danaparoid sodium

General

Canada-Approved Medicine

This monograph describes a medication approved for use in Canada by the Therapeutic Products Directorate, a division of Health Canada’s Health Products and Food Branch. The medication is not approved by the United States Food and Drug Administration; however, a similar formulation carrying a different generic or brand name might be available in the US.

Pronunciation:
da-nap-a-roid

Trade Name(s)

  • Orgaran Canadian Trade name

Ther. Class.

anticoagulants

Pharm. Class.

low molecular weight heparins

Indications

  • Prevention of thromboembolic phenomena including deep vein thrombosis and pulmonary emboli after surgical procedures known to increase the risk of such complications (knee/hip replacement, abdominal surgery).
  • Management of non-hemorrhagic stroke.
  • Treatment/prevention of thromboembolic phenomena in patients with a history of heparin-induced thrombocytopenia (HIT)

Action

  • Potentiates the inhibitory effect of antithrombin on factor Xa and thrombin.
  • Danaparoid sodium is a heparinoid.

Therapeutic Effect(s):

Prevention of thrombus formation.

Pharmacokinetics

Absorption: 100% absorbed after SUBQ administration; IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Excreted mostly by the kidneys.

Half-life: 25 hr.

TIME/ACTION PROFILE (anticoagulant effect)

ROUTEONSETPEAKDURATION
SUBQunknown2–5 hr12 hr

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity to danaparoid sodium, pork products, or sulfites;
  • Uncontrolled bleeding;
  • Imminent/threatened abortion;
  • Lactation: Avoid breastfeeding.

Use Cautiously in:

  • Severe hepatic or renal impairment (dosage ↓ may be necessary in severe renal impairment);
  • Retinopathy (hypertensive or diabetic);
  • Untreated hypertension;
  • Recent history of ulcer disease;
  • Spinal/epidural anesthesia;
  • History of congenital or acquired bleeding disorder;
  • Malignancy;
  • History of thrombocytopenia related to heparin (HIT), has been used successfully;
  • OB:  Safe use in pregnancy has not been established;
  • Geri:  Dosage ↓ may be necessary in severe renal impairment;
  • Pedi:  Safety not established.

Exercise Extreme Caution in:

  • Severe uncontrolled hypertension;
  • Bacterial endocarditis, bleeding disorders;
  • GI bleeding/ulceration/pathology;
  • Hemorrhagic stroke;
  • Recent CNS or ophthalmologic surgery;
  • Active GI bleeding/ulceration.

Adverse Reactions/Side Effects

CNS: dizziness, headache, insomnia

CV: edema

GI: constipation, nausea, reversible increase in liver enzymes, vomiting

GU: urinary retention

Derm: ecchymoses, pruritus, rash, urticaria

Hemat: BLEEDING, anemia, thrombocytopenia

Local: erythema at injection site, hematoma, irritation, pain

Misc: fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Risk of bleeding may be ↑ by concurrent use of other  anticoagulants  including  warfarin  or  drugs that affect platelet function, including  aspirin,  NSAIDs,  dipyridamole, some  penicillins,  clopidogrel,  ticlopidine, and  dextran.

Route/Dosage

Prophylaxis of DVT (non HIT patients)

SUBQ (Adults): 750 anti-factor Xa IU every 12 hr starting 1–4 hr preop and at least 2 hr postop for 7–10 days or until ambulatory (up to 14 days).  Prophylaxis of DVT following Orthopedic, Major Abdominal Surgery, and Thoracic Surgery: 750 anti-factor Xa units, twice daily up to 14 days, initiate 1–4 hr preop.

IV SUBQ (Adults): Prophylaxis of Deep Vein Thrombosis in Non-hemorrhagic Stroke Patients: up to 1000 anti-Xa units IV, followed by 750 anti-Xa units subcutaneously, twice daily for 7–14 days.

