Prophylaxis and treatment of venous thrombosis and pulmonary embolism;
Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation;
Treatment of acute and chronic consumption coagulopathies (disseminated intravascular coagulation);
Prevention of clotting in arterial and cardiac surgery;
Prophylaxis and treatment of peripheral arterial embolism;
Anticoagulant use in blood transfusions, extracorporeal circulation, and dialysis procedures. HEPARIN SODIUM INJECTION is an anticoagulant indicated for ( 1 ):
Prophylaxis and treatment of venous thrombosis and pulmonary embolism
Prophylaxis and treatment of the thromboembolic complications associated with atrial fibrillation
Treatment of acute and chronic consumption coagulopathies
Prevention of clotting in arterial and cardiac surgery
Prophylaxis and treatment of peripheral arterial embolism
Anticoagulant use in transfusion, extracorporeal circulation, and dialysis procedures
Contraindications
The use of HEPARIN SODIUM INJECTION is contraindicated in patients:
History of heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis
History of thrombocytopenia with pentosan polysulfate
Known hypersensitivity to heparin or pork products (e.g., anaphylactoid reactions) [see Adverse Reactions (6.1) ]
In whom suitable blood coagulation tests (e.g., whole-blood clotting time, partial thromboplastin time) cannot be performed at appropriate intervals. This contraindication refers to full-dose heparin regimens only; there is usually no need to monitor coagulation parameters in patients receiving low-dose heparin
An uncontrollable bleeding state [see Warnings and Precautions (5.2) ] , except when this is due to disseminated intravascular coagulation
History of heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis (HITTS) ( 4 )
Two medicines in one question?
Name two or more medicines and Osler runs an interaction check. A severe interaction is stated at the very top of the answer.
History of thrombocytopenia with pentosan polysulfate ( 4 )
Known hypersensitivity to heparin or pork products ( 4 )
In whom suitable blood coagulation tests cannot be performed at appropriate intervals ( 4 )
An uncontrollable bleeding state, except when this is due to disseminated intravascular coagulation ( 4 )
Warnings and precautions
Fatal Medication Errors: Confirm choice of correct strength prior to administration ( 5.1 )
Hemorrhage: Hemorrhage, including fatal events, has occurred in patients receiving heparin. Use caution in conditions with increased risk of hemorrhage ( 5.2 )
HIT and HITTS: Monitor for signs and symptoms and discontinue if indicative of HIT and HITTS ( 5.3 )
Benzyl Alcohol Toxicity: Use preservative-free formulation in neonates and infants ( 5.4 )
Monitoring: Blood coagulation tests guide therapy for full-dose heparin. Periodically monitor platelet count, hematocrit, and occult blood in stool in all patients receiving heparin ( 5.6 , 5.7 )
Hyperkalemia: Measure blood potassium in patients at risk of hyperkalemia before starting heparin therapy and periodically in all patients ( 5.10 )
5.1Fatal Medication Errors Do
not use HEPARIN SODIUM INJECTION as a "catheter lock flush" product. HEPARIN SODIUM INJECTION is supplied in vials containing various strengths of heparin, including vials that contain a highly concentrated solution of 10,000 units in 1 mL. Fatal hemorrhages have occurred due to medication errors. Carefully examine all HEPARIN SODIUM INJECTION vials to confirm the correct vial choice prior to administration of the drug.
5.2Hemorrhage
Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks. Hemorrhage, including fatal events, has occurred in patients receiving heparin. Hemorrhage can occur at virtually any site in patients receiving heparin. 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 puncture 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, continuous tube drainage of the stomach or small intestine, and clinical settings in which stress-induced gastrointestinal hemorrhage is possible.
Other – Menstruation, liver disease with impaired hemostasis, severe renal disease, or in patients with indwelling catheters.
5.3Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis
Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT occurs in patients treated with heparin and is due to the development of antibodies to a platelet Factor 4-heparin complex that induce in vivo platelet aggregation. HIT may progress to the development of venous and arterial thromboses, a condition known 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. 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 HITT, and, if necessary, administer an alternative anticoagulant.
HIT and HITT 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.
5.4 Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative Use preservative-free HEPARIN SODIUM INJECTION in neonates and infants. Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and low-birth weight infants treated with benzyl alcohol-preserved formulation in infusion solutions, including HEPARIN SODIUM INJECTION. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations.
When prescribing HEPARIN SODIUM INJECTION in infants consider the combined daily metabolic load of benzyl alcohol from all sources including HEPARIN SODIUM INJECTION (HEPARIN SODIUM INJECTION contains 9.45 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which toxicity may occur is not known [see Use in Specific Populations (8.4) ].
5.5Unresponsiveness to Heparin with Concomitant Use with Andexanet Alfa Unresponsiveness
to unfractionated heparin leading to non-prolongation of activated clotting times and serious thrombotic events has occurred when unfractionated heparin was administered after use of andexanet alfa for the reversal of direct Factor Xa inhibitors (apixaban and rivaroxaban). Avoid use of heparin after use of andexanet alfa. Use an alternative anticoagulant to heparin [see Drug Interactions (7.3) ] .
5.6Thrombocytopenia Thrombocytopenia
in patients receiving heparin has been reported at frequencies 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 HITT, and, if necessary, administer an alternative anticoagulant [see Warnings and Precautions (5.3) ] .
