- factor IX
POM: Prescription only medicine
This information is intended for use by health professionals
Previously untreated patientsThe safety and efficacy of OCTANINE in previously untreated patients have not yet been established.
Treatment monitoringDuring the course of treatment, appropriate determination of factor IX levels is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor IX, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor IX activity) is indispensable.
PosologyDose and duration of the substitution therapy depend on the severity of the factor IX deficiency, on the location and extent of the bleeding and on the patient's clinical condition.The number of units of factor IX administered is expressed in International Units (IU), which are related to the current WHO standard for factor IX products. Factor IX activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to an International Standard for factor IX in plasma).One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX in one ml of normal human plasma.
On demand treatmentThe calculation of the required dosage of factor IX is based on the empirical finding that 1 International Unit (IU) factor IX per kg body weight raises the plasma factor IX activity by 1 % of normal activity. The required dosage is determined using the following formula:Required units = body weight (kg) x desired factor IX rise (%) (IU/dl) x 0.8The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case. In the case of the following haemorrhagic events, the factor IX activity should not fall below the given plasma activity level (in % of normal) in the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:
|Degree of haemorrhage / Type of surgical procedure||Factor IX level required (%) (IU/dl)||Frequency of doses (hours) / Duration of therapy (days)|
|Early haemarthrosis, muscle bleeding or oral bleeding||20 - 40||Repeat every 24 hours. At least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved.|
|More extensive haemarthrosis, muscle bleeding or haematoma||30 - 60||Repeat infusion every 24 hours for 3 - 4 days or more until pain and acute disability are resolved.|
|Life-threatening haemorrhages||60 - 100||Repeat infusion every 8 to 24 hours until threat is resolved.|
|Minor Surgery including tooth extraction||30 - 60||Every 24 hours, at least 1 day, until healing is achieved.|
|Major Surgery||80 100 (pre-and/post-operative)||Repeat infusion every 8-24 hours until adequate wound healing, then therapy for at least another 7 days to maintain a factor IX activity of 30% to 60% (IU/dl).|
ProphylaxisFor long term prophylaxis against bleeding in patients with severe haemophilia B, the usual doses are 20 to 40 IU of factor IX per kilogram of body weight at intervals of 3 to 4 days. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.
Continuous infusionThere is not enough data available to recommend continous infusion of OCTANINE in surgical procedures.
Paediatric PopulationIn the study conducted in 25 children under 6 years of age, the median dose administered per exposure day was similar for prophylaxis and treatment of bleeding, i.e. 35 to 40 IU/kg BW.
Method of administrationIntravenous use. It is recommended not to administer more than 2 - 3 ml per minute.For instructions on reconstitution of the medicinal product before administration, see section 6.
HypersensitivityAllergic type hypersensitivity reactions are possible with OCTANINE. The product contains traces of human proteins other than factor IX and heparin. If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the medicinal product immediately and contact their physician. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.In case of shock, standard medical -treatment for shock should be implemented.
InhibitorsAfter repeated treatment with human coagulation factor IX products, patients should be monitored for the development of neutralising antibodies (inhibitors) that should be quantified in Bethesda Units (BU) using appropriate biological testingThere have been reports in the literature showing a correlation between the occurrence of a factor IX inhibitor and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated for the presence of an inhibitor. It should be noted that patients with factor IX inhibitors may be at an increased risk of anaphylaxis with subsequent challenge with factor IX. Because of the risk of allergic reactions with factor IX products, the initial administrations of factor IX should, according to the treating physician's judgement, be performed under medical observation where proper medical care for allergic reactions could be provided
ThromboembolismBecause of the potential risk of thrombotic complications, clinical surveillance for early signs of thrombotic and consumptive coagulopathy should be initiated with appropriate biological testing when administering this product to patients with liver disease, to patients post-operatively, to new-born infants, or to patients at risk of thrombotic phenomena or disseminated intravascular coagulation (DIC). In each of these situations, the benefit of treatment with OCTANINE should be weighed against the risk of these complications
Cardiovascular eventsIn patients with existing cardiovascular risk factors, substitution therapy with FIX may increase the cardiovascular risk.
Catheter-related complicationsIf a central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.
Transmissible agentsStandard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.The measures taken are considered effective for enveloped viruses such as human immunodeficieny virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and for the non-enveloped virus hepatitis A virus (HAV). The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia). Appropriate vaccination (hepatitis A and B) should be considered for patients in regular / repeated receipt of human plasma-derived factor IX concentrates.It is strongly recommended that every time that OCTANINE is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Patients on controlled sodium dietThis medicinal product contains up to 3 mmol (or 69 mg) sodium for 1 vial OCTANINE 500 IU and up to 6 mmol (or 138 mg) sodium for 1 vial OCTANINE 1000 IU per dose. To be taken into consideration by patients on a controlled sodium diet.
Paediatric populationThe listed warnings and precautions apply both to adults and children.
