No

Anticoagulant

Prevention of postoperative deep vein thrombosis following elective hip replacement surgery

B

Hypersensitivity to danaparoid or thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of danaparoid; hypersensitivity to pork products or to sulfites (contains metabisulfite); patients with active major bleeding; severe hemorrhagic diathesis (hemophilia, idiopathic thrombocytopenic purpura); 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 danaparoid 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. Cautious use with known hypersensitivity to methylparaben or propylparaben. Cautious use in patient with 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 hypertension; hemorrhagic stroke; use shortly after brain, spinal, or ophthalmology surgery; patient treated concomitantly with platelet inhibitors; recent GI bleeding; thrombocytopenia or platelet defects; severe liver disease; hypertensive or diabetic retinopathy; or patients undergoing invasive procedures. Cautious use 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. A similar reaction could occur with danaparoid. Monitor for hyperkalemia. Discontinue therapy if platelets are <100,000/mm³.

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

Central nervous system: Fever (22.2%)

Gastrointestinal: Nausea (4.1% to 14.3%), constipation (3.5% to 11.3%)

1% to 10%:

Central nervous system: Insomnia (3.1%), headache (2.6%), asthenia (2.3%), dizziness (2.3%), pain (8.7%)

Cardiovascular: Peripheral edema (3.3%), edema (2.6%)

Dermatologic: Rash (2.1% to 4.8%), pruritus (3.9%)

Gastrointestinal: Vomiting (2.9%)

Genitourinary: Urinary tract infection (2.6% to 4.0%), urinary retention (2.0%)

Hematologic: Anemia (2.2%)

Local: Injection site pain (7.6% to 13.7%), injection site hematoma (5%)

Neuromuscular & skeletal: Joint disorder (2.6%)

Miscellaneous: Infection (2.1%)

<1% (Limited to important or life-threatening symptoms): 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, thrombocytopenia, hyperkalemia, wound infection, skin rash, allergic reaction.

Symptoms of overdose include hemorrhage

Protamine zinc 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 (and other oral anticoagulants) may increase the risk of bleeding with danaparoid.

Store intact vials or ampuls under refrigeration

Prevents fibrin formation in coagulation pathway via thrombin generation inhibition by anti-Xa and anti-IIa effects.

Onset of effect: Maximum antifactor Xa and antithrombin (antifactor IIa) activities occur 2-5 hours after S.C. administration

Half-life, plasma: Mean terminal half-life: ~24 hours

Elimination: Primarily by the kidneys

S.C.:

Adults: 750 anti-Xa units twice daily; beginning 1-4 hours before surgery and then not sooner than 2 hours after surgery and every 12 hours until the risk of DVT has diminished. The average duration of therapy is 7-10 days.

Adults: Treatment: Based on diagnosis/indication:

Deep vein thrombosis OR acute pulmonary embolism:

I.V. bolus (aFXaU) based on body weight:

<55 kg: 1250

55-90 kg: 2500

>90 kg: 3750

Long-term infusion (aFXaU):

400 units/hour over 4 hours, then 300 units/hour over 4 hours, then 150-200 units/hour maintenance dose

Level of aFXaU/mL: 0.5-0.8

Monitoring: Days 1-3 daily, then every alternate day

Deep vein thrombosis OR pulmonary embolism >5 days old:

I.V. bolus (aFXaU) based on body weight:

<90 kg: 1250

>90 kg: 1250

Long-term infusion (aFXaU):

<90 kg: S.C.: 3 x 750/day

>90 kg: S.C.: 3 x 1250/day

Level of aFXaU/mL: <0.5

Monitoring: Not necessary

Embolectomy:

I.V. Bolus (aFXaU) based on body weight:

<90 kg: 2500 preoperatively

>90 kg and high risk: 2500 preoperatively

Long-term infusion (aFXaU):

<90 kg: S.C.: 1250 twice daily postoperatively

>90 kg: 150-200 units/hour I.V.; peri-operative arterial irrigation if necessary, 750 units/20 mL NaCl

Level of aFXaU/mL:

<90 kg: < 0.4

>90 kg: 0.5-0.8

Monitoring:

<90 kg: Not necessary

>90 kg: Days 1-3 daily, then every alternate day

Peripheral arterial bypass:

I.V. bolus (aFXaU): 2500 preoperatively

Long-term infusion (aFXaU): 150-200 units/hour

Level of aFXaU/mL: 0.5-0.8

Monitoring: Days 1-3 daily, then every alternate day

Cardiac catheter:

I.V. bolus (aFXaU) based on body weight:

<90 kg: 2500 preoperatively

>90 kg: 3750 preoperatively

Surgery (excluding vascular):

Long-term infusion (aFXaU):

S.C.: 750, 1-4 hours preoperatively

S.C.: 750, 2-5 hours postoperatively, then 2 x 750/day

Level of aFXaU/mL: <0.35

Monitoring: Not necessary

Dosing adjustment in elderly and severe renal impairment: Adjustment may be necessary. Patients with serum creatinine levels greater than or equal to 2.0 mg/dL should be carefully monitored.

Hemodialysis:

Dialysis on alternate days (Doses in aFXaU, given prior to dialysis)

First dialysis:

3750 (2500 for body wt <55 kg)

Second dialysis:

3750 (2000 for body wt <55 kg)

Further dialysis: (See Note)

Before dialysis level <0.3: Bolus 3000 (2000 if <55 kg)

Before dialysis level 0.3-0.35: Bolus 2500 (2000 if < 55kg)

Before dialysis level 0.35-0.4: Bolus 2000 (1500 if < 55kg)

Before dialysis level > 0.4: No bolus. If fibrin strands occur, 1500 aFXaU I.V.

Note: Bolus dose based on aFXa level before dialysis, eg, day 5, giving an aFXa level during dialysis of 0.5-0.8. Bolus dose should be given before next dialysis, eg day 7.

Monitoring: 30 minutes before dialysis and after 4 hours of dialysis

Daily dialysis (doses in FXaU):

First dialysis:

3750 (2500 for body wt <55 kg)

Second dialysis:

2500 (2000 for body wt <55 kg)

Further dialysis: As above. As with "dialysis on alternate days," always take the aFXa activity preceding the previous dialysis as a basis for the current dosage.

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

May cause insomnia

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 unusual swelling of extremities or sudden increase in weight; unusual fever; persistent nausea, vomiting, or GI upset; unusual bleeding or bruising (bleeding gums, nosebleed, blood in urine, dark stool); pain in joints or back; pain or itching on urination; skin rash; or redness, swelling, or pain at injection site.

Injection, as sodium: 750 anti-Xa units/0.6 mL