BeneFIX 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
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):
Amount nonacog alfa (IU/ml)
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
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
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
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
Any unused product or waste material should be disposed of in accordance with local
Contra-indications: Hypersensitivity to the active substance or to any of the
excipients. Known allergic reaction to hamster proteins.
Special Warnings and Precautions:
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
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 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.
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
In patients with existing cardiovascular risk factors, substitution therapy with FIX
may increase the cardiovascular risk.
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.
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
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;
Uncommon: Visual impairment
Common: Phlebitis; flushing, Uncommon: Hypotension, Frequency unknown:
Superior vena cava syndrome; deep vein thrombosis; thrombosis; thrombophlebitis
Respiratory, thoracic and mediastinal disorders:
Very common: Cough
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
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.
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
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
Basic NHS Cost: 60.7p per IU.
250 IU: £151.80, 500 IU: £303.60, 1000 IU: £607.20, 2000 IU: £1214.40, 3000IU:
For further information and details of other side effects see Summary of Product
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