Heparin (Monograph)

Brand name: HepFlush
Drug class: Heparins
CAS number: 9041-08-1

Medically reviewed by Drugs.com on Feb 21, 2024. Written by ASHP.

Warning

A standardized concentration for this drug has been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. The drug is included in a standard concentration list which may apply to an IV or oral compounded liquid formulation. For additional information, see the ASHP website [Web].

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

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^{† [off-label]}; 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^{† [off-label]} (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^{† [off-label]}, total knee-replacement surgery^{† [off-label]}, or hip-fracture surgery^{† [off-label]}.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

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).¹⁷⁶ ¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ¹⁸² ¹⁸³ ¹⁸⁴ ¹⁸⁵ ¹⁸⁶ ⁵²⁷

The American College of Cardiology Foundation (ACCF) and AHA state that patients with STEMI undergoing thrombolytic therapy should receive an anticoagulant (e.g., heparin, enoxaparin, fondaparinux) for ≥48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization is performed.⁵²⁷ Enoxaparin is preferred over heparin if extended anticoagulation (>48 hours) is necessary.⁵²⁷

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

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Reduction in the risk of acute cardiac ischemic events (death and/or MI) in patients with NSTE ACS (unstable angina or non-ST-segment-elevation MI [NSTEMI])^†.³⁴⁸ ³⁶¹ ⁴⁴⁴ ⁹⁹¹ ⁹⁹⁴ ¹¹⁰⁰

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

Initial parenteral anticoagulants with established efficacy in patients with NSTE ACS include enoxaparin, heparin, bivalirudin (only in patients managed with an early invasive strategy), and fondaparinux.¹¹⁰⁰

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 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 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 requiringcardiac 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.⁵²⁷

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 or until revascularization.⁵²⁷

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

NSTE ACS

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.⁵²⁷

Maintenance dosage: Maximum 1000 units/hour.⁴⁵⁵ ⁵²⁷

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

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 ([Web]).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

Drug Interactions

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 hemorrhage^e	Use with caution^e
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 complications^e	Individualize dosage and monitor aPTT in patients receiving concomitant therapy²⁸¹ ²⁸²

Heparin 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

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 (X_a).^e Low-dose therapy neutralizes X_a 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

Heparin Sodium
Routes	Dosage Forms	Strengths	Brand Names
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
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
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

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

References

50. Kakkar VV, Stamatakis JD, Bentley PG et al. Prophylaxis for postoperative deep-vein thrombosis: synergistic effect of heparin and dihydroergotamine. JAMA. 1979; 241:39-42. http://www.ncbi.nlm.nih.gov/pubmed/758493?dopt=AbstractPlus

51. Sagar S, Nairn D, Stamatakis JD et al. Efficacy of low-dose heparin in prevention of extensive deep-vein thrombosis in patients undergoing total-hip replacement. Lancet. 1976; 1:1151-4. http://www.ncbi.nlm.nih.gov/pubmed/58199?dopt=AbstractPlus

90. Bell WR, Royall RM. Heparin-associated thrombocytopenia: a comparison of three heparin preparations. N Engl J Med. 1980; 303:902-7. http://www.ncbi.nlm.nih.gov/pubmed/6997743?dopt=AbstractPlus

100. Dukes GE Jr, Sanders SW, Russo J Jr et al. Transaminase elevations in patients receiving bovine or porcine heparin. Ann Intern Med. 1984; 100:646-50. http://www.ncbi.nlm.nih.gov/pubmed/6712030?dopt=AbstractPlus

101. Sandoz Pharmaceuticals Corporation. Embolex (dihydroergotamine mesylate and heparin sodium; with lidocaine hydrochloride) injection prescribing information. East Hanover, NJ; 1987 Jun 26.

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