. adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage, and retroperitoneal hemorrhage have occurred during anticoagulant therapy with heparin [ see adverse reactions (6.1) ]. a higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age [ see clinical pharmacology (12.3) ]. an unexplained fall in hematocrit or fall in blood pressure should lead to serious consideration of a hemorrhagic event. use heparin sodium with caution in disease states in which there is increased risk of hemorrhage, including: cardiovascular — subacute bacterial endocarditis. severe hypertension. surgical — during and immediately following (a) spinal tap or spinal anesthesia or (b) major surgery, especially involving the brain, spinal cord or eye. hematologic — conditions associated with increased bleeding tendencies, such as hemophilia, thrombocytopenia and some vascular purpuras. patients with hereditary antithrombin iii deficiency receiving concurrent antithrombin iii therapy – the anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin iii (human) in patients with hereditary antithrombin iii deficiency. to reduce the risk of bleeding, reduce the heparin dose during concomitant treatment with antithrombin iii (human). gastrointestinal — ulcerative lesions and continuous tube drainage of the stomach or small intestine. other — menstruation, liver disease with impaired hemostasis. 5.3 heparin-induced thrombocytopenia (hit) (with or without thrombosis) hit is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. hit may progress to the development of venous and arterial thromboses, a condition known as hit with thrombosis. thrombotic events may also be the initial presentation for hit. these serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, thrombus formation on a prosthetic cardiac valve, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death. monitor thrombocytopenia of any degree closely. if the platelet count falls below 100,000/mm 3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for hit, and, if necessary, administer an alternative anticoagulant. hit can occur up to several weeks after the discontinuation of heparin therapy. patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for hit. 5.4 thrombocytopenia thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of up to 30%. it can occur 2 to 20 days (average 5 to 9) following the onset of heparin therapy. obtain platelet counts before and periodically during heparin therapy. monitor thrombocytopenia of any degree closely. if the count falls below 100,000/mm 3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for hit, and, if necessary, administer an alternative anticoagulant [ see warnings and precautions (5.3) ]. 5.5 hypersensitivity reactions patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations [ see adverse reactions (6.1) ]. because heparin sodium in 0.9% sodium chloride injection is derived from animal tissue, monitor for signs and symptoms of hypersensitivity when it is used in patients with a history of allergy.

nical condition of the patient, and the procedure being employed, an infusion rate of 3 ml/hour has been found to be satisfactory.

imate their frequency. hemorrhage - hemorrhage is the chief complication that may result from heparin therapy [ see warnings and precautions (5.2) ]. gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. bleeding can occur at any site but certain specific hemorrhagic complications may be difficult to detect: adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred with heparin therapy, including fatal cases. ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term anticoagulant therapy. retroperitoneal hemorrhage. heparin-induced thrombocytopenia (hit) (with or without thrombosis) and thrombocytopenia : [ see warnings and precautions (5.3 and 5.4) ] hypersensitivity - generalized hypersensitivity reactions have been reported with chills, fever, and urticaria as the most usual manifestations, and asthma, rhinitis, lacrimation, headache, nausea and vomiting, and anaphylactoid reactions, including shock, occurring more rarely. itching and burning, especially on the plantar site of the feet, may occur [ see warnings and precautions (5.5) ]. elevations of serum aminotransferases – significant elevations of aspartate aminotransferase (ast) and alanine aminotransferase (alt) levels have occurred in patients who have received heparin. others - osteoporosis following long-term administration of high-doses of heparin, cutaneous necrosis after systemic administration, suppression of aldosterone synthesis, delayed transient alopecia, priapism, and rebound hyperlipemia on discontinuation of heparin sodium have also been reported.

fects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data ​ human data the maternal and fetal outcomes associated with uses of heparin via various dosing methods and administration routes during pregnancy have been investigated in numerous studies. these studies generally reported normal deliveries with no maternal or fetal bleeding and no other complications. animal data in a published study conducted in rats and rabbits, pregnant animals received heparin intravenously during organogenesis at a dose of 10,000 usp units/kg/day, approximately 2777 times the human daily dose. the number of early resorptions increased in both species. there was no evidence of teratogenic effects. 8.2 lactation risk summary there is no information regarding the presence of heparin sodium in 0.9% sodium chloride injection in human milk, the effects on the breastfed infant, or the effects on milk production. due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for heparin sodium in 0.9% sodium chloride injection and any potential adverse effects on the breastfed infant from heparin sodium in 0.9% sodium chloride injection or from the underlying maternal condition [ see use in specific populations (8.4) ]. 8.4 pediatric use there are no adequate and well controlled studies on heparin use in pediatric patients. 8.5 geriatric use there are limited adequate and well-controlled studies in patients 65 years and older. however, a higher incidence of bleeding has been reported in patients over 60 years of age, especially women [ see warnings and precautions (5.2) ].

cally recognized pregnancies is 2-4% and 15-20%, respectively. data ​ human data the maternal and fetal outcomes associated with uses of heparin via various dosing methods and administration routes during pregnancy have been investigated in numerous studies. these studies generally reported normal deliveries with no maternal or fetal bleeding and no other complications. animal data in a published study conducted in rats and rabbits, pregnant animals received heparin intravenously during organogenesis at a dose of 10,000 usp units/kg/day, approximately 2777 times the human daily dose. the number of early resorptions increased in both species. there was no evidence of teratogenic effects.

uloendothelial system are the sites of biotransformation. the biphasic elimination curve, a rapidly declining alpha phase (t ½ = 10 minutes) and after the age of 40 a slower beta phase, indicates uptake in organs. the absence of a relationship between anticoagulant half-life and concentration half-life may reflect factors such as protein binding of heparin.

hypersensitivity inform patients that generalized hypersensitivity reactions have been reported. other medications because of the risk of hemorrhage, advise patients to inform their physicians and dentists of all medications they are taking, including non-prescription medications, and before starting any new medication [ see drug interactions (7.1) ].