Note: A different parenteral anticoagulant may be preferred; long half-life and irreversibility of danaparoid make other parenteral agents more desirable if quick offset of anticoagulant activity is desired. Dosing recommendations are expressed as anti-Xa units per manufacturer labeling unless otherwise noted.
Catheter patency: Mix 750 units with 50 mL normal saline. Flush catheter with 5 to 10 mL of resulting solution as needed.
Deep vein thrombosis prophylaxis:
Orthopedic, major abdominal, or thoracic surgery:
SUBQ: 750 units every 12 hours for up to 14 days; it is recommended that patients begin prophylactic therapy preoperatively and receive their last preoperative dose 1 to 4 hours before surgery.
Nonhemorrhagic stroke:
IV: Initial: Bolus up to 1,000 units as single dose followed by SUBQ maintenance dose.
SUBQ: Maintenance: After IV bolus dose, administer 750 units every 12 hours for 7 to 14 days.
Heparin-induced thrombocytopenia:
Note: In addition to the indications below, danaparoid may be used for various procedures and/or surgeries in the setting of heparin induced thrombocytopenia (HIT) (eg, perioperative venous thromboembolism prophylaxis, cardiac procedures, peripheral vascular bypass, cardiopulmonary bypass, and hemodialysis). Refer to manufacturer's labeling for dosing in these situations. However, a different anticoagulant may be preferred due to danaparoid’s long half-life and irreversibility.
Deep vein thrombosis prophylaxis (with current or past heparin-induced thrombocytopenia) in nonsurgical patients:
Note: Dosing based on manufacturer’s labeling; may not reflect clinical practice. In patients with current (acute) HIT, therapeutic dose rather than prophylactic dose anticoagulation is recommended for at least 4 weeks and up to 3 months (ACCP [Linkins 2012]; ASH [Cucker 2018]).
IV bolus (optional):
Current HIT (<3 months ago): May administer an initial IV bolus of 1,250 units to rapidly attain prophylaxis levels (if clinically necessary) or may initiate maintenance SUBQ regimen without a bolus as follows:
Past HIT (>3 months ago): IV bolus not recommended.
SUBQ (maintenance):
≤90 kg:
Current HIT or past HIT: 750 units every 8 to 12 hours.
>90 kg:
Current HIT (<3 months ago): 1,250 units every 8 to 12 hours.
Past HIT (>3 months ago): 1,250 units every 12 hours or 750 units every 8 hours.
Treatment of deep vein thrombosis or pulmonary embolism:
Initial:
Thrombosis <5 days old: Administer weight-based IV bolus followed by maintenance IV infusion or maintenance SUBQ injections (weight-based dosing).
IV bolus:
≤55 kg: 1,250 to 1,500 units.
55 to 90 kg: 2,250 to 2,500 units.
>90 kg: 3,750 units.
Thrombosis ≥5 days old: IV bolus: 1,250 units (regardless of weight) followed by maintenance SUBQ injections.
Maintenance:
Thrombosis <5 days old:
IV infusion (after IV bolus administered): 400 units/hour for 4 hours, then 300 units/hour for 4 hours, then 150 to 200 units/hour; adjust rate according to target anti-Xa levels. Note: IV infusion dose is not weight-based.
or
SUBQ (after IV bolus administered):
≤55 kg: 1,500 units every 12 hours.
55 to 90 kg: 2,000 units every 12 hours.
>90 kg: 1,750 units every 8 hours.
Thrombosis ≥5 days old:
SUBQ:
≤90 kg: 750 units every 8 to 12 hours.
>90 kg: 750 units every 8 hours or 1,250 units every 8 to 12 hours.
Conversion to oral anticoagulant therapy:
Note: Establish adequate antithrombotic effect with danaparoid prior to initiation of oral anticoagulant therapy. Laboratory values (eg, PT/INR) taken within 5 hours of danaparoid administration may be unreliable.
Conversion of SUBQ danaparoid to warfarin (based on current danaparoid dose):
Danaparoid 750 units every 12 hours: Initiate warfarin and maintain danaparoid therapy until PT/INR is therapeutic; may take up to 5 days.
Danaparoid 1,250 units every 12 hours: Initiate warfarin and decrease danaparoid to 750 units every 12 hours; maintain danaparoid therapy until PT/INR is therapeutic; may take up to 5 days.
