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Pediatric Use 

Follow recommendations of appropriate pediatric reference texts. In general, the following dosage 

schedule may be used as a guideline: 

Initial Dose 

50 units/kg (IV, drip) 

Maintenance Dose 

100 units/kg (IV, drip) every 4 hours, or 20,000 units/m

2

/24 hours continuously 



Geriatric Use 

Patients over 60 years of age may require lower doses of heparin. 



Surgery of the Heart and Blood Vessels 

Patients undergoing total body perfusion for open-heart surgery should receive an initial dose of not 

less than 150 units of heparin sodium per kilogram of body weight. Frequently, a dose of 300 units per 

kilogram is used for procedures estimated to last less than 60 minutes, or 400 units per kilogram for 

those estimated to last longer than 60 minutes. 


NDA 17-037/S-158 

Page 11 


 

Low-Dose Prophylaxis of Postoperative Thromboembolism 

A number of well-controlled clinical trials have demonstrated that low-dose heparin prophylaxis, given 

just prior to and after surgery, will reduce the incidence of postoperative deep vein thrombosis in the 

legs (as measured by the I-125 fibrinogen technique and venography) and of clinical pulmonary 

embolism. The most widely used dosage has been 5000 units 2 hours before surgery and 5000 units 

every 8 to 12 hours thereafter for 7 days or until the patient is fully ambulatory, whichever is longer. 

The heparin is given by deep subcutaneous injection in the arm or abdomen with a fine needle (25- to 

26-gauge) to minimize tissue trauma. A concentrated solution of heparin sodium is recommended. 

Such prophylaxis should be reserved for patients over the age of 40 who are undergoing major surgery. 

Patients with bleeding disorders and those having neurosurgery, spinal anesthesia, eye surgery or 

potentially sanguineous operations should be excluded, as should patients receiving oral anticoagulants 

or platelet-active drugs (see WARNINGS). The value of such prophylaxis in hip surgery has not been 

established. The possibility of increased bleeding during surgery or postoperatively should be borne in 

mind. If such bleeding occurs, discontinuance of heparin and neutralization with protamine sulfate are 

advisable. If clinical evidence of thromboembolism develops despite low-dose prophylaxis, full 

therapeutic doses of anticoagulants should be given unless contraindicated. All patients should be 

screened prior to heparinization to rule out bleeding disorders, and monitoring should be performed 

with appropriate coagulation tests just prior to surgery. Coagulation test values should be normal or 

only slightly elevated. There is usually no need for daily monitoring of the effect of low-dose heparin 

in patients with normal coagulation parameters. 



Extracorporeal Dialysis 

Follow equipment manufacturers’ operating directions carefully. 



Blood Transfusion 

Addition of 400 to 600 USP units per 100 mL of whole blood is usually employed to prevent 

coagulation. Usually, 7500 USP units of heparin sodium are added to 100 mL of 0.9

% Sodium 

Chloride Injection, USP (or 75,000 USP units per 1000 mL of 0.9

% Sodium Chloride Injection, USP) 

and mixed; from this sterile solution, 6 to 8 mL are added per 100 mL of whole blood. 

Laboratory Samples 

Addition of 70 to 150 units of heparin sodium per 10 to 20 mL sample of whole blood is usually 

employed to prevent coagulation of the sample. Leukocyte counts should be performed on heparinized 

blood within 2 hours after addition of the heparin. Heparinized blood should not be used for 

isoagglutinin, complement, or erythrocyte fragility tests or platelet counts. 

HOW SUPPLIED 

Heparin Sodium Injection, USP 

1000 USP units/mL 

1 mL DOSETTE vial packaged in 25s (NDC  0641-0391-25) 

10 mL Multiple Dose vial packaged in 25s (NDC  0641-2440-45) 

30 mL Multiple Dose vial packaged in 25s (NDC  0641-2450-45) 

5000 USP units/mL 

1 mL DOSETTE vial packaged in 25s (NDC  0641-0400-25) 

10 mL Multiple Dose vial packaged in 25s (NDC  0641-2460-45) 

10,000 USP units/mL 

1 mL DOSETTE vial packaged in 25s (NDC  0641-0410-25) 


NDA 17-037/S-158 

Page 12 


 

4 mL Multiple Dose vial packaged in 25s (NDC  0641-2470-45) 

Also available from Baxter: HEP-LOCK (Heparin Lock Flush Solution, USP) and HEP-LOCK U/P 

(Preservative-Free Heparin Lock Flush Solution, USP). 



Storage 

Store at 20

°-25°C (68°-77°F) [see USP Controlled Room Temperature]

Baxter, Hep-Lock and Dosette are trademarks of Baxter International, Inc., or its subsidiaries. 

REFERENCES: 

 

1. 



Tahata T, Shigehito M, Kusuhara K, Ueda Y, et al.  Delayed-Onset of Heparin  

Induced 


Thrombocytopenia – A Case Report – J Jpn Assn Torca Surg.  

1992;40(3):110-111. 

 

2. 


