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Heparin Sodium

Pronunciation

Class: Heparins
CAS Number: 9041-08-1
Brands: HepFlush

Introduction

Anticoagulant; a heterogeneous group of anionic, sulfated glycosaminoglycans.e

Unless otherwise specified in this monograph, the term “heparin” refers to “unfractionated heparin”, not low molecular weight heparin (LMWH) or both types of heparin.

Uses for Heparin Sodium

Treatment of Venous Thromboembolism

Treatment of DVT and PE.116 118 364 500 1005

Recommended by the American College of Chest Physicians (ACCP) as an appropriate choice of anticoagulant for initial treatment of acute proximal DVT or PE.1005

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment.1005 IV heparin also may be preferred over sub-Q therapies in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.1005

After full-dose heparin therapy, warfarin or an LMWH generally is administered as follow-up anticoagulant therapy for ≥3 months in adults with venous thromboembolism.1005

Thromboprophylaxis in General Surgery

Prophylaxis of postoperative DVT and PE in patients undergoing general (e.g., abdominal) surgery who are at risk of thromboembolism.500 1002

ACCP recommends pharmacologic (e.g., low-dose heparin) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding.1002 In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.1002

If pharmacologic prophylaxis is indicated in patients undergoing general surgery, ACCP states that an LMWH or low-dose heparin is preferred.1002

ACCP states that the same recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.1002

Thromboprophylaxis in Cardiac Surgery

Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that low-dose heparin may be considered in cardiac surgery patients with a complicated postoperative course.1002

Thromboprophylaxis in Neurosurgery

Has been used for prevention of venous thromboembolism in patients undergoing craniotomy; however, benefits may be outweighed by possible increased risk of intracranial hemorrhage.1002 ACCP states that the addition of low-dose heparin to a mechanical method of prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.1002

Also may be considered as a possible addition to mechanical prophylaxis in high-risk patients undergoing spinal surgery (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.1002

Thromboprophylaxis in Thoracic Surgery

Prevention of postoperative DVT and PE in patients undergoing major thoracic surgery.500

Pharmacologic thromboprophylaxis (e.g., low-dose heparin) recommended by ACCP in patients undergoing thoracic surgery who are at high risk of venous thromboembolism, provided risk of bleeding is low.1002

Thromboprophylaxis in Major Orthopedic Surgery

Has been used for prevention of DVT and PE in patients undergoing total hip-replacement surgery, total knee-replacement surgery, or hip-fracture surgery.1003

ACCP recommends routine thromboprophylaxis (with a pharmacologic and/or mechanical method) in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.1003

Among several antithrombotic agents (e.g., LMWH, fondaparinux, low-dose heparin, warfarin, aspirin) recommended for pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery, ACCP states LMWHs generally preferred; may consider alternative agents when an LMWH is not available or cannot be used.1003

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy and safety of the drugs in addition to other logistics and compliance issues.1003

Thromboprophylaxis in Selected Medical Conditions

Used for prevention of DVT and PE in acutely ill hospitalized medical patients and in those with medical conditions associated with a high risk of thromboembolism (e.g., cancer).1001

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.1001

ACCP recommends anticoagulant prophylaxis (e.g., low-dose heparin) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding.1001 Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or hospital discharge.1001

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Low-dose heparin also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.1001

Risk of venous thromboembolism is particularly high in patients with cancer.1001 Use of low-dose heparin suggested by ACCP in cancer (solid tumors) outpatients who have additional risk factors for thromboembolism, provided risk of bleeding is low.1001

Thromboprophylaxis in Trauma

Low-dose heparin may be used for thromboprophylaxis in patients with major trauma.1002 For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests the use of both a pharmacologic and mechanical method of prophylaxis, unless contraindications exist.1002

Thromboembolism During Pregnancy

Has been used for prevention and treatment of venous thromboembolism during pregnancy; however, an LMWH generally is recommended by ACCP because of a more favorable safety profile.1012

Complications of Pregnancy

Has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibodies (APLA) syndrome.1012

Also has been used with aspirin (often combined with immune globulin) for prevention of venous thromboembolism and early pregnancy loss in women who have undergone in vitro fertilization.294 311 312 313 314 1012

Venous Thromboembolism in Pediatric Patients

Has been used for treatment and secondary prevention of venous thromboembolism in neonates and children; venous thromboembolism usually occurs secondary to an identifiable risk factor (e.g., presence of central venous access device) in such patients.1013

Recommendations regarding use of antithrombotic therapy in children generally based on extrapolation from adult guidelines.1013

In children with central venous catheters (or umbilical venous catheters) who experience venous thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation suggested prior to removal.1013 If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.1013

Cardioversion of Atrial Fibrillation/Flutter

Has been used to reduce the risk of stroke and systemic embolism in patients undergoing electrical or pharmacologic cardioversion for atrial fibrillation or atrial flutter.1007

Therapeutic anticoagulation with heparin may be used in patients in whom prolonged anticoagulation (e.g., with warfarin for ≥3 weeks) prior to cardioversion is not necessary or not possible; in these situations, heparin or an LMWH generally is administered at the time of transesophageal echocardiograph (TEE) or at presentation (for those with atrial fibrillation ≤48 hours) just prior to cardioversion.1007

In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of IV heparin or an LMWH prior to cardioversion, if possible; however, such anticoagulant therapy must not delay any emergency intervention.999 1007

Thromboembolism Associated with Prosthetic Heart Valves

Used during conversion to maintenance warfarin therapy to reduce the incidence of thromboembolism (e.g., stroke) in patients with prosthetic mechanical heart valves.293 359 996 1008 1012

ACCP suggests bridging anticoagulation (administration of an LMWH in either prophylactic or therapeutic dosages or IV heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve until patient is stable on warfarin therapy.1008

Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., for major surgery).1004 ACC and AHA state that perioperative use of heparin should be considered for noncardiac surgery, invasive procedures, or dental procedures in patients with prosthetic heart valves who are at high risk for thrombosis without oral antithrombotic therapy (e.g., those with any mechanical mitral valve or a mechanical aortic valve with additional risk factors).996

Used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves.996 1012 (See Thromboembolism During Pregnancy under Dosage and Administration.)

