heparin (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

heparin lock solution

  • 1unit/mL
  • 2units/mL
  • 10units/mL
  • 100units/mL

injectable solution

  • 1000units/mL
  • 2500units/mL
  • 5000units/mL
  • 10,000units/mL
  • 20,000units/mL

premixed IV solution

  • 12,500units/250mL
  • 20,000units/500mL
  • 25,000units/250mL
  • 25,000units/500mL
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DVT & PE

Prophylaxis

  • 5000 units SC q8-12hr, OR
  • 7500 units SC q12hr

Treatment

  • 80 units/kg IV bolus, THEN continuous infusion of 18 units/kg/hr, OR 
  • 5000 units IV bolus, THEN continuous infusion of 1300 units/hr, OR
  • 250 units/kg (alternatively, 17,500 units) SC, THEN 250 units/kg q12hr

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error

Acute Coronary Syndromes

PCI

  • Without GPIIb/IIIa inhibitor: Initial IV bolus of 70-100 units/kg (target ACT 250-300 sec) 
  • With GPIIb/IIIa inhibitor: Initial IV bolus of 50-70 units/kg (target ACT >200 sec)

STEMI

  • Patient on fibrinolytics: IV bolus of 60 units/kg (max: 4000 units), THEN 12 units/kg/hr (max 1000 units/hr) as continuous IV infusion
  • Dose should be adjusted to maintain aPTT of 50-70 sec

Unstable Angina/NSTEMI

  • Initial IV bolus of 60-70 units/kg (max: 5000 units), THEN initial IV infusion of 12-15 units/kg/hr (max: 1000 units/hr)
  • Dose should be adjusted to maintain aPTT of 50-70 sec

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error

Anticoagulation

Intermittent IV injection

  • 8000-10,000 units IV initially, THEN 50-70 units/kg (5000-10,000 units) q4-6hr 

Continuous IV infusion

  • 5000 units IV injection, followed by continuous IV infusion of 20,000-40,000 units/24 hr

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error
  • Heparin sodium may prolong one-stage prothrombin time; when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hr after last intravenous dose or 24 hr after last subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained

Catheter Patency

Prevention of clot formation within venous and arterial catheters

Use 100 units/mL; instill enough volume to fill lumen of catheter

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error
  • Amount and frequency depends on catheter volume and type
  • Peripheral heparin locks typically are flushed q6-8hr

Dosing Modifications

Hepatic impairment: Caution is advised; dosage adjustment may be required

Dosage Forms & Strengths

heparin lock solution

  • 10units/mL
  • 100units/mL

injectable solution

  • 1000units/mL
  • 5000units/mL
  • 10,000units/mL
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Venous Thromboembolic Prophylaxis (Off-label)

100-150 units/kg IV once  

Venous Thromboembolic Treatment (Off-label)

<1 year

  • Loading dose of 75 units/kg IV, THEN 28 units/kg/hr IV as initial maintenance dose 

>1 year

  • Loading dose of 75 units/kg IV, THEN 20 units/kg/hr IV as initial maintenance dose

Intermittent IV injection

  • Initially give 50-100 units/kg IV infusion, THEN 100 units/kg IV infusion q4hr as a maintenance dose

Catheter Patency (Off-label)

Initially give 50-100 units/kg IV infusion, THEN 100 units/kg IV infusion q4hr as maintenance dose 

Infants under 10 kg: 10 units/mL; instill enough volume to fill lumen of catheter

Children and infants over 10 kg: 10-100 units/mL; instill enough volume to fill lumen of catheter

Dosing Considerations

Numerous concentrations available; extreme caution is required to avoid medication error

When prescribing in infants, consider combined daily metabolic load of benzyl alcohol from all sources including heparin sodium injection (contains 9.45 mg of benzyl alcohol) and other drugs containing benzyl alcohol; the minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known

There are no adequate, well-controlled studies on heparin use in pediatric patients; pediatric dosing recommendations are based on clinical experience

Use preservative-free heparin in neonates and infants; benzyl alcohol preservative has been associated with serious adverse effects (ie, gasping syndrome, which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations) and death in pediatric patients

Venous thromboembolic treatment (off-label)

  • Adjust heparin dose based on desired aPTT

Catheter patency (off-label)

  • Dosage amount and frequency depend on catheter volume and type
  • Peripheral heparin locks typically are flushed q6-8hr
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Interactions

Interaction Checker

and heparin

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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Heparin-induced thrombocytopenia, possibly delayed (10-30% )

            Frequency Not Defined

            Mild pain

            Hematoma

            Hemorrhage

            Local irritation

            Erythema

            Injection site ulcer (after deep SC injection)

            Increased liver aminotransferase

            Anaphylaxis

            Immune hypersensitivity reaction

            Osteoporosis (long-term, high-dose use)

            Postmarketing Reports

            Heparin resistance

            Gasping syndrome in infants due to benzyl alcohol preservative

            Hypersensitivity

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            Warnings

            Contraindications

            History of heparin-induced thrombocytopenia (HIT) (with or without thrombosis)

            Uncontrolled, active bleeding (except DIC)

            Conditions in which coagulation tests cannot be performed at appropriate intervals

            Cases where the administration of sodium or chloride could be clinically detrimental (large volume heparin 2 unit/mL IV solutions only)

            Known hypersensitivity to heparin or pork products

            Cautions

            Any risk factor for hemorrhage (eg, subacute bacterial endocarditis, blood dyscrasias, menorrhagia, dissecting aneurysm, major surgery, spinal anesthesia, hemophilia, GI ulcerative lesions, liver disease, impaired hemostasis)

            Heparin-induced thrombocytopenia may occur (with or without thrombosis) including thrombus formation on a prosthetic cardiac valve; immune-mediated reaction resulting from irreversible aggregation of platelets; monitor thrombocytopenia of any degree; if platelet count falls below 100,000/m³, discontinue anticoagulants

