Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, have been reported in patients receiving anti-inhibitor coagulant complex (AICC). The symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. These reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Pruritus and wheezing have also been reported during postmarketing use. Discontinue administration immediately and provide appropriate supportive care if signs and symptoms of a severe allergic reaction occurs.[41546]

Injection site reaction (i.e., injection site pain) has been reported during postmarketing use of anti-inhibitor coagulant complex (AICC). Infusion-related reactions, such as chills, fever, and hypertension, have also been reported.[41546]

Thromboembolism including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur with anti-inhibitor coagulant complex (AICC), especially after the administration of high doses (more than 200 units/kg/day) and/or in patients with thrombotic risk factors. Disseminated intravascular coagulation (DIC) and increased fibrin D-dimer have been reported with postmarketing use. Monitor patients receiving more than 100 units/kg for the development of DIC, acute coronary ischemia, and signs and symptoms of other thromboembolic events. Discontinue the infusion and initiate appropriate diagnostic and therapeutic measures if symptoms occur.[41546]

Anti-inhibitor coagulant complex (AICC) products are derived from human plasma donors and carry the possibility of causing iatrogenic infection via blood borne pathogens. The risk with AICC is considered to be low due to the careful screening of plasma donors and manufacturing processes. However, new blood borne pathogens not controlled by present measures can theoretically emerge at any time.[41546]

Hypoesthesia, dizziness, and drowsiness were reported in clinical trials of anti-inhibitor coagulation complex (AICC) for the treatment of acute bleeding episodes. Headache was reported in 6.7% of subjects receiving 50% reduced volume of AICC at increased infusion rates up to 10 units/kg/minute during postmarketing experience in a clinical trial evaluating the tolerability and safety of infusing reduced volume of AICC at increased rates. Malaise and feeling hot (hot flashes) have been reported with postmarketing use.[41546]

In a clinical trial of anti-inhibitor coagulant complex (AICC) for prophylaxis, the most frequently reported gastrointestinal-related adverse reactions observed in more than 5% of subjects were diarrhea (5.6%), nausea (5.6%), and vomiting (5.6%). Dysgeusia and nausea were also reported in clinical trials of AICC for acute bleeding episodes. Abdominal discomfort has been reported during postmarketing use.[41546]

Anemia (5.6%) and hemarthrosis (8.3%) were reported in a clinical trial of anti-inhibitor coagulant complex (AICC) for prophylaxis. Chest pain (unspecified), chest discomfort, and dyspnea were reported during acute bleeding clinical trials. Sinus tachycardia and flushing have been reported during postmarketing use.[41546]

Anti-inhibitor coagulant complex (AICC) is contraindicated in patients with disseminated intravascular coagulation (DIC) and patients with acute thrombosis or embolism, including myocardial infarction. Thromboembolism, including DIC, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have been reported following AICC administration. Many of these events occurred after high doses (more than 200 units/kg/day) and/or in patients with thrombotic risk factors. Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with recombinant factor VIIa have an increased risk of thrombosis due to predisposing coagulopathy or circulating tissue factor. Potential benefit of treatment with AICC should be weighed against risk for thromboembolic event. Monitor patients receiving AICC more than 100 units/kg for signs and symptoms of DIC, acute coronary ischemia, and other thromboembolic events. If signs or symptoms such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain occur, discontinue the AICC infusion and initiate appropriate diagnostic and therapeutic measures.[41546]

Anti-inhibitor coagulant complex (AICC) is derived from human plasma and may therefore carry a risk of transmitting viral infection, and theoretically, the Creutzfeldt-Jakob disease agent. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents; however, none of the processes are completely effective. All infections thought to have been transmitted by AICC should be reported to the manufacturer and/or the FDA (1-800-FDA-1088 or www.fda.gov/medwatch).[41546]

Anti-inhibitor coagulant complex (AICC) contains blood group isohemagglutinins (anti-A and anti-B). Passive transmission of antibodies to erythrocyte antigens, e.g., A, B, D, may cause laboratory test interference with some serological tests for red cell antibodies, such as antiglobulin test (Coombs test).[41546]

It is not known whether anti-inhibitor coagulant complex (AICC) can cause fetal harm or affect reproduction capacity when administered during pregnancy. There are no data with AICC use in pregnant women to determine a drug-associated risk. There are no adequate and well-controlled studies with AICC in pregnant women and animal reproduction studies have not been conducted.[41546]

There is no information regarding the presence of anti-inhibitor coagulant complex (AICC) in human milk, the effect on the breast-fed child, or the effects on milk production. Consider the benefits of breast-feeding along with the mother's clinical need for AICC and any potential adverse effects on the breast-fed child from AICC or the underlying maternal condition.[41546]