IDELVION

/ Genmedix

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia B.
Previously untreated patients: The safety and efficacy of IDELVION in previously untreated patients have not yet been established.
Treatment monitoring: During 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 responses 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.
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining Factor IX activity in patients’ blood samples, plasma factor IX activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. Measurement with a one-stage clotting assay using a kaolin based aPTT reagent or Actin FS aPTT reagent will likely result in an underestimation of activity level. This is of importance particularly when changing the laboratory and/or reagents used in the assay.
Posology: Dose 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 treatment: The calculation of the required dose of factor IX is based on the empirical finding that 1 International Unit (IU) factor IX per kg body weight is expected to increase the circulating level of factor IX by an average of 1.3 IU/dl (1.3 % of normal) in patients ≥ 12 years of age and by 1.0 IU/dl (1.0 % of normal) in patients < 12 years of age. The required dose is determined using the following formulae:
Required dose (IU) = body weight (kg) x desired factor IX rise (% of normal or IU/dl) x {reciprocal of observed recovery (IU/kg per IU/dl)}
Expected factor IX rise (IU/dl or % of normal) = Dose (IU) x Recovery (IU/dl per IU/kg)/body weight (kg)
The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
Patients < 12 years of age: For an incremental recovery of 1 IU/dl per 1 IU/kg, the dose is calculated as follows:
Dose (IU) = body weight (kg) x desired factor IX increase (IU/dl) x 1 dl/kg
Example
1. A peak level of 50 % of normal is required in a 20 kg patient with severe haemophilia B. The appropriate dose would be 20 kg x 50 IU/dl x 1 dl/kg = 1000 IUs.
2. A dose of 1000 IUs of IDELVION, administered to a 25 kg patient, should be expected to result in a peak post-injection factor IX increase of 1000 IUs/25 kg x 1.0 (IU/dl per IU/kg) = 40 IU/dl (40 % of normal).
Patients ≥ 12 years of age: For an incremental recovery of 1.3 IU/dl per 1 IU/kg, the dose is calculated as follows:
Dose (IU) = body weight (kg) x desired factor IX increase (IU/dl) x 0.77 dl/kg
Example
3. A peak level of 50 % of normal is required in a 80 kg patient with severe haemophilia B. The appropriate dose would be 80 kg x 50 IU/dl x 0.77 dl/kg = 3080 IUs.
4. A dose of 2000 IUs of IDELVION, administered to a 80 kg patient, should be expected to result in a peak post-injection factor IX increase of 2000 IUs x 1.3 (IU/dl per IU/kg)/80 kg = 32.5 IU/dl (32.5 % of normal).
In the case of the following haemorrhagic events, the factor IX activity should not fall below the given plasma activity level (in % of normal or in IU/dl) in the corresponding period. Please refer to table 1 at the attached doctor’s leaflet for guide dosing in bleeding episodes and surgery.
Prophylaxis: For long-term prophylaxis against bleeding in patients with severe hemophilia B, the usual doses are 35 to 50 IU/kg once weekly.
Some patients who are well-controlled on a once-weekly regimen might be treated with up to 75 IU/kg on an interval of 10 or 14 days.
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.
After a bleeding episode during prophylaxis, patients should maintain their prophylaxis regimen as closely as possible, with 2 doses of IDELVION being administered at least 24 hours apart but longer as deemed suitable for the patient.
Paediatric population: For routine prophylaxis the recommended dose regimen for paediatric subjects is 35 to 50 IU/kg once weekly.
Method of administration: Intravenous use. The reconstituted preparation should be injected slowly intravenously at a rate comfortable for the patient up to a maximum of 5 ml/min.

Treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency).
IDELVION can be used for all age groups.

Hypersensitivity to the active substance (recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP)) or to any of the excipients.
Known allergic reaction to hamster protein.

Hypersensitivity: Allergic type hypersensitivity reactions are possible with IDELVION. The product contains traces of hamster proteins. 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. It is suggested that the initial administrations of factor IX should, according to the treating physician’s judgment, be performed under medical observation where proper medical care for allergic reactions could be provided.
In case of shock, standard medical treatment for shock should be implemented.
Inhibitors Formation of inhibitor to factor IX has been reported during factor replacement therapy with IDELVION in the treatment of haemophilia B. After 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 testing.
There 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 administration 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.
Thromboembolism: Because 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 DIC. In each of these situations, the benefit of treatment with IDELVION should be weighed against the risk of these complications.
Cardiovascular events: In patients with existing cardiovascular risk factors, substitution therapy with FIX may increase the cardiovascular risk.
Catheter-related complications: If a central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.
Paediatric population: The listed warnings and precautions apply both to adults and children.
Elderly: Clinical studies of IDELVION did not include subjects aged 65 and over. It is not known whether they respond differently from younger subjects.
Immune tolerance induction: The safety and efficacy of using IDELVION for immune tolerance induction has not been established.
Sodium content: This medicinal product contains up to 25.8 mg (1.13 mmol) sodium per dose (bodyweight 70 kg) if the maximal dose (15 ml = 6000 IU) is applied. To be taken into consideration by patients on a controlled sodium diet.
Record of use: It is strongly recommended that every time that IDELVION 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 medicinal product.

Hypersensitivity 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 rarely and may in some cases progress to severe anaphylaxis (including shock). In some cases, these reactions have progressed to severe anaphylaxis, and they have occurred in close temporal association with development of factor IX inhibitors. Nephrotic syndrome has been reported following attempted immune tolerance induction in haemophilia B patients with factor IX inhibitors and a history of allergic reaction.
With the use of factor IX products obtained from CHO cells very rarely development of antibodies to hamster protein 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. Inhibitor development was reported in an ongoing clinical study with previously untreated patients. Inhibitor development has been observed in previously treated patients in the post-marketing experience with IDELVION.
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.
See prescribing information for full details.

No interactions of human coagulation factor IX products with other medicinal products have been reported.

Animal reproduction studies have not been conducted with factor IX. Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy and breastfeeding is not available.
Therefore, factor IX should be used during pregnancy and lactation only if clearly indicated.
There is no information on the effects of factor IX on fertility.

No symptoms of overdose with IDELVION have been reported.

Storage: Do not store above 25°C.