Summary of safety profileHypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed infrequently in patients treated with factor IX containing products. In some cases, these reactions have progressed to severe anaphylaxis, and they have occurred in close temporal association with development of factor IX inhibitors (see also 4.4). Nephrotic syndrome has been reported following attempted immune tolerance induction in haemophilia B patients with factor IX inhibitors and a history of allergic reactionOn rare occasions, fever has been observed.Patients with haemophilia B may develop neutralising antibodies (inhibitors) to factor IX. If such inhibitors occur, the condition will manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia centre be contacted. A study in 25 children with Haemophilia B was conducted, thereof 6 patients were previously untreated and had a median no. of exposure days to OCTANINE of 38 (range 8-90). All patients had a factor IX inhibitor level of <0.4 BU at baseline. No inhibitor was observed during the study.There is a potential risk of thromboembolic episodes following the administration of factor IX products, with a higher risk for low purity preparations. The use of low purity factor IX products has been associated with instances of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism. The use of high purity factor IX is rarely associated with such adverse reactions.For safety with respect to transmissible agents, see 4.4.Tabulated list of adverse reactionsThe table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level).Frequencies have been evaluated according to the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
|MedDRA Standard System Organ Class||Adverse reactions|
|Immune system disorders||hypersensitivity||anaphylactic shock|
|Vascular disorders||thromboembolic event*|
|Renal and urinary disorders||nephrotic syndrome|
|General disorders and administration site conditions||heparin induced thrombocytopenia pyrexia|
|Investigations||anti factor IX antibody positive|
Description of selected adverse reactionsDue to the amount of heparin contained, a sudden, allergy induced reduction of the blood platelet count below 100,000/µl or 50% of the starting count may be observed (thrombocytopenia type II) in rare cases. In patients not previously hypersensitive to heparin, this decrease in thrombocytes may occur 6-14 days after the start of treatment. In patients with a previous heparin hypersensitivity this reduction may set in a few hours after treatment.This severe form of blood platelet reduction may be accompanied by, or result in, arterial and venous thrombosis, thromboembolism, severe clotting disorder (consumptive coagulopathy), skin necrosis in the area of injection, flea bite-like bleeding (petechial haemorrhages), purpura and tarry stool. If the specified allergic reactions are observed, the injections with OCTANINE should be stopped immediately. The patient should be advised not to use any heparin containing medicinal products in the future. Because of this rarely occurring heparin induced effect on the blood platelets, the patient's blood platelet count should be monitored closely, especially at the initiation of treatment.
Paediatric populationFrequency, type and severity of adverse reactions in children are expected to be the same as in adults.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
United KingdomYellow Card SchemeWebsite: www.mhra.gov.uk/yellowcard
Paedriatric populationA study in 25 children below 6 years of age was conducted. Thereof, 6 patients were previously untreated. The recovery after administration of >25 IU of OCTANINE/kg body weight was investigated during the first 3 months of treatment and after 12-24 months. The incremental recovery (geometric mean ± s.d., one-stage assay, actual potency) was calculated to be 0.8±1.4 and 0.9±1.3 %/IU/kg at the 1st and the 2nd assessment, respectively.
|Incremental Recovery [IU/dl]/[IU/kg]||1.2||1.3||0.5||0.8||2.4|
|AUC*norm (IU x dl-1 x h x IU-1 x kg)||32.4||37.7||13.0||24.5||64.0|
|Clearance (ml x h-1 x kg)||3.1||2.9||0.9||1.6||4.1|
Please read all the instructions and follow them carefully!Do not use Octanine after expiry date given on the label and carton.During the procedure described below, sterility must be maintained!The solution in the syringe should be clear or slightly pearly shimmery. Do not inject solutions that are cloudy or have deposits.Use the prepared solution immediately, to prevent microbial contamination.Only use the injection set provided. The use of other injection/infusion equipment can cause additional risks and treatment failure.
Instructions for preparing the solution:
|1. Do not use the product directly from the refrigerator. Allow the solvent and the powder in the closed vials to reach room temperature.|
|2. Remove the flip off caps from both vials and clean the rubber stoppers with one of the provided alcohol swabs.|
|3. The Mix2vial is depicted in Fig. 1. Place the solvent vial on an even surface and hold it firmly. Take the Mix2Vial and turn it upside down. Place the blue part of the Mix2Vial on top of the solvent vial and press firmly down until it snaps (Fig. 2+3).|
|4. Place the powder vial on an even surface and hold it firmly. Take the solvent vial with the attached Mix2Vial and turn it upside down. Place the transparent part on top of the powder vial and press firmly down until it snaps (Fig. 4). The solvent flows automatically into the powder vial.|
|5. With both vials still attached, gently swirl the powder vial until the product is dissolved. The dissolving is completed in less than 10 minutes at room temperature. Slight foaming might occur during preparation. Unscrew the Mix2Vial into two parts (Fig. 5). Foaming will disappear. Dispose the empty solvent vial with the blue part of the Mix2Vial.|
Instructions for injection:As a precaution, your pulse rate should be taken before and during the injection. If a marked increase in your pulse rate occurs, reduce the injection speed or interrupt the administration for a short time.1. Attach the syringe to the transparent part of the Mix2Vial. Turn the vial upside down and draw the solution into the syringe (Fig. 6).The solution in the syringe should be clear or slightly pearly shimmery. Once the solution has been transferred, firmly hold the plunger of the syringe (keeping it facing down) and remove the syringe from the Mix2Vial (Fig. 7). Dispose the Mix2Vial and the empty vial. 2. Clean the chosen injection site with one of the provided alcohol swabs.3. Attach the provided injection needle to the syringe4. Insert the injection needle into the chosen vein. If you have used a tourniquet to make the vein easier to see, this tourniquet should be released before you start injecting OCTANINE.No blood must flow into the syringe due to the risk of formation of fibrin clots.5. Inject the solution into the vein at a slow speed, not faster than 2-3 ml per minute.If you use more than one vial of OCTANINE powder for one treatment, you may use the same injection needle and syringe again. The Mix2Vial is for single use only.Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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