed after the last dose of CYTOVENE-IV is unknown.<br/>Pediatric Use: SAFETY AND EFFICACY OF CYTOVENE-IV IN PEDIATRIC PATIENTS HAVE NOT BEEN ESTABLISHED. THE USE OF CYTOVENE-IV IN THE PEDIATRIC POPULATION WARRANTS EXTREME CAUTION DUE TO THE PROBABILITY OF LONG-TERM CARCINOGENICITY AND REPRODUCTIVE TOXICITY. ADMINISTRATION TO PEDIATRIC PATIENTS SHOULD BE UNDERTAKEN ONLY AFTER CAREFUL EVALUATION AND ONLY IF THE POTENTIAL BENEFITS OF TREATMENT OUTWEIGH THE RISKS. The spectrum of adverse events reported in 120 immunocompromised pediatric clinical trial participants with serious CMV infections receiving CYTOVENE-IV solution were similar to those reported in adults. Granulocytopenia (17%) and thrombocytopenia (10%) were the most common adverse events reported. Sixteen pediatric patients (8 months to 15 years of age) with life- or sight-threatening CMV infections were evaluated in an open-label, CYTOVENE-IV solution, pharmacokinetics study. Adverse events reported for more than one pediatric patient were as follows: hypokalemia (4/16, 25%), abnormal kidney function (3/16, 19%), sepsis (3/16, 19%), thrombocytopenia (3/16, 19%), leukopenia (2/16, 13%), coagulation disorder (2/16, 13%), hypertension (2/16, 13%), pneumonia (2/16, 13%) and immune system disorder (2/16, 13%). There has been very limited clinical experience using CYTOVENE-IV for the treatment of CMV retinitis in patients under the age of 12 years. Two pediatric patients (ages 9 and 5 years) showed improvement or stabilization of retinitis for 23 and 9 months, respectively. These pediatric patients received induction treatment with 2.5 mg/kg tid followed by maintenance therapy with 6 to 6.5 mg/kg once per day, 5 to 7 days per week. When retinitis progressed during once-daily maintenance therapy, both pediatric patients were treated with the 5 mg/kg bid regimen. Two other pediatric patients (ages 2.5 and 4 years) who received similar induction regimens showed only partial or no response to treatment. Another pediatric patient, a 6-year-old with T-cell dysfunction, showed stabilization of retinitis for 3 months while receiving continuous infusions of CYTOVENE-IV at doses of 2 to 5 mg/kg/24 hours. Continuous infusion treatment was discontinued due to granulocytopenia. Eleven of the 72 patients in the placebo-controlled trial in bone marrow transplant recipients were pediatric patients, ranging in age from 3 to 10 years (5 treated with CYTOVENE-IV and 6 with placebo). Five of the pediatric patients treated with CYTOVENE-IV received 5 mg/kg intravenously bid for up to 7 days; 4 patients went on to receive 5 mg/kg qd up to day 100 posttransplant. Results were similar to those observed in adult transplant recipients treated with CYTOVENE-IV. Two of the 6 placebo-treated pediatric patients developed CMV pneumonia vs none of the 5 patients treated with CYTOVENE-IV. The spectrum of adverse events in the pediatric group was similar to that observed in the adult patients.<br/>Geriatric Use: The pharmacokinetic profiles of CYTOVENE-IV in elderly patients have not been established. Since elderly individuals frequently have a reduced glomerular filtration rate, particular attention should be paid to assessing renal function before and during administration of CYTOVENE-IV . Clinical studies of CYTOVENE-IV did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. CYTOVENE-IV is known tobe substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. In addition, renal function should be monitored and dosage adjustments should be made accordingly .<br/>Use in Patients With Renal Impairment: CYTOVENE-IV should be used with caution in patients with impaired renal function because the half-life and plasma/serum concentrations of ganciclovir will be increased due to reduced renal clearance . Hemodialysis has been shown to reduce plasma levels of ganciclovir by approximately 50%.
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ganciclovir sodium
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Cytovene-IV (Injection, Powder, Lyophilized, For Solution)
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Hematologic: CYTOVENE-IV should not be administered if the absolute neutrophil count is less than 500 cells/��L or the platelet count is less than 25,000 cells/��L. Granulocytopenia (neutropenia), anemia and thrombocytopenia have been observed in patients treated with CYTOVENE-IV. The frequency and severity of these events vary widely in different patient populations . CYTOVENE-IV should, therefore, be used with caution in patients with pre-existing cytopenias or with a history of cytopenic reactions to other drugs, chemicals or irradiation. Granulocytopenia usually occurs during the first or second week of treatment but may occur at any time during treatment. Cell counts usually beginto recover within 3 to 7 days of discontinuing drug. Colony-stimulating factors have been shown to increase neutrophil and white blood cell counts in patients receiving CYTOVENE-IV solution for treatment of CMV retinitis.<br/>Impairment of Fertility: Animal data indicate that administration of ganciclovir causes inhibition of spermatogenesis and subsequent infertility. These effects were reversible at lower doses and irreversible at higher doses . Although data in humans have not been obtained regarding this effect, it is considered probable that ganciclovir at the recommended doses causes temporary or permanent inhibition of spermatogenesis. Animal data also indicate that suppression of fertility in females may occur.<br/>Teratogenesis: Because of the mutagenic and teratogenic potential of ganciclovir, women of childbearing potential should be advised to use effective contraception during treatment. Similarly, men should be advised to practice barrier contraception during and for at least 90 days following treatment with CYTOVENE-IV .
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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.
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Cytovene-IV
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