Warkentin T, Kelton J. Delayed-Onset Heparin-Induced Thrombocytopenia and   Thrombosis. 

Annals of Internal Medicine. 2001;135:502-506. 

 

3. 



Rice L, Attisha W, Drexler A, Francis J. Delayed-Onset Heparin Induced   Thrombocytopenia. 

Annals of Internal Medicine, 2002;136:210-215. 

 

4. 



Dieck, J., C. Rizo-Patron, et al. (1990). “A New Manifestation and Treatment  

Alternative 

for Heparin-Induced Thrombosis.”. Chest 98(1524-26). 

 

5. 



Smythe M, Stephens J, Mattson. Delayed-Onset Heparin Induced Thrombocytopenia. 

 

Annals of Emergency Medicine, 2005;45(4):417-419 

 

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Manufactured by 

Baxter Healthcare Corporation 

Deerfield, IL 60015 USA 

For Product Inquiry  1 800 ANA DRUG (1-800-262-3784)

 

MLT-01119/3.0 



 

 

 



 

NDA 17-037/S-158 

Page 13 


 

HEP-LOCK

 

 (Heparin Lock Flush Solution, USP) 

R



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): 

 

HEP-LOCK (Heparin Lock Flush Solution, USP) is a sterile solution for intravenous flush only. It is 



not to be used for anticoagulant therapy. Each mL contains heparin sodium 10 or 100 USP units, 

derived from porcine intestines and standardized for use as an anticoagulant, sodium chloride 9 mg and 

benzyl alcohol 0.01 mL in Water for Injection. pH 5.0-7.5; sodium hydroxide and/or hydrochloric acid 

used, if needed, for pH adjustment. The potency is determined by biological assay using a USP 

reference standard based on units of heparin activity per milligram. 

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 



NDA 17-037/S-158 

Page 14 


 

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. 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 reticulo-endothelial system are the sites of 

biotransformation. The biphasic elimination curve, a rapidly declining alpha phase (t

½

 

= 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. 

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. 

Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots. 

INDICATIONS AND USAGE 

Heparin Lock Flush Solution, USP is intended to maintain patency of an indwelling venipuncture 

device designed for intermittent injection or infusion therapy or blood sampling. Heparin Lock Flush 

Solution may be used following initial placement of the device in the vein, after each injection of a 

medication or after withdrawal of blood for laboratory tests. (See DOSAGE AND 

ADMINISTRATIONMaintenance Of Patency Of Intravenous Devices for directions for use.) 

HEP-LOCK is not to be used for anticoagulant therapy. 

CONTRAINDICATIONS 

Heparin sodium should NOT be used in patients with the following conditions: severe 

thrombocytopenia; an uncontrollable active bleeding state (see WARNINGS), except when this is due 

to disseminated intravascular coagulation. 



WARNINGS 

Heparin is not intended for intramuscular use. 



NDA 17-037/S-158 

Page 15 


 

Hypersensitivity 

Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-

threatening situations. (See ADVERSE REACTIONSHypersensitivity.) 

Hemorrhage 

Hemorrhage can occur at virtually any site in patients receiving heparin. An unexplained fall in 

hematocrit, fall in blood pressure or any other unexplained symptom should lead to serious 

consideration of a hemorrhagic event. 

Heparin sodium should be used with extreme caution in infants and in patients with disease states in 

which there is increased danger of hemorrhage. Some of the conditions in which increased danger of 

hemorrhage exists are: 

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. 

Gastrointestinal  

Ulcerative lesions and continuous tube drainage of the stomach or small intestine. 



Other  

Menstruation, liver disease with impaired hemostasis. 



Thrombocytopenia 

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence 

of 0 to 30%. Platelet counts should be obtained at baseline and periodically during heparin 


NDA 17-037/S-158 

Page 16 


 

administration. Mild thrombocytopenia (count greater than 100,000/mm

3

) may remain stable or reverse 



even if heparin is continued.  However, thrombocytopenia of any degree should be monitored closely. 

If the count falls below 100,000/mm

3

 or if recurrent thrombosis develops (see Heparin-induced 



Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis), the heparin product 

should be discontinued and, if necessary, an alternative anticoagulants administered.  

 

 

  

Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and 



Thrombosis (HITT) 

Heparin-induced Thrombocytopenia (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 referred to as Heparin-induced Thrombocytopenia and 

Thrombosis (HITT).  Thrombotic events may also be the initial presentation for HITT.  These 

serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral 

vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal 

arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and 

possibly death.  Thrombocytopenia of any degree should be monitored closely.  If the platelet 

count falls below 100,000/mm



or if recurrent thrombosis develops, the heparin product should 

be promptly discontinued and alternative anticoagulants considered if patients require continued 

anticoagulation. 

Delayed Onset of HIT and HITT 

Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis 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 and 

HITT. 

Use In Neonates 

This product contains the preservative benzyl alcohol and is not recommended for use in neonates. 

There have been reports of fatal ‘gasping syndrome’ in neonates (children less than one month of age) 

following the administration of intravenous solutions containing the preservative benzyl alcohol. 

Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and 

cardiovascular collapse. 

Preservative-Free Heparin Lock Flush Solution, USP should be used for maintaining the patency of 

intravenous injection devices in neonates. 



NDA 17-037/S-158 

Page 17 


 

PRECAUTIONS 

General 

In infants, the cumulative amounts of heparin and benzyl alcohol received from the frequent 

administration of Heparin Lock Flush Solution during a 24-hour period must be considered. Where 

preservative-free heparin lock flush solution is indicated, HEP-LOCK

 

U/P is available. 



Precautions must be exercised when drugs that are incompatible with heparin are administered through 

an indwelling intravenous catheter containing Heparin Lock Flush Solution. (See DOSAGE AND 



ADMINISTRATIONMaintenance Of Patency Of Intravenous Devices.) 

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced 

Thrombocytopenia and Thrombosis (HITT) 

See WARNINGS



Increased Risk To Older Patients, Especially Women 

A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age. 



Laboratory Tests 

Periodic platelet counts, hematocrits and tests for occult blood in stool are recommended during the 

entire course of heparin use (see DOSAGE AND ADMINISTRATION). 

Drug Interactions 

Platelet Inhibitors 

Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole, 

hydroxychloroquine and others that interfere with platelet-aggregation reactions (the main hemostatic 

defense of heparinized patients) may induce bleeding and should be used with caution in patients 

receiving heparin sodium. 

Other Interactions 

Digitalis, tetracyclines, nicotine or antihistamines may partially counteract the anticoagulant action of 

heparin sodium. 


NDA 17-037/S-158 

Page 18 


 

Carcinogenesis, Mutagenesis, Impairment Of Fertility 

No long-term studies in animals have been performed to evaluate the carcinogenic potential of heparin 

sodium. Also, no reproduction studies in animals have been performed concerning mutagenesis or 

impairment of fertility. 



Pregnancy 

Teratogenic Effects—Pregnancy Category C  

Animal reproduction studies have not been conducted with heparin sodium. It is also not known 

whether heparin sodium can cause fetal harm when administered to a pregnant woman or can affect 

reproduction capacity. Heparin sodium should be given to a pregnant woman only if clearly needed. 



Nonteratogenic Effects 

Heparin does not cross the placental barrier. 



Nursing Mothers 

Heparin is not excreted in human milk. 



Pediatric Use 

Safety and effectiveness in pediatric patients have not been established. Not for use in neonates (see 



WARNINGS). 

Geriatric Use 

A higher incidence of bleeding has been reported in patients over 60 years of age, especially women 

(see CLINICAL PHARMACOLOGY and PRECAUTIONSGeneral). 

ADVERSE REACTIONS 

Hemorrhage 

Hemorrhage is the chief complication that may result from heparin use (see WARNINGS



Hemorrhage). An overly prolonged clotting time or minor bleeding during therapy can usually be 

controlled by withdrawing the drug (see OVERDOSAGE). 



NDA 17-037/S-158 

Page 19 


 

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced 

Thrombocytopenia and Thrombosis (HITT) and Delayed Onset of HIT and HITT 

See WARNINGS. Local Irritation 

Local irritation and erythema have been reported with the use of Heparin Lock Flush Solution. 



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 side of the feet, may occur. 

Thrombocytopenia has been reported to occur in patients receiving heparin, with a reported incidence 

of 0 to 30

%. While often mild and of no obvious clinical significance, such thrombocytopenia can be 

accompanied by severe thromboembolic complications such as skin necrosis, gangrene of the 

extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke, and 

possibly death. (See WARNINGS and PRECAUTIONS.) 

Certain episodes of painful, ischemic and cyanosed limbs have in the past been attributed to allergic 

vasospastic reactions. Whether these are in fact identical to the thrombocytopenia-associated 

complications remains to be determined. 



OVERDOSAGE 

Symptoms 

Bleeding is the chief sign of heparin overdosage. Nosebleeds, blood in urine or tarry stools may be 

noted as the first sign of bleeding. Easy bruising or petechial formations may precede frank bleeding. 

Treatment—Neutralization Of Heparin Effect 

When clinical circumstances (bleeding) require reversal of heparinization, protamine sulfate (1

solution) by slow infusion will neutralize heparin sodium. No more than 50 mg should be 



administered, very slowly, in any 10-minute period. Each mg of protamine sulfate neutralizes 

approximately 100 USP heparin units. The amount of protamine required decreases over time as 

heparin is metabolized. Although the metabolism of heparin is complex, it may, for the purpose of 

choosing a protamine dose, be assumed to have a half-life of about 

1

/

2



 hour after intravenous injection. 

NDA 17-037/S-158 

Page 20 


 

Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. 

Because fatal reactions often resembling anaphylaxis have been reported, the drug should be given 

only when resuscitation techniques and treatment of anaphylactoid shock are readily available. 

For additional information consult the labeling of Protamine Sulfate Injection, USP products. 


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