INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo HAEMOSOLVEX FACTOR IX (Powder for Injection)

REGISTRATION NUMBER
W/30.3/191

PROPRIETARY NAME
(and dosage form):

HAEMOSOLVEX FACTOR IX (Powder for Injection)

DESCRIPTIVE NAME OF MEDICINE
Human
Factor IX Complex

PHARMACOLOGICAL CLASSIFICATION
A 30.3 Biologicals (Blood Fractions)

SCHEDULING STATUS
S4

COMPOSITION
Factor IX complex (prothrombin complex) is a lyophilised concentrate containing the following coagulation factors: factor II (prothrombin), factor VII (proconvertin), factor IX (Christmas factor) and factor X (Stuart-Prower factor).
Haemosolvex Factor IX is prepared from pooled fresh plasma donated by healthy, non-remunerated donors. Each unit of plasma has been individually tested and found non-reactive for hepatitis B surface antigen, antibodies to the hepatitis C virus and antibodies to the human immunodeficiency viruses, HIV-1 and HIV-2, using approved methods.
To reduce the risk of transmission of infective agents, selection of donors and donations by suitable measures is performed and removal and/or inactivation procedures are included in the production process. The manufacturing method includes a process of solvent detergent treatment developed to inactivate lipid-enveloped viruses. The efficacy of this process has been tested against hepatitis B, hepatitis C and HIV.
When each vial of the product is reconstituted with the 10 mL Water for Injection provided, the solution per vial, will contain factor IX 500 IU (50 IU/ml), factor II > 400 IU, factor VII > 65 IU and factor X > 400 IU.
The preparation has been tested and found negative for the presence of active thrombin. The product is stabilised with 10 IU heparin per ml. The reconstituted solution is isotonic with a sodium content of approximately 300 mmol/L.

IDENTIFICATION
Lyophilised powder:
A friable, off-white to light blue powder.
Reconstituted solution: The powder, when reconstituted with Water for Injection, forms a colourless to light blue solution, which may exhibit slight flocculation.

PHARMACOLOGICAL ACTION OF THE MEDICINE
Factor IX is a vitamin K-dependant clotting factor synthesised in the liver. Factor IX is part of the intrinsic pathway of blood coagulation and is required for the pathway’s completion. This pathway results ultimately in the conversion of prothrombin to thrombin and thereby facilitates the formation of a fibrin clot.
Haemosolvex Factor IX complex also contains vitamin K-dependant coagulation factors II, VII and X.
In anti-coagulant haemorrhage (e.g. coumarin drug overdose), the coumarin-derivative anticoagulants act indirectly in the liver by inhibiting the vitamin K-mediated gamma-carboxylation of precursor proteins, thus preventing the usage of these factors in the clotting cascade. The administration of factor IX complex concentrates containing additional vitamin K-dependant clotting factors, increases the plasma concentration of these clotting factors to overcome the effect of the anticoagulant.
Pharmacokinetics:
The plasma half-life of factor IX ranges from 16-30 hours. The plasma half-life of factor II ranges from 40-60 hours, factor VII from 3-6 hours, and factor X from 30-60 hours.

INDICATIONS
Haemosolvex Factor IX
may be used for the treatment of coagulation defects caused by either a congenital or an acquired deficiency of factor IX.
Congenital: Haemophilia B.
Acquired: The treatment of severe bleeding resulting from an overdose of oral coumarin-derivative anticoagulants.

CONTRA-INDICATIONS
This preparation is not intended for the treatment of haemophilia A (classical haemophilia) due to factor VIII deficiency.
Do not use the factor IX complex, unless the deficiency has been confirmed.
Factor IX complex is ineffective in bleeding due to heparin.
This product should not be administered to patients with a known allergic reaction to the product, or to those with a high risk of thrombosis or disseminated intravascular coagulation (DIC).
Factor IX complex should not be given in cases of liver damage with evident antithrombin III deficiency as coagulation activation with paradoxical haemorrhage occurs.

