Angiomax Warnings, Precautions, Pregnancy, Nursing, Abuse - Bivalirudin

Angiomax Warnings, Precautions, Pregnancy, Nursing, Abuse - Bivalirudin

WARNINGS

Angiomax is not intended for intramuscular administration. Although most bleeding associated with the use of Angiomax in PTCA occurs at the site of arterial puncture, hemorrhage can occur at any site. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration.

An increased risk of thrombus formation has been associated with the use of Angiomax in gamma brachytherapy, including fatal outcomes.

There is no known antidote to Angiomax. Angiomax is hemodialyzable (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

Clinical trials have provided limited information for use of Angiomax in patients with heparin-induced thrombocy-topenia/heparin-induced thrombocytopenia-thrombosis syndrome (HIT/HITTS) undergoing PTCA. The number of HIT/HITTS patients treated is inadequate to reliably assess efficacy and safety in these patients undergoing PTCA. Angiomax was administered to a small number of patients with a history of HIT/HITTS or active HIT/HITTS and undergoing PTCA in an uncontrolled, open-label study and in an emergency treatment program and appeared to provide adequate anticoagulation in these patients. In in vitro studies, bivalirudin exhibited no platelet aggregation response against sera from patients with a history of HIT/HITTS.

Caution should be used when Angiomax is used as the anti-thrombin during brachytherapy procedures. Operators are advised to maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of Angiomax. Bivalirudin displayed no genotoxic potential in the in vitro bacterial cell reverse mutation assay (Ames test), the in vitro Chinese hamster ovary cell forward gene mutation test (CHO/HGPRT), the in vitro human lymphocyte chromosomal aberration assay, the in vitro rat hepatocyte unscheduled DNA synthesis (UDS) assay, and the in vivo rat micronucleus assay. Fertility and general reproductive performance in rats were unaffected by subcutaneous doses of bivalirudin up to 150 mg/kg/day, about 1.6 times the dose on a body surface area basis (mg/m²) of a 50 kg person given the maximum recommended dose of 15 mg/kg/day.

Pregnancy

Angiomax^® (bivalirudin) is intended for use with aspirin (see INDICATIONS AND USAGE). Because of possible adverse effects on the neonate and the potential for increased maternal bleeding, particularly during the third trimester, Angiomax and aspirin should be used together during pregnancy only if clearly needed.

Pregnancy Category B

Teratogenicity studies have been performed in rats at subcutaneous doses up to 150 mg/kg/day, (1.6 times the maximum recommended human dose based on body surface area) and rabbits at subcutaneous doses up to 150 mg/kg/day (3.2 times the maximum recommended human dose based on body surface area). These studies revealed no evidence of impaired fertility or harm to the fetus attributable to bivalirudin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether bivalirudin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Angiomax is administered to a nursing woman.

Geriatric Patients

Of the total number of patients in clinical studies of Angiomax undergoing PTCA, 41% were ³65 years of age, while 11% were >75 years old. A difference of ³5% between age groups was observed for heparin-treated but not Angiomax-treated patients with regard to the percentage of patients with major bleeding events. There were no individual bleeding events which were observed with a difference of ³5% between treatment groups, although puncture site hemorrhage and catheterization site hematoma were each observed in a higher percentage of patients ³65 years than in patients <65 years. This difference between age groups was more pronounced for heparin-treated than Angiomax-treated patients.

Pediatric Use

The safety and effectiveness of Angiomax in pediatric patients have not been established.