activation fragment (F1+2) is indicative of activation of prothrombin.
During the period from 1992 to 1996, five subjects showed transient ALT elevations that were greater than twice the upper normal limit. These subjects were investigated thoroughly and none of the ALT elevations was associated with seroconversion. In three of the five subjects, a single ALT elevation greater than 2 times the upper limit of normal was recorded during the course of the study. No concomitant symptoms occurred and the virus hepatitis serology tests did not reveal any abnormalities. In addition, in one of these three subjects with single ALT elevations, a relationship to Mononine® could be excluded due to a span of 18 months between the infusion of Mononine® and occurrence of the elevated ALT level. In one of the two remaining subjects, the ALT level had been elevated prior to the first infusion of Mononine® and normalized thereafter. Subsequently, this subject's ALT levels were elevated intermittently over a period of 24 months, which appeared to be temporally related to the administration of concomitant medications: acetaminophen, amoxicillin, cephalosporins and halothane. These medications are known to cause liver enzyme elevations. Further, there were no clinical signs of viral hepatitis, nor any other viral disease in these four subjects. The remaining subject of the five was found to have recurring ALT elevations that persisted for a period of five months, gradually decreasing to normal levels. Approximately three days after his first Mononine® infusion this subject received hepatitis B immune globulin and his first injection of hepatitis B vaccine. At that time, the subject's ALT level was slightly above the upper limit of normal (55 IU/L, upper limit of normal: 35). Five days later, the subject experienced flu-like symptoms, nausea and vomiting, which were treated with ampicillin and promethazine. The ALT value recorded eight days thereafter (approximately 13 days after the Mononine® infusion) was found to be clearly elevated at 629 IU/L. ALT levels subsequently decreased again and were in the range of 160 to 220 IU/L for the next four to five months, with mildly elevated aspartate aminotransferase and creatinine phosphokinase values. Serology for hepatitis A, B, and C remained negative (except for the expected positive serology of anti-HBs due to the vaccination against hepatitis B). As a result, there was no serological evidence of hepatitis A, B, or C. This subject's idiosyncratic spikes in aminotransferase values and gastrointestinal symptoms were not considered to be of viral origin. However, a causal relationship between prior administration of Mononine® and these aminotransferase elevations and mild symptoms could not be ruled out.
INDICATIONS AND USAGE
Mononine® is indicated for the prevention and control of bleeding in Factor IX deficiency, also known as Hemophilia B or Christmas disease.
Mononine® is not indicated in the treatment or prophylaxis of Hemophilia A patients with inhibitors to Factor VIII.
Mononine® contains non-detectable levels of Factors II, VII and X (<0.0025 IU per Factor IX unit using standard coagulation assays) and is, therefore, not indicated for replacement therapy of these clotting factors.
Mononine® is also not indicated in the treatment or reversal of coumarin-induced anticoagulation or in a hemorrhagic state caused by hepatitis-induced lack of production of liver dependent co |