Renal Vein Thrombosis

Renal vein thrombosis is the most common cause of spontaneous venous thromboembolism in neonates.1013 Although use of anticoagulant therapy in patients with renal vein thrombosis is controversial, heparin is suggested by ACCP as a possible treatment option in selected neonates.1013

Arterial Thromboembolism

Used to reduce the extent of ischemic injury in patients with acute arterial emboli or thrombosis; however, ACCP states formal studies demonstrating improved outcomes have not been conducted.1011

In patients with limb ischemia secondary to arterial emboli or thrombosis, immediate systemic anticoagulation with heparin to prevent thrombotic propagation is suggested by ACCP.1011

Prophylaxis during cardiac catheterization via an artery in neonates and children.1013 If femoral artery thrombosis occurs following cardiac catheterization, therapeutic-dose IV heparin is recommended, followed by subsequent conversion to an LMWH or continued treatment with heparin to complete 5–7 days of therapeutic anticoagulation.1013

Thromboembolism Associated with Cardiac and Arterial Vascular Surgery

Prevention of activation of the coagulation mechanism during arterial and cardiac surgery.373 380 453 500

A nonheparin anticoagulant (e.g., bivalirudin) may be used in place of heparin in patients with acute heparin-induced thrombocytopenia (HIT) or subacute HIT (platelets have recovered, but HIT antibodies still present) who require urgent cardiac surgery.1006 Because HIT antibodies are transient, ACCP states that short-term use of heparin may be appropriate in patients with a remote (>3 months) history of HIT and no detectable antibodies who require cardiac surgery.1006

Disseminated Intravascular Coagulation

Treatment of acute and chronic consumptive coagulopathies, including disseminated intravascular coagulation.500

Thrombosis Associated with Indwelling Venous or Arterial Devices

Maintenance of patency of indwelling peripheral or central venipuncture devices designed for intermittent injections and/or blood sampling.112 214 215 216 217 218 219 221 222 223 224 225 232 233 234 1013

ACCP suggests use of heparin flushes as an option for primary thromboprophylaxis of central venous access devices in children.1013

In neonates and children with peripheral arterial catheters, ACCP recommends continuous IV infusion of heparin (in low concentrations) via the catheter for prophylaxis.1013 Also may consider use of heparin for treatment if symptomatic catheter-related thromboembolism occurs.1013

In neonates with umbilical arterial catheters, ACCP also suggests thromboprophylaxis with low-dose heparin via the catheter to maintain patency.1013

ST-Segment Elevation MI (STEMI)

Used in combination with antiplatelet agents (e.g., aspirin) during and after successful coronary artery reperfusion (e.g., thrombolytic agents) for prevention of ischemic complications of STEMI (e.g., death, reinfarction, stroke).159 176 177 178 179 180 181 182 183 184 185 186 283

ACC and AHA recommend heparin or an LMWH for prevention of systemic embolism following STEMI in patients (e.g., those with large or anterior MI, atrial fibrillation, previous embolus, left ventricular thrombus, or cardiogenic shock) at high risk for such events.439

Used IV in conjunction with fibrin-selective thrombolytic agents (e.g., alteplase, reteplase, tenecteplase).332 439

Use of IV or sub-Q heparin suggested in patients not receiving reperfusion therapy who do not have a contraindication for anticoagulation.439

Acute Ischemic Complications of PCI

Used to reduce the risk of thrombotic complications in patients undergoing PCI.380 994 Used in conjunction with aspirin and other standard therapy (e.g., GP IIb/IIIa-receptor inhibitors, P2Y12 receptor antagonists).380 385 455 991 994

Use of a parenteral anticoagulant is recommended in patients undergoing PCI to prevent thrombus formation during the procedure.994 IV heparin is recommended by AHA, the American College of Cardiology Foundation (ACCF), and the Society for Cardiovascular Angiography and Interventions (SCAI) as an appropriate choice of anticoagulant.994

Unstable Angina or Non-ST-Segment Elevation MI (NSTEMI)

Reduction in the risk of acute cardiac ischemic events (death and/or MI) in patients with unstable angina or NSTEMI.348 361 444 991 994

Used concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blockers, P2Y12 receptor antagonists).348 361 444 991

Administer anticoagulant therapy as soon as possible after presentation of unstable angina or NSTEMI.991

In patients undergoing an invasive management strategy, ACC, AHA, and ACCF state anticoagulants with established efficacy include enoxaparin, heparin, bivalirudin, and fondaparinux.991

In patients undergoing a conservative management strategy, recommended anticoagulant regimens include enoxaparin, heparin, and fondaparinux; fondaparinux is preferred in patients with increased risk of bleeding.991

In patients who will undergo CABG, if heparin is already being administered, continue during surgery.991 If patient is receiving other anticoagulants (enoxaparin, fondaparinux, or bivalirudin), discontinue other anticoagulant and use heparin during CABG.991

In patients in whom conservative medical therapy is selected as a postangiographic management strategy, recommendations for continued antiplatelet and anticoagulant therapy generally are based on the presence of CAD.991

Treatment of Cerebral Venous Sinus Thrombosis

May be used for treatment of acute cerebral venous sinus (sinovenous) thrombosis in adults.1009 May convert to oral anticoagulant therapy once patient is stabilized.1009

Recommended by ACCP as an option for initial anticoagulation in children with cerebral venous sinus thrombosis without substantial intracranial hemorrhage.1013 Also has been suggested for use in such children with substantial hemorrhage.1013

Acute Ischemic Stroke

Heparin anticoagulants (i.e., LMWH or heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke; those with additional risk factors for venous thromboembolism are more likely to benefit.1009

ACCP suggests thromboprophylaxis with an LMWH (in prophylactic dosages), sub-Q heparin, or intermittent pneumatic compression in patients with acute ischemic stroke and restricted mobility; LMWH is preferred over heparin.1009

Prophylactic-dose heparin usually initiated within 48 hours of onset of stroke and continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.1009

Also has been used for initial management of acute arterial ischemic stroke in children until dissection and embolic causes have been excluded.1013

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy, ACCP recommends ongoing antithrombotic therapy (e.g., heparin) for 3 months.1013

Heparin may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source.1013

Perioperative Management of Antithrombotic Therapy

Used in the perioperative management of patients who require temporary interruption of long-term warfarin therapy for surgery or other invasive procedures.1004

