warnings and cautions
5 WARNINGS AND PRECAUTIONS VWD patients receiving Humate-P may be at risk of developing thromboembolic events ( 5.1 ). Monitor for intravascular hemolysis and decreasing hematocrit values in patients with A, B, and AB blood groups who are receiving large or frequent doses ( 5.2 ). Monitor VWF:RCo and FVIII levels in VWD patients, especially those undergoing surgery ( 5.3 ). Products made from human plasma may contain infectious agents (e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent ( 5.4 ). 5.1 Thromboembolic Events (VWD Patients) Thromboembolic events have been reported in VWD patients receiving Antihemophilic Factor/von Willebrand Factor Complex replacement therapy, especially in the setting of known risk factors for thrombosis. 3,4 Early reports indicate a higher incidence may occur in females. Endogenous high levels of FVIII have also been associated with thrombosis, but no causal relationship has been established. Exercise caution and consider antithrombotic measures in all at-risk VWD patients who are receiving coagulation factor replacement therapy. 5.2 Monitoring for Intravascular Hemolysis Humate-P contains blood group isoagglutinins (anti-A and anti-B). When doses are very large or need to be repeated frequently (for example, when inhibitors are present or when pre- and post-surgical care is involved), monitor patients of blood groups A, B, and AB for signs of intravascular hemolysis and decreasing hematocrit values and treat appropriately. 5.3 Monitoring VWF:RCo and FVIII Levels Monitor the VWF:RCo and FVIII levels of VWD patients receiving Humate-P using standard coagulation tests, especially in cases of surgery. It is advisable to monitor trough VWF:RCo and FVIII:C levels at least once a day in order to adjust the dosage of Humate-P as needed to avoid excessive accumulation of coagulation factors (s ee Dosage and Administration [2.2 , 2.3] ). 5.4 Transmission of Infectious Agents Humate-P is made from human plasma. Products made from human plasma may contain infectious agents (e.g., viruses and theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that can cause disease ( see Description [11] and Patient Counseling Information [17.1] ). The risk that such products will transmit 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/or removing certain viruses during manufacturing ( see Description [11.1] for virus reduction measures ). 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. Thus the risk of transmission of infectious agents cannot be eliminated completely. Report all infections thought by a physician possibly to have been transmitted by this product to CSL Behring Pharmacovigilance at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Some viruses, such as Parvovirus B19 virus (B19V) or hepatitis A (HAV), are particularly difficult to remove or inactivate. B19V may most seriously affect pregnant women and immune-compromised individuals. Although the overwhelming number of B19V and HAV cases are community acquired, reports of these infections have been associated with the use of some plasma-derived products. Therefore, physicians should be alert to the potential symptoms of B19V and HAV infections ( see Patient Counseling Information [17.1] ). Symptoms of B19V may include low-grade fever, rash, arthralgias, and transient symmetric, nondestructive arthritis. Diagnosis is often established by measuring B19V-specific IgM and IgG antibodies. Symptoms of HAV include low-grade fever, anorexia, nausea, vomiting, fatigue, and jaundice. A diagnosis may be established by measuring specific IgM antibodies. Physicians should strongly consider administration of hepatitis A and hepatitis B vaccines to individuals receiving plasma derivatives. Potential risks and benefits of vaccination should be weighed by the physician and discussed with the patient.