GENERIC NAME: Recombinant coagulation factor IX; Nonacog alfa.
 

PRESENTATION: BeneFIX 250 IU, 500 IU, 1000 IU powder and solvent for solution for injection. White/almost white powder and clear and colorless solvent. The potency (IU) is determined using the European Pharmacopoeia one-stage clotting assay.
 

INDICATIONS: Treatment and prophylaxis of bleeding in patients with hemophilia B (congenital factor IX deficiency).

DOSAGE AND ADMINISTRATION: Treatment should be under the supervision of a physician experienced in the treatment of hemophilia. During treatment, appropriate determination of factor IX levels is advised. Individual patients may vary in their response to factor IX. Dose and duration of the substitution therapy depend on the severity of the factor IX deficiency, on the location and extent of bleeding, and on the patient's clinical condition. The number of units of factor IX administered is expressed in International Units (IU). One IU of factor IX activity is equivalent to that quantity of factor IX in one mL of normal human plasma. Close monitoring of factor IX plasma activity should be performed as clinically indicated, as well as calculation of pharmacokinetic parameters such as recovery and half-life, to adjust doses as appropriate. BeneFIX is administered by IV infusion after reconstitution of the lyophilized powder with sterile 0.234% sodium chloride solution. Only the provided infusion set should be used. BeneFIX should be administered at a slow infusion rate (up to 4 mL/min). Administration by continuous infusion is not recommended.
 

On demand treatment: The required dose is determined using the following formula: Number of factor IX IU required = body weight (in kg) X desired factor IX increase (%) or (IU/dL) X reciprocal of observed recovery. The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case. The following table can be used to guide dosing in bleeding episodes and surgery
 

Prophylaxis: BeneFIX may be administered for long term prophylaxis against bleeding in patients with hemophilia B. The average dose for previously treated patients (PTP) is 40 IU/kg (range 13 to 78 IU/kg) at intervals of 3 to 4 days. Shorter dosage intervals or higher doses may be necessary in some cases, especially in younger patients.
 

SPECIAL POPULATION: BeneFIX can be used for all age groups. There is limited documentation of on-demand treatment and surgery in pediatric patients less than 6 years of age treated with BeneFIX. Dose selection for an elderly patient should be individualized. The safety and efficacy of using BeneFIX for immune tolerance induction has not been established. Sufficient data have not been obtained from clinical studies on the treatment of previously untreated patients (PUPs) with BeneFIX. Factor IX should be used during pregnancy and breast-feeding only if clearly indicated. The effect of BeneFIX on fertility has not been established.
 

CONTRAINDICATIONS: * Hypersensitivity to the active substance or to any of the excipients. * Known allergic reaction to hamster proteins.
 

Patients experiencing allergic reactions should be evaluated for the presence of an inhibitor. Because of the risk of allergic reactions with factor IX concentrates, the initial administrations of factor IX should be performed under medical observation where proper medical care for allergic reactions could be provided.
 

Inhibitors: Inhibitors are an uncommon event in PTPs receiving factor IX-containing products. Patients treated with BeneFIX should be carefully monitored for the development of factor IX inhibitors. If such inhibitors occur, the condition will manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialized hemophilia center be contacted.
 

Thrombosis: There is a potential risk of thromboembolic episodes following the administration of factor IX products. The use of factor IX- containing products may be potentially hazardous in patients with signs of fibrinolysis and in patients with disseminated intravascular coagulation (DIC).
 

Cardiovascular events: In patients with existing cardiovascular risk factors, substitution therapy with FIX may increase the cardiovascular risk.
 

Nephrotic syndrome: Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with factor IX inhibitors and a history of allergic reaction.
 

Sodium content: After reconstitution, BeneFIX contains 0.2 mmol sodium (4.6 mg) per vial, that is to say essentially ‘sodium-free’. Depending on body weight of the patient and posology of BeneFIX, patients could receive multiple vials. This should be taken into consideration if the patient is on a low salt diet.
 

DRUG INTERACTIONS: No interactions of human coagulation factor IX (rDNA) products with other medicinal products have been reported.
 

OVERDOSE: No symptoms of overdose have been reported with recombinant coagulation factor IX products.
 

ADVERSE REACTION: Very common adverse reactions (≥ 1/10) include Headache, Cough, and Pyrexia. Common adverse reactions (≥ 1/100 to < 1/10) include hypersensitivity, Dizziness, Dysgeusia, Phlebitis, Flushing, Vomiting, Nausea, Rash, Urticaria, Chest discomfort, infusion-site reaction, and infusion-site pain.
 

PHARMACEUTICAL PRECAUTIONS: Keep out of the sight and reach of children.
 

Before reconstitution: Shelf life is 2 years. Store at 2-30°C. Do not freeze. Do not use BeneFIX after the expiry date which is stated on the Vial label after EXP:.
 

After reconstitution: The reconstituted product does not contain a preservative and should be used immediately, but no longer than 3 hoursafter reconstitution. Chemical and physical in-use stability has been demonstrated for 3 hours at temperatures up to 25°C.
 

REFERENCE: BeneFIX 250 500 1000 IU LPD (Date of Revision: Nov-20) Egypt
 

DATE OF THIS DOCUMENT: 13-Jan-22

-BeneFIX Egyptian Drug Authority leaflet approval date: 14/11/2021.
 

DIC: disseminated intravascular coagulation; FIX: factor IX; IU: international unit; PTP: previously treated patient.

Reference:

1. Benefix Egyptian Drug Authority leaflet approval date: 14/11/2021. Revision Date: November 2020.