openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Adverse reactions sections page 1 of 2 · 5 matching rows.
adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: • Hematologic Toxicity [see Warnings and Precautions ( 5.1 )] • Impairment of Renal Function [see Warnings and Precautions ( 5.2 )] • Impairment of Fertility [see Warnings and Precautions ( 5.3 )] • Fetal Toxicity [see Warnings and Precautions ( 5.4 )] • Mutagenesis and Carcinogenesis [see Warnings and Precautions ( 5.5 )] Most common adverse reactions and laboratory abnormalities reported in at least 20% of patients were fever, diarrhea, leukopenia, anemia, catheter-related events (including catheter infection and catheter sepsis), and elevated creatinine levels. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, Contact Exela Pharma Sciences, LLC at 1-888-451-4321 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Patients with CMV Retinitis Three controlled, randomized, phase 3 trials comparing intravenous ganciclovir and ganciclovir capsules for maintenance treatment of CMV retinitis have been completed. During these trials, 9% of subjects were prematurely discontinued because of adverse reactions. Selected adverse reactions and laboratory abnormalities reported during the conduct of these controlled trials are summarized in Table 2 and Table 3, respectively [see Clinical Studies ( 14 )] . Table 2. Pooled Selected Adverse Events Reported in ≥ 5% of Subjects Comparing Intravenous Ganciclovir to Ganciclovir Capsules for Maintenance Treatment of CMV Retinitis Adverse Event Maintenance Treatment Studies Intravenous Ganciclovir (n=179) Ganciclovir Capsules (n=326) Fever 48% 38% Diarrhea 44% 41% Leukopenia 41% 29% Anemia 25% 19% Total catheter events: 22% 6% Catheter infection 9% 4% Catheter sepsis 8% 1% Other catheter related events 5% 1% Sepsis 15% 4% Anorexia 14% 15% Vomiting 13% 13% Infection 13% 9% Sweating 12% 11% Chills 10% 7% Neuropathy 9% 8% Thrombocytopenia 6% 6% Pruritus 5% 6% 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 intravenous ganciclovir and in 8% of patients treated with ganciclovir capsules. Table 3. Selected Laboratory Abnormalities in Trials for Treatment of CMV Retinitis Laboratory Abnormalities CMV Retinitis Treatment* Intravenous Ganciclovir† 5mg/kg/day (N=175) % Ganciclovir Capsules‡ 3000mg/day (N=320) % Neutropenia with Absolute Neutrophil Count (ANC) per µL: <500 25% 18% 500 - <749 14% 17% 750 - <1000 16% 19% Anemia with Hemoglobin (g/dL): <6.5 5% 2% 6.5 - <8.0 16% 10% 8.0 - <9.5 26% 25% Serum Creatinine (mg/dL): ≥2.5 2% 1% ≥1.5 - <2.5 14% 12% * Pooled data from treatment studies ICM 1653, ICM 1774, and AVI 034 † Mean time on therapy = 103 days, including allowed re-induction treatment periods ‡ Mean time on therapy = 91 days, including allowed re-induction treatment periods Adverse Reactions in Transplant Recipients There have been three controlled clinical trials of intravenous ganciclovir for the prevention of CMV disease in transplant recipients. Selected laboratory abnormalities are summarized in Tables 4 and 5 below. Table 4 shows the frequency of neutropenia and thrombocytopenia and Table 5 shows the frequency of elevated serum creatinine values observed in these trials [see Clinical Studies ( 14 )]. Table 4. Laboratory Abnormalities in Controlled Trials – Transplant Recipients who Received Intravenous Ganciclovir or Placebo Laboratory Abnormalities Heart Allograft* Bone Marrow Allograft† Intravenous Ganciclovir (N=76) Placebo (n=73) Intravenous Ganciclovir (n=57) Control (n=55) Neutropenia Absolute Neutrophil Count (ANC) per µL: <500 4% 3% 12% 6% <500-1000 3% 8% 29% 17% TOTAL ANC ≤1000/µL 7% 11% 41% 23% Thrombocytopenia Platelet count per µL: <25,000 3% 1% 32% 28% 25,000-50,000 5% 3% 25% 37% TOTAL Platelet Count ≤50,000/µL 8% 4% 57% 65% Table 5. Serum Creatinine Levels in Controlled Trials – Transplant Recipients who Received Intravenous Ganciclovir or Placebo Serum Creatinine Levels (mg/dL) Heart Allograft ICM 1496 Bone Marrow Allograft ICM 1570 Bone Marrow Allograft ICM 1689 Intravenous Ganciclovir (N=76) Placebo (n=73) Intravenous Ganciclovir (n=20) Placebo (n=73) Intravenous Ganciclovir (n=37) Placebo (n=35) ≥2.5 18% 14% 20% 0% 0% 0% ≥1.5 - <2.5 58% 69% 50% 35% 43% 44% Other Adverse Reactions in Clinical Trials in Patients with CMV Retinitis and in Transplant Recipients Other adverse reactions with intravenous ganciclovir or ganciclovir capsules in controlled clinical studies in either subjects with AIDS or transplant recipients are listed below [see Clinical Studies (14)]. All these events occurred in at least 3 subjects. Ear and labyrinth disorders: tinnitus Eye disorders: abnormal vision, vitreous disorder Gastrointestinal disorders: enlarged abdomen, aphthous stomatitis, constipation, dyspepsia, eructation, gastrointestinal perforation, pancreatitis, dry mouth General disorders and administration site conditions: asthenia, injection site inflammation, edema, malaise, multiple organ failure, pain, chest pain Blood and lymphatic system disorders: pancytopenia Infections and infestations: sepsis Investigations: abnormal liver function test, decreased creatinine clearance Metabolism and nutritional disorders: weight loss Musculoskeletal and connective tissue disorders: arthralgia, leg cramps, myalgia, myasthenia Renal and urinary disorders: kidney failure, abnormal kidney function, urinary frequency Respiratory, thoracic and mediastinal disorders: increased cough, dyspnea Nervous system disorders: confusion, dizziness, headache, insomnia, seizures, somnolence, abnormal thinking, tremor, taste perversion Psychiatric disorders: abnormal dreams, anxiety, depression Skin and subcutaneous disorders: alopecia, dry skin Vascular disorders: hypertension, phlebitis, vasodilation 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of intravenous ganciclovir. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders: hemolytic anemia Cardiac disorders: cardiac arrest, cardiac conduction abnormality, torsades de pointes, ventricular tachycardia Congenital, familial and genetic disorders: congenital anomaly Eye disorders: cataracts, dry eyes Gastrointestinal disorders: intestinal ulceration Hepatobiliary disorders: hepatic failure, cholestasis, cholelithiasis, hepatitis Immune system disorders: anaphylactic reaction, allergic reaction, vasculitis Investigations: increased blood triglycerides, increased blood antidiuretic hormone Metabolism and nutrition disorders: acidosis, hypercalcemia, hyponatremia Musculoskeletal and connective tissue disorders: arthritis, rhabdomyolysis Nervous system disorders: dysesthesia, dysphasia, encephalopathy, extrapyramidal disorder, facial palsy, intracranial hypertension, loss of memory, loss of smell, myelopathy, oculomotor nerve paralysis, stroke Renal and urinary disorders: hemolytic uremic syndrome, renal tubular disorder Reproductive system and breast disorders: infertility, testicular hypotrophy Respiratory, thoracic and mediastinal disorders: bronchospasm, pulmonary fibrosis Psychiatric disorders: hallucinations, irritability Skin and subcutaneous tissue disorders: exfoliative dermatitis, Stevens-Johnson syndrome Vascular disorders: peripheral ischemia