openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Potential risk of thrombosis if absorbed systemically ( 5.1 ). May carry a risk of transmitting infectious agents such as viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) agent, despite manufacturing steps designed to reduce the risk of viral transmission ( 5.2 ). 5.1 Thrombosis Potential risk of thrombosis if absorbed systemically 5.2 Transmission of Infectious Agents Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk of transmitting an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections and by inactivating and removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. The physician should discuss the risks and benefits of this product with the patient.
6 ADVERSE REACTIONS The most common adverse reactions during clinical trial (reported in at least 2% of subjects treated with EVITHROM) were prolonged activated partial thromboplastin time, increased INR, decreased lymphocyte count, prolonged prothrombin time and increased neutrophil count. The most common adverse reactions during clinical trial (reported in at least 2% of subjects treated with EVITHROM) were prolonged activated partial thromboplastin time, increased INR, decreased lymphocyte count, prolonged prothrombin time and increased neutrophil count. Adverse events were reported in the clinical trial with similar frequency in the two study groups (EVITHROM or bovine thrombin group) ( 6 ) . Anaphylactic reactions may occur ( 6 ). Immunogenicity was evaluated by testing for the development of antibodies to highly purified antigens: human thrombin, human Factor V/Va, bovine thrombin and bovine Factor V/Va. None of the patients treated with EVITHROM developed antibodies to human thrombin or to human Factor V/Va. To report SUSPECTED ADVERSE REACTIONS, contact ETHICON Customer Support Center at (877) 384-4266 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 product cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Anaphylactic reactions may occur in rare cases. No adverse events of this type were reported during the conduct of the clinical trials. Mild reactions can be managed with anti-histamines. Severe hypotensive reactions require immediate intervention using current principles of shock therapy. In a phase III multicenter, prospective, controlled, randomized, double-blinded study of 305 subjects where EVITHROM (n=153) was compared with bovine thrombin (n=152), occurrence of adverse events was not statistically different between the two groups. Overall, adverse events occurred in similar proportions of subjects in the two study groups (see Table 1 ). No clinically significant differences were seen in age (<65 years, >65 years) or gender subgroup analyses of adverse events. At least one serious adverse event (SAE) was reported for 26/153 (17%) subjects treated with human thrombin and 17/152 (11%) subjects treated with bovine thrombin. The SAEs reported were associated with post-surgical complications (e.g. wound infection 3/153 for EVITHROM and 2/152 for bovine thrombin) and the medical condition of the subject and were not considered related to study drug. Two subjects (1.3%) in EVITHROM group experienced a treatment emergent severe adverse event: respiratory arrest and post-procedural hematoma (in one subject) and extradural hematoma. Three subjects in the bovine thrombin group experienced a treatment emergent severe adverse event: hyperhidrosis, pyrexia and post-procedural hematoma. No deaths were reported during the study period. Viral serology was not monitored during the study with EVITHROM. However, no adverse events indicative of infection with transfusion-transmissible agents were reported. Table 1: Incidence of subjects with related adverse events reported in at least 2% of subjects treated with either human or bovine thrombin Thrombin Type System Organ Class/Adverse Event EVITHROM (n=153) Bovine (n=152) Total (n=305) Investigations 11 (7.2%) 14 (9.2%) 25 (8.2%) Activated partial thromboplastin time increased 4 (2.6%) 8 (5.3%) 12 (3.9%) International normalized ratio increased 4 (2.6%) 5 (3.3%) 9 (3.0%) Lymphocyte count decreased 4 (2.6%) 2 (1.3%) 6 (2.0%) Prothrombin time prolonged 4 (2.6%) 8 (5.3%) 12 (3.9%) Neutrophil count increased 3 (2.0%) 2 (1.3%) 5 (1.6%) Skin and Subcutaneous Tissue Disorders 1 (0.7%) 3 (2.0%) 4 (1.3%) Pruritis 1 (0.7%) 3 (2.0%) 4 (1.3%) General Disorders and Administration Site Conditions 0 3 (2.0%) 3 (1.0%) Immunogenicity In the clinical study, serum samples were collected at baseline and at 5 weeks post-surgery for evaluation of antibodies to bovine thrombin, bovine Factor V/Va, human thrombin, and human Factor V/Va. Samples were collected at both time points for 81.3% of the subjects. The ELISA data were adjudicated by a panel of experts blinded to treatment assignment. After reviewing all data, the panel used an algorithm for assigning outcomes for each antigen: seroconversion negative or seroconversion positive. The protocol did not specify any comparative analysis for immunogenicity data, only descriptive statistics. The adjudicated results show that 3.3% of the subjects treated with EVITHROM (frozen formulation) developed antibodies to any of the four antigens, compared to 12.7% of the subjects developing antibodies in the control group (bovine thrombin). 7.94% of the subjects treated with bovine thrombin (control group) developed antibodies to bovine thrombin and 9.52% of these subjects developed antibodies to bovine Factor V/Va. A few control subjects had antibodies that cross-reacted with human thrombin, but none had antibodies that cross-reacted with human Factor V/Va. None of the patients treated with EVITHROM developed detectable antibodies to human thrombin or to human Factor V/Va. The detection of antibody formation is highly dependent upon the sensitivity and specificity of the assay. The observed incidence of a positive signal in an assay may be influenced by several factors including timing of sampling, sample handling, concomitant medications, or underlying disease. Therefore, direct comparison of incidence of antibody development to human thrombin, bovine thrombin, human Factor V/Va or bovine Factor V/Va following administration of EVITHROM with incidence of antibody development following administration of other products may be misleading and the clinical significance of these findings is unknown. 6.2 Post Marketing Experience No adverse reactions have been identified from spontaneous post-marketing reports.