Orgaran Ref.[2696] Active ingredients: Danaparoid

a) Non-HIT patients (DVT prophylaxis)

In general Orgaran should be administered by subcutaneous injection at a dose of 750 anti-factor Xa units, twice daily for 7 to 10 days or until the risk of thromboembolism has diminished.

In surgical patients it is recommended to start this dosing pre-operatively and to give the last pre-operative dose 1-4 hours before surgery.

Plasma anti-Xa activity is linearly related to the dose of Orgaran given. If it is necessary to monitor anticoagulant activity, and for individual dose setting, a functional anti-factor Xa test using a chromogenic peptide substrate should be used. In this test Orgaran should be used as standard for constructing the reference curve.

b) HIT patients

The diagnosis of HIT should as a minimum be based on:

1. thrombocytopenia (platelet count<100x109/L) occurring during heparin administration and
2. exclusion of all other causes of thrombocytopenia

In general monitoring of plasma anti-Xa activity is not necessary. However, in patients suffering from renal insufficiency and/or patients weighing over 90kg, monitoring (using an amidolytic assay) is recommended.

Orgaran should be administered intravenously as a bolus of 2500 anti-Xa units (for patients less than 55kg 1250 units, if over 90kg, 3750 units) followed by an intravenous infusion of 400units/h for 2 hours, then 300 units/h for 2 hours, then a maintenance infusion of 200 units/h for 5 days. The expected plasma anti-Xa levels are 0.5-0.7 units/ml 5-10 minutes after the bolus, not higher than 1.0 units/ml during the adjustment phase of maintenance infusion and 0.5-0.8 units/ml during the maintenance infusion.

Dosage in the elderly

Clearance of anti-factor Xa activity has not been shown to be markedly reduced in the elderly and the usual dosage is recommended.

Children

There is insufficient experience with the use of Orgaran in children to suggest a dosage regimen for this group of patients.

Dosage in patients with moderately impaired renal and/or liver function

Orgaran should be used with caution in patients with moderately impaired renal and/or liver function with impaired haemostasis.

Conversion to anticoagulants is possible, however it is advisable only to start such a therapy once there is adequate antithrombotic control with Orgaran.

Oral anticoagulants can be given with the infusion (maximum rate 300units/h) which can then be stopped when the international normalised ratio is ≥1.5. If the bleeding risk is high then either:

(a) stop the infusion and start Orgaran 750 anti-Xa units subcutaneously twice a day, then 24 hours later start anticoagulants 48-72 hours before Orgaran is withdrawn to give time for the prothrombin time, Thrombotest and international normalised ratio to reach therapeutic levels (measurement of these parameters is not reliable within 5 hours of Orgaran injection (See “Interactions with other medicaments and other forms of interactions”)) or

(b) stop the infusion, give no further Orgaran then start the anticoagulants 12 hours later.

In the event of serious bleeding other than caused by a surgical error, Orgaran should be stopped and transfusion of fresh frozen plasma or, if uncontrollable, plasmapheresis should be considered. Although protamine partially neutralises the anticoagulant activity of Orgaran the relevance for the reversal of the bleeding is not clear and therefore cannot be recommended. The effects of Orgaran on anti-Xa activity cannot be antagonized with any known agent at this time.

3 years.

Do not store above 30°C. Do not freeze. Keep the ampoules in the outer carton to protect from light.

1-ml glass ampoules containing 750 anti-factor Xa units (0.6ml) danaparoid sodium per ampoule (1250 anti-factor Xa units/ml) in packs of 10 or 20 ampoules.

See section 4.2