Conversion of IV danaparoid to warfarin: Initiate warfarin with concurrent danaparoid IV infusion (maximum 300 units/hour); discontinue IV infusion once INR is therapeutic (maximum INR: 3.0). If bleeding risk is present, IV infusion should be reduced to 75 units/hour and warfarin initiation withheld for 24 hours or danaparoid IV infusion may be switched to SUBQ route at a dose of 1,250 units every 12 hours and the recommended conversion of SUBQ danaparoid to warfarin regimen followed (ie, subsequent reduction to 750 units every 12 hours while warfarin is initiated).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Danaparoid half-life is significantly prolonged in renal impairment; anti-Xa levels should be closely monitored. Dosage reduction, especially with maintenance doses, may be required.
Mild or moderate impairment: There are no dosage adjustments provided in manufacturer's labeling.
Severe impairment (serum creatinine ≥220 micromol/L [≥2.5 mg/dL]): Following initial dose, dose reductions or temporary discontinuation of therapy may be necessary to prevent accumulation of plasma anti-Xa (indicated by consistent, steady state-plasma anti-Xa activity >0.5 anti-Xa units).
Hemodialysis:
IV: 1,500 to 3,750 units before dialysis session. Note: Dose depends on frequency of dialysis regimen (eg, daily dialysis vs every-other-day or less frequently) and weight of patient with the lower dose recommended for patients <55 kg. Do not administer prior to dialysis if plasma antifactor Xa levels >400 units/L and not receiving daily dialysis; however, if fibrin threads are present in bubble chamber may administer 1,500 units.
Hemofiltration: IV: 55 to 90 kg: 2,500 units as a bolus, followed by 600 units/hour for 4 hours, then 400 units/hour for 4 hours, then 200 to 600 units/hour to maintain adequate anti-Xa levels. Note: If patient is <55 kg, reduce bolus dose to 2,000 units, followed by 400 units/hour for 4 hours, then 150 to 400 units/hour to maintain anti-Xa levels of 500 to 1,000 units/L.
There are no dosage adjustments provided in manufacturer's labeling.
Refer to adult dosing.
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Orgaran: 750 units/0.6 mL (0.6 mL) [contains sodium sulfite]
Not available in the US
IV, SUBQ: May administer intravenously as bolus or infusion, or by subcutaneous injection. When administered intravenously, do not mix with other drugs. For subcutaneous administration, rotate injection sites. Do not administer intramuscularly.
Note: Not approved in the United States.
Catheter patency: Intermittent flushing to maintain patency of catheters/IV lines and/or access ports.
Deep vein thrombosis prophylaxis: Prevention of postoperative deep vein thrombosis (DVT) following orthopedic or major abdominal and thoracic surgery; prevention of DVT in patients with confirmed diagnosis of nonhemorrhagic stroke.
Heparin-induced thrombocytopenia: Management of heparin-induced thrombocytopenia (HIT).
Orgaran may be confused with argatroban
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined. 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.
1% to 10%:
Central nervous system: Pain (5%)
Dermatologic: Skin rash (1%)
Gastrointestinal: Nausea (3%), constipation (2%)
Genitourinary: Urinary retention (1%)
Hematologic & oncologic: Leukocytosis (1%)
Infection: Infection (2%)
Local: Hematoma at injection site (≤5%)
Respiratory: Pneumonia (1%)
Miscellaneous: Fever (2% to 5%)
Frequency not defined:
Cardiovascular: Atrial fibrillation, cerebral infarction, decreased blood pressure (arterial), deep vein thrombosis, hypotension, peripheral edema
Central nervous system: Cerebral hemorrhage, confusion, fatigue, hemiparesis, insomnia, loss of consciousness, restlessness
Genitourinary: Hematuria, urinary incontinence, urinary tract hemorrhage (including microscopic), urine abnormality
Hematologic & oncologic: Bruise, hematoma, hemorrhage (dose-related), thrombocytopenia
Hypersensitivity: Hypersensitivity reaction
Infection: Sepsis
Neuromuscular & skeletal: Muscle spasm, tremor
Respiratory: Apnea, asthma
<1%, postmarketing, and/or case reports: Increased serum alkaline phosphatase, increased serum ALT (transient), increased serum AST (transient)
Hypersensitivity to danaparoid, or any component of the formulation (including sulfites); history of thrombocytopenia while receiving danaparoid or when associated with a positive in vitro test for antiplatelet antibodies in the presence of danaparoid; hemorrhagic stroke (without systemic emboli); history of thrombosis with danaparoid; acute hemorrhagic stroke; major blood clotting disorder; uncontrollable active bleeding state; severe hemorrhagic diathesis; acute or subacute bacterial endocarditis; active gastric or duodenal ulcer; surgery of CNS, eyes, or ears; diabetic or hemorrhagic retinopathy; severe uncontrolled hypertension; other conditions or diseases that increase risk of hemorrhage; not for intramuscular use
Concerns related to adverse effects:
• Bleeding: Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding (eg, severe hepatic disease, patients undergoing knee surgery or other invasive procedures, concomitant therapy with platelet inhibitors, elderly). Discontinue if bleeding occurs. Note: Routine clotting assays are not suitable for monitoring danaparoid anticoagulant activity; determining anti-factor Xa levels is the only available method but may not correlate with efficacy. Danaparoid is not effectively antagonized by protamine sulfate. No other antidote is available, so extreme caution is needed in monitoring dose given and resulting factor Xa inhibition effect. Plasmapheresis may be effective in reducing anti-Xa levels in emergency situations.
