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Heparin Sodium in Sodium Chloride 5000 [USP'U]/100mL Injection
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Unfractionated Heparin class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Heparin is used to: prevent blood clots from forming in people who have certain medical conditions or who are undergoing certain medical procedures. stop the growth of clots that have already formed in the blood vessels. prevent blood clots from forming in catheters (small plastic tubes through which medication can be administered or blood drawn). treat certain types of blood disorders. Heparin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.
Read the full MedlinePlus article ↗- Heparin is a powerful blood thinner that stops dangerous clots from forming or getting bigger. Depending on your situation, it might be preventing a clot from traveling to your lun...
- Why do I need heparin — what is it actually doing for me?
- Heparin is always injected — your stomach can't absorb it, so pills aren't an option. In the hospital, it's often given as a continuous drip into a vein (IV infusion) or as an inte...
- How is heparin given — do I have to get it through an IV the whole time?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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0.037 g / 100 mL
UNII XF417D3PSL
Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
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0.45 g / 100 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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0.43 g / 100 mL
UNII GR686LBA74
Sodium phosphate, dibasic is a salt derived from phosphoric acid. It acts as a buffer to help maintain the medicine's pH balance and may serve as a binder or filler in tablets and capsules.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
4 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J1644 | $0.199 / J1644 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Heparin Sodium in Sodium Chloride 5000 [USP'U]/100mLthis 00264-3301-10 | B. | 500 ml | — | AP | FDA listed | — |
| Heparin Sodium in Dextrose 5000 [USP'U]/100mL; 5 g/100mL 00264-9577-10 | B. | 500 ml | — | — | FDA listed | — |
| Heparin Sodium 5000 [USP'U]/100mL 00409-3150-20 | Hospira, | 20 pouches | — | AP | FDA listed | — |
| Heparin Sodium 5000 [USP'U]/100mL 63323-0518-77 | Fresenius | 500 ml | — | AP | FDA listed | — |
| Heparin Sodium 5000 [USP'U]/100mL 63323-0522-77 | Fresenius | 500 ml | — | AP | FDA listed | — |
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⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
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🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00264-3301-10 You're viewing this | 24 CONTAINER in 1 CASE (0264-3301-10) / 500 mL in 1 CONTAINER | 2025-07-18 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Heparin Sodium in 0.45% Sodium Chloride Injection is indicated for: 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 is indicated for: (1) 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.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended Adult Dosages: Therapeutic Anticoagulant Effect with Full-Dose Heparin* (2.3) Intermittent Intravenous Injection Initial Dose 10,000 Units Subsequent Doses 5,000 Units to 10,000 Units every 4 to 6 hours Continuous Intravenous Infusion Initial Dose 5,000 Units by intravenous injection Continuous 20,000 Units to 40,000 Units every 24 hours *Based on 150 lb. (68 kg) patient. Cardiovascular Surgery (2.5) Intravascular via Total Body Perfusion Initial Dose Greater than or equal to 150 units/kg; adjust for longer procedures Extracorporeal Dialysis (2.8) Intravascular via Extracorporeal Dialysis Follow equipment manufacturer’s operating directions carefully.
For pediatric dosing, see section 2.4 of full prescribing information.
2.1Preparation for Administration Confirm the selection of the correct formulation and strength prior to administration of the drug. This product should be administered by intravenous infusion only. Do not use Heparin Sodium in 0.45% Sodium Chloride Injection as a “catheter lock flush” product.
Do not admix with other drugs. Discard unused portion. Do not use plastic containers in series connection.
This product should not be infused under pressure. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and container and seals are intact.
2.2Laboratory Monitoring for Efficacy and Safety Adjust the dosage of heparin sodium according to the patient’s coagulation test results. When heparin is given by continuous intravenous infusion, determine the coagulation time approximately every 4 hours in the early stages of treatment. When the drug is administered intermittently by intravenous injection, perform coagulation tests 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 the normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value. Periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy.
