Heparin

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

Symptoms

Bleeding is the chief sign of heparin overdosage. Nosebleeds, blood in urine or tarry stools may be noted as the first sign of bleeding. Easy bruising or petechial formations may precede frank bleeding.

Treatment

Neutralization of heparin effect.

When clinical circumstances (bleeding) require reversal of heparinization, protamine sulfate (1% solution) by slow infusion will neutralize heparin sodium. No more than 50 mg should be administered, very slowly in any 10 minute period. Each mg of protamine sulfate neutralizes approximately 100 USP heparin units. The amount of protamine required decreases over time as heparin is metabolized. Although the metabolism of heparin is complex, it may, for the purpose of choosing a protamine dose, be assumed to have a half-life of about ½ hour after intravenous injection.

Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions often resembling anaphylaxis have been reported, the drug should be given only when resuscitation techniques and treatment of anaphylactoid shock are readily available.

For additional information, the labeling of Protamine Sulfate Injection, USP products should be consulted.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• the method of administration
• other medical conditions you have
• how you respond to this medication
• your weight

Doses of heparin must be individualized for each patient according to the condition being treated, the route and frequency of administration, and the clinical response.

Call your doctor for instructions if you miss a dose of heparin.

Your doctor or pharmacist can provide more information about heparin.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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• Deep Vein Thrombosis (DVT, Blood Clot in the Legs)

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Very bad dizziness or passing out.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Change in skin color where the shot was given.
• Feeling confused.
• Very bad headache.
• Chills.
• Fever.
• Chest pain.
• Back pain.
• Shortness of breath.
• Redness or swelling where the shot is given.

  Oral Anticoagulants

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

  Platelet Inhibitors

Drugs such as NSAIDS (including salicylic acid, ibuprofen, indomethacin, and celecoxib), dextran, phenylbutazone, thienopyridines, dipyridamole, hydroxychloroquine, glycoprotein IIb/IIIa antagonists (including abciximab, eptifibatide, and tirofiban), and others that interfere with platelet-aggregation reactions (the main hemostatic defense of Heparinized patients) may induce bleeding and should be used with caution in patients receiving Heparin sodium. To reduce the risk of bleeding, a reduction in the dose of antiplatelet agent or Heparin is recommended.

 Other Interactions

Digitalis, tetracyclines, nicotine or antihistamines may partially counteract the anticoagulant action of Heparin sodium. Intravenous nitroglycerin administered to Heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of Heparin dosage are recommended during coadministration of Heparin and intravenous nitroglycerin.

Antithrombin III (human) – The anticoagulant effect of Heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency. To reduce the risk of bleeding, a reduced dosage of Heparin is recommended during treatment with antithrombin III (human).

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate carcinogenic potential of Heparin. Also, no reproduction studies in animals have been performed concerning mutagenesis or impairment of fertility.

NOT for Lock Flush
Heparin
Sodium Injection, USP
50,000 USP Units/10 mL
(5,000 USP Units/mL)
For Intravenous or Subcutaneous Use
10 mL Multiple Dose Vial

NOT for Lock Flush
NDC 0641-2460-30 Rx only
From Porcine Intestines
Each mL contains Heparin sodium
5,000 USP units, sodium chloride
7 mg and benzyl alcohol 0.01 mL in
Water for Injection. pH 5.0-7.5;
NaOH and/or HCI added, if  needed, for
pH adjustment.
Store at 20º-25ºC (58º-77ºF).

NDC 0641-2460-55  Rx only
Heparin
Sodium Injection, USP
50,000 USP Units/10 mL
(5,000 USP Units/mL)
For Intravenous or Subcutaneous Use
25 x 10 mL Multiple Dose Vials

NOT for Lock Flush
From Porcine Intestines
Each mL contains Heparin sodium
5,000 USP units, sodium chloride 7 mg
and benzyl alcohol 0.01 mL in Water for
Injection. pH 5.0-7.5; NaOH and/or
HCI added, if needed, for pH adjustment.
Usual Dosage: See package insert.
Store at 20º-25ºC (58º-77ºF)

The half-life may be increased.

