Heparin - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Fatal Medication Errors: Confirm choice of correct strength prior to administration • Hemorrhage: Fatal cases have occurred.

Use caution in conditions with increased risk of hemorrhage • HIT (With or Without Thrombosis): Monitor for signs and symptoms and discontinue if indicative of HIT (With or Without Thrombosis) • Monitoring: Blood coagulation tests guide therapy for full-dose heparin.

Monitor platelet count and hematocrit in all patients receiving heparin • Hyperkalemia: Measure blood potassium in patients at risk of hyperkalemia before starting heparin therapy and periodically in all patients 5.1 Fatal Medication Errors Do not use this product as a "catheter lock flush" product.

Heparin is supplied in various strengths.

Fatal hemorrhages have occurred due to medication errors.

Carefully examine all heparin products to confirm the correct container choice prior to administration of the drug.

5.2 Hemorrhage Hemorrhage, including fatal events, has occurred in patients receiving heparin sodium.

Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks.

Hemorrhage can occur at virtually any site in patients receiving heparin.

Adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage, and retroperitoneal hemorrhage have occurred during anticoagulant therapy with heparin [see Adverse Reactions ] .

A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age [see Clinical Pharmacology ] .

These patients may require a lower dose .

An unexplained fall in hematocrit or fall in blood pressure should lead to serious consideration of a hemorrhagic event.

Use heparin sodium with caution in disease states in which there is increased risk of hemorrhage, including: • Cardiovascular — Subacute bacterial endocarditis.

Severe hypertension. • Surgical — During and immediately following (a) spinal tap or spinal anesthesia or (b) major surgery, especially involving the brain, spinal cord or eye. • Hematologic — Conditions associated with increased bleeding tendencies, such as hemophilia, thrombocytopenia and some vascular purpuras. • Patients with hereditary antithrombin III deficiency receiving concurrent antithrombin III therapy – The anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency.

To reduce the risk of bleeding, reduce the heparin dose during concomitant treatment with antithrombin III (human). • Gastrointestinal — Ulcerative lesions and continuous tube drainage of the stomach or small intestine. • Other — Menstruation, liver disease with impaired hemostasis.

5.3 Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) HIT is a serious immune-mediated reaction resulting from irreversible aggregation of platelets.

HIT may progress to the development of venous and arterial thromboses, a condition known as HIT with thrombosis.

Thrombotic events may also be the initial presentation for HIT.

These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, thrombus formation on a prosthetic cardiac valve, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and fatal outcomes.

Once HIT (with or without thrombosis) is diagnosed or strongly suspected, all heparin sodium sources (including heparin flushes) should be discontinued and an alternative anticoagulant used.

Future use of heparin sodium, especially within 3 to 6 months following the diagnosis of HIT (with or without thrombosis), and while patients test positive for HIT antibodies, should be avoided.

Thrombocytopenia of any degree should be monitored closely.

If the platelet count falls below 100,000/mm 3 or if recurrent thrombosis develops, the heparin product should be promptly discontinued and alternative anticoagulants considered if patients require continued anticoagulation.

Delayed Onset of HIT (With or Without Thrombosis): Heparin-induced Thrombocytopenia (HIT) (With or Without Thrombosis) can occur up to several weeks after the discontinuation of heparin therapy.