2.3Therapeutic Anticoagulant Effect with Full-Dose Heparin The dosing recommendations in Table 1 are based on clinical experience. 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: Table 1: Recommended Adult Full-Dose Heparin Regimens for Therapeutic Anticoagulant Effect Method of Administration Frequency Recommended Dose* Intermittent Intravenous Injection Initial Dose 10,000 Units Subsequent Doses 5,000 Units to 10,000 Units every 4 to 6 hours Continuous Intravenous Infusion Initial Dose 5,000 Units by intravenous injection Continuous 20,000 Units to 40,000 Units every 24 hours * Based on 150 lb.
(68 kg) patient.
2.4Pediatric Use There are no adequate and well-controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience. In general, the following dosage schedule may be used as a guideline in pediatric patients: Initial Dose 75 units/kg to 100 units/kg (intravenous bolus over 10 minutes) Maintenance Dose Infants: 25 units/kg/hour to 30 units/kg/hour; Infants less than 2 months have the highest requirements (average 28 units/kg/hour) Children greater than 1 year of age: 18 units/kg/hour to 20 units/kg/hour; Older children may require less heparin, similar to weight-adjusted adult dosage Monitoring Adjust heparin to maintain APTT of 60 to 85 seconds, assuming this reflects an anti-Factor Xa level of 0.35 to 0.70.
2.5Cardiovascular Surgery 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 weigh…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION is a sterile, single-dose, clear, nonpyrogenic solution available as: Heparin Sodium 25,000 USP units per 500 mL (50 USP units per mL) in 0.45% Sodium Chloride Injection. Heparin Sodium 25,000 USP units per 250 mL (100 USP units per mL) in 0.45% Sodium Chloride Injection. Heparin Sodium 25,000 USP units per 500 mL (50 USP units per mL) in 0.45% Sodium Chloride Injection (3) Heparin Sodium 25,000 USP units per 250 mL (100 USP units per mL) in 0.45% Sodium Chloride Injection (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS The use of HEPARIN SODIUM in 0.45% SODIUM CHLORIDE INJECTION is contraindicated in patients with the following conditions: History of heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis (HITT) [ see Warnings and Precautions (5.3) ] Known hypersensitivity to heparin or pork products (e.g., anaphylactoid reactions) [ see Warnings and Precautions (5.7) and Adverse Reactions (6.1) ] 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) [see Warnings and Precautions (5.5) ] Uncontrollable active bleeding state except when this is due to disseminated intravascular coagulation [see Warnings and Precautions (5.2) ] History of heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis (HITT) (5.3) Known hypersensitivity to heparin or pork products (5.7) In whom suitable blood coagulation tests cannot be performed at appropriate intervals (5.5) Uncontrollable active bleeding state, except when this is due to disseminated intravascular coagulation (5.2)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Fatal Medication Errors: Confirm choice of correct strength prior to administration. (5.1) Hemorrhage: Fatal cases have occurred. Monitor for signs of bleeding and manage promptly.
(5.2) HIT or HITT: Monitor for signs and symptoms and discontinue if indicative of HIT or HITT. (5.3) Thrombocytopenia: Monitor platelet count during therapy; discontinue heparin in HIT or HITT is suspected. (5.4) Monitoring: Blood coagulation tests guide therapy for full-dose heparin.
Monitor platelet count and hematocrit in all patients receiving heparin. (5.5) Heparin Resistance: Increased resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer and in postsurgical patients. (5.6) Hypersensitivity Reactions: Use in patients with prior reactions only in life-threatening situations.
(5.7) Hyperkalemia: Measure plasma potassium in patients at risk of hyperkalemia before starting heparin therapy and periodically in all patients (5.8) Elevations of serum aminotransferases: Interpret elevation of these enzymes with caution. (5.9)
5.1Fatal Medication Errors Do not use this product as a “catheter lock flush” product. Heparin is supplied in various strengths. Fatal hemorrhages have occurred due to medication errors. Carefully examine all heparin products to confirm the correct container choice prior to administration of the drug.