ACCP suggests perioperative use of an LMWH or IV heparin (bridging anticoagulation) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves depending on their risk of developing thromboembolism without warfarin therapy.1004

In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.1004

Anticoagulant in Blood Transfusions, Blood Samples, and Other Procedures

Used as an in vitro anticoagulant in blood transfusions.500

Used for anticoagulation during extracorporeal circulation and dialysis procedures.500

Heparin Sodium Dosage and Administration

General

Laboratory Monitoring of Therapy

  • Individualize dosage carefully based on clinical and laboratory findings.e 373 The generally accepted therapeutic range for the aPTT during full-dose IV or sub-Q heparin therapy is 1.5–2 times the control value in seconds.500 The generally accepted therapeutic range for the activated clotting time (ACT) is 2.5–3 times the control value in seconds.500

  • Laboratory monitoring of coagulation tests usually not performed with fixed low-dose sub-Q heparin therapy because such tests are generally unaffected or only minimally prolonged.e If monitoring is required, it is best performed on samples drawn 4–6 hours after injections.373 500

  • With continuous IV infusion, perform coagulation tests prior to initiation of therapy, approximately every 4 hours during the early stages of therapy, and daily thereafter.373 453 e 500

  • With intermittent IV injection, perform coagulation tests prior to each injection during the early stages of therapy, and at appropriate intervals thereafter.373 453 500

  • Perform periodic platelet counts, hematocrit, and tests for occult blood in stool during the entire course of therapy.373 453 373

Conversion to Oral Anticoagulation

  • When warfarin is indicated for follow-up therapy after initial therapy with heparin, overlap therapy for a minimum of 5 days and until INR is at least 2 for ≥24 hours.500 1005

  • When converting to oral dabigatran in patients currently receiving heparin therapy by continuous IV infusion, administer first dose of dabigatran, then immediately discontinue heparin infusion; for those currently receiving intermittently dosed IV heparin therapy, initiate dabigatran within 2 hours prior to what would have been the time of the next scheduled heparin dose.373

  • Some manufacturers recommend abrupt discontinuance of heparin therapy after confirmation of adequate response to warfarin.373 453 500 However, some clinicians recommend gradual discontinuance of heparin infusions (e.g., reducing the rate by 50% over 6 hours and then discontinuing over the next 12 hours) because of concern about possible rebound thrombosis.e

Administration

Administer by IV infusion, intermittent IV injection, or deep sub-Q (intrafat) injection.373 453 500 Do not administer IM because of frequency of hematoma at injection site.373 453 462 463 464 500

Do not use heparin lock flush solutions for systemic anticoagulation.462 464 Conversely, do not use heparin sodium injections as catheter lock flush products.373 500

Use preservative-free formulations in neonates and infants, and also in pregnant and nursing women, if available.373 500 (See Pediatric Use under Cautions.)

Effective May 1, 2013, USP changed its labeling standard for Heparin Sodium Injection, USP and Heparin Lock Flush Solution, USP to require that labels of these products clearly state the strength of the entire container (amount of heparin per total volume of container), followed in close proximity by the strength per mL in parentheses.501 During the transition, both current and revised heparin container labels will be available simultaneously on the US market.501 To reduce the risk of medication errors, implement measures to avoid confusion between the 2 types of product labeling (e.g., separate supplies of current and revised labeled heparin on pharmacy shelves, exhaust current supply of heparin before transitioning to products with revised labeling).501 Also, carefully check the labels on all heparin products for correct formulation and strength prior to dispensing and administering the drug.373 500 501

IV Administration

For solution and drug compatibility information, see Compatibility Under Stability.

Dilution

When adding heparin to a solution for continuous IV infusion, invert the container at least 6 times to ensure adequate mixing and to prevent pooling of the drug in solution.373 453

Sub-Q Administration

Inject with a 25- or 26-gauge needle sub-Q deeply above the iliac crest or into the abdominal fat layer, or arm to minimize tissue trauma.373 453 e 471

Intracatheter Instillation

Instill a quantity of heparin lock flush solution (e.g., containing 10 or 100 units/mL) sufficient to fill the indwelling venipuncture device into the lumen of the device following the initial placement of the device in the vein and after each use.462 463 464 465 Consult device manufacturer’s instructions for specific directions.234 462 464

When the indwelling venipuncture device is used for repeated withdrawal of blood samples for laboratory analysis and the presence of heparin or 0.9% sodium chloride is likely to alter results of the analysis, aspirate and discard heparin lock flush solution from the device before withdrawing the blood sample.234 462 464 465 After the blood sample is drawn, may instill another dose of heparin lock flush solution into the device.219 234 462 464 465

Following injection of heparin lock flush solution from a single-dose vial into an indwelling venipuncture device, discard unused portions of the solution.462 Multiple-dose vials are available for repeated use.464

Dosage

Available as heparin sodium; dosage is expressed in terms of heparin sodium in USP units.373 453 462 464 465 One USP unit is equivalent to one international unit (IU).489 490

Dosage requirements for full-dose therapy vary greatly among individuals; carefully individualize dosage based on the clinical and laboratory findings.e

Pediatric Patients

Treatment of DVT and PE
IV

Because of a lack of adequate and well-controlled studies, dosage recommendations in pediatric patients are generally based on clinical experience.373 500 In children receiving full-dose (therapeutic) heparin, ACCP suggests a dosage sufficient to achieve an anti-factor Xa concentration of 0.35–0.7 units/mL or prolong the aPTT to a corresponding anti-factor Xa range or to a protamine titration range of 0.2–0.4 units/mL.1013 Initial treatment for at least 5 days recommended.1005 1013 Convert to oral anticoagulation (e.g., warfarin) or an LMWH, or continue with heparin for ongoing therapy.1013 (See Conversion to Oral Anticoagulation under Dosage and Administration.)