DOSAGE AND DIRECTIONS FOR USE
Warnings:
This preparation must be administered as a slow intravenous infusion over at least 2 minutes.
Measures to treat anaphylaxis, including adrenaline and corticosteroids, must be at hand when administering Haemosolvex Factor IX.
If a gel forms on reconstitution, the preparation must not be used.
Do not administer concomitantly with other medicines.
General dosing information:
Dissolve the contents of each vial before use by adding 10 mL Water for Injection (see reconstitution procedure).
Individualised dosage:
The dosage and duration of treatment is based on the patient’s body mass, type of haemorrhage, location of the bleed, type of surgery to be performed and the clinical picture.
Paediatric factor IX dose: Dose is calculated according to the body mass. Refer to the determination of dosage section.
The determination of the factor IX plasma level is useful initially in determining the dose required and thereafter in assuring whether adequate factor IX concentrations have been achieved and are being maintained.
Determination of the dosage:
The calculated required dosage for treatment is based on the empirical finding that 1 IU of factor IX per kg body weight raises the plasma factor IX activity by 0,8% of normal.
The required dosage is determined using the following formula (initial dose):
Required units (IU) = Body weight (kg) x desired factor IX increase (%) x 1,2
The amount to be administered and the frequency of administration should always be oriented towards clinical efficacy and therefore the recommended dosage regimens must be used as a guideline for therapy only. Longer or shorter periods and higher or lower levels of replacement therapy may be necessary.

Treatment guidelines
Haemorrhagic event (with examples) Therapeutically necessary plasma level of factor IX activity
Period during which it is necessary to maintain the therapeutic plasma level of factor IX activity
Minor:
Spontaneous early bleed;Minor oral bleeds;Nasal haemorrhage;Trauma without the signs of bleeding;Haematuria without pain.
30% At least one day, depending on the severity of the haemorrhage.
Major:
Oral bleeds (including molar tooth extraction and haemorrhage of the throat and tongue);
Full symptoms of haemarthrosis;
Haemorrhage in the calf or the forearm;
30-50% 3-4 days or until adequate wound healing (see ‘Pharmacokinetics’).
Mild trauma capitis;
Severe epistaxis;
Retroperitonal bleeding;
Trauma with bleeding;
Haematuria with pain.
Serious injuries;
Major operations;
Intracranial haemorrhage; Gastro-intestinal haemorrhage.
50% - 75% 3-4 days or until adequate wound healing (see ‘Pharmacokinetics’).
Anticoagulant haemorrhage 30% At least one day, depending on the severity of the haemorrhage.
Note:
The potential benefit of treatment with high doses (> 50%) of factor IX complex concentrate should be weighed against the risk of complications resulting from withholding administration.
Patients receiving high doses for 4-5 days of treatment should be carefully monitored for potential complications (see SIDE EFFECTS AND SPECIAL PRECAUTIONS).
If the patient is not responsive to therapy, consideration should be given to the presence of inhibitors (antibodies to factor IX).
Prevention of bleeding during and following surgical procedures:
Replacement therapy must be initiated one hour prior to the procedure. The factor IX level must be maintained high enough to prevent haemorrhage and promote epithelialisation until healing is complete and sutures are removed (see ‘Treatment guidelines’). Concurrent antifibrinolytic therapy to prevent or decrease bleeding during and following dental surgery may be required (see SIDE EFFECTS AND SPECIAL PRECAUTIONS).

