BeneFIX prescribing information

PRESCRIBING INFORMATION

 

Before prescribing BeneFIX please refer to full Summary of Product Characteristics.

 

BeneFIX powder and solvent for solution for injection, nonacog alfa

(recombinant coagulation factor IX). Available in strengths 250, 500, 1000, 2000

and 3000 IU

 

UK

Prescribing Information:

Presentation: Each vial of powder for solution for injection contains nominally 250,

500, 1000, 2000 or 3000 IU nonacog alfa. When reconstituted with the accompanying

5 ml 0.234% sodium chloride solution, each ml of the product contains approximately

the following amounts of nonacog alfa (IU/ml):

 

Strength (IU)

Amount nonacog alfa (IU/ml)

250

50

 

500

100

 

1000

200

 

2000

400

 

3000

600

 

 

Indications: Treatment and prophylaxis of bleeding in patients with haemophilia B

(congenital factor IX deficiency).

 

BeneFIX can be used for all age groups.

 

Dosage and Administration: Treatment should be under the supervision of a

physician experienced in the treatment of haemophilia.

Dosage and duration of the substitution therapy depend on the severity of the factor

IX deficiency, on the location and extent of bleeding, and the patient's clinical

condition.

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 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.

In some cases, especially in younger patients, shorter dosage intervals or higher doses

may be necessary.

There is limited documentation of on-demand treatment and surgery in paediatric

patients less than 6 years of age treated with BeneFIX.

Clinical studies of BeneFIX 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 BeneFIX, dose selection for an elderly patient should be

individualised.

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. This is of importance particularly when changing

the laboratory and/or reagents used in the assay.

BeneFIX is administered by IV infusion after reconstitution of the lyophilised powder

for solution for injection with 0.234% sodium chloride.

The reconstituted solution does not contain a preservative and should be used

immediately, but no longer than 3 hours after reconstitution.

Only the provided infusion set should be used.

BeneFIX should be administered at a slow infusion rate. In most of the cases, an

infusion rate of up to 4 ml per minute has been used. The rate of administration

should be determined by the patient’s comfort level. Administration by continuous

infusion has not been approved and is not recommended.

If any suspected hypersensitivity reaction takes place that is thought to be related to

the administration of BeneFIX, the rate of infusion should be decreased or the

infusion stopped.

There have been reports of agglutination of red blood cells in the tube/syringe with

the administration of BeneFIX. No adverse events have been reported in association

with this observation. To minimize the possibility of agglutination, it is important to

limit the amount of blood entering the tubing. Blood should not enter the syringe. If

agglutination of red blood cells in the tubing/syringe is observed, discard all this

material (tubing, syringe and BeneFIX solution) and resume administration with a

new package.

Any unused product or waste material should be disposed of in accordance with local

requirements.

 

Contra-indications: Hypersensitivity to the active substance or to any of the

excipients. Known allergic reaction to hamster proteins.

 

Special Warnings and Precautions:

Hypersensitivity :

Allergic-type hypersensitivity reactions are possible with BeneFix. The product

contains traces of hamster proteins. Potentially life-threatening

anaphylactic/anaphylactoid reactions have occurred with factor IX products, including

BeneFIX. 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 early signs of hypersensitivity reactions including

difficult breathing, shortness of breath, swelling, hives, generalised urticaria itching,

tightness of the chest, bronchospasm, laryngospasm, wheezing, hypotension, blurred

vision, and anaphylaxis. In some cases, these reactions have progressed to severe

anaphylaxis.

Because of the risk of allergic reactions with factor IX concentrates, 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.

Inhibitors

Inhibitors are an uncommon event in previously treated patients (PTPs) receiving

factor IX-containing products. As one PTP treated with BeneFIX developed a

clinically relevant low responding inhibitor during clinical studies and experience on

antigenicity with recombinant factor IX is still limited, patients treated with BeneFIX

should be carefully monitored for the development of factor IX inhibitors that should

be titrated in Bethesda Units using appropriate biological testing.

 

Thrombosis

Although BeneFIX contains only factor IX, the risk of thrombosis and disseminated

intravascular coagulation (DIC) should be recognised. Since the use of factor IX

complex concentrates has historically been associated with the development of

thromboembolic complications, the 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,

with appropriate biological testing should be initiated when administering BeneFIX to

post-operative patients, new-born infants, patients at risk of thrombotic phenomena or

DIC, or with liver disease.