Initial loading dose of 75–100 units/kg (by direct IV injection over 10 minutes) has been suggested.500 503 1013 Follow with a maintenance IV infusion of 25–30 units/kg per hour in infants or 18–20 units/kg per hour in children >1 year of age; appropriate maintenance dosage appears to be age dependent, with infants <2 months having the highest requirements (e.g., average of 28 units/kg per hour) and older children having lower requirements (e.g., average of 20 units/kg per hour in children >1 year of age).373 500 1013 Although not preferred, a maintenance dosage of 75–100 units/kg every 4 hours by intermittent IV administration also has been used.503

Individualize initial dosing strategy in children based on risk of thrombosis and risk of bleeding; in general, withhold or reduce loading doses if there are substantial bleeding risks and avoid long-term use of heparin.1013

Arterial Thromboembolism
IV

For neonates and children requiring cardiac catheterization via an artery: 100 units/kg by direct IV injection recommended by ACCP; additional doses may be required in prolonged procedures.1013

Neonates or children with femoral artery thrombosis associated with cardiac catheterization: Therapeutic-dose IV heparin recommended.1013

Disseminated Intravascular Coagulation
IV

25–50 units/kg given by IV infusion or IV injection every 4 hours.e Discontinue after 4–8 hours if there is no improvement.e

Thrombosis Associated with Indwelling Venous or Arterial Devices
IV

For thromboprophylaxis of central venous access devices in neonates, ACCP recommends 0.5 units/kg per hour as a continuous infusion.1013

For thromboprophylaxis of umbilical arterial catheters in neonates, ACCP suggests low-dose infusion (0.25–1 units/mL) through the catheter for a total dosage of 25–200 units/kg per day.1013

For thromboprophylaxis in neonates and children with peripheral arterial catheters, ACCP recommends continuous low-dose infusion (5 units/mL at 1 mL/hour).1013

Adults

Treatment of DVT and PE
IV, then Sub-Q

Full-dose intermittent therapy (68-kg adult): 5000 units by IV injection initially, then 10,000–20,000 units sub-Q for 1 dose, followed by 8000–10,000 units sub-Q every 8 hours or 15,000–20,000 units sub-Q every 12 hours.373 453 471 500

IV

Full-dose continuous therapy (68-kg adult): 5000 units initial loading dose by IV injection, then 20,000–40,000 units in 1 L of compatible IV solution infused over 24 hours recommended by some manufacturers.373 453 500

Full-dose intermittent therapy (68-kg adult): 10,000 units initial loading dose (either undiluted or diluted in 50 or 100 mL of 0.9% sodium chloride injection), then 5000–10,000 units every 4–6 hours recommended by some manufacturers.500

ACCP suggests a weight-adjusted dosage (loading dose of 80 units/kg followed by continuous infusion of 18 units/kg per hour) or a fixed dosage (loading dose of 5000 units followed by continuous infusion of 1000 units/hour).1000 Although the aPTT can be used to monitor either dosage regimen, ACCP states there is no evidence that monitoring improves clinical outcomes.1000

Sub-Q

For outpatients receiving sub-Q therapy, ACCP suggests weight-based dosing (initial dose of 333 units/kg followed by 250 units/kg twice daily) without monitoring.1000

General Surgery Thromboprophylaxis
Sub-Q

Usual dosage is 5000 units administered 2 hours prior to surgery and every 8–12 hours after surgery for 7 days or until patient is fully ambulatory, whichever is longer.500

Thromboembolism During Pregnancy
Sub-Q

Women with APLA syndrome and a history of multiple pregnancy losses: Antepartum administration of sub-Q heparin in a prophylactic or intermediate dosage in combination with low-dose aspirin (75–100 mg daily) has been recommended.290 295 299 300 315 1012

Pregnant women with mechanical prosthetic heart valves: Initially, 17,500–20,000 units every 12 hours and adjusted to maintain the mid-interval aPTT at least twice the control value or anti-factor Xa concentration of 0.35–0.7 units/mL throughout pregnancy suggested.1012

Alternatively, in pregnant women with mechanical prosthetic heart valves, 17,500–20,000 units every 12 hours adjusted to maintain the mid-interval aPTT at least twice the control value or an anti-factor Xa concentration of 0.35–0.7 units/mL until week 13 of pregnancy, then switch to warfarin until close to delivery when heparin may be resumed.1012

Pregnant women with atrial fibrillation and additional risk factors for thromboembolism: 10,000–20,000 units every 12 hours with dosage adjusted to maintain the mid-interval aPTT (6 hours after dose) at 1.5 times the control value during the first trimester and last month of pregnancy.999

IV

Pregnant women with atrial fibrillation and additional risk factors for thromboembolism: Adjusted-dose continuous therapy suggested to maintain the aPTT at 1.5–2 times control value during first trimester and last month of pregnancy.999

Perioperative Management of Antithrombotic Therapy
IV

If heparin is used for bridging anticoagulation in patients who require temporary interruption of warfarin therapy (e.g., for surgery or other invasive procedure), ACCP recommends therapeutic dosages (e.g., continuous infusion adjusted to maintain an aPTT of approximately 1.5–2 times the control value); however, other dosage regimens have been used.1004

ACCP suggests that heparin be discontinued approximately 4–6 hours prior to surgery.1004

Administer postoperative anticoagulation with caution and only when hemostasis established.1004

Disseminated Intravascular Coagulation
IV

50–100 units/kg by IV infusion or IV injection every 4 hours.e Discontinue after 4–8 hours if there is no improvement.e

Thrombosis Associated with Indwelling Venipuncture Devices
Intracatheter Instillation

Inject a quantity of heparin lock flush solution (e.g., containing 10 or 100 units/mL) sufficient to fill the device after each use.234 462 464 465 (See Intracatheter Instillation under Dosage and Administration: Administration.)

STEMI
IV

Conjunctive therapy with fibrin-selective thrombolytic agents: Initially, 60 units/kg (maximum 4000 units) loading dose.439 455

Maintenance dosage: 12 units/kg per hour (maximum 1000 units/hour), adjusted to maintain a therapeutic aPTT (1.5–2 times control value or approximately 50–70 seconds) for 48 hours.439 455

May discontinue after 48 hours in patients at low risk for thromboembolism, convert to sub-Q therapy in patients at high risk of systemic embolization, or continue IV therapy in patients at high risk for coronary reocclusion.439

IV or Sub-Q

Acute MI and concurrent atrial fibrillation: Continuous IV infusion or intermittent sub-Q injection recommended in a dosage sufficient to prolong aPTT to 1.5–2 times the control value.999

Cardiac and Arterial Surgery Thromboprophylaxis
IV

Total body perfusion for open-heart surgery: Initially, ≥150 units/kg.373 453 373 500 Administer 300 units/kg for procedures estimated to last <1 hour.373 453 500 Administer 400 units/kg for those procedures estimated to last >1 hour.373 453 500

