FDA label d5c7ef89-dc5d-41fc-9aa0-69b45b53e99c

WARNINGS CMV-IGIV is made from human plasma and, like other plasma products, carries the possibility for transmission of blood-borne viral agents and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk of transmission of recognized blood-borne viruses is considered to be low because of the viral inactivation and removal properties in the Cohn-Oncley cold ethanol precipitation procedure used for purification of immune globulin products. 13-15 Until 1993, cold ethanol manufactured immune globulins licensed in the United States had not been documented to transmit any viral agent. However, during a brief period in late 1993 to early 1994, intravenous immune globulin made by one U.S. manufacturer was associated with transmission of Hepatitis C virus. 16 To further guard against possible transmission of blood-borne viruses, including Hepatitis C, CMV-IGIV is treated with a solvent detergent viral inactivation procedure 2 known to inactivate a wide spectrum of lipid enveloped viruses, including HIV-1, HIV-2, Hepatitis B, and Hepatitis C. 17 However, because new blood-borne viruses may yet emerge, some of which may not be inactivated by the manufacturing process or by solvent detergent treatment, CMV-IGIV, like any other blood product, should be given only if a benefit is expected. Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis and death. 18-25 Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentrations available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many IGIV products, those containing sucrose as a stabilizer (and given at daily doses of 350 mg/kg or greater) account for a disproportionate share of the total number. 18 Cytogam contains sucrose as a stabilizer. See PRECAUTIONS and DOSAGE AND ADMINISTRATION sections for important information intended to reduce the risk of acute renal failure. During administration, the patient's vital signs should be monitored continuously and careful observation made for any symptoms throughout the infusion. Epinephrine should be available for the treatment of an acute anaphylactic reaction ( see PRECAUTIONS section).

ADVERSE REACTIONS Minor reactions such as flushing, chills, muscle cramps, back pain, fever, nausea, vomiting, arthralgia, and wheezing were the most frequent adverse reactions observed during the clinical trials of Cytogam, Cytomegalovirus Immune Globulin Intravenous (Human). The incidence of these reactions during the clinical trials was less than 6.0% of all infusions and such reactions were most often related to infusion rates. A decrease in blood pressure was observed in 1 of 1039 infusions in clinical trials of Cytogam. If a patient develops a minor side effect, slow the rate immediately or temporarily interrupt the infusion. Increases in serum creatinine and blood urea nitrogen (BUN) have been observed as soon as one to two days following IGIV infusion. Progression to oliguria or anuria requiring dialysis has been observed. Types of severe renal adverse events that have been seen following IGIV therapy include acute renal failure, acute tubular necrosis, proximal tubular nephropathy and osmotic nephrosis. 18-25 Severe reactions such as angioneurotic edema and anaphylactic shock, although not observed during clinical trials, are a possibility. Clinical anaphylaxis may occur even when the patient is not known to be sensitized to immune globulin products. A reaction may be related to the rate of infusion; therefore, carefully adhere to the infusion rates as outlined under " DOSAGE AND ADMINISTRATION ." If anaphylaxis or drop in blood pressure occurs, discontinue infusion and use antidote such as diphenhydramine and adrenalin. Postmarketing The following adverse reactions have been identified and reported during the post-approval use of IGIV products: 38 Respiratory: Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion-Related Acute Lung Injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm Cardiovascular: Cardiac arrest, thromboembolism, vascular collapse, hypotension Neurological: Coma, loss of consciousness, seizures, tremor Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis Hematologic: Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs) test General/Body as a Whole: Pyrexia, Rigors Musculoskeletal: Back pain Gastrointestinal : Hepatic dysfunction, abdominal pain Because postmarketing reporting of these reactions is voluntary and the at-risk populations are of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to exposure to the product. Such is also the case with literature reports authored independently.