FDA label 0cc9ca35-2e33-495a-8c7b-390fa2daad19

WARNING THE CLINICAL TOXICITY OF GANCICLOVIR INCLUDES GRANULOCYTOPENIA, ANEMIA AND THROMBOCYTOPENIA. IN ANIMAL STUDIES GANCICLOVIR WAS CARCINOGENIC, TERATOGENIC AND CAUSED ASPERMATOGENESIS. GANCICLOVIR 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 ATRISK FOR CMV DISEASE (see INDICATIONS AND USAGE ).

WARNINGS Hematologic Ganciclovir should not be administered if the absolute neutrophil count is less than 500 cells/μL or the platelet count is less than 25,000 cells/μL. Granulocytopenia (neutropenia), anemia and thrombocytopenia have been observed in patients treated with ganciclovir. The frequency and severity of these events vary widely in different patient populations (see ADVERSE REACTIONS ). Ganciclovir 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 begin to 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 ganciclovir IV solution for treatment of CMV retinitis. 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 (see PRECAUTIONS : Carcinogenesis, Mutagenesis, Impairment of Fertility ). 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. 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 ganciclovir (see PRECAUTIONS : Pregnancy : Teratogenic Effects: Pregnancy Category C ).

ADVERSE REACTIONS Adverse events that occurred during clinical trials of ganciclovir are summarized below, according to the participating study subject population. Subjects with AIDS Three controlled, randomized, phase 3 trials comparing ganciclovir IV and ganciclovir capsules for maintenance treatment of CMV retinitis have been completed. During these trials, ganciclovir IV or ganciclovir capsules were prematurely discontinued in 9% of subjects because of adverse events. Laboratory data and adverse events reported during the conduct of these controlled trials are summarized below. Laboratory Data: Table 4. Selected Laboratory Abnormalities in Trials for Treatment of CMV Retinitis Adverse Events: The following table shows selected adverse events reported in 5% or more of the subjects in three controlled clinical trials during treatment with either ganciclovir IV solution (5 mg/kg/day) or ganciclovir capsules (3000 mg/day), and in one controlled clinical trial with ganciclovir capsules (3000 mg/day). Table 5. Selected Adverse Events Reported in ≥ 5% of Subjects in Three Randomized Phase 3 Studies Comparing Ganciclovir Capsules to Ganciclovir IV Solution for Maintenance Treatment of CMV Retinitis The following events were frequently observed in clinical trials but occurred with equal or greater frequency in placebo-treated subjects: abdominal pain, nausea, flatulence, pneumonia, paresthesia, rash. Retinal Detachment: Retinal detachment has been observed in subjects with CMV retinitis both before and after initiation of therapy with ganciclovir. Its relationship to therapy with ganciclovir is unknown. Retinal detachment occurred in 11% of patients treated with ganciclovir solution and in 8% of patients treated with ganciclovir capsules. Patients with CMV retinitis should have frequent ophthalmologic evaluations to monitor the status of their retinitis and to detect any other retinal pathology. Transplant Recipients There have been three controlled clinical trials of ganciclovir solution for the prevention of CMV disease in transplant recipients. Laboratory data and adverse events reported during these trials are summarized below. Laboratory Data: The following table shows the frequency of granulocytopenia (neutropenia) and thrombocytopenia observed: The following table shows the frequency of elevated serum creatinine values in these controlled clinical trials: In these three trials, patients receiving ganciclovir IV solution had elevated serum creatinine levels when compared to those receiving placebo. Most patients in these studies also received cyclosporine. The mechanism of impairment of renal function is not known. However, careful monitoring of renal function during therapy with ganciclovir IV solution is essential, especially for those patients receiving concomitant agents that may cause nephrotoxicity. General Other adverse events that were thought to be "probably" or "possibly" related to ganciclovir IV solution or ganciclovir capsules in controlled clinical studies in either subjects with AIDS or transplant recipients are listed below. These events all occurred in at least 3 subjects. Body as a Whole: abdomen enlarged, asthenia, chest pain, edema, headache, injection site inflammation, malaise, pain Digestive System: abnormal liver function test, aphthous stomatitis, constipation, dyspepsia, eructation Hemic and Lymphatic System: pancytopenia Respiratory System: cough increased, dyspnea Nervous System: abnormal dreams, anxiety, confusion, depression, dizziness, dry mouth, insomnia, seizures, somnolence, thinking abnormal, tremor Skin and Appendages: alopecia, dry skin Special Senses: abnormal vision, taste perversion, tinnitus, vitreous disorder Metabolic and Nutritional Disorders: creatinine increased, SGOT increased, SGPT increased, weight loss Cardiovascular System: hypertension, phlebitis, vasodilatation Urogenital System: creatinine clearance decreased, kidney failure, kidney function abnormal, urinary frequency Musculoskeletal System: arthralgia, leg cramps, myalgia, myasthenia The following adverse events reported in patients receiving ganciclovir may be potentially fatal: gastrointestinal perforation, multiple organ failure, pancreatitis and sepsis. Adverse Events Reported During Postmarketing Experience With Ganciclovir The following events have been identified during postapproval use of the drug. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either the seriousness, frequency of reporting, the apparent causal connection or a combination of these factors: acidosis, allergic reaction, anaphylactic reaction, arthritis, bronchospasm, cardiac arrest, cardiac conduction abnormality, cataracts, cholelithiasis, cholestasis, congenital anomaly, dry eyes, dysesthesia, dysphasia, elevated triglyceride levels, encephalopathy, exfoliative dermatitis, extrapyramidal reaction, facial palsy, hallucinations, hemolytic anemia, hemolytic uremic syndrome, hepatic failure, hepatitis, hypercalcemia, hyponatremia, inappropriate serum ADH, infertility, intestinal ulceration, intracranial hypertension, irritability, loss of memory, loss of sense of smell, myelopathy, oculomotor nerve paralysis, peripheral ischemia, pulmonary fibrosis, renal tubular disorder, rhabdomyolysis, Stevens-Johnson syndrome, stroke, testicular hypotrophy, Torsades de Pointes, vasculitis, ventricular tachycardia Table 4. Selected Laboratory Abnormalities in Trials for Treatment of CMV Retinitis Table 5. Selected Adverse Events Reported in Greater Than or Equal to 5% of Subjects in Three Randomized Phase 3 Studies Comparing Ganciclovir Capsules to Ganciclovir IV Solution for Maintenance Treatment of CMV Retinitis Table 6. Controlled Trials - Transplant Recipients Table 7. Controlled Trials - Transplant Recipients