Acute Ischemic Complications of PCI
IV

PCI without concurrent GP IIb/IIIa-receptor inhibitor: In patients who have not received prior anticoagulant therapy, a loading dose of 70–100 units/kg targeted to achieve an ACT of 250–300 seconds with the HemoTec device or 300–350 seconds with the Hemochron device suggested.994 If patient has received prior anticoagulant therapy, administer additional doses as needed to achieve an ACT of 250–300 seconds with the HemoTec device or 300–350 seconds with the Hemochron device.994

PCI with concurrent GP IIb/IIIa-receptor inhibitors: In patients who have not received prior anticoagulant therapy, a loading dose of 50–70 units/kg targeted to an ACT of 200–250 seconds suggested.994 If patient has received prior anticoagulant therapy, administer additional doses (e.g., 2000–5000 units) as needed to achieve an ACT of 200–250 seconds.994

Discontinue therapy after successful PCI procedures.994 The femoral sheath generally is removed when ACT <150–180 seconds or when aPTT <50 seconds.994

Unstable Angina and NSTEMI
IV

ACCF/AHA/ACC recommends a weight-adjusted dosing regimen (e.g., 60 units/kg [maximum 4000 units] loading dose followed by continuous infusion of 12 units/kg per hour [maximum 1000 units/hr]).991 Initiate therapy as soon as possible upon presentation.991 Optimum duration of therapy not established; in clinical trials, heparin was continued for 2–5 days.991

Anticoagulant in Blood Transfusions and Blood Samples
In vitro

In blood transfusions, add 7500 units to 100 mL of 0.9% sodium chloride injection and then add 6–8 mL of this solution to each 100 mL of whole blood.453 500

When used as an in vitro anticoagulant for blood samples, add 70–150 units to each 10–20 mL of whole blood.453 500

Extracorporeal Dialysis

Consult equipment manufacturer's operating instructions;500 if not available, dose of 25–30 units/kg, followed by infusion of 1500–2000 units/hour is suggested based on pharmacodynamic data.373

Prescribing Limits

Adults

STEMI
IV

Conjunctive therapy with fibrin-selective thrombolytic agents: Maximum 4000 units loading dose.439 455

Maintenance dosage: Maximum 1000 units/hour in patients weighing >70 kg, adjusted to maintain a therapeutic aPTT for 48 hours.439 455

Special Populations

Geriatric Patients

Patients >60 years of age may require a lower dosage.373 471 500 Consider lower dosages in geriatric patients undergoing PCI, particularly when combined with GP IIb/IIIa-receptor inhibitors.455

Women

Consider lower dosages in women undergoing PCI, particularly when combined with GP IIb/IIIa-receptor inhibitors.455

Cautions for Heparin Sodium

Contraindications

  • Uncontrollable bleeding, unless such bleeding is secondary to disseminated intravascular coagulation.e 373 500

  • Severe thrombocytopenia, history of HIT, or HIT with thrombosis.373

  • Inability to perform suitable blood coagulation tests at required intervals in patients receiving full-dose therapy.101 234 373 453 373 500 Lack of such tests generally is not a contraindication for fixed low-dose therapy, since monitoring of coagulation tests usually is not required.101 373 453 373 500

  • Known hypersensitivity to heparin or pork products.373 (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Hematologic Effects

Hemorrhage can range from minor local ecchymoses to major hemorrhagic complications.e Bleeding may occur at any site; some hemorrhagic complications may be difficult to detect.500

Use with extreme caution in patients with an increased risk of hemorrhage.373 e 464 471 Such patients include those with subacute bacterial endocarditis; ulcerative GI lesions; hemorrhagic blood dyscrasias (e.g., hemophilia, some vascular purpuras, thrombocytopenia); menstruation; hepatic disease with impaired hemostasis; severe hypertension; major surgery, especially involving the eye, brain, or spinal cord; continuous tube drainage of the stomach or small intestine; and spinal tap or spinal anesthesia.373 453 464 471 Screen patients prior to treatment initiation to rule out bleeding disorders.373 453 471

Monitor patients with appropriate coagulation tests just prior to surgery.373 453 471 Discontinue therapy immediately if hemorrhage occurs or if coagulation tests are unduly prolonged.373 453 Nosebleed, hematuria, or tarry stools may be noted as the first sign of bleeding or overdosage.373 453 500 Easy bruising or petechiae may precede frank bleeding.373 453 500 If severe hemorrhage or overdosage occurs, administer protamine sulfate immediately.e Blood transfusions may also be required following massive blood loss.e

If signs and symptoms of acute adrenal hemorrhage and insufficiency occur, measure plasma cortisol concentrations.e Initiate vigorous therapy with IV corticosteroids after discontinuance.e Do not delay initiation of corrective therapy until laboratory confirmation of the diagnosis, since any delay may be fatal.500

Perform periodic hematocrit and tests for occult blood in stool during the entire course of therapy.373 453 500

Obtain baseline aPTT value prior to insertion of an indwelling venipuncture device (e.g., heparin lock) since repeated injections of small doses of heparin sodium can alter aPTT results.215 220 231 234 462 464 465

Risk of thrombocytopenia, including HIT (immune-mediated reaction caused by development of IgG platelet-aggregating antibodies).373 453 e 471 500 (See HIT under Cautions and also see Contraindications under Cautions.) Monitor thrombocytopenia of any degree closely.108 373 453 471 500 Mild thrombocytopenia (platelet count >100,000/mm3) may remain stable or reverse with continued therapy.90 108 373 453 471 500 If clinically important HIT occurs, discontinue the drug immediately and substitute a nonheparin anticoagulant (e.g., argatroban, bivalirudin).405 406 407 408 471 500 502 1006

Sensitivity Reactions

Hypersensitivity

Generally contraindicated in patients who are hypersensitive to the drug.e Patients with documented hypersensitivity should be given the drug only in clearly life-threatening situations.373 453 500

