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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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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.
INDICATIONS AND USAGE
Heparin Sodium Injection is indicated for:
Anticoagulant therapy in prophylaxis and treatment of venous thrombosis and its extension;
Low-dose regimen for prevention of postoperative deep venous thrombosis and pulmonary embolism in patients undergoing major abdominothoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease (see DOSAGE AND ADMINISTRATION );
Prophylaxis and treatment of pulmonary embolism; Atrial fibrillation with embolization; Diagnosis and treatment of acute and chronic consumptive coagulopathies (disseminated intravascular coagulation); Prevention of clotting in arterial and cardiac surgery; Prophylaxis and treatment of peripheral arterial embolism. Heparin may also be employed as an anticoagulant in blood transfusions, extracorporeal circulation, and dialysis procedures and in blood samples for laboratory purposes.
CONTRAINDICATIONS Heparin sodium should NOT be used in patients with the following conditions:
Severe thrombocytopenia;
When suitable blood coagulation tests, e.g., the whole blood clotting time, partial thromboplastin time, etc., cannot be performed at appropriate intervals (this contraindication refers to full-dose heparin; there is usually no need to monitor coagulation parameters in patients receiving low-dose heparin).
An uncontrolled active bleeding state (see WARNINGS ), except when this is due to disseminated intravascular coagulation.
WARNINGS Heparin is not intended for intramuscular use.
Hypersensitivity Patients with documented hypersensitivity to heparin should be given the drug only in clearly life- threatening situations. (See ADVERSE REACTIONS , Hypersensitivity .)
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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.
PRECAUTIONS
General
Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT):
see WARNINGS.
Heparin Resistance
Increased resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer and in postsurgical patients.
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 therapy, regardless of the route of administration. (See DOSAGE AND ADMINISTRATION .)
Drug Interactions Oral Anticoagulants Heparin sodium may prolong the one-stage prothrombin time. Therefore, when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours after the last intravenous dose or 24 hours after the last subcutaneous dose should elapse before blood is drawn, if a valid prothrombin time is to be obtained.
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. Intravenous nitroglycerin administered to heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of
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nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of heparin dosage are recommended during coadministration of heparin and intravenous nitroglycerin.
Drug/Laboratory Tests Interactions Hyperaminotransferasemia Significant elevations of aminotransferase (SGOT [S-AST] and SGPT [S-ALT]) levels have occurred in a high percentage of patients (and healthy subjects) who have received heparin. Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease and pulmonary emboli, increases that might be caused by drugs (like heparin) should be interpreted with caution.
Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term studies in animals have been performed to evaluate carcinogenic potential of heparin. 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 See DOSAGE AND ADMINISTRATION–Pediatric Use.
Geriatric Use A higher incidence of bleeding has been reported in patients over 60 years of age, especially women (see PRECAUTIONS , General ). Clinical studies indicate that lower doses of heparin may be indicated in these patients (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ).
ADVERSE REACTIONS Hemorrhage Hemorrhage is the chief complication that may result from heparin therapy. (See WARNINGS .) An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug. (See OVERDOSAGE .) It should be appreciated that 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:
a. Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred during anticoagulant therapy. Therefore, such treatment should be discontinued in patients who develop signs and symptoms of acute adrenal hemorrhage and insufficiency. Initiation of corrective therapy should not depend on laboratory confirmation of the diagnosis, since any delay in an acute situation may result in the patient’s death.
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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.
DOSAGE AND ADMINISTRATION Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Slight discoloration does not alter potency.
When heparin is added to an infusion solution for continuous intravenous administration, the container should be inverted at least six times to ensure adequate mixing and prevent pooling of the heparin in the solution.
Heparin sodium is not effective by oral administration and should be given by intermittent intravenous injection, intravenous infusion, or deep subcutaneous (intrafat, i.e., above the iliac crest or abdominal fat layer) injection. The intramuscular route of administration should be avoided because of the frequent occurrence of hematoma at the injection site.
The dosage of heparin sodium should be adjusted according to the patient’s coagulation test results. When heparin is given by continuous intravenous infusion, the coagulation time should be determined approximately every 4 hours in the early stages of treatment. When the drug is administered intermittently by intravenous injection, coagulation tests should be performed before each injection during the early stages of treatment and at appropriate intervals thereafter. Dosage is considered adequate when the activated partial thromboplastin time (APTT) is 1.5 to 2 times normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value. After deep subcutaneous (intrafat) injections, tests for adequacy of dosage are best performed on samples drawn 4 to 6 hours after the injection.
Periodic platelet counts, hematocrits and tests for occult blood in stool are recommended during the entire course of heparin therapy, regardless of the route of administration.
Converting to Oral Anticoagulant When an oral anticoagulant of the coumarin or similar type is to be begun in patients already receiving heparin sodium, baseline and subsequent tests of prothrombin activity must be determined at a time when heparin activity is too low to affect the prothrombin time. This is about 5 hours after the last intravenous bolus and 24 hours after the last subcutaneous dose. If continuous IV heparin infusion is used, prothrombin time can usually be measured at any time.