SubQ: Inject in subcutaneous tissue only (not muscle tissue). Injection sites should be rotated (usually left and right portions of the abdomen, above iliac crest).

IM: Do not administer IM due to pain, irritation, and hematoma formation.

Continuous IV infusion: Infuse via infusion pump. If preparing solution, mix thoroughly prior to administration.

Heparin lock: Inject via injection cap using positive pressure flushing technique. Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Central venous catheters: Must be flushed with heparin solution when newly inserted, daily (at the time of tubing change), after blood withdrawal or transfusion, and after an intermittent infusion through an injectable cap. A volume of at least 10 mL of blood should be removed and discarded from a heparinized line before blood samples are sent for coagulation testing.

Intravesical (off-label use): Various dosage regimens of heparin (20,000 to 50,000 units) alone or with alkalinized lidocaine (1% to 4%) have been instilled into the bladder.

You should not use this medicine if you are allergic to heparin or pork products, or if you have:

• a severe lack of platelets in your blood; or

• uncontrolled bleeding.

To make sure heparin is safe for you, tell your doctor if you have ever had:

• an infection of the lining of your heart (also called bacterial endocarditis);

• uncontrolled high blood pressure;

• a bleeding or blood clotting disorder;

• a stomach or intestinal disorder;

• liver disease;

• if you use a blood thinner (warfarin, Coumadin, Jantoven) and you have routine "INR" or prothrombin time tests; or

• if you are having a menstrual period.

It is not known whether heparin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Do not use heparin without telling your doctor if you are breast-feeding a baby.

Women over 60 years of age may be more likely to have bleeding episodes while using heparin.

The manufacturer provides the following dosing guidelines based on clinical experience:

Continuous IV infusion:
-Initial dose: 5000 units by IV injection
-Maintenance dose: 20,000 to 40,000 units per 24 hours by continuous IV infusion

Intermittent IV injection:
-Initial dose: 10,000 units IV
-Maintenance dose: 5000 to 10,000 units IV every 4 to 6 hours

Deep subcutaneous (intrafat) injection:
333 units/kg subcutaneously followed by 250 units/kg subcutaneously every 12 hours; the following dosage regimen has also been recommended: 5000 units by IV injection followed by 10,000 to 20,000 units subcutaneously, and then 8000 to 10,000 units subcutaneously every 8 hours or 15,000 to 20,000 units subcutaneously every 12 hours.

Comments:
-Recommended doses are based on a 68 kg patient.
-Consult the latest guidelines regarding duration and intensity of anticoagulation for the indicated conditions.
-Dosage and administration must be individualized according to the results of suitable laboratory tests.

Uses:
-Prophylaxis and treatment of venous thrombosis and pulmonary embolism.
-Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation.
-Treatment of acute and chronic consumption coagulopathies (disseminated intravascular coagulation).
-Prophylaxis and treatment of peripheral arterial embolism.


5000 units subcutaneously 2 hours before surgery and 5000 units subcutaneously every 8 to 12 hours thereafter for 7 days or until the patient is ambulatory, whichever is longer.

Comments:
-Administer by deep subcutaneous (intrafat, e.g., above the iliac crest or abdominal fat layer, arm, or thigh) injection with a fine (25 to 26 gauge) needle to minimize tissue trauma.
-Consult the latest guidelines regarding duration and intensity of anticoagulation for the indicated conditions.
-Dosage and administration must be individualized according to the results of suitable laboratory tests.

Use: Low-dose regimen for prevention of postoperative deep venous thrombosis and pulmonary embolism in patients greater than 40 years old undergoing major abdominothoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease.

• Heparin acts on multiple sites within the coagulation cascade to prevent blood from clotting and preexisting blood clots from becoming larger.
• Small amounts of heparin prevent the conversion of prothrombin to thrombin and large amounts prevent the conversion of fibrinogen to fibrin.

• Heparin is usually given into a vein (intravenously), although it can be given by injection just under the skin (subcutaneously). Heparin rapidly reduces the ability of the blood to clot.
• Initially, daily blood tests that measure activated partial thromboplastin time [aPTT] (a measure of how fast the blood is clotting) are required. However, daily blood tests are not usually required with low-dose, long-term heparin.

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