Major Toxicities

HIT

Risk of HIT; may lead to severe thromboembolic complications including DVT, cerebral vein thrombosis, limb ischemia, mesenteric thrombosis, renal artery thrombosis, skin necrosis, gangrene of the extremities (possibly requiring amputation), MI, PE, stroke, and possibly, death.101 106 108 214 228 373 453 471 500 Can occur even with heparin lock flush solutions.214 215 226 228 1006 Usually evident 5–10 days after exposure to heparin, but can occur more rapidly (e.g., within 24 hours) or as late as several weeks after discontinuance of therapy.500 1006

If HIT with or without thrombosis is diagnosed or strongly suspected, discontinue all sources of heparin (including heparin flushes) and substitute a nonheparin anticoagulant (e.g., argatroban, bivalirudin).405 406 407 408 500 502 1006 Initiate conversion to warfarin therapy only after substantial recovery from acute HIT has occurred (i.e., platelet counts ≥150,000/mm3).1006 The manufacturer recommends against future use of heparin in patients who experience HIT, particularly within 3–6 months following the event and if HIT antibodies are still present.500

Evaluate patients who develop thrombocytopenia or thrombosis after treatment discontinuance for HIT and HIT with thrombosis.471

General Precautions

Heparin Resistance

Increased resistance to the antithrombotic effects of heparin reported; associated with fever, MI, thrombophlebitis, infections with thrombosing tendencies, thrombosis, antithrombin III deficiency, malignant neoplasms, and surgery (i.e., postoperatively).373 453 e

Dispensing and Administration Precautions

Fatal medication errors (including in pediatric patients) have occurred as a result of confusion between different formulations of heparin, in particular with heparin sodium injection and catheter lock flush vials.472 500 Ensure accuracy of dispensing; take appropriate measures to carefully distinguish between heparin formulations when dispensing and review all labels for correct drug name, strength, and volume.472 500 501

Report dispensing errors to manufacturers or directly to FDA MedWatch program by phone (800-FDA-1088), fax (800-FDA-1078), or internet ().472

Specific Populations

Pregnancy

Category C.453 Manufacturers recommend use of a preservative (benzyl alcohol)-free formulation in pregnant women.373 500

Lactation

Not likely to be distributed into milk.500 However, if benzyl alcohol is present in maternal serum, it is likely to distribute into milk and be absorbed by a nursing infant.500 Caution is advised when using heparin in nursing women; manufacturers recommend use of a preservative (benzyl alcohol)-free formulation.500

ACCP recommends that heparin be continued in nursing women who are already receiving such therapy.1012

Pediatric Use

There are no adequate and well-controlled studies evaluating use of heparin in pediatric patients.500

Some heparin sodium injections and heparin lock flush solutions contain benzyl alcohol as a preservative.373 453 e 500 Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity (e.g., “gasping syndrome”) in neonates.123 124 125 126 127 453 471 500 Manufacturers recommend use of preservative-free formulations in neonates and infants.373 471 500 AAP states that presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates.123 378 If other benzyl alcohol-containing preparations are being used, consider the total daily metabolic load of benzyl alcohol from all sources.500

Fatal medication dispensing errors reported in pediatric patients, including neonates.472 500 Take appropriate precautions when dispensing and administering the drug.500 (See Dispensing and Administration Precautions under Cautions.)

Because of the potential risk of systemic anticoagulation, avoid use of heparin lock flush solutions containing 100 units/mL in neonates and in infants <10 kg.464 Caution also advised when using heparin lock flush solutions containing 10 units/mL in premature infants <1 kg who are receiving frequent flushes.462 464

Geriatric Use

Manufacturers state that risk of hemorrhage may be higher in patients >60 years of age, particularly women.373 453 471 (See Geriatric Patients and see Women under Dosage and Administration.)

Renal Impairment

Patients with renal failure may be at increased risk of bleeding complications.386

Common Adverse Effects

Hemorrhage, thrombocytopenia, HIT or HIT with thrombosis, injection site irritation, general hypersensitivity reactions, elevated aminotransferase concentrations.373 453

Interactions for Heparin Sodium

Drugs Affecting Platelet Function

Potential pharmacodynamic interaction (increased risk of bleeding complications).453 Use with caution.453

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Anticoagulants, oral

Potential for prolongation of one-stage PT373 453

Determine PT for oral anticoagulant effect ≥5 hours after IV heparin sodium dose or 24 hours after sub-Q dose373 453

Antihistamines

May partially counteract anticoagulant effect373 453

Antithrombin III

Enhanced anticoagulant effect, increased risk of bleeding complications373

Reduce heparin sodium dosage during concurrent treatment with antithrombin III373

Dextran

May increase risk of hemorrhagee

Use with cautione

Digitalis

May partially counteract anticoagulant effect373 453

Dipyridamole

Possible increased risk of bleeding complications373 453

Use with caution373 453

Hydroxychloroquine

Possible increased risk of bleeding complications373 453

Use with caution373 453

Liver function tests (e.g., ALT, AST)

False elevations in plasma AST and ALT366 453

Interpret elevation of these enzymes during heparin therapy with caution101 234 373 453

Nicotine

May partially counteract the anticoagulant effect373 453

Nitroglycerin

Possible antagonism of anticoagulant effect155 156 245 246 471

Monitor patients receiving concomitant IV nitroglycerin and adjust dosage of heparin to avoid inadequate anticoagulation155 156 256 471

NSAIAs

Possible increased risk of bleeding complications373 453

Use with caution373 453

Phenylbutazone (no longer commercially available in the US)

Possible increased risk of bleeding complications373 453

Tetracyclines

May partially counteract anticoagulant effect373 453

Thrombolytic agents

Possible increased risk of bleeding complicationse

Individualize dosage and monitor aPTT in patients receiving concomitant therapy281 282

Heparin Sodium Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration achieved 2–4 hours following sub-Q administration.373 453

Onset

Immediate following direct IV injection or IV infusion of full doses.e

Within 20–60 minutes following deep sub-Q injection.e

Duration

Heparin lock flush solutions: Anticoagulation maintained within the device for generally up to 4 hours.462 464

Special Populations

Plasma heparin concentrations may be increased and aPTTs more prolonged in geriatric (>60 years of age) patients compared with younger adults.471 500

Distribution

Extent

Does not cross the placenta and is not distributed into milk.293 359 453

Plasma Protein Binding

Extensively bound to LDL, globulins, and fibrinogen.e May contribute to the lack of relationship between duration of anticoagulant effect and blood concentration half-life.373

