Danaparoid (Orgaran) is a low molecular weight heparinoid that acts as an anticoagulant by inhibiting thrombin generation. It also inhibits antithrombin III mediated factor Xa activity.

Danaparoid (Orgaran) Uses:

Note: Not approved in the US

• Catheter patency:

  • Occasionally flush for maintaining the patency of catheters, IV lines, and access ports

• Deep vein thrombosis:

  • It’s used to prevent  DVT after orthopedic, thoracic, or abdominal surgery and in patients with diagnosed non-hemorrhagic stroke.

• Heparin-induced thrombocytopenia:

  • To treat heparin-induced thrombocytopenia (HIT)

Danaparoid (Orgaran) Dose in Adults

Note: Dosing is suggested as manufacturer labeling unless otherwise noted. Dose expressed as anti-Xa units.

Danaparoid (Orgaran) Dose in the Prevention of DVT following orthopedic, major abdominal, or thoracic surgery:

• Subcutaneous: 750 units 2 times a day for 2 weeks;
• it’s suggested for patients to take prophylactic therapy preoperatively and take the last preoperative dose 1-4 hours ahead of surgery.

Danaparoid (Orgaran) dose in the Prevention of DVT in stroke (non-hemorrhagic):

• The first intravenous single dose is up to 1,000 units
• Maintenance dose: Subcutaneous dose of 750 units is given every 12 hours for 7-14 days

Danaparoid (Orgaran) Dose in the HIT:

• Prevention of DVT (with current or past HIT):

Note:

• An intravenous bolus of 1,250 units can be administered if found clinically important (ie, current HIT) and it can also be started as a maintenance regimen without giving a bolus in the following manner via subcutaneous route if the weight is:
  • ≤90 kg:
    • Present HIT or history of HIT: 750 units in every 8-12 hours for 7-10 days
  • >90 kg:
    • Present HIT: 1,250 units every 8 to 12 hours for 7 to 10 days;
    • History of HIT: 1,250 units every 12 hours or 750 units every 8 hours for 7 to 10 days

• Treatment of DVT/PE:

  • Starting Intravenous dose: If thrombosis is <5 days old and weight is:
  • ≤55 kg give 1,250 to 1,500 units;
  • 55 to 90 kg: 2,250 to 2,500 units;
  • >90 kg: 3,750 units; followed by a maintenance intravenous infusion or maintenance subcutaneous injections.

Note: If thrombosis is ≥5 days old, give an intravenous bolus dose of 1,250 units followed by maintenance dose through subcutaneous routes.

• Maintenance:
  • Intravenous infusion (after Intravenous bolus is given):
    • if Thrombosis is <5 days old administer 400 units/hour for 4 hours, then 300 units/hour for 4 hours, followed with 150 to 200 units/hour for 5 to 7 days;
    • The rate can be adjusted according to the target anti-Xa level.
• Maintenance:
  • Subcutaneous injections (after Intravenous bolus administered):

• If Thrombosis is <5 days old and the weight is

  • ≤55 kg administer 1,500 units in every 12 hours;
  • 55 to 90 kg administer 2,000 units every 12 hours;
  • >90 kg administer 1,750 units every 8 hours for 4 to 7 days.

• Thrombosis ≥5 days old:

  • ≤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

Danaparoid (Orgaran) Dose in the HIT/surgical thromboprophylaxis:

• Nonvascular surgery: subcutaneous route:

  • ≤90 kg:
    • 750 units 1 to 4 hours preoperatively then at ≥6 hours postoperatively, then by 750 units every 12 hours starting on 1st day postoperatively and continue it for 7 to 10 days
  • >90 kg:
    • 750 units 1 to 4 hours preoperatively and then at ≥6 hours postoperatively, then by 750 units every 8 hours or 1,250 units every 12 hours starting on 1st-day post-operatively and then continue for 7 to 10 days

• Embolectomy:

  • 55 to 90 kg:
    • Intravenously give 2,250 to 2,500 units as a bolus preoperatively, then through subcutaneous route give 1,250 units every 12 hours, starting ≥6 hours postoperatively
  • Note:
    • After a few days of therapy, it can be switched to a lower subcutaneous dose of 750 units every 8 to 12 hours or anticoagulant therapy via the oral route.
  • >90 kg:
    • Intravenously give 2,250 to 2,500 units as a bolus preoperatively, then 150 to 200 units/hour starting ≥6 hours postoperatively for 5 to 7 days.
    • Note: After a few days of intravenous therapy, it can be switched to the subcutaneous route giving 750 units every 8 to 12 hours or anticoagulant therapy via the oral route.