5.7Coagulation Testing and Monitoring
When using a full dose heparin regimen, adjust the heparin dose based on frequent blood coagulation tests. If the coagulation test is unduly prolonged or if hemorrhage occurs, discontinue heparin promptly [see Overdosage (10) ] . Periodically monitor platelet counts, hematocrit, and occult blood in stool during the entire course of heparin therapy, regardless of the route of administration [see Dosage and Administration (2.2) ] .
5.8Heparin Resistance Resistance
to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer, in postsurgical patients, and patients with antithrombin III deficiency. Close monitoring of coagulation tests is recommended in these cases. Adjustment of heparin doses based on anti-Factor Xa levels may be warranted.
5.9Hypersensitivity Patients
with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations. Because HEPARIN SODIUM INJECTION is derived from animal tissue, it should be used with caution in patients with a history of allergy.
5.10Hyperkalemia
Heparin can suppress adrenal secretion of aldosterone leading to hyperkalemia, particularly in patients with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium, or taking potassium sparing drugs. The risk of hyperkalemia appears to increase with
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
Drugs that interfere with coagulation, platelet aggregation or drugs that counteract coagulation may induce bleeding ( 7.2 )
Andexanet alfa may reduce the efficacy of heparin when used concomitantly ( 7.3 )
7.1Oral 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.
7.2Platelet Inhibitors
Drugs such as NSAIDs (including salicylic acid, ibuprofen, indomethacin, and celecoxib), dextran, phenylbutazone, thienopyridines, dipyridamole, hydroxychloroquine, glycoprotein IIb/IIIa antagonists (including abciximab, eptifibatide, and tirofiban), 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.
7.3Unresponsiveness to Heparin with Concomitant Use with Andexanet Alfa
Andexanet binds to heparin-bound antithrombin III (ATIII) and may reduce the anticoagulant effect of heparin. Unresponsiveness to unfractionated heparin may lead to serious and life-threatening thrombotic events. Use of andexanet alfa as an antidote for heparin has not been established. Avoid use of heparin after use of andexanet alfa for the reversal of direct Factor Xa inhibitors (apixaban and rivaroxaban). If anticoagulation is needed, use an alternative anticoagulant to heparin [see Warnings and Precautions (5.5) ] .
7.4Other Interactions
Digitalis, tetracyclines, nicotine, or antihistamines, or intravenous (IV) nitroglycerin may partially counteract the anticoagulant action of heparin sodium. Antithrombin III (human) – 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, a reduced dosage of heparin is recommended during treatment with antithrombin III (human).
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
There are no available data on heparin sodium use in pregnant women to infor a drug associated risk of major birth defects and miscarriage. In published reports, heparin exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes in humans. No teratogenicity, but early embryo-fetal death was observed in animal reproductive studies with administration of heparin sodium to pregnant rats and rabbits during organogenesis at doses approximately 10 times the maximum recommended human dose (MRHD) of 40,000 USP units/24 hours infusion (see Data ) .
Consider the benefits and risks of HEPARIN SODIUM INJECTION to a pregnant woman and possible risks to the fetus when prescribing HEPARIN SODIUM INJECTION to a pregnant woman. If available, preservative-free HEPARIN SODIUM INJECTION is recommended when heparin therapy is needed during pregnancy. There are no known adverse outcomes associated with fetal exposure to the preservative benzyl alcohol through maternal drug administration; however, the preservative benzyl alcohol can cause serious adverse events and death when administered intravenously to neonates and infants [see Use in Specific Populations (8.4) ].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects 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 units/kg/day, approximately 10 times the maximum human daily dose based on body weight. The number of early resorptions increased in both species. There was no evidence of teratogenic effects.
Adverse reactions
The following clinically significant adverse reactions are described elsewhere in the labeling:
Hemorrhage [see Warnings and Precautions (5.2) ]
Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis [see Warnings and Precautions (5.3) ]
Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative [see Warnings and Precautions (5.4) ]
Thrombocytopenia [see Warnings and Precautions (5.6) ]
Heparin Resistance [see Warnings and Precautions (5.8) ]
Hypersensitivity [see Warnings and Precautions (5.9) ]
Hyperkalemia [see Warnings and Precautions (5.10) ] Most common adverse reactions are hemorrhage, thrombocytopenia, HIT and HITTS, injection site irritation, general hypersensitivity reactions, and elevations of aminotransferase levels. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Postmarketing Experience
The following adverse reactions have been identified during post approval use of HEPARIN SODIUM INJECTION. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate 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 including: - 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 heparin therapy. - Retroperitoneal hemorrhage.
HIT and HITT, including delayed onset cases [see Warnings and Precautions (5.3) ] .
Local irritation – Local irritation, erythema, mild pain, hematoma, or ulceration have occurred following deep subcutaneous (intrafat) injection of heparin sodium. Because such reactions occur more frequently after intramuscular administration, the IM route is not recommended.
Histamine-like reactions – Such reactions have been observed at the site of injection. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin, occasionally requiring skin grafting [see Warnings and Precautions (5.3) ] .
Hypersensitivity – Generalized hypersensitivity reactions have been reported with chills, fever, and urticaria as the most usual manifestations; asthma, rhinitis, lacrimation, headache, nausea and vomiting, and anaphylactoid reactions, including shock, occur less frequently. Itching and burning, especially on the plantar site of the feet, may occur.
Metabolism and Nutrition Disorders – Hyperkalemia.
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 been reported.
Composition
Active ingredients
HEPARIN SODIUM 1,000 UNITS/ML
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