• Hyperkalemia: Monitor for hyperkalemia. Heparin can cause hyperkalemia by affecting aldosterone; similar reactions could occur with danaparoid.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Peptic ulcer disease: Use with caution in patients with a history of peptic ulcer disease.
• Prosthetic heart valves: Safety and efficacy have not been established for use as thromboprophylaxis in patients with prosthetic heart valves.
• Renal impairment: Use with caution in patients with severe renal impairment; primarily renally eliminated. Dosage adjustment may be needed.
• Stroke: Hemorrhagic stroke should be ruled out by CT scan prior to initiating therapy.
• Thrombocytopenia: Use caution in patients with or with a history of thrombocytopenia (heparin-induced, congenital) or platelet defects. The manufacturer labeling recommends that patients with a history of heparin-induced thrombocytopenia be tested for cross-reactivity with danaparoid prior to initiating therapy; if test is positive, alternative therapy should be employed unless otherwise not available. If danaparoid is administered, therapy must be discontinued immediately with clinical signs of positive cross-reactivity (eg, increased reduction in platelet counts, thrombosis, skin necrosis). May resume therapy (if needed) only after laboratory confirmed negative test for danaparoid activated antiplatelet antibodies. Cutaneous allergy tests may help detect the presence of cross-reactivity between heparins and danaparoid (Grassegger 2001).
Dosage form specific issues:
• Sodium sulfite: This product contains sodium sulfite which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people; this is seen more frequently in asthmatics.
Other warnings/precautions:
• Conversion to other products: Not to be used interchangeably (unit for unit) with heparin or any other low molecular weight heparins.
• Neuraxial anesthesia: Spinal or epidural hematomas, including subsequent paralysis, may occur with recent or anticipated neuraxial anesthesia (epidural or spinal anesthesia) or spinal puncture in patients anticoagulated with LMWH or heparinoids. Consider risk versus benefit prior to spinal procedures; risk is increased by the use of concomitant agents which may alter hemostasis, the use of indwelling epidural catheters for analgesia, a history of spinal deformity or spinal surgery, as well as a history of traumatic or repeated epidural or spinal punctures. Spinal procedures should be avoided for 12 hours after the last danaparoid dose; allow at least 2 hours after procedure before resuming danaparoid therapy. Patient should be observed closely for bleeding and signs and symptoms of neurological impairment if therapy is administered during or immediately following diagnostic lumbar puncture, epidural anesthesia, or spinal anesthesia.
None known.
Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination
Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy
Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination
Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification
Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Risk X: Avoid combination
Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination
Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination
Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Oritavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy
Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination
Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Telavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor therapy
Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Risk C: Monitor therapy
Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Urokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid combination
Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
The manufacturer labeling states that incidental observations in pregnant women during the last trimesters, gave no indication that use during pregnancy results in fetal abnormalities or exacerbation of bleeding in the mother or infant during delivery. Use in pregnant women however is generally not recommended unless deemed medically necessary and alternative therapy is unavailable. Danaparoid does not cross the placenta and is the preferred anticoagulant in pregnant women with HIT (Guyatt 2012).
Only low amounts of anti-Xa activity have been found breast milk following maternal use of danaparoid; however, because it is not absorbed when taken orally, it is unlikely to cause adverse events in a breastfeeding infant. Use of danaparoid may be continued in breastfeeding (Guyatt 2012). The manufacturer labeling recommends that women receiving danaparoid avoid breast-feeding.
Platelets (baseline, every other day during week 1, twice weekly during weeks 2 and 3, and once weekly thereafter); occult blood or other signs of bleeding; anti-Xa activity (if available). See manufacturer’s recommendations within labeling regarding anticipated anti-Xa levels.
Inhibits factor Xa and IIa (anti-Xa effects >20 times anti-IIa effects). Prevents fibrin formation in the coagulation pathway via thrombin generation inhibition.
Onset of action: Peak effect: SubQ: Maximum antifactor Xa activities occur in 4-5 hours
Bioavailability: SubQ: ~100%
Half-life elimination: Anti-Xa activity: ~25 hours (renal impairment: 29-35 hours); Thrombin generation inhibition activity: ~7 hours
Excretion: Primarily urine