No

Low Molecular Weight Heparin

Prevention of deep vein thrombosis following hip or knee replacement surgery or abdominal surgery in patients at risk for thromboembolic complications; inpatient treatment of acute deep vein thrombosis with and without pulmonary embolism when administered in conjunction with warfarin sodium; outpatient treatment of acute deep vein thrombosis without pulmonary embolism when administered in conjunction with warfarin sodium; prevention of ischemic complications of unstable angina and non-Q wave myocardial infarction (when administered with aspirin)

B

Hypersensitivity to enoxaparin or thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of enoxaparin; hypersensitivity to pork products; active major bleeding; not for I.M. or I.V. use

Patients with recent or anticipated neuraxial anesthesia (epidural or spinal anesthesia) are at risk of spinal or epidural hematoma and subsequent paralysis. Consider risk versus benefit prior to neuraxial anesthesia; risk is increased by concomitant agents which may alter hemostasis, as well as traumatic or repeated epidural or spinal puncture. Patient should be observed closely for bleeding if enoxaparin is administered during or immediately following diagnostic lumbar puncture, epidural anesthesia, or spinal anesthesia.

As with all anticoagulants, bleeding is the major adverse effect of enoxaparin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables. At the recommended doses, single injections of enoxaparin do not significantly influence platelet aggregation or affect global clotting time (ie, PT or APTT).

Central nervous system: Fever (5% to 8%), confusion, pain

Dermatologic: Erythema, bruising

Gastrointestinal: Nausea (3%), increased ALT/AST (5.9% to 6.1%)

Hematologic: Hemorrhage (5% to 13%), thrombocytopenia (2%), hypochromic anemia (2%)

Local: Injection site hematoma (9%), local reactions (irritation, pain, ecchymosis, erythema)

<1% (Limited to important or life-threatening symptoms): Hyperlipidemia, hypertriglyceridemia, pruritus, allergic reaction, urticaria, anaphylactoid reaction, vesicobullous rash, purpura, thrombocytosis. Spinal or epidural hematomas can occur following neuraxial anesthesia or spinal puncture, resulting in paralysis. Risk is increased in patients with indwelling epidural catheters or concomitant use of other drugs affecting hemostasis.

Case reports: Skin necrosis, eczematous plaques, itchy erythematous patches.

Symptoms of overdose include hemorrhage

Protamine sulfate has been used to reverse effects

Drugs which affect platelet function (eg, aspirin, NSAIDs, dipyridamole, ticlopidine, clopidogrel) may potentiate the risk of hemorrhage.

Thrombolytic agents increase the risk of hemorrhage.

Warfarin: Risk of bleeding may be increased during concurrent therapy. Enoxaparin is commonly continued during the initiation of warfarin therapy to assure anticoagulation and to protect against possible transient hypercoagulability.

Do not mix with other injections or infusions; store at less than or equal to 25°C (77°F); do not freeze

Standard heparin consists of components with molecular weights ranging from 4000-30,000 daltons with a mean of 16,000 daltons. Heparin acts as an anticoagulant by enhancing the inhibition rate of clotting proteases by antithrombin III impairing normal hemostasis and inhibition of factor Xa. Low molecular weight heparins have a small effect on the activated partial thromboplastin time and strongly inhibit factor Xa. Enoxaparin is derived from porcine heparin that undergoes benzylation followed by alkaline depolymerization. The average molecular weight of enoxaparin is 4500 daltons which is distributed as ( less than or equal to 20%) 2000 daltons, ( greater than or equal to 68%) 2000-8000 daltons, and ( less than or equal to 15%) >8000 daltons. Enoxaparin has a higher ratio of antifactor Xa to antifactor IIa activity than unfractionated heparin.

Onset of effect: Maximum antifactor Xa and antithrombin (antifactor IIa) activities occur 3-5 hours after S.C. administration

Duration: Following a 40 mg dose, significant antifactor Xa activity persists in plasma for ~12 hours

Protein binding: Low molecular weight heparins do not bind to heparin binding proteins

Half-life, plasma: Low molecular weight heparin is 2-4 times longer than standard heparin independent of the dose

S.C.:

Children: Safety and effectiveness have not been established.

Adults:

DVT prophylaxis in hip replacement:

30 mg twice daily: First dose within 12-24 hours after surgery and every 12 hours until risk of deep vein thrombosis has diminished or the patient is adequately anticoagulated on warfarin. Average duration of therapy: 7-10 days.

40 mg once daily: First dose within 9-15 hours before surgery and daily until risk of deep vein thrombosis has diminished or the patient is adequately anticoagulated on warfarin. Average duration of therapy: 7-10 days unless warfarin is not given concurrently, then 40 mg S.C. once daily should be continued for 3 more weeks (4 weeks total).