Elimination

Metabolism

Cleared from the circulation mainly by the reticuloendothelial system.e 373 May be partially metabolized in the liver to uroheparin, which is partially desulfated heparin.e 373

Elimination Route

Small fraction excreted in urine as unchanged drug.e

Half-life

1–2 hours in healthy adults.e Half-life increases with increasing doses.e Plasma half-life averages 56, 96, and 152 minutes following IV heparin sodium doses of 100, 200, or 400 units/kg, respectively.e Shorter plasma half-life in patients with pulmonary embolism than in healthy individuals or patients with other thrombotic disorders.e

Special Populations

Decreased plasma half-life in patients with liver impairment; half-life may be prolonged in patients with cirrhosis.e

Half-life may be slightly prolonged in anephric patients or patients with severe renal impairment.e

Stability

Storage

Parenteral

Solution for Injection

Heparin lock flush solutions: 20–25°C.462 464

Heparin sodium injections: 20–25°C.373 471 500

Heparin sodium injection in 5% dextrose or in 0.45 or 0.9% sodium chloride injection: 20–25°C; protect from freezing.504 505 506

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

When administered in a venipuncture device with an incompatible drug, flush the entire device with 0.9% sodium chloride injection, a compatible isotonic injection, or sterile water prior to and immediately after administration of the incompatible drug.234 462 463 464 465 Inject another dose of heparin lock flush solution (e.g., 1 mL of 10 units/mL) into the device after the second flush.234 462 463 464 465

Solution Compatibility

Compatible

Amino acids 4.25%, dextrose 25%

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose 5% in Ringer’s injection, lactated

Dextrose–saline combinations

Dextrose 2.5% in sodium chloride 0.45%

Dextrose 5% in sodium chloride 0.45%

Dextrose 2.5% in water

Dextrose 25% in water

Ionosol products

Normosol R

Ringer’s injection

Sodium chloride 0.45%

Incompatible

Dextrose 4.3% in sodium chloride 0.18%

Sodium lactate

Variable

Dextrose 5% in sodium chloride 0.9%

Dextrose 5 or 10% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Aminophylline

Amphotericin B

Amphotericin B with hydrocortisone sodium phosphate

Ascorbic acid injection

Bleomycin sulfate

Calcium gluconate

Cefepime HCl

Chloramphenicol sodium succinate

Clindamycin phosphate

Colistimethate sodium

Dimenhydrinate

Dopamine HCl

Enalaprilat

Esmolol HCl

Fluconazole

Flumazenil

Furosemide

Hydromorphone HCl

Isoproterenol HCl

Lidocaine HCl

Lincomycin HCl

Magnesium sulfate

Meropenem

Methyldopate HCl

Methylprednisolone sodium succinate

Nafcillin sodium

Norepinephrine bitartrate

Octreotide acetate

Potassium chloride

Ranitidine HCl

Sodium bicarbonate

Teicoplanin

Verapamil HCl

Incompatible

Alteplase

Amikacin sulfate

Atracurium besylate

Ciprofloxacin

Cytarabine

Daunorubicin HCl

Erythromycin lactobionate

Gentamicin sulfate

Kanamycin sulfate

Meperidine HCl

Morphine sulfate

Polymyxin B sulfate

Promethazine HCl

Streptomycin sulfate

Variable

Ampicillin sodium

Antithymocyte globulin (rabbit) with hydrocortisone sodium succinate

Dobutamine HCl

Hydrocortisone sodium succinate

Mitomycin

Penicillin G potassium

Penicillin G sodium

Vancomycin HCl

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Allopurinol sodium

Amifostine

Aminophylline

Ampicillin sodium

Ampicillin sodium–sulbactam sodium

Anidulafungin

Atracurium besylate

Atropine sulfate

Aztreonam

Bivalirudin

Bleomycin sulfate

Calcium gluconate

Cefazolin sodium

Cefotetan disodium

Ceftazidime

Ceftriaxone sodium

Chlorpromazine HCl

Cisplatin

Cladribine

Clindamycin phosphate

Cyanocobalamin

Cyclophosphamide

Cytarabine

Daptomycin

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Digoxin

Diphenhydramine HCl

Docetaxel

Dopamine HCl

Doripenem

Doxapram HCl

Doxorubicin HCl liposome injection

Edrophonium chloride

Enalaprilat

Epinephrine HCl

Ertapenem

Erythromycin lactobionate

Esmolol HCl

Estrogens, conjugated

Ethacrynate sodium

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Fluconazole

Fludarabine phosphate

Fluorouracil

Foscarnet sodium

Furosemide

Gallium nitrate

Gemcitabine HCl

Granisetron HCl

Hetastarch in lactated electrolyte injection (Hextend)

Hydralazine HCl

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Insulin, regular

Isoproterenol HCl

Leucovorin calcium

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Melphalan HCl

Meperidine HCl

Meropenem

Methotrexate sodium

Methoxamine HCl

Methyldopate HCl

Methylergonovine maleate

Metoclopramide HCl

Metronidazole

Micafungin sodium

Midazolam HCl

Milrinone lactate

Mitomycin

Morphine sulfate

Nafcillin sodium

Neostigmine methylsulfate

Nitroglycerin

Norepinephrine bitartrate

Ondansetron HCl

Oxacillin sodium

Oxaliplatin

Oxytocin

Paclitaxel

Palonosetron HCl

Pancuronium bromide

Pemetrexed disodium

Penicillin G potassium

Pentazocine lactate

Phytonadione

Piperacillin sodium–tazobactam sodium

Potassium chloride

Procainamide HCl

Prochlorperazine edisylate

Propofol

Propranolol HCl

Pyridostigmine bromide

Ranitidine HCl

Remifentanil HCl

Sargramostim

Scopolamine HBr

Sodium bicarbonate

Sodium nitroprusside

Succinylcholine chloride

Tacrolimus

Theophylline

Thiopental sodium

Thiotepa

Ticarcillin disodium–clavulanate potassium

Tigecycline

Tirofiban HCl

Trimethobenzamide HCl

Vasopressin

Vecuronium bromide

Vinblastine sulfate

Vincristine sulfate

Warfarin sodium

Zidovudine

Incompatible

Alteplase

Amiodarone HCl

Amphotericin B cholesteryl sulfate complex

Amsacrine

Caspofungin acetate

Ciprofloxacin

Clarithromycin

Diazepam

Doxycycline hyclate

Ergotamine tartrate

Filgrastim

Gentamicin sulfate

Haloperidol lactate

Idarubicin HCl

Isosorbide dinitrate

Levofloxacin

Nesiritide

Phenytoin sodium

Tobramycin sulfate

Variable

Aldesleukin

Antithymocyte globulin (rabbit)

