No

Low Molecular Weight Heparin

Prevention of deep vein thrombosis (DVT) which may lead to pulmonary embolism following knee replacement surgery

C

Hypersensitivity to ardeparin or thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of ardeparin; hypersensitivity to pork products or to sulfites (contains metabisulfite); patient with 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 ardeparin is administered during or immediately following diagnostic lumbar puncture, epidural anesthesia, or spinal anesthesia.

Not to be used interchangeably (unit for unit) with heparin or any other low molecular weight heparins. Use caution in patients with known hypersensitivity to methylparaben or propylparaben. Use caution in patients with a history of heparin-induced thrombocytopenia. Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding. Risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; severe uncontrolled HTN; hemorrhagic stroke; use shortly after brain, spinal, or ophthalmologic surgery; patients treated concomitantly with platelet inhibitors; recent GI bleeding; thrombocytopenia or platelet defects; severe liver disease; hypertensive or diabetic retinopathy; or patients undergoing invasive procedures. Use caution in patients with severe renal failure (has not been studied). Safety and efficacy in pediatric patients have not been established. Heparin can cause hyperkalemia by affecting aldosterone. Similar reactions could occur with LMWHs. Monitor for hyperkalemia. Discontinue therapy if platelets are <100,000/mm³.

As with all anticoagulants, bleeding is the major adverse effect of ardeparin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables.

Central nervous system: Fever (3%), confusion (<1%)

Dermatologic: Pruritus (2%), rash (2%), ecchymosis (2%)

Gastrointestinal: Nausea (3%), constipation (<1%), vomiting (1%)

Hematologic: Hemorrhage (5%), bleeding (clinically significant) (up to 7%), thrombocytopenia (2%), anemia (8%), ecchymosis (2%)

Local: Injection site hematoma (7%)

<1% (Limited to important or life-threatening symptoms): Epistaxis, gastrointestinal hemorrhage, hematemesis, hematuria, melena, petechiae, rectal hemorrhage, retroperitoneal hemorrhage, guaiac-positive stools, immune thrombocytopenia, thrombocytosis, allergic reaction, maculopapular rash, vesiculobullous rash, chest pain, dizziness, dyspnea, headache, injection site reactions, insomnia, peripheral edema. 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, transaminase increases.

Main symptom of overdose is bleeding which may first be indicated with bleeding at the surgical site or at the venipuncture site; other symptoms include epistaxis, hematuria, or blood in stool; easy bruising or petechiae may precede frank bleeding.

Treatment includes discontinuing the drug and applying pressure to the site, if possible, and replacing volume and hemostatic blood elements (eg, fresh frozen plasma, platelets) as necessary. 1 mg protamine neutralizes approximately 100 anti-Xa units of ardeparin. Anti-IIa activity of I.V. ardeparin is completely neutralized within 10 minutes following I.V. infusion dose of equal weight protamine sulfate (about 1 mg protamine sulfate for each 100 anti-Xa units of ardeparin). The anti-Xa and Heptest® activities of ardeparin are reduced by ~75% within 10 minutes and are almost completely neutralized within 30 minutes after protamine sulfate administration. Protamine sulfate may cause anaphylactoid reactions that can be life-threatening; it should be given only when resuscitation techniques and treatment of anaphylactic shock are available.

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 (and other oral anticoagulants) may increase the risk of bleeding with ardeparin.

Store at room temperature 15°C to 25°C (59°F to 77°F)

A low molecular weight heparin with antithrombotic properties; a partially depolymerized porcine mucosal heparin that has the same molecular subunits as heparin sodium, although its molecular weight is lower; acts at multiple sites in the normal coagulation system; binds to and accelerates the activity of antithrombin III, thereby inhibiting thrombosis by inactivating factor Xa and thrombin; inhibits thrombin by binding to heparin cofactor II

Duration: ~12 hours

Absorption: S.C.: Well absorbed

Bioavailability: ~90%

Peak plasma levels: 2-3 hours (anti-Xa activity)

Note: Peak anti-Xa plasma levels produced by ardeparin are about twice as high as those produced by heparin, and ardeparin anti-Xa half-life in plasma is longer than that for unfractionated heparin

Half-life: 3 hours

Elimination: Like other low-molecular-weight heparins, elimination of ardeparin appears to be via renal excretion as unchanged drug. Pharmacokinetic parameters for ardeparin suggest saturable elimination.

Adults: S.C.: DVT prophylaxis: 50 anti-Xa units/kg every 12 hours

Patient's weight (kg) x 0.005 mL/kg = volume (mL)

If the ardeparin formulation used contains 10,000 anti-Xa units/0.5 mL (recommended for patients >100 kg or 220 lb), the volume to be administered is calculated as follows:

Patient's weight (kg) x 0.0025 mL/kg = volume (mL)

Dosage adjustment in renal impairment: No adjustment is necessary, although there is limited experience in this population.

Not dialyzable

Monitor CBC including platelet counts, urinalysis, and occult blood in stool. Patients should be observed closely for bleeding if administered during or immediately following diagnostic lumbar puncture, epidural anesthesia, or spinal anesthesia. If thromboembolism develops despite ardeparin prophylaxis, ardeparin should be discontinued and appropriate treatment should be initiated. It is recommended during therapy to monitor complete blood counts including platelet counts, urinalysis, and occult blood in stools. Monitoring of coagulation parameters (APTT) during thromboprophylaxis with ardeparin is not required nor recommended.

At recommended doses, ardeparin has no effect on PT; APTT may show no change or be prolonged; asymptomatic increases in AST and ALT levels >3 times the upper limit of normal have been reported in 20 of 16 and 4 of 16 normal subjects; because aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary embolism, elevations should be interpreted with caution; ardeparin may increase activity of lipoprotein lipase; paradoxical elevations in serum triglyceride levels have been seen in clinical trials

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.

Ardeparin has not been as extensively evaluated in the treatment of unstable angina or non-Q-wave myocardial infarction.

Rare reports of confusion

None reported

No information available to require special precautions

No effects or complications reported

Inform prescriber of any over-the-counter or prescription medication you may take including aspirin, warfarin, NSAID (eg, ibuprofen, naproxen). Because this drug can alter the effects of certain laboratory tests, be sure to remind your prescriber that you are taking this medication when you are scheduled for any tests. This medication should not be mixed with, or added to, any other drug in the same syringe. Laboratory tests will be done periodically while taking this medication to monitor its effects and to prevent side effects. Use each dose at the scheduled time. If you miss a dose, use it as soon as remembered; do not use it if it is near the time for the next dose. Instead, skip the missed dose and resume your usual dosing schedule. Do not "double-up" the dose to catch up. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant.

Injection, as sodium: 5000 anti-Xa units (0.5 mL); 10,000 anti-Xa units (0.5 mL)

Levine MN, Gent M, Hirsh J, et al, "Ardeparin (Low-Molecular-Weight Heparin) vs Graduated Compression Stockings for the Prevention of Venous Thromboembolism. A Randomized Trial in Patients Undergoing Knee Surgery," Arch Intern Med, 1996, 156(8):851-6.

Troy S, Fruncillo, R, Ozawa T, et al, "Absolute and Comparative Subcutaneous Bioavailability of Ardeparin Sodium, a Low Molecular Weight Heparin," Thromb Haemost, 1997, 78(2):871-5.