            Monitor therapy with aPTT

            Heparin may prolong PT

            Potential medication errors: Do not use heparin sodium injection as a catheter lock-flush product; heparin sodium injection is supplied in vials containing various strengths of heparin; these include vials containing a highly concentrated solution of 10,000 units in 1 mL, which have been mistaken for 1 mL low-concentration catheter lock-flush vials

            Geriatric dosing: Lower doses may be necessary; patients over 60 years may have enhanced serum levels and response compared with patients under 60 years receiving similar dosages

            Heparin sodium may prolong one-stage prothrombin time; when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hr after last intravenous dose or 24 hr after last subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained

            If preserved with benzyl alcohol, do not administer to neonates, infants, pregnant women, or breastfeeding women; benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients (gasping syndrome)

            Blood coagulation tests guide therapy for full-dose heparin; monitor platelet count and hematocrit in all patients receiving heparin

            Anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency; to reduce risk of bleeding, reduce heparin dose during concomitant treatment with antithrombin III (human)

            Heparin resistance may be observed in patients with antithrombin deficiency, increased heparin clearance, elevations of heparin binding proteins, elevations of in factor VIII and/or fibrinogen and may require doses >35,000 units/24hr to maintain therapeutic aPTT; frequently encountered in patients with fever, thrombosis, infections with thrombosing tendencies, thrombophlebitis, cancer, myocardial infarction, and postsurgical patients; may benefit from measurements of anticoagulant effects using antifactor Xa levels

            May suppress aldosterone production and cause hyperkalemia

            Use with caution in patients with documented hypersensitivity to heparin; use only in life-threatening situations when use of alternate anticoagulant is not possible

            Osteoporosis may occur with prolonged ( >6 months) use due to a reduction in mineral bone density

            Some preparations may contain sulfite which may cause allergic reactions

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            Pregnancy & Lactation

            Pregnancy

            There are no available data on heparin sodium injection use in pregnant women to inform a drug- associated risk of major birth defects and miscarriage; in published reports, heparin exposure during pregnancy did not show evidence of increased risk of adverse maternal or fetal outcomes in humans; no teratogenicity, but early embryo-fetal death reported in animal reproduction studies with administration of heparin sodium to pregnant rats and rabbits during organogenesis at doses approximately 10 times maximum recommended human dose (MRHD) of 45,000 units/ day; consider benefits and risks of heparin sodium Injection for mother and possible risks to fetus when prescribing heparin sodium injection to pregnant woman

            Lactation

            There is no information regarding presence of heparin sodium injection in human milk, effects on breastfed infant, or on milk production; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for heparin sodium injection and potential adverse effects on breastfed infant from therapy or from the underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Mechanism for low dose: Inactivates factor Xa and inhibits conversion of prothrombin to thrombin

            Mechanism for high dose: Inactivates factors IX, X, XI, and XII and thrombin and inhibits conversion of fibrinogen to fibrin

            Also inhibits activation of factor VIII

            Absorption

            Bioavailability: 22-40%

            Onset: IV (immediate); SC (20-30 min)

            Peak plasma time: 2-4 hr

            Distribution

            Protein bound: Extensive

            Metabolism

            Metabolized in the liver (partial) and reticuloendothelial system (partial)

            Metabolites: None

            Elimination

            Half-life: 60-90 min average (longer at higher doses)

            Dialyzable: No

            Excretion: Urine

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            Administration

            IV Incompatibilities

            Additive

            • Dobutamine
            • Erythromycin
            • Gentamicin
            • Haloperidol
            • Hydrocortisone
            • Meperidine
            • Morphine
            • Vancomycin

            Syringe

            • Amiodarone
            • Diazepam
            • Erythromycin
            • Gentamicin
            • Haloperidol
            • Meperidine
            • Morphine(?)
            • Vancomycin

            Y-site

            • Amiodarone
            • Diazepam
            • Dobutamine
            • Gentamicin
            • Haloperidol
            • Vancomycin

            Not spec

            • Hydroxyzine
            • Tetracycline

            IV Compatibilities

            Additive

            • Aminophylline
            • Ampho B
            • Ampicillin
            • Ca gluconate
            • Clindamycin
            • Dopamine
            • Esmolol
            • Furosemide
            • Lidocaine
            • Norepinephrine
            • KCl
            • Na bicarbonate
            • Verapamil
            • Vitamins B/C

            Syringe

            • Aminophylline
            • Ampho B
            • Ampicillin
            • Atropine
            • Cimetidine
            • Clindamycin
            • Dobutamine
            • Dopamine
            • Epinephrine
            • Furosemide
            • Lidocaine
            • Morphine(?)
            • Norepinephrine
            • Na bicarbonate
            • Verapamil

            Y-site

            • Aminophylline, ampicillin, atropine, Ca gluconate, cimetidine, clindamycin, dopamine, epinephrine, erythromycin, esmolol, furosemide, hydrocortisone, lidocaine, norepinephrine, meperidine, morphine, KCl, Na bicarbonate

            IV Preparation

            Recommended infusion concentration for most patients is 25,000 units in 500 mL D5W (50 units/mL premixed infusion solution)

            IV Administration

            IV injection may be given undiluted or diluted in 50-100 mL NS or D5W

            Infusion: Dilute in NS, D5W, or other compatible fluid

            Continuous IV therapy is preferred because intermittent IV therapy produces a higher incidence of bleeding abnormalities

            Invert IV bag at least 6 times to ensure mixing and prevent pooling of medication

            Use constant-rate IV infusion pump

            Storage

            Store heparin solutions at room temperature; do not freeze

            Do not use if discolored/precipitates

            Autoclavable

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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