HIT

IV SUBQ (Adults): DVT prophylaxis, current HIT, ≤90 kg: 750 anti-Xa units SC two or three times daily for 7–10 days (initial bolus of 1250 anti-Xa units IV may be used);  DVT prophylaxis, current HIT, >90 kg: 1250 anti-Xa units SC two or three times daily for 7–10 days (initial bolus of 1250 anti-Xa units IV may be used);  DVT prophylaxis, past (>3 mo) HIT, ≤90 kg: 750 anti-Xa units SC two or three times daily for 7–10 days;  DVT prophylaxis, past (>3 mo) HIT, >90 kg: 750 anti-Xa units SC three times daily or 1250 anti-Xa units SC twice daily for 7–10 days;  Established pulmonary embolism or DVT, thrombus <5 days, >90 kg: 3750 anti-Xa units IV bolus, then 400 anti-Xa units/hr for 4 hr, then 300 anti-Xa units/hr for 4 hr, then 150–200 anti-Xa units/hr for 5–7 days or 1750 anti-Xa units SC twice daily for 4–7 days;  Established pulmonary embolism or DVT, thrombus <5 days, 55–90 kg: 2250–2500 anti-Xa units IV bolus, then 400 anti-Xa units/hr for 4 hr, then 300 anti-Xa units/hr for 4 hr, then 150–200 anti-Xa units/hr for 5–7 days or 2000 anti-Xa units SC twice daily for 4–7 days;  Established pulmonary embolism or DVT, thrombus <5 days, <55 kg: 1250–1500 anti-Xa units IV bolus, then 400 anti-Xa units/hr for 4 hr, then 300 anti-Xa units/hr for 4 hr, then 150–200 anti-Xa units/hr for 5–7 days or 1500 anti-Xa units SC twice daily for 4–7 days;  Established pulmonary embolism or DVT, thrombus ≥5 days, >90 kg: 1250 anti-Xa units IV bolus, then 750 anti-Xa units SC three times daily or 1250 anti-Xa units twice daily;  Established pulmonary embolism or DVT, thrombus ≥5 days, ≤90 kg: 1250 anti-Xa units IV bolus, then 750 anti-Xa units SC 2–3 times daily;  Surgical prophylaxis, nonvascular surgery, >90 kg: 750 anti-Xa units SC 1–4 hr before procedure, repeat ≥6 hr after procedure, then 1250 anti-Xa units SC twice daily for 7–10 days;  Surgical prophylaxis, nonvascular surgery, ≤90 kg: 750 anti-Xa units SC 1–4 hr before procedure, repeat ≥6 hr after procedure, then 750 anti-Xa units SC twice daily for 7–10 days;  Surgical prophylaxis, embolectomy, >90 kg: 2250–2500 anti-Xa units IV bolus before procedure, then 150–200 anti-Xa units/hr IV starting ≥6 hr after procedure for 5–7 days or 750 anti-Xa units 2–3 times daily or change to oral anticoagulants after several days;  Surgical prophylaxis, embolectomy, 55–90 kg: 2250–2500 anti-Xa units IV bolus before procedure, then 1250 anti-Xa units SC twice daily starting ≥6 hr after procedure, then 750 anti-Xa units 2–3 times daily or change to oral anticoagulants after several days;  Cardiac catheterization >90 kg: 3750 anti-Xa units IV bolus prior to procedure;  Cardiac catheterization <90 kg: 2500 anti-Xa units IV bolus prior to procedure;  Percutaneous transluminal coronary angioplasty: 2500 anti-Xa units IV prior to procedure, then 150–200 anti-Xa units/hr IV for 1–2 days after procedure, may be followed by 750 anti-Xa units SC for several days;  Intra-aortic balloon pump catherization, >90 kg: 3750 anti-Xa units IV bolus before procedure, then 150–200 anti-Xa units/hr IV or a 2nd bolus of 1250 anti-Xa units IV or 750 anti-Xa units SC two or three times daily or 1250 anti-Xa units SC twice daily;  Intra-aortic balloon pump catherization, <90 kg: 2500 anti-Xa units IV bolus before procedure, then 150–200 anti-Xa units/hr IV or a 2nd bolus of 1250 anti-Xa units IV or 750 anti-Xa units SC two or three times daily or 1250 anti-Xa units SC twice daily;  Peripheral vascular bypass: 2250–2500 anti-Xa units IV bolus before procedure, then 150–200 anti-Xa units/hr IV started ≥6 hr after procedure for 5–7 days or 750 anti-Xa units SC two or three times daily or change to oral anticoagulants;  Hemodialysis, every other day or less frequently: 3750 anti-Xa units IV bolus before first 2 hemodialysis, then 3000 anti-Xa units IV bolus (if plasma antifactory Xa level <300 U/L) or 2500 anti-Xa units IV (if plasma antifactory Xa levels 350–400);  Hemodialysis, every other day or less frequently, <55kg:  2500 anti-Xa units IV bolus before first 2 hemodialysis, then 2000 anti-Xa units IV bolus (if plasma antifactory Xa level <300 U/L), or 1500 anti-Xa units IV (if plasma antifactory Xa levels 350–400);  Hemodialysis, daily: 3750 anti-Xa units IV before first dialysis, then 2500 before second dialysis;  Hemodialysis, daily, <55kg:  2500 anti-Xa units IV before first dialysis, then 2000 before second dialysis;  Hemofiltration, 55–90kg: 2500 anti-Xa units IV bolus, then 600/h for 4h, then 400/h for 4/h, then 200–600/h to maintain plasma antifactory Xa levels of 500–1000 U/L;  Hemofiltration, <55kg:  2000 anti-Xa units IV bolus, then 400/h for 4h, then 150–400/h to maintain plasma antifactory Xa levels of 500–1000 U/L.

