Heparin Sodium - Heparin Sodium injection, Solution
(Heparin Sodium)Heparin Sodium - Heparin Sodium injection, Solution Prescribing Information
Warnings and Precautions, Hyperkalemia (
Heparin sodium injection is indicated for:
- Prophylaxis and treatment of venous thrombosis and pulmonary embolism;
- 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;
- Atrial fibrillation with embolization;
- 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.
- Anticoagulant use in blood transfusions, extracorporeal circulation, and dialysis procedures.
Confirm the choice of the correct heparin sodium injection vial to ensure that the 1 mL vial is not confused with a “catheter lock flush” vial or other 1 mL vial of incorrect strength
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 in pediatric patients due to medication errors in which 1 mL heparin sodium injection vials were confused with 1 mL “catheter lock flush” vials. Carefully examine all heparin sodium injection vials to confirm the correct vial choice prior to administration of the drug.
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and the seal is intact. Do not use if solution is discolored or contains a precipitate.
When heparin is added to an infusion solution for continuous intravenous (IV) administration, invert the container at least six times to ensure adequate mixing and prevent pooling of the heparin in the solution. Storage of prepared infusion solution should not exceed 4 hours at room temperature or 24 hours at 2°C to 8°C (36° to 46°F).
Administer heparin sodium injection 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 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 or establish a causal relationship to drug exposure.
- Hemorrhage−Hemorrhage is the chief complication that may result from heparin therapy[see Warnings and Precautions ]. 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 ].
- Local Irritation – Local irritation, erythema, mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat) injection of heparin sodium. Because these complications are much more common after intramuscular use, the intramuscular route is not recommended.
- Histamine-like reactions – Such reactions have been observed at the site of injections. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin, occasionally requiring skin grafting[see Warnings and Precautions ].
- 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 less frequently. Itching and burning, especially on the plantar side of the feet, may occur.[see Warnings and Precautions ]
- Elevations of 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.
- Metabolism and Nutrition Disorders – Hyperkalemia.
Heparin sodium injection, USP is available as:
Heparin sodium injection, USP contains
- 1,000 USP units per mL, multiple-dose vial
- 5,000 USP units per mL, multiple-dose vial
- 10,000 USP units per mL, multiple-dose vial
The use of heparin sodium injection is contraindicated in patients with the following conditions:
- History of heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis [see Warnings and Precautions (;)]
5.3 Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and ThrombosisHeparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction. 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 referred to as heparin-induced thrombocytopenia with 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. If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT and HITT, and, if necessary, administer an alternative anticoagulant.
HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin sodium should be evaluated for HIT or HITT.
- Known hypersensitivity to heparin or pork products (e.g., anaphylactoid reactions)[see Adverse Reactions (;)]
6.1 Postmarketing ExperienceThe 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 or establish a causal relationship to drug exposure.
- Hemorrhage−Hemorrhage is the chief complication that may result from heparin therapy[see Warnings and Precautions ]. 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 ].
- Local Irritation – Local irritation, erythema, mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat) injection of heparin sodium. Because these complications are much more common after intramuscular use, the intramuscular route is not recommended.
- Histamine-like reactions – Such reactions have been observed at the site of injections. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin, occasionally requiring skin grafting[see Warnings and Precautions ].
- 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 less frequently. Itching and burning, especially on the plantar side of the feet, may occur.[see Warnings and Precautions ]
- Elevations of 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.
- Metabolism and Nutrition Disorders – Hyperkalemia.
- Hemorrhage−Hemorrhage is the chief complication that may result from heparin therapy
- In whom 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 and Precautions (], except when this is due to disseminated intravascular coagulation.)
5.4 Risk of Serious Adverse Reactions in Infants Due to Benzyl Alcohol PreservativeSerious and fatal adverse reactions including “gasping syndrome” can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including heparin sodium injection multiple-dose vials. The “gasping syndrome” is characterized by central nervous system depression, metabolic acidosis, and gasping respirations.
When prescribing Heparin Sodium Injection multiple-dose vials in infants consider the combined daily metabolic load of benzyl alcohol from all sources including heparin sodium injection multiple-dose vials 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 ].
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 in pediatric patients due to medication errors in which 1 mL heparin sodium injection vials were confused with 1 mL “catheter lock flush” vials. Carefully examine all heparin sodium injection vials to confirm the correct vial choice prior to administration of the drug.