5.2Hemorrhage Hemorrhage, including fatal events, has occurred in patients receiving HEPARIN SODIUM. Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks. 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 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. 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 and continuous tube drainage of the stomach or small intestine. Other — Menstruation, liver disease with impaired hemostasis.
5.3Heparin-Induced Thrombocytopenia (HIT) and Heparin-Induced Thrombocytopenia and Thrombosis (HITT) HIT is a serious immune-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 HITT.
Thrombotic events may also be the initial presentation for HIT. These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, thrombus formation on a prosthetic cardiac valve, mesenteric thrombosis, ren…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious 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) ] Thrombocytopenia [ see Warnings and Precautions (5.4) ] Heparin Resistance [ see Warnings and Precautions (5.6) ] Hypersensitivity [ see Warnings and Precautions (5.7) ] Hyperkalemia [see Warnings and Precautions (5.8) ] Elevations of Serum Aminotransferases [see Warnings and Precautions (5.9) ] Most common adverse reactions are: hemorrhage, thrombocytopenia, HIT or HITT, hypersensitivity reactions, heparin resistance, hyperkalemia, and elevations of aminotransferase levels.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at 1-800-227-2862 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. 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) ] .
An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug [see Overdosage (10)] . 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: 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 anticoagulant therapy. Retroperitoneal hemorrhage. Vascular Disorders – Contusion, Vasospastic reactions (including episodes of painful, ischemic, and cyanosed limbs).
HIT and HITT, including delayed onset cases, and Thrombocytopenia – [ see Warnings and Precautions (5.3 and 5.4) ] 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. 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 site of the feet, may occur [ see Warnings and Precautions (5.7) ] . Musculoskeletal, Connective Tissue and Bone Disorders – Osteoporosis with long-term administration of heparin. Metabolism and Nutrition Disorders – Hyperkalemia.
General Disorders and Administration Site Conditions – Erythema, mild pain, ulceration. 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 also been reported.
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Drugs that interfere with coagulation, platelet aggregation or drugs that counteract coagulation may induce bleeding. (7)
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 acetylsalicylic acid, ibuprofen, indomethacin, and celecoxib), dextran, phenylbutazone, thienopyridines, dipyridamole, hydroxychloroquine, glycoprotein IIv/IIa 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. To reduce the risk of bleeding, a reduction in the dose of antiplatelet agent or heparin is recommended.
7.3Other Medications that May Interfere with Heparin Digitalis, tetracyclines, nicotine, antihistamines, or intravenous nitroglycerin 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 nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of heparin dosage are recommended during coadministration of heparin and intravenous nitroglycerin.
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).
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary 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 was observed in animal reproduction studies with administration of heparin sodium to pregnant rats and rabbits during organogenesis at doses up to 10,000 USP units/kg/day, approximately 10 times the maximum recommended human dose (MRHD) of 40,000 USP units/24 hours infusion [ see Data ] . In pregnant animals, doses up to 10 times higher than the maximum human daily dose based on body weight resulted in increased resorptions.
Consider the benefits and risks of HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION to a pregnant woman and possible risks to the fetus when prescribing HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 USP 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.
8.2Lactation Risk Summary There is no information regarding the presence of HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION in human milk, the effects on the breastfed infant, or the effects on milk production. Due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION and any potential adverse effects on the breastfed infant from HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION or from the underlying maternal condition [ see Use in Specific Populations (8.4) ] .
8.4Pediatric Use There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience [ see Dosage and Administration (2.4) ] .
8.5Geriatric Use There are limited adequate and well-controlled studies in patients 65 years and older. However, a higher incidence of bleeding has been reported in patients over 60 years of age, especially women [ see Warnings and Precautions (5.2) ] . Lower doses of heparin may be indicated in these patients [ see Clinical Pharmacology (12.3) ] .
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary 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 was observed in animal reproduction studies with administration of heparin sodium to pregnant rats and rabbits during organogenesis at doses up to 10,000 USP units/kg/day, approximately 10 times the maximum recommended human dose (MRHD) of 40,000 USP units/24 hours infusion [ see Data ] . In pregnant animals, doses up to 10 times higher than the maximum human daily dose based on body weight resulted in increased resorptions.