Dose in the HIT/ cardiac procedures:

Note: Other therapies may be preferred (eg, bivalirudin); the long half-life and irreversibility of danaparoid make it a poor choice in these settings. Refer to the product labeling for dosing recommendations.

• Catheter patency:

  • 750 units mixed with normal saline 50 mL.
  • The catheter can be flushed with 5 to 10 mL of the solution if required.

• Conversion to oral anticoagulant therapy (OAC):

  • It is recommended to maintain a sufficient antithrombotic effect with danaparoid before starting on oral anticoagulant (OAC) therapy.
  • Monitor PT/INR before discontinuation of danaparoid.
  • Note: Within 5 hours of use of danaparoid, the Laboratory values may be doubtful.

• Conversion of SubQ danaparoid to OAC (based on current danaparoid dose):

  • 750 units per 12 hours of Danaparoid:
    • Start OAC, while maintaining danaparoid therapy until PT/INR is therapeutic; could be up to 5 days.
  • 1,250 units per 12 hours of Danaparoid:
    • Start OAC along with decreasing danaparoid to 750 units per 12 hours; maintaining danaparoid therapy until PT/INR is therapeutic; could be up to 5 days.

• Conversion of intravenous danaparoid to oral anticoagulant:

  • Start oral anticoagulant simultaneously with danaparoid infusion intravenously (maximum 300 units/hour);
  • Once INR is therapeutic stop intravenous infusion (maximum INR: 3.0).
  • With any risk of bleeding, the dose of intravenous infusion should be decreased to 75 units/hour and OAC commencement stopped for 24 hours or the route of IV infusion of danaparoid changed to subcutaneous route in a dose of 1,250 units per 12 hours and conversion of SubQ danaparoid to OAC regimen followed as advised (i.e: decreasing to 750 units per 12 hours prior to initiating OAC ).

Use in Children:

Not indicated.

Pregnancy Risk Category: B

• No unfavorable events were observed during animal reproduction studies.
• According to the manufacturer, this has not been reported to cause any congenital anomaly in the foetus during pregnancy.
• Pregnancy is not recommended unless it is considered medically necessary.
• Danaparoid is not able to cross the placenta. It is preferred for pregnant women with HIT.

Danaparoid use during breastfeeding:

• After maternal use of danaparoid, only low levels of anti-Xa activity were found in breastmilk.
• However, since it is not absorbed orally, it is unlikely that it will cause adverse reactions in a nursing infant.
• Breast-feeding may continue to be allowed with danaparoid.
• According to the manufacturer's recommendations, women who use danaparoid should not breastfeed.

Danaparoid (Orgaran) Dose in Kidney Disease:

Note:

• The half-life of Danaparoid is increased in renal dysfunction;
• Monitor anti-Xa levels. Dosage reduction can be needed, mostly when the maintenance doses are being administered.

• Mild or moderate impairment:

  • There are no dosage adjustments provided in the manufacturer's labeling.

• Severe impairment (serum creatinine ≥ 220 micromol/L [≥2.5 mg/dL]):

  • While giving the starting dose, the need of decreasing the dose, or stopping the therapy for some time can be needed to avoid getting plasma anti-Xa from being accumulated. the plasma level can be monitored with an unvarying anti-Xa activity>0.5 anti-Xa units.

• Hemodialysis:

  • Intravenous: give 1,500 to 3,750 units via IV route before dialysis session.

Note: Dose is dependent upon:

• the regularity of dialysis regimen (eg, daily dialysis vs every-other-day or less frequently)
• weight of the patient  (less dose for patients <55 kg)
• if plasma anti-factor Xa levels >400 units/L or
• the patient not on daily dialysis it shall not be administered prior to dialysis and if fibrin threads are present in the bubble chamber 1,500 units can be administered.

Hemofiltration:

• IV: initially 55 to 90 kg:
  • 2,500 units as a bolus,
  • then 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 the patient is <55 kg, decrease bolus dose to 2,000 units, followed by 400 units/hour for 4 hours, and then 150 to 400 units/hour to maintain anti-Xa levels of 500 to 1,000 units/L.

Dose in Liver Disease:

There are no dosage adjustments provided in manufacturer's labeling.

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.

Side Effects of Danaparoid (Orgaran):

• Central Nervous System:

  • Pain

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Nausea
  • Constipation

• Genitourinary:

  • Urinary Retention

• Hematologic & Oncologic:

  • Leukocytosis

• Infection:

  • Infection

• Local:

  • Hematoma At Injection Site

• Respiratory:

  • Pneumonia

• Miscellaneous:

  • Fever

Rare side effects of Danaparoid (Orgaran):

• 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

Contraindications to Danaparoid (Orgaran):

• Hypersensitivity to danaparoid or any other component of the formulation (including sulfurites);
• History of thrombocytopenia after receiving danaparoid, or when danaparoid is associated with a positive antiplatelet antibody in vitro test;
• Hemorrhagic stroke (without systemic emoli);
• History of thrombosis caused by danaparoid
• Acute hemorhagic stroke
• major blood clotting disorder;
• Uncontrollable active bleeding;
• Hemorrhagic severe diathesis
• Acute or subacute bacterial heart disease;
• Active gastric or duodenal ulcer
• Surgery of the CNS, eyes or ears; diabetes or hemorhagic retinalopathy;
• Hypertension uncontrolled and severe
• Other conditions and diseases that can increase hemorhage risk
• Contraindicated intramuscular use

Warnings and precautions

• Bleeding

  • Watch out for bleeding symptoms or signs in patients.
  • Some patients are more at risk of bleeding than others (eg patients with severe hepatic diseases, patients who have had knee surgery or any other invasive procedure, and patients receiving platelet inhibitors in combination with the procedure, elderly).
  • Discontinue if bleeding occurs.

NotificationRoutine clotting tests are not appropriate for monitoring anticoagulant activity of danaparoid danaparoid.

• • The only way to determine anti-factorXa levels is by using the available methods, but it may not correlate well with efficacy.
  • Danaparoid is not effectively antagonized by protamine sulfate.
  • There is no other antidote available. Therefore, extreme caution must be taken when monitoring the dose and factor Xa inhibition effects.
  • In emergency situations, plasmapheresis might be an effective way to reduce anti-Xa levels.

• Hyperkalemia:

  • Monitor for hyperkalemia. Hyperkalemia can be caused by Heparin, which affects aldosterone. Similar reactions may occur with danaparoid.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.

• Peptic ulcer disease:

  • Patients with a history or peptic ulcer disease should be cautious.

• Prosthetic heart valves:

  • Patients with prosthetic heart valves have not been shown to be safe or effective in thromboprophylaxis.

• Renal impairment

  • Extra care is required if you administer medication to someone with renal impairment. It is possible to adjust the dosage.

• Stroke

  • To rule out hemorhagic stroke, CT should be performed before beginning therapy.
• Thrombocytopenia:
  • Patients with a history or risk factors for thrombocytopenia (either congenital, heparin-induced, or platelet defects) should be treated with caution.
  • Cross-reactivity of Danaparoid should be tested for patients with heparin-induced bleeding as per the manufacturer. If positive other therapies are available, they should be used.
  • If there are any clinical signs of a positive cross-reaction, such as an increase in platelet count, thrombosis or skin necrosis, Danaparoid use should be stopped immediately
  • If necessary, therapy can be resumed after confirmation of negative tests for antiplatelet antibodies.
  • The cross-reactivity between heparins or danaparoid may be diagnosed by cutting allergy tests.

Danaparoid: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

1. Platelets (baseline, alternatively during week 1, two times a week in week 2 and 3, and once a week after that);
2. occult blood or other signs of bleeding;
3. anti-Xa activity (if available).

How to administer Danaparoid (Orgaran)?

it can be administered through 2 routes

1. Intravenous (bolus, infusion): administer seperately
2. subcutaneous: switch sites of injection

Note: avoid IM route

Mechanism of action of Danaparoid (Orgaran):

• Inhibits factor IIa and Xa (anti-Xa effect >20 times anti IIa effects).
• Through thrombin generation inhibition, fibrin is prevented from entering the coagulation pathway.

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

International Brand Names of Danaparoid:

• Orgaran
• Ogaran

Danaparoid Brand Names in Pakistan:

No Brands Available in Pakistan.