DVT prophylaxis in knee replacement:

30 mg twice daily: First dose within 12-24 hours after surgery and every 12 hours until risk of deep vein thrombosis has diminished. Average duration of therapy: 7-10 days; maximum course: 14 days.

Patients who weigh <100 lb or are >65 years of age: Some clinicians recommend 0.5 mg/kg/dose every 12 hours to reduce the risk of bleeding.

DVT prophylaxis in high-risk patients undergoing abdominal surgery: 40 mg once daily, with initial dose given 2 hours prior to surgery; usual duration: 7-10 days and up to 12 days has been tolerated in clinical trials.

Treatment of acute proximal DVT: Start warfarin within 72 hours and continue enoxaparin until INR is between 2.0 and 3.0 (usually 7 days).

Inpatient treatment of DVT with or without pulmonary embolism: Adults: S.C. 1 mg/kg/dose every 12 hours or 1.5 mg/kg once daily.

Outpatient treatment of DVT without pulmonary embolism: Adults: S.C.: 1 mg/kg/dose every 12 hours.

Prevention of ischemic complications with unstable angina or non-Q-wave myocardial infarction: S.C.: 1 mg/kg twice daily in conjunction with oral aspirin therapy (100-325 mg once daily); treatment should be continued for a minimum of 2 days and continued until clinical stabilization (usually 2-8 days).

Dosing adjustment in renal impairment: Total clearance is lower and elimination is delayed in patients with renal failure; adjustment may be necessary in elderly and patients with severe renal impairment.

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics.

Platelets, occult blood, and anti-Xa activity, if available; the monitoring of PT and/or PTT is not necessary

Low molecular weight heparins (LMWHs) compare favorably to unfractionated heparin in the prevention and treatment of venous thromboembolism. LMWHs are associated with less thrombocytopenia, compared to heparin, and do not require routine therapeutic monitoring. There is no consensus for adjusting/correcting the weight-based dosage of LMWH for patients who are morbidly obese or very lean. Monitoring of antifactor Xa concentration may be warranted in patients who weigh <50 kg or >90 kg and in those patients with renal insufficiency.

May cause confusion

None reported

No information available to require special precautions

No effects or complications reported

This drug can only be administered by injection. You may have a tendency to bleed easily while taking this drug; brush teeth with soft brush, floss with waxed floss, use electric razor, avoid scissors or sharp knives, and potentially harmful activities. Report chest pain; persistent constipation; persistent erection; unusual bleeding or bruising (bleeding gums, nosebleed, blood in urine, dark stool); pain in joints or back; or numbness, tingling, swelling, or pain at injection site.

Administer S.C. only; do not administer I.M. injection When using the 30 and 40 mg prefilled syringes, do not expel air bubble from syringe before injection.

Injection, as sodium, preservative free:

Graduated prefilled syringe: 60 mg/0.6 mL, 80 mg/0.8 mL, 100 mg/1.0 mL

Ampul: 30 mg/0.3 mL

Buckley MM and Sorkin EM, "Enoxaparin: A Review of Its Pharmacology and Clinical Applications in the Prevention and Treatment of Thromboembolic Disorders," Drugs, 1992, 44(3):465-97.

deVeber G, Chan A, Monagle P, et al, "Anticoagulation Therapy in Pediatric Patients With Sinovenous Thrombosis: A Cohort Study," Arch Neurol, 1998, 55(12):1533-7.

Hirsh J, Warkentin TE, Raschke R, et al, "Heparin and Low-Molecular-Weight Heparin: Mechanisms of Action, Pharmacokinetics, Dosing Considerations, Monitoring, Efficacy, and Safety," Chest, 1998, 114(5 Suppl):489S-510S.

Levine M, Gent M, Hirsh J, et al, "A Comparison of Low-Molecular-Weight Heparin Administered Primarily at Home With Unfractionated Heparin Administered in the Hospital for Proximal Deep Vein Thrombosis," N Engl J Med, 1996, 334(11):677-81.

Martineau P and Tawil N, "Low-Molecular-Weight Heparins in the Treatment of Deep-Vein Thrombosis," Ann Pharmacother, 1998, 32(5):588-98, 601.

Massicotte P, Adams M, Marzinotto V, et al, "Low-Molecular-Weight Heparin in Pediatric Patients With Thrombotic Disease: A Dose Finding Study," J Pediatr, 1996, 128(3):313-8.

Michelson AD, Bovill E, Monagle P, et al, "Antithrombotic Therapy in Children," Chest, 1998, 114(5 Suppl):748S-69S.

Simonneau G, Charbonnier B, Decousus H, et al, "Subcutaneous Low-Molecular-Weight Heparin Compared With Continuous Intravenous Unfractionated Heparin in the Treatment of Proximal Deep Vein Thrombosis," Arch Intern Med, 1993, 153(13):1541-6.