Last Updated on eMC 12-02-2016 View medicine  | Aspen Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 1 - Name of the medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.2 - Incompatibilities
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

Date of revision of text on the SPC:29-01-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
Text strikethrough = deleted text

1. NAME OF THE MEDICINAL PRODUCT

Orgaran Danaparoid Sodium 750 anti-Xa units/0.6 ml, solution for injection

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Orgaran Danaparoid Sodium contains danaparoid sodium, which is a non-heparin mixture of low molecular weight sulphated glycosaminoglycuronans derived from animal mucosa, comprising heparan sulphate, dermatan sulphate and a minor amount of chondroitin sulphates.  One ampoule (0.6mL) contains 750 amidolytic anti-factor Xa units orgaran danaparoid sodium and corresponding to 1250 anti-factor Xa units per mL. The anti-Xa unit is derived from the international heparin standard in an antithrombin containing buffer system.

 

4.2       Posology and method of administration

 

a)         Non-HIT patients (DVT prophylaxis)

In general Orgaran Danaparoid Sodium 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 Danaparoid Sodium 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 Danaparoid Sodium should be used as standard for constructing the reference curve.




4.3       Contra-indications

    As with heparins, in patients receiving Orgaran Danaparoid Sodium for treatment rather than for prophylaxis, locoregional anaesthesia in elective surgical procedures is contra-indicated.

a positive in vitro aggregation test for the heparin-induced antibody in the presence of Orgaran Danaparoid Sodium in patients with a history of thrombocytopenia induced by heparin or heparin-like anticoagulants

 

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 Danaparoid Sodium 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 Danaparoid Sodium in children to suggest a dosage regimen for this group of patients.

 

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

Orgaran Danaparoid Sodium 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  Danaparoid Sodium.

Oral anticoagulants can be given with the infusion (maximum rate 300units/h) which can then be stopped when the international normalised ratio is ³1.5. If the bleeding risk is high then either:

(a) stop the infusion and start Orgaran  Danaparoid Sodium 750 anti-Xa units/0.6 ml subcutaneously twice a day, then 24 hours later start anticoagulants 48-72 hours before Orgaran Danaparoid Sodium 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  Danaparoid Sodium injection (See “Interactions with other medicaments and other forms of interactions”)) or

(b)       stop the infusion, give no further Orgaran  Danaparoid Sodium then start


4.4       Special Warnings and Special precautions for use

Orgaran Danaparoid Sodium should not be used if an in vitro test for the heparin-induced antibody in the presence of Orgaran  Danaparoid Sodium is positive in patients with thrombocytopenia induced by heparin or heparin-like anticoagulants, unless no suitable alternative antithrombotic treatment is available.

The incidence of serological cross-reactivity of Orgaran  Danaparoid Sodium with the heparin-induced antibody before the start of therapy is approximately 5%. The incidence of clinical cross-reactivity developing during  Orgaran  Danaparoid Sodium therapy is approximately 3% and many of these patients had a negative pre-treatment serological cross-reactivity test. Although the risk of antibody-induced thrombocytopenia and thrombosis during  Orgaran Danaparoid Sodium therapy (i.e. clinical cross-reactivity) is very small, it is advisable to check the number of platelets daily during the first week of treatment, on alternate days during the second and third weeks, and weekly to monthly thereafter. If a pre-treatment cross-reactivity test with Orgaran  Danaparoid Sodium is positive but it is decided to use Orgaran  Danaparoid Sodium, then the number of platelets should be checked daily until Danaparoid Sodium treatment is stopped. If antibody-induced thrombocytopenia occurs, one should stop the use of Orgaran  Danaparoid Sodium and consider alternative treatment.

 

Orgaran  Danaparoid Sodium should not be administered to patients with severe hemorrhagic diathesis, e.g. hemophilia and idiopathic thrombocytopenic purpura, unless the patient also has HIT and no suitable alternative antithrombotic treatment is available.

 

Orgaran  Danaparoid Sodium should not be used in patients with severe renal and hepatic insufficiency unless the patient also has HIT and no alternative antithrombotic treatment is available.

 

Orgaran  Danaparoid Sodium should be used with caution in patients with moderately impaired renal, and/or liver function with impaired haemostasis, ulcerative lesions of the gastro-intestinal tract or other diseases which may lead to an increased danger of haemorrhage into a vital organ or site.

 

Orgaran  Danaparoid Sodium should not be administered to patients with active gastric or duodenal ulceration, unless it is the reason for operation.

 

Since severe bleeding may occur post-operatively in HIT patients undergoing a cardiopulmonary bypass procedure, Orgaran Danaparoid Sodium is not recommended during the procedure, unless no other antithrombotic treatment is available.

Orgaran Danaparoid Sodium contains sodium sulphite.  In asthma patients hypersensitive to sulphite the latter can result in bronchospasm and/or anaphylactic shock.

Orgaran Danaparoid Sodium should not be given by the intramuscular route.

The safety and efficacy of Danaparoid Sodium in patients with non-haemorrhagic stroke remains to be confirmed.

No incidences of osteoporosis have been reported in patients treated with the recommended dose of Orgaran Danaparoid Sodium However, as for heparin, treatment with glycosaminoglycuronan may result in osteoporosis if the dosage is inappropriate.

It should be noted that the anti-Xa units of Orgaran Danaparoid Sodium have a different relationship to clinical efficacy than those of heparin and low molecular weight heparins.

As with heparins, in patients undergoing peridural or spinal anaesthesia or spinal puncture, the prophylactic use of Orgaran Danaparoid Sodium may theoretically be associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis. The risk is increased by the prolonged use of a peridural or spinal catheter for analgesia, by the concomitant use of drugs affecting haemostasis such as nonsteroidal anti-inflammatory drugs (NSAIDs), and by traumatic or repeated puncture.

In decision-making on the interval between the last administration of Orgaran Danaparoid Sodium at prophylactic doses and the placement or removal of a peridural or spinal catheter, the product characteristics and the patient profile should be taken into account. Subsequent dose should not take place before at least four hours have elapsed. Re-administration should be delayed until the surgical procedure is completed.

Should a physician decide to administer Orgaran Danaparoid Sodium in the context of peridural or spinal anaesthesia, extreme vigilance and frequent monitoring must be exercised to detect any signs and symptoms of neurologic impairment, such as back pain, sensory and motor deficits (numbness and weakness in lower limbs) and bowel or bladder dysfunction. Nurses should be trained to detect such signs and symptoms. Patients should be instructed to inform immediately a nurse or a clinician if they experience any of these.

4.5       Interactions with other Medicaments and other forms of Interaction

 

In clinical studies no clinically significant interactions with other medications have been found. Orgaran Danaparoid Sodium may be used together with oral anticoagulants, drugs which interfere with platelet function (such as aspirin and non-steroidal anti-inflammatory drugs) or potentially ulcerogenic drugs (such as corticosteroids), but caution remains necessary this is particularly important in patients undergoing peridural or spinal anaesthesia or spinal puncture (see section 4.4.). Monitoring of anticoagulant activity of oral anticoagulants by prothrombin time and thrombotest is unreliable within 5 hours after Orgaran Danaparoid Sodium administration.

There is no data available on the effect of Orgaran Danaparoid Sodium on thyroid function tests


4.6       Pregnancy and Lactation

Pregnancy
Orgaran Danaparoid Sodium has been used in over 60 pregnancies (starting during the first trimester in almost 50% of the pregnancies, the second trimester in approximately 20% of the pregnancies and the third trimester in 25% of the pregnancies. For a small number of patients the starting trimester is unknown). Overall, the use of Orgaran Danaparoid Sodium was successful.

Animal studies have not demonstrated any teratogenic effect or placental transfer. In the few cases in which human umbilical cord blood was tested for the presence of anti-Xa activity, no activity was found.

Although Orgaran Danaparoid Sodium has been used with success in a small number of pregnancies, the available information is still considered to be insufficient to assess whether deleterious effects may occur in pregnancy during the use of  Orgaran Danaparoid Sodium.

 

Caution should be exercised when prescribing to pregnant women. If alternative antithrombotic treatment is unacceptable for medical reasons (e.g. HIT patients) Danaparoid Sodium can be used.

 

Lactation
In five cases in which breast milk samples were tested for anti-Xa activity, all showed no or negligible amounts of anti-Xa activity (which would be hydrolyzed in the infant’s stomach and rendered harmless).
Although the data are limited, if alternative antithrombotic treatment is unacceptable for medical reasons (e.g. HIT patients) Danaparoid Sodium can be used during lactation.


4.7       Effects on Ability to Drive and Use Machines

Orgaran Danaparoid Sodium is not known to have any effect on the ability to drive and use machines.

 

4.8       Undesirable Effects

Antibody induced thrombocytopenia, as can be caused by (low molecular weight) heparin, was observed in rare cases during the use of Orgaran Danaparoid Sodium, but only in patients who were already sensitised to either heparin or low molecular weight heparin (see section 4.4).

 

All above terms in this section and synonym terms (with same or less severity) coded with the MedDRA dictionary are considered as ‘listed’.

 

All hemorrhages are listed adverse events for Orgaran Danaparoid Sodium. This also means that symptoms or signs which are clearly directly related to a hemorrhage (e.g. anaemia, decreased Hb, rbc, hematocrit, faintness, tiredness, tamponade) are listed adverse events.



4.9       Overdose

 

In the event of serious bleeding other than caused by a surgical error, Orgaran Danaparoid Sodium 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 Danaparoid Sodium  the relevance for the reversal of the bleeding is not clear and therefore cannot be recommended.  The effects of Orgaran Danaparoid Sodium on anti-Xa activity cannot be antagonized with any known agent at this time.



5.1       Pharmacodynamic Properties


Orgaran Danaparoid Sodium shows low cross-reactivity (<10%) with the heparin induced antibody. This can be explained by the absence of heparin in Orgaran Danaparoid Sodium and its low degree of sulphation (see section 4.4).



6.2       Incompatibilities

 

When administered as an intravenous bolus or infusion,  Orgaran Danaparoid Sodium should be given separately and not mixed with other drugs.  However, Orgaran  Danaparoid Sodium is compatible with, and therefore can be added to, infusions of saline, dextrose or dextrose-saline.




10. DATE OF REVISION OF THE TEXT

01/ 20105 Nov 2015

Reasons for adding or updating:

  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:11-04-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Updated file with date of revison added

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): NO