Cisatracurium besylate

Dacarbazine

Diltiazem HCl

Dobutamine HCl

Doxorubicin HCl

Droperidol

Drotrecogin alfa (activated)

Labetalol HCl

Methylprednisolone sodium succinate

Nicardipine HCl

Promethazine HCl

Quinidine gluconate

Vancomycin HCl

Vinorelbine tartrate

Actions

  • Acts as a catalyst to markedly accelerate the rate at which antithrombin III (heparin cofactor) neutralizes thrombin and activated coagulation factor X (Xa).e Low-dose therapy neutralizes Xa which prevents the conversion of prothrombin to thrombin.e Low doses of heparin have very little effect on thrombin and exert a measurable antithrombogenic effect only if thrombin formation has not already occurred.e

  • Full-dose therapy neutralizes thrombin, which prevents the conversion of fibrinogen to fibrin.e Also prevents the formation of a stable fibrin clot by inhibiting activation of fibrin stabilizing factor.e Low-dose or full-dose therapy inhibits thrombus formation when stasis is induced.e Full-dose therapy may prevent extension of existing thrombi.e

  • Full-dose therapy prolongs several coagulation assays including the ACT, aPTT, plasma recalcification time, PT, thrombin time, and whole blood clotting time.373 453 471 e Clotting time is generally unaffected or only minimally prolonged by low-dose therapy.453 e

Advice to Patients

  • Importance of reporting any unexplained bleeding or bruising to clinician.373 453 471

  • Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary and herbal supplements, and any concomitant illnesses.373 453 462 463 464 465

  • Importance of women informing clinician if they are or plan to become pregnant or to breast-feed.373 453 462 463 464 465

  • Importance of informing patients of other important precautionary information.373 453 471 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Effective May 1, 2013, a new USP labeling standard for Heparin Sodium Injection, USP and Heparin Lock Flush Solutions, USP has been implemented.501 The labels for these products will now state the strength of the entire container (amount of heparin per total volume of container), followed in close proximity by the strength per mL in parentheses.501 During the transition, both current and revised heparin container labels will be simultaneously available in the US market; implement measures to avoid confusion between the 2 types of product labeling.501

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Heparin Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (porcine intestinal mucosa)

1000 units/mL*

Heparin Sodium Injection

5000 units/mL*

Heparin Sodium Injection

10,000 units/mL*

Heparin Sodium Injection

20,000 units/mL*

Heparin Sodium Injection

Solution, lock flush (porcine intestinal mucosa)

10 units/mL (10, 20, 30, 50, 100, 300 units)*

Heparin Lock Flush Solution

100 units/mL (100, 200, 300, 500, 1000, 3000 units)*

Heparin Lock Flush Solution

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Heparin Sodium (Preservative-free)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (porcine intestinal mucosa)

1000 units/mL*

Heparin Sodium Injection

10,000 units/mL*

Heparin Sodium Injection

Solution, lock flush (porcine intestinal mucosa)

10 units/mL (10, 30, 50, or 100 units)*

HepFlush-10

APP Pharmaceuticals

Heparin Lock Flush Solution

100 units/mL (100, 300 or 500 units)*

Heparin Lock Flush Solution

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Heparin Sodium in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion (porcine intestinal mucosa)

40 units/mL (20,000 units) Heparin Sodium in 5% Dextrose*

Heparin Sodium 20,000 units in 5% Dextrose Injection

50 units/mL (12,500 units) Heparin Sodium in 5% Dextrose*

Heparin Sodium 12,500 units in 5% Dextrose Injection

50 units/mL (25,000 units) Heparin Sodium in 5% Dextrose*

Heparin Sodium 25,000 units in 5% Dextrose Injection

100 units/mL (10,000 units) Heparin Sodium in 5% Dextrose*

Heparin Sodium 10,000 units in 5% Dextrose Injection

100 units/mL (25,000 units) Heparin Sodium in 5% Dextrose*

Heparin Sodium 25,000 units in 5% Dextrose Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Heparin Sodium in Sodium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion (porcine intestinal mucosa)

2 units/mL (1000 units) Heparin Sodium in 0.9% Sodium Chloride*

Heparin Sodium 1000 units in 0.9% Sodium Chloride Injection

2 units/mL (2000 units) Heparin Sodium in 0.9% Sodium Chloride*

Heparin Sodium 2000 units in 0.9% Sodium Chloride Injection

50 units/mL (12,500 units) Heparin Sodium in 0.45% Sodium Chloride*

Heparin Sodium 12,500 units in 0.45% Sodium Chloride Injection

50 units/mL (25,000 units) Heparin Sodium in 0.45% Sodium Chloride*

Heparin Sodium 25,000 units in 0.45% Sodium Chloride Injection

100 units/mL (25,000 units) Heparin Sodium in 0.45% Sodium Chloride*

Heparin Sodium 25,000 units in 0.45% Sodium Chloride Injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Heparin Sodium (Porcine) 1000UNIT/ML Solution (APP PHARMACEUTICAL): 10/$188.99 or 30/$541.97

Heparin Sodium (Porcine) 10000UNIT/ML Solution (APP PHARMACEUTICAL): 5/$29.99 or 20/$95.97

Heparin Sodium (Porcine) 10000UNIT/ML Solution (APP PHARMACEUTICAL): 25/$259.20 or 75/$673.90

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 17, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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137. Fredin H, Gustafson C, Rosberg B. Hypotensive anesthesia, thromboprophylaxis and postoperative thromboembolism in total hip arthroplasty. Acta Anaesthesiol Scand. 1984; 28:503-7. [PubMed 6208742]

138. Fredin H, Nilsson B, Rosberg B et al. Pre- and postoperative levels of antithrombin III with special reference to thromboembolism after total hip replacement. Thromb Haemost. 1983; 49:158-61. [PubMed 6192514]

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