Description

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NDA 17-037/S-158 
Page 3 
Heparin Sodium Injection, USP 
Rx only 
DESCRIPTION 
Heparin is a heterogeneous group of straight-chain anionic mucopolysaccharides, called 
glycosaminoglycans, having anticoagulant properties. Although others may be present, the main sugars 
occurring in heparin are: (1) 
α-L-iduronic acid 2-sulfate, (2) 2-deoxy-2-sulfamino-α-D-glucose 6-
sulfate, (3) 
β-D-glucuronic acid, (4) 2-acetamido-2-deoxy-α-D-glucose and (5) α-L-iduronic acid. 
These sugars are present in decreasing amounts, usually in the order (2)
>(1)>(4)>(3)>(5), and are 
joined by glycosidic linkages, forming polymers of varying sizes. Heparin is strongly acidic because of 
its content of covalently linked sulfate and carboxylic acid groups. In heparin sodium, the acidic 
protons of the sulfate units are partially replaced by sodium ions. 
Structural formula of Heparin Sodium (representative sub-units): 
Heparin Sodium Injection, USP is a sterile solution of heparin sodium derived from porcine intestinal 
mucosa, standardized for anticoagulant activity. It is to be administered by intravenous or deep 
subcutaneous routes. The potency is determined by a biological assay using a USP reference standard 
based on units of heparin activity per milligram. 
Heparin Sodium Injection, USP is available in the following concentrations/mL: 
Heparin Sodium 
Sodium Chloride Benzyl 
Alcohol 
1000 USP units 
8.6 mg 
0.01 mL 
5000 USP units 
7 mg 
0.01 mL 
10,000 USP units 
5 mg 
0.01 mL 
pH 5.0-7.5; sodium hydroxide and/or hydrochloric acid added, if needed, for pH adjustment. 
CLINICAL PHARMACOLOGY 
Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in 
vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of 
heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating 
activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis 
has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and 
preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin 
clot by inhibiting the activation of the fibrin stabilizing factor. 
Bleeding time is usually unaffected by heparin. Clotting time is prolonged by full therapeutic doses of 
heparin; in most cases, it is not measurably affected by low doses of heparin. 

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NDA 17-037/S-158 
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Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of 
heparin and longer activated partial thromboplastin times (APTTs) compared with patients under 60 
years of age. 
Peak plasma levels of heparin are achieved 2 to 4 hours following subcutaneous administration, 
although there are considerable individual variations. Loglinear plots of heparin plasma concentrations 
with time, for a wide range of dose levels, are linear, which suggests the absence of zero order 
processes. Liver and the reticuloendothelial system are the sites of biotransformation. The biphasic 
elimination curve, a rapidly declining alpha phase (t
1/2
=10 min.) 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. 
Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots.