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 

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 subcut administration; IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Excreted mostly by the kidneys.

Half-life: 24 hr.

TIME/ACTION PROFILE (anticoagulant effect)

Contraindication/Precautions

Contraindicated in:

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

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)

Subcut (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 Subcut (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 Subcut (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, 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, 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 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.

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.
• Subcut 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.

Potential Diagnoses

• Ineffective tissue perfusion (Indications) 
• Risk for injury (Side Effects) 
• Deficient knowledge, related to medication regimen (Patient/Family/Teaching) 

Implementation

• Cannot be used interchangeably (unit for unit) with unfractionated heparin or other low-molecular-weight heparins.
• Conversion to oral anticogulant 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.
• Subcut Administer deep into subcut 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.

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.
• Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Prevention of deep vein thrombosis and pulmonary emboli.