Prescribing Information

Summary of Prescribing Information

BeneFIX® (Nonacog alfa) Summary of Prescribing Information 

PRESENTATION: BeneFIX® contains Nonacog alfa (recombinant coagulation factor IX). BeneFIX® is supplied in kits that include single-use vials that contain nominally 250 IU, 500 IU, 1000 IU or 2000 IU, 3000 IU powder and solvent for solution for injection.

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

DOSAGE AND ADMINISTRATION: Treatment should be initiated under supervision of physician experienced in treatment of hemophilia. The dosage and duration of substitution therapy depends on severity of factor IX deficiency, location and extent of bleeding, and patient's clinical condition.  Number of units of factor IX administered is expressed in International Units (IU). Factor IX activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (IU)  (relative to an international standard for factor IX in plasma). One IU  of factor IX activity is equivalent to that quantity of factor IX in one mL of normal human plasma. 

Dosing for Bleeding and Surgery:  Calculation of  required dose of Nonacog alfa (recombinant coagulation factor IX) can be based on finding that one unit of factor IX activity per kg body weight is expected to increase circulating level of factor IX, an average of 0.8 IU/dL (range from 0.4 to 1.4 IU/dL) in patients  ≥ 12 years. Required dose is determined using  following formula: Number of Factor IX IU required = body weight (kg) x desired factor IX rise (IU/dL or % of normal)  x reciprocal of observed recovery. In case of following hemorrhagic events, factor IX activity should not fall below given plasma activity levels (in % of normal or in IU/dl) in the corresponding period. The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case. 

Dosage for Prophylaxis: Nonacog alfa (recombinant coagulation factor IX) may be administered for long term prophylaxis against bleeding in patients with hemophilia B. In a clinical study for routine secondary prophylaxis the average dose for previously treated patients (PTP) was 40 IU/kg (range 13 to 78 IU/kg) at intervals of 3 to 4 days. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary. For long term prophylaxis against bleeding, the recommended regimen is 100 IU/kg once weekly. Children (<12 years) have lower recovery, shorter half-life and higher clearance (based on per kg body weight) as compared to adolescents and adults. Adjust dosing regimen (dose or frequency) based on the patient’s clinical response. 

Administration: Nonacog alfa (recombinant coagulation factor IX) is administered by intravenous infusion after reconstitution of the lyophilized powder for solution for injection with sterile 0.234% sodium chloride solution. Nonacog alfa (recombinant coagulation factor IX) should be administered at a slow infusion rate. In most  cases, an infusion rate of up to 4 mL per minute has been used. Rate of administration should be  determined by patient’s comfort level. If any suspected hypersensitivity reaction takes place rate of infusion should be decreased or infusion should be stopped.

Special populations: Pediatric: There is limited documentation of on-demand treatment and surgery in paediatric patients less than 6 years of age treated with Nonacog alfa (recombinant coagulation factor IX).  Mean dosage (± standard deviation) for prophylaxis was 63.7 (± 19.1) IU/kg at intervals of 3 to 7 days. In younger patients, shorter dosage intervals or higher doses may be necessary. 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, in order to adjust doses as appropriate.

Pregnancy and Lactation: 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 breast-feeding only if clearly indicated. Effect of Nonacog alfa (recombinant coagulation factor IX) on fertility has not been established.

Elderly Population (≥ 65 years of age): Clinical studies of Nonacog alfa (recombinant coagulation factor IX) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. As with any patient receiving Nonacog alfa (recombinant coagulation factor IX), dose selection for an elderly patient should be individualized.

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

WARNINGS AND PRECAUTIONS: Hypersensitivity; Allergic-type hypersensitivity reactions are possible with Nonacog alfa (recombinant coagulation factor IX). The product contains traces of hamster proteins. Potentially life-threatening anaphylactic/anaphylactoid reactions have occurred with factor IX products, including Nonacog alfa (recombinant coagulation factor IX). If hypersensitivity symptoms occur, administration of Nonacog alfa (recombinant coagulation factor IX) has to be discontinued immediately and an appropriate treatment has to be  initiated.  Post discontinuation patient should immediately contact their physician. Patients should be informed of early signs of hypersensitivity reactions including difficult breathing, shortness of breath swelling, hives, generalized urticaria, itching, tightness of the chest, bronchospasm, laryngospasm, wheezing, hypotension, blurred vision, and anaphylaxis.  In some cases, these reactions may be severe anaphylaxis and alternative haemostatic measures should be considered.

Inhibitors; Inhibitors are an uncommon event in previously treated patients (PTPs) receiving factor IX-containing products. As one PTP treated with Nonacog alfa (recombinant coagulation factor IX)  developed a clinically relevant low responding inhibitor during clinical studies and experience on antigenicity with recombinant factor IX is still limited, patients treated with Nonacog alfa (recombinant coagulation factor IX) should be carefully monitored for the development of factor IX inhibitors that should be titrated in Bethesda Units using appropriate biological testing. There have been reports in literature showing a correlation between occurrence of a factor IX inhibitor and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated for 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.  

Thrombosis; Risk of thrombosis and disseminated intravascular coagulation (DIC) should be recognised. Since use of factor IX complex concentrates has  been associated with development of thromboembolic complications, use of factor IX-containing products may be potentially hazardous in patients with signs of fibrinolysis and in patients with DIC.  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. Benefit of Nonacog alfa (recombinant coagulation factor IX) should be weighed against risk.

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 haemophilia B patients with factor IX inhibitors and a history of allergic reaction.  Safety and efficacy of Nonacog alfa (recombinant coagulation factor IX) for immune tolerance induction is not established.  

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

ADVERSE REACTIONS: The very common  adverse reactions include headache, Cough and Pyrexia. Common side effects are  as follows  hypersensitivity, dizziness , dysgeusia , phlebitis flushing, rash, vomiting , nausea, urticaria , chest discomfort, infusion site reaction and infusion site pain  If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the medicinal product immediately and contact their physician.

Special precautions for storage and disposal Store between 2 - 30°C. Do not freeze The reconstituted product does not contain a preservative and should be used immediately, but no longer than 3 hours after reconstitution. Chemical and physical in-use stability has been demonstrated for 3 hours at temperatures up to 25⁰C. 

Adapted from: Approved local product document, Nonacog alfa (recombinant coagulation factor IX) BeneFIX®: BeneFIX®Injection; LPDBEN092021

Trademark Owner: Wyeth LLC, USA. Licensed User: Pfizer Products India Pvt. Ltd. India