Hypersensitivity Reactions Allergic-type hypersensitivity reactions are possible. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. If these symptoms occur during administration, treatment must be discontinued immediately and emergency treatment should be administered. Coagulation Monitoring Tests The anticoagulant effect of drugs that use antithrombin to exert their anticoagulation may be altered when ATryn (recombinant lyophilized powder) is added or withdrawn. To avoid excessive or insufficient anticoagulation, coagulation tests suitable for the anticoagulant used (e.g., aPTT and anti-Factor Xa activity) are to be performed regularly, at close intervals, and in particular in the first hours following the start or withdrawal of ATryn (recombinant lyophilized powder) . Additionally, monitor the patients for the occurrence of bleeding or thrombosis in such situation. Nonclinical Toxicology Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis No carcinogenicity data for ATryn (recombinant lyophilized powder) are available in animals or humans. Mutagenesis and Genotoxicity ATryn (recombinant lyophilized powder) was not mutagenic when tested in the Ames bacterial test and in in vitro cytogenetic assays nor was it shown to be genotoxic when tested in an in vivo test to assess chromosomal aberration. Impairment of Fertility No studies have been conducted to evaluate the effects of ATryn (recombinant lyophilized powder) on fertility in humans. Use In Specific Populations Pregnancy Pregnancy Category C: In rats, a dose of 210 mg/kg/day ATryn (recombinant lyophilized powder) (5-6 times the human dose for pregnant women) administered during most of the pregnancy and entire lactation showed a slight but statistically significant increase in pup mortality in day one through day four when compared to concurrent control (90% compared to 94% viability index for 210 mg/kg/day versus control). This slight statistical difference does not reflect a true treatment-related effect. This same dose was shown to be safe in a second rat study when administered around parturition and during lactation where the no adverse effect level for dam and pups was 210 mg/kg/day. There are no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Studies in pregnant women have not shown that ATryn (recombinant lyophilized powder) increases the risk of fetal abnormalities if administered during the third trimester of pregnancy. In clinical trials in hereditary AT deficient patients, 22 pregnant women have been treated with ATryn (recombinant lyophilized powder) around parturition. No adverse reactions were reported in 22 neonates born from pregnant women treated with ATryn (recombinant lyophilized powder) during clinical trials. Labor and Delivery ATryn (recombinant lyophilized powder) is indicated for the treatment of pregnant women during the peri-partum period. Pregnant patients who need a surgical procedure other than Cesarean section are to be treated according to the dosing formulae for pregnant patients. Nursing Mothers ATryn (recombinant lyophilized powder) will be present in breast milk at levels estimated to be 1/50 to 1/100 of its concentration in the blood. This level is the same as that estimated to be present in breast milk of normal lactating women which is not known to be harmful to breastfed neonates. However, caution should be exercised when ATryn (recombinant lyophilized powder) is administered to a nursing woman. Use only if clearly needed. In 2 reproductive toxicology studies performed in rats, antithrombin (Recombinant) was administered to pregnant dams at doses up to 210 mg/kg/day, resulting in supraphysiologic plasma levels of antithrombin. Pups were allowed to breastfeed and were monitored for changes in prothrombin (PT) or aPTT, as well as pup viability, body weight at birth, growth, and development. In these studies, there were no adverse effects in offspring who consumed milk from dams treated with ATryn (recombinant lyophilized powder) . Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Clinical studies of ATryn (recombinant lyophilized powder) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Last reviewed on RxList: 3/10/2009
This monograph has been modified to include the generic and brand name in many instances.