Consider the benefits and risks of HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION to a pregnant woman and possible risks to the fetus when prescribing HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 USP 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.
🧒 Pediatric Use ▾
8.4Pediatric Use There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience [ see Dosage and Administration (2.4) ] .
🧓 Geriatric Use ▾
8.5Geriatric Use There are limited adequate and well-controlled studies in patients 65 years and older. However, a higher incidence of bleeding has been reported in patients over 60 years of age, especially women [ see Warnings and Precautions (5.2) ] . Lower doses of heparin may be indicated in these patients [ see Clinical Pharmacology (12.3) ] .
🆘 Overdosage ▾
10 OVERDOSAGE An overdose requires immediate medical attention and treatment. Symptoms Bleeding is the chief sign of heparin overdosage. Easy bruising, petechial formations, nosebleeds, blood in urine or tarry stools may be the first signs or symptoms of a heparin overdose.
In the event of symptomatic heparin overdose, consider stopping heparin infusion. 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 30 minutes after intravenous injection.
Ideally, the dose required to neutralize the action of heparin should be guided by blood coagulation tests or calculated from a protamine neutralization test. Because fatal reactions often resembling anaphylaxis have been reported, protamine sulfate should be given only when resuscitation techniques and treatment of anaphylactoid shock are readily available. For additional information, consult the prescribing information for Protamine Sulfate Injection, USP.
Blood or plasma transfusions may be necessary; these dilute but do not neutralize heparin.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Heparin interacts with the naturally occurring plasma protein, Antithrombin III, to induce a conformational change, which markedly enhances the serine protease activity of Antithrombin III, thereby inhibiting the activated coagulation factors involved in the closing sequence, particularly Xa and IIa. Small amounts of heparin inhibit Factor Xa, and larger amounts inhibit thrombin (Factor IIa). Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.
Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots.
12.2Pharmacodynamics Various times (activated clotting time, activated partial thromboplastin time, prothrombin time, whole blood clotting time) are prolonged by full therapeutic doses of heparin; in most cases, they are not measurably affected by low doses of heparin. Bleeding time is usually unaffected by heparin.
12.3Pharmacokinetics Absorption Heparin is not absorbed through the gastrointestinal tract and therefore administered via parenteral route. Peak plasma concentration and the onset of action are achieved immediately after intravenous administration. Distribution Heparin is highly bound to antithrombin, fibrinogens, globulins, serum proteases and lipoproteins. The volume of distribution is
0.07L/kg. Elimination Metabolism Heparin does not undergo enzymatic degradation. Excretion Heparin is mainly cleared from the circulation by liver and reticuloendothelial cells mediated uptake into extravascular space.
Heparin undergoes biphasic clearance, a) rapid saturable clearance (zero order process due to binding to proteins, endothelial cells and macrophages) and b) slower first order elimination. Low doses of heparin are cleared mostly by a saturable, rapid, zero-order process. Slower first order elimination usually occurs with very high doses of heparin and is dependent on renal function.
The plasma half-life is dose-dependent, and it ranges from 0.5 to 2 hours. Specific Populations Geriatric Patients 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 [see Use in Specific Populations (8.5 ) ] . Renal and Hepatic Impairment The rate of clearance of unfractionated heparin may be decreased in patients with renal or hepatic impairment.
Patients with renal or hepatic impairment, following similar doses of heparin may have higher plasma levels of heparin compared with patient with normal renal and hepatic function [see Warnings and Precautions (5.2) ] .
🧬 Mechanism of Action ▾
12.1Mechanism of Action Heparin interacts with the naturally occurring plasma protein, Antithrombin III, to induce a conformational change, which markedly enhances the serine protease activity of Antithrombin III, thereby inhibiting the activated coagulation factors involved in the closing sequence, particularly Xa and IIa. Small amounts of heparin inhibit Factor Xa, and larger amounts inhibit thrombin (Factor IIa). Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.
Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Heparin Sodium in 0.45% Sodium Chloride Injection is a clear solution and is supplied sterile and nonpyrogenic in single-dose EXCEL ® Containers packaged 24 per case. NDC REF Concentration Size 0264-3301-10 P3301 Heparin Sodium 25,000 USP units per 500 mL (50 USP units per mL) in 0.45% Sodium Chloride Injection 500 mL 0264-3462-20 P3462 Heparin Sodium 25,000 USP units per 250 mL (100 USP units per mL) in 0.45% Sodium Chloride Injection 250 mL Exposure of pharmaceutical products to heat should be minimized.
Avoid excessive heat. Protect from freezing. Store at 20°C to 25°C (68°F to 77°F).
Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.]
📋 Description ▾
11 DESCRIPTION Heparin is a heterogenous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans having anticoagulant properties. It is composed of polymers of alternating derivations of alpha-L-iduronic acid 2-sulfate (1), 2-deoxy-2-sulfamino- alpha-D-glucose 6-sulfate (2), beta-D-glucuronic acid (3), 2-acetamido-2- deoxy-alpha-D-glucose (4), and alpha-L-iduronic acid (5). Structure of Heparin Sodium (representative subunits): Heparin Sodium in 0.45% Sodium Chloride Injection is a sterile, single-dose, clear, nonpyrogenic solution prepared from Heparin Sodium USP (derived from porcine intestinal mucosa and standardized for use as an anticoagulant) in 0.45% Sodium Chloride Injection.
It is to be administered by intravenous injection. The potency is determined by a biological assay using a USP reference standard based on units of heparin activity per milligram. The pH range is 7.0 (6.8-7.2) and the osmolarity mOsmol/L (calc.) is 206.
The concentration of electrolytes is 109 mEq/L Sodium, 77 mEq/L Chloride, 32 mEq/L Phosphate, and 6 mEq/L Citrate. 50 USP units/mL: Each 100 mL of the 25,000 USP units per 500 mL preparation contains: 5,000 USP units of heparin sodium, 0.45 g Sodium Chloride USP, 0.43 g Dibasic Sodium Phosphate USP, 0.037 g Citric Acid Anhydrous USP, and Water for Injection USP until quantity sufficient. 100 USP units/mL: Each 100 mL of the 25,000 USP units per 250 mL preparation contains: 10,000 USP units of heparin sodium, 0.45 g Sodium Chloride USP, 0.43 g Dibasic Sodium Phosphate USP, 0.037 g Citric Acid Anhydrous USP, and Water for Injection USP until quantity sufficient.
The plastic container is made from a multilayered film specifically developed for parenteral drugs. The solution contact layer is a rubberized copolymer of ethylene and propylene. The container is nontoxic and biologically inert.
The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary. The plastic container is not made with natural rubber latex, PVC or DEHP.
The closure system has two ports; the one for the administration set has a tamper evident plastic protector. heparin sodium chemical formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Hemorrhage Inform patients that it may take them longer than usual to stop bleeding, that they may bruise and/or bleed more easily when they are treated with heparin, and that they should report any unusual bleeding or bruising to their physician. Hemorrhage can occur at virtually any site in patients receiving heparin. Fatal hemorrhages have occurred [ see Warnings and Precautions (5.2) ] .
Prior to Surgery Advise patients to inform physicians and dentists that they are receiving heparin before any surgery is scheduled [ see Warnings and Precautions (5.2) ] . Heparin-Induced Thrombocytopenia Inform patients of the risk of heparin-induced thrombocytopenia (HIT). HIT may progress to the development of venous and arterial thromboses, a condition known as heparin-induced thrombocytopenia and thrombosis (HITT).
HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy [ see Warnings and Precautions ( 5.3 and 5.4 ) ] . Hypersensitivity Inform patients that generalized hypersensitivity reactions have been reported. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin [ see Warnings and Precautions (5.7) , Adverse Reactions (6) ] .
Other Medications Because of the risk of hemorrhage, advise patients to inform their physicians and dentists of all medications they are taking, including non-prescription medications, and before starting any new medication [see Drug Interactions (7.2) ] .