RECONSTITUTION PROCEDURE
Read all instructions before commencing the reconstitution procedure. Use only the injection/infusion set supplied as Haemosolvex Factor IX must be administered via plastic syringes only and filtered before use.
1. Remove the plastic cap from the stopper of the product vial and swab the exposed rubber stopper with a suitable anti-bacterial agent.
2. Attach the FILTER NEEDLE (short metal needle) to the syringe. This must remain attached until just before infusion.
3. Open the diluent and draw up 10 mL of Water for Injection. Insert the filter needle, with syringe attached, through the stopper of the product vial.
4. The vacuum will draw the diluent into the vial. Rotate the vial to ensure complete wetting of the powder.
  Do not use the product if there is no vacuum present.
5. Gently swirl the vial until the powder is dissolved. Do not shake and avoid foaming. The reconstitution process should take 30 minutes at the most. Do not use if the solution is turbid or contains particulate matter or if a gel forms after reconstitution.
6. When the solution is ready for administration, after complete dissolution, pierce the stopper with the AIR VENT needle to release the remaining vacuum in the vial. Remove and discard the air vent needle.
7. Withdraw the contents of the vial into the syringe.
8. Remove the syringe and the filter needle from the vial. Invert the syringe, expel any air, then remove and discard the filter needle.
9. Attach the BUTTERFLY NEEDLE to the syringe.
10. Administer the solution as soon as possible after reconstitution but not more than three hours after reconstitution, as a slow intravenous infusion over at least 2 minutes
11. Discard any unused solution.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Allergic/anaphylactic type reactions, characterised by chills, fever and urticaria, may occur.
In the event of acute anaphylactic shock, the injection must be stopped immediately and appropriate treatment initiated.
Other adverse events such as nausea, vomiting, headache and flushing have been reported particularly following rapid administration. Factor IX complex concentrates have been associated with thrombo-embolic complications, with reports of thrombosis and intravascular coagulation in patients with liver disease. Myocardial infarction has occurred in patients receiving factor IX complex concentrates, and may be associated with high doses.
Infectious diseases due to the transmission of infectious agents cannot be totally excluded. Consideration should be given to appropriate vaccination of patients receiving human blood or plasma-derived medicinal products.
Dental:
Caution should be exercised when administering systemic antifibrinolytics in conjunction with factor IX complex as they may potentiate the thrombogenic effects of factor IX complex concentrates. Using the antifibrinolytic agent as an oral rinse, or delaying its use for 8 to 12 hours after administration of the concentrate, may minimise this complication.
Because of the potential risk of thrombo-embolic complications, caution should be exercised when administering Haemosolvex Factor IX to patients with a history of coronary heart disease or myocardial infarction, to patients with liver disease, to patients post-operatively, to neonates, or to patients at risk of thrombo-embolic episodes.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF TREATMENT
The use of high doses or prolonged continuous usage of factor IX complex concentrates, has been associated with instances of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism, due to accumulation of factors II and X. Therefore, in cases of overdosage, the development of thrombo-embolic complications or disseminated intravascular coagulation is enhanced in patients at risk of these complications.
Appropriate measures for the treatment of thrombo-embolic complications or disseminated intravascular coagulation should be initiated, should these occur.

PRESENTATION
500 IU:
One vial of a sterile, off-white to light blue dried powder, containing 500 IU factor IX complex in a clear glass, evacuated, 30 mL vial fitted with a rubber stopper and an aluminium closure. One 10 mL Water for Injection ampoule, a reconstitution set and an administration set are also provided.

STORAGE DIRECTIONS
Store below 25ºC.
Protect from light.
Keep out of reach of children.

NAME AND BUSINESS ADDRESS OF THE APPLICANT
NATIONAL BIOPRODUCTS INSTITUTE
Reg. No. 1994/002044/08
NPO Reg. No. 020-898-NPO

PRIVATE BAG X9043
PINETOWN
3600
10 EDEN ROAD
PINETOWN
3610
Telephone : (031) 719 6789        Telefax: (031) 708 5614

DATE OF PUBLICATION OF PACKAGE INSERT
01/91

2004/01P49

Updated on this site: June 2010
STILL CURRENT: August 2014
Source: Pharmaceutical Industry

Disclaimer:
Please note that the National Bioproducts Institute cannot be held responsible for the accuracy of the text. The package insert on the screen may not be the latest version. We therefore recommend that an alternative source of information be consulted, particularly when confirmation of dosages and indications are required. Please refer to the printed package inserts inside the packs, recognised reference books or alternatively, you may contact the NBI Information Centre at +27 (031) 714 6700 or +27 082 870 3705 or +27 082 320 3306
.
Email: info@nbisa.org.za

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2014