Availability

Solution for injection (contains sulfites): 750 anti-factor Xa units/0.6 mL ampule

Assessment

  • Assess for signs of bleeding and hemorrhage (bleeding gums; nosebleed; unusual bruising; black, tarry stools; hematuria; fall in hematocrit or BP; guaiac-positive stools); bleeding from surgical site. Notify health care professional if these occur.
    • Assess for evidence of additional or increased thrombosis. Symptoms will depend on area of involvement. Monitor neurological status frequently for signs of neurological impairment. May require urgent treatment.
    • Monitor patient for hypersensitivity reactions (chills, fever, urticaria).
    • Monitor patients with epidural catheters frequently for signs and symptoms of neurologic impairment.
  • SUBQ Observe injection sites for hematomas, ecchymosis, or inflammation.

Lab Test Considerations:

Monitor CBC, and stools for occult blood periodically during therapy. Monitor platelet count every other day for first wk, twice weekly for next 2 wk, and weekly thereafter. If thrombocytopenia occurs, monitor closely. If hematocrit decreases unexpectedly, assess patient for potential bleeding sites.

  • Special monitoring of clotting times (aPTT) is not necessary.
  • May cause ↑ in AST, ALT, and alkaline phosphatase levels.

Toxicity and Overdose:

Danaparoid sodium is not reversed with protamine sulfate. If overdose occurs, discontinue danaparoid sodium. Transfusion with fresh frozen plasma and plasmapheresis has been used if bleeding is uncontrollable.

Implementation

  • Cannot be used interchangeably (unit for unit) with unfractionated heparin or other low-molecular-weight heparins.
  • Conversion to oral anticoagulant therapy (unless it is contraindicated) should not be started until adequate antithrombotic control with parenteral danaparoid sodium has been achieved; conversion may take up to 5 days.
  • SUBQ Administer deep into SUBQ tissue. Alternate injection sites daily between the left and right anterolateral and left and right posterolateral abdominal wall. Inject entire length of needle at a 45° or 90° angle into a skin fold held between thumb and forefinger; hold skin fold throughout injection. Do not aspirate or massage. Rotate sites frequently. Do not administer IM because of danger of hematoma formation. Solution should be clear; do not inject solution containing particulate matter.
    • If excessive bruising occurs, ice cube massage of site before injection may lessen bruising.

IV Administration

  • IV Push:  SUBQ is preferred route. Dilution:  If administered IV, give as a bolus. May dilute with 0.9% NaCl, D5/0.9% NaCl, Ringer's, LR, and mannitol. Stable for up to 48 hr at room temperature.
  • Y-Site Incompatibility: Administer separately; do not mix with other drugs.

Patient/Family Teaching

  • Instruct patient in correct technique for self-injection, care and disposal of equipment.
  • Advise patient to report any symptoms of unusual bleeding or bruising, dizziness, itching, rash, fever, swelling, or difficulty breathing to health care professional immediately.
  • Instruct patient not to take aspirin, naproxen, or ibuprofen without consulting health care professional while on danaparoid sodium therapy.
  • Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Prevention of deep vein thrombosis and pulmonary emboli.