The safety and efficacy of BeneFIX administration by continuous infusion have not

been established. There have been post-marketing reports of thrombotic events,

including life-threatening superior vena cava (SVC) syndrome in critically ill new

born infants, while receiving continuous-infusion BeneFIX through a central venous

catheter.

 

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. The safety and efficacy of using BeneFIX for immune tolerance induction

has not been established.

 

Special populations

Sufficient data have not been obtained from clinical studies on the treatment of

previously untreated patients (PUPs), with BeneFIX.

In each of these situations, the benefit of treatment with BeneFIX should be weighed

against the risk of these complications.

 

It is strongly recommended that every time BeneFIX 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. Patients can affix one of

the peel off labels found on the vial to document the batch number in their diary or for

reporting any side effects.

 

Interactions: No interactions of human coagulation factor IX (rDNA) products with

other medicinal products have been reported.

 

Fertility, 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 lactation only if

clearly indicated.

The effect of BeneFIX on fertility has not been established.

 

Side Effects: Adverse events are presented 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), not known (cannot be estimated from the

available data). The adverse reactions listed below were reported in clinical trials of

previously treated patients and identified in postmarketing use. The frequencies are

based on all causality treatment emergent adverse events in pooled clinical trials with

224 subjects.Within each frequency grouping, adverse reactions are presented in order

of decreasing seriousness.

 

Infections and infestations

Uncommon: Infusion-site cellulitis

 

Blood and lymphatic system disorders

Uncommon: Factor IX inhibition

 

Immune system disorders

Common: Hypersensitivity; Frequency unknown: Anaphylactic reaction

 

Nervous system disorders

Very common: Headache; Common: Dizziness; Dysgeusia; Uncommon: Somnolence;

tremor

 

Eye disorders

Uncommon: Visual impairment

 

Cardiac disorders

Uncommon: Tachycardia

 

Vascular disorders

Common: Phlebitis; flushing, Uncommon: Hypotension, Frequency unknown:

Superior vena cava syndrome; deep vein thrombosis; thrombosis; thrombophlebitis

 

Respiratory, thoracic and mediastinal disorders:

Very common: Cough

 

Gastrointestinal disorders:

Common: Vomiting; nausea

 

Skin and subcutaneous tissue disorders:

Common: Rash; urticaria

 

Renal and urinary disorders:

Uncommon: Renal infarct

 

General disorders and administration site conditions:

Very common: Pyrexia, Common: Chest discomfort; infusion site reaction; infusion

site pain, Frequency unknown: Inadequate therapeutic response

 

Investigations

Frequency unknown Inadequate factor IX recovery

 

If any suspected hypersensitivity reaction takes place that is thought to be related to

the administration of BeneFIX see posology and warnings and precautions.

 

Paediatric population

Allergic reactions might be experienced more frequently in children than in adults.

There is insufficient data to provide information on inhibitor incidence in PUPs (see

pharmacodynamics properties).

 

Legal Category: POM.

 

Package Quantities: The 250 IU, 500 IU, 1000 IU, 2000 & 3000 IU packs consist of a

vial of BeneFIX, a pre-filled syringe of solvent, a sterile vial adapter reconstitution

device, a sterile infusion set, two alcohol swabs, a plaster and a gauze pad.

 

Product Licence Number:

EU/1/97/047/004 – 250 IU

EU/1/97/047/005 – 500 IU

EU/1/97/047/006 – 1000 IU

EU/1/97/047/007 – 2000 IU

EU/1/97/047/008- 3000IU

 

Basic NHS Cost: 60.7p per IU.

250 IU: £151.80, 500 IU: £303.60, 1000 IU: £607.20, 2000 IU: £1214.40, 3000IU:

£1821.60

 

For further information and details of other side effects see Summary of Product

Characteristics

Further information is available on request from Medical Information Department at

Pfizer Limited, Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS, UK.

 

Marketing Authorisation Holder:

Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

 

Date of Preparation: 09/2018

 Adverse events should be reported. Reporting forms and information can be

found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the

Google Play or Apple App Store. Adverse events should also be reported to

Pfizer Medical Information on 01304 616161

 Ref: BF 8_0

PP-BEN-GBR-0273. June 2019