In converting from heparin to an oral anticoagulant, the dose of the oral anticoagulant should be the usual initial amount and thereafter prothrombin time should be determined at the usual intervals. To ensure continuous anticoagulation, it is advisable to continue full heparin therapy for several days after the prothrombin time has reached the therapeutic range. Heparin therapy may then be discontinued without tapering.
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Therapeutic Anticoagulant Effect With Full-Dose Heparin Although dosage must be adjusted for the individual patient according to the results of suitable laboratory tests, the following dosage schedules may be used as guidelines:
METHOD OF ADMINISTRATION FREQUENCY
RECOMMENDED DOSE
[based on 150 lb (68 kg) patient] Deep Subcutaneous (Intrafat) Injection
Initial dose 5000 units by IV injection, followed by 10,000 to 20,000 units of a concentrated solution, subcutaneously
A different site should be used for each injection to prevent the development of massive hematoma
Every 8 hours
or
8000 to 10,000 units of a concentrated solution
Every 12 hours 15,000 to 20,000 units of a concentrated solution Intermittent Intravenous Injection Initial dose 10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP
Every 4 to 6 hours 5000 to 10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP Intravenous Infusion Initial dose 5000 units by IV injection
Continuous 20,000 to 40,000 units/24 hours in 1000 mL of 0.9% Sodium Chloride Injection, USP (or in any compatible solution) for infusion
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.
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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:
- 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.
- Warkentin T, Kelton J. Delayed-Onset Heparin-Induced Thrombocytopenia and Thrombosis. Annals of Internal Medicine. 2001;135:502-506.
- Rice L, Attisha W, Drexler A, Francis J. Delayed-Onset Heparin Induced Thrombocytopenia. Annals of Internal Medicine , 2002;136:210-215.
- Dieck, J., C. Rizo-Patron, et al. (1990). “A New Manifestation and Treatment Alternative for Heparin-Induced Thrombosis.”. Chest 98(1524-26).
- Smythe M, Stephens J, Mattson. Delayed-Onset Heparin Induced Thrombocytopenia. Annals of Emergency Medicine , 2005;45(4):417-
- DIVGI A. (REPRINT), T HUMMA S., H ARI P., FRIEDMAN K., DELAYED ONSET HEPARIN - INDUCED T HROMBOCYTOPENIA (HIT) PRESENTING AFTER UNDOCUMENTED DRUG EXPOSURE AS POST - ANGIOGRAPHY PULMONARY EMBOLISM. BLOOD .2003;102(11):127 B.
Manufactured by Baxter Healthcare Corporation Deerfield, IL 60015 USA
For Product Inquiry 1 800 ANA DRUG (1-800-262-3784)
MLT-01119/3.
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HEP-LOCK (Heparin Lock Flush Solution, 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):
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
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Hypersensitivity
Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-
threatening situations. (See ADVERSE REACTIONS , Hypersensitivity .)
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
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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^3 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.
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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 PRECAUTIONS , General ).
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 ).
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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.
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1 mL DOSETTE vials packaged in 25s (NDC 0641-0392-25)
2 mL DOSETTE vials packaged in 25s (NDC 0641-0393-25)
10 mL Multiple Dose vials packaged in 25s (NDC 0641-2438-45)
30 mL Multiple Dose vials packaged in 25s (NDC 0641-2442-45)
100 USP units/mL
1 mL DOSETTE vials packaged in 25s (NDC 0641-0389-25)
2 mL DOSETTE vials packaged in 25s (NDC 0641-0387-25)
10 mL Multiple Dose vials packaged in 25s (NDC 0641-2436-45)
30 mL Multiple Dose vials packaged in 25s (NDC 0641-2443-45)
Storage
Store at 20 ° -25 ° C (68 ° -77 ° F) [ see USP Controlled Room Temperature ].
REFERENCES
- 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.
- Warkentin T, Kelton J. Delayed-Onset Heparin-Induced Thrombocytopenia and Thrombosis. Annals of Internal Medicine. 2001;135:502-506.
- Rice L, Attisha W, Drexler A, Francis J. Delayed-Onset Heparin Induced Thrombocytopenia. Annals of Internal Medicine , 2002;136:210-215.
- Dieck J., C. Rizo-Patron, et al. (1990). “A New Manifestation and Treatment Alternative for Heparin- Induced Thrombosis.” Chest 98(1524-26).
- Smythe M, Stephens J, Mattson. Delayed-Onset Heparin Induced Thrombocytopenia. Annals of Emergency Medicine , 2005;45(4):417-419.
- Divgi A. (Reprint), Thumma S., Hari P., Friedman K., Delayed Onset Heparin-Induced Thrombocytopenia (HIT) Presenting After Undocumented Drug Exposure as Post-Angiography Pulmonary Embolism. Blood. 2003;102(11):127b.
Hep-Lock, Baxter and Dosette are registered trademarks of Baxter International, Inc., or its
subsidiaries.
Manufactured by
Baxter Healthcare Corporation
Deerfield, IL 60015 USA
Page 22
For Product Inquiry 1 800 ANA DRUG (1-800-262-3784)
MLT-00103/3.
