ADVERSE REACTIONS
See also CLINICAL PHARMACOLOGY: Clinical Studies.
As with the intravenous administration of any protein product, the following reactions may be observed after administration: headache, fever, chills, flushing, nausea, vomiting, lethargy, or manifestations of allergic reactions. Should evidence of an acute hypersensitivity reaction be observed, the infusion should be stopped promptly and appropriate counter measures and supportive therapy should beadministered.
During uncontrolled open-label clinical studies with BeneFIX® , Coagulation Factor IX (Recombinant), conducted in previously treated patients (PTPs), 131 adverse reactions with definite, probable, possible or unknown relation to BeneFIX® therapy were reported among 27 of 65 subjects (with some subjects reporting more than one event) who received a total of 7573 infusions. These adverse reactions are summarized in Table 1 below.
Table 1: Adverse Events Reported for PTPs *
|
Reaction
|
Total number of events
with definite, probable, possible or unknown
relation to therapy
(n=129) |
Number and (%) of
patients from which the
reports originated
(n=65) |
Number and (%) of
infusions temporally
associated with the
reaction 1
(n=7573) |
|
Nausea
|
27
|
4 (6.2 %)
|
27 (0.36 %)
|
Taste perversion
(Altered taste)
|
14
|
3 (4.6 %)
|
19 (0.25 %)
|
Hypoxia
(Urge to cough with hypoxemia)
|
11
|
1 (1.5 %)
|
11 (0.15 %)
|
|
Injection site reaction
|
11
|
5 (7.7 %)
|
12 (0.16 %)
|
|
Injection site pain
|
10
|
4 (6.2 %)
|
16 (0.21 %)
|
|
Headache
|
10
|
7 (10.8 %)
|
13 (0.17 %)
|
|
Dizziness
|
7
|
5 (7.7 %)
|
8 (0.11 %)
|
|
Allergic rhinitis
|
7
|
3 (4.6 %)
|
9 (0.12 %)
|
Pain (Burning sensation in the
jaw and skull)
|
6
|
1 (1.5 %)
|
7 (0.09 %)
|
|
Rash
|
6
|
5 (7.7 %)
|
7 (0.09 %)
|
|
Hives
|
3
|
2 (3.1 %)
|
3 (0.04 %)
|
|
Flushing
|
3
|
2 (3.1 %)
|
4 (0.05 %)
|
|
Fever
|
2
|
2 (3.1 %)
|
2 (0.03 %)
|
|
Shaking
|
2
|
2 (3.1 %)
|
1 (0.01 %)
|
|
Factor IX inhibitor 2 |
1
|
1 (1.5 %)
|
2 (0.03 %)
|
|
Chest tightness
|
1
|
1 (1.5 %)
|
4 (0.05 %)
|
|
Drowsiness
|
1
|
1 (1.5 %)
|
1 (0.01 %)
|
|
Visual disturbance
|
1
|
1 (1.5 %)
|
1 (0.01 %)
|
|
Cellulitis at the IV site
|
1
|
1 (1.5 %)
|
7 (0.09 %)
|
|
Phlebitis at the IV site
|
1
|
1 (1.5 %)
|
7 (0.09 %)
|
|
Dry cough
|
1
|
1 (1.5 %)
|
0 (0.00 %)
|
|
Allergic reaction
|
1
|
1 (1.5 %)
|
1 (0.01 %)
|
|
Diarrhea
|
1
|
1 (1.5 %)
|
1 (0.01 %)
|
|
Lung disorder
|
1
|
1 (1.5 %)
|
1 (0.01 %)
|
|
Vomiting
|
1
|
1 (1.5 %)
|
1 (0.01 %)
|
|
Renal infarct 3 |
1
|
1 (1.5 %)
|
1 (0.01 %)
|
|
Total
|
131
|
27/65 (41.5 %)
|
148/7573 (2.2 %)
|
|
*More than one event in the table could have been assoc. with an infusion; however, the total represents the actual number of infusions given.
|
|
1 Reaction occurring within 72 hours after infusion.
|
|
2 Low titer transient inhibitor formation.
|
|
3 The renal infarct developed in a hepatitis C antibody positive patient 12 days after a dose of BeneFIX® for a bleeding episode. The relationship of the infarct to the prior administration of BeneFIX® is uncertain. (See PRECAUTIONS, General).
|
|
One subject discontinued BeneFIX® due to pulmonary allergic-type symptoms.
In the 63 treated PUPS, who received a total of 5538 infusions, 22 adverse reactions were reported as having definite, probable, possible or unknown relationship to BeneFIX® . These events are summarized in Table 2 below.
Table 2: Adverse Events reported for PUPs *
|
Reaction
|
Total number of events
with definite, probable, possible or unknown
relation to therapy
(n=22) |
Number and (%) of
patients from which the
reports originated
(n=63) |
Number and (%) of
infusions temporally
associated with the
reaction 1
(n=5538) |
|
Diarrhea
|
5
|
1 (1.6 %)
|
11 (0.20 %)
|
|
Urticaria (hives)
|
3
|
3 (4.8 %)
|
3 (0.05 %)
|
|
Factor IX inhibitor 2 |
2
|
2 (3.2 %)
|
4 (0.07 %)
|
|
Dyspnea (Respiratory distress)
|
2
|
2 (3.2 %)
|
2 (0.04 %)
|
|
Increased alkaline phosphatase
|
1
|
1 (1.6 %)
|
3 (0.05 %)
|
|
Elevated ALT
|
1
|
1 (1.6 %)
|
0 (0.00 %)
|
|
Rash (Body rash)
|
1
|
1 (1.6 %)
|
1 (0.02 %)
|
|
Elevated AST
|
1
|
1 (1.6 %)
|
0 (0.00 %)
|
|
Chills (Rigors)
|
1
|
1 (1.6 %)
|
3 (0.05 %)
|
|
Photosensitivity reaction
|
1
|
1 (1.6 %)
|
0 (0.00 %)
|
|
Injection site reaction
|
1
|
1 (1.6 %)
|
2 (0.04 %)
|
|
HAV seroconversion 3 |
1
|
1 (1.6 %)
|
2 (0.04 %)
|
|
Parvovirus B19 seroconversion 4 |
1
|
1 (1.6 %)
|
1 (0.02 %)
|
|
Asthma
|
1
|
1 (1.6 %)
|
1 (0.02 %)
|
|
Total
|
22
|
11/63 (17.5%) |
27/5538 (0.60%) |
|
*More than one event in the table could have been assoc. with an infusion; however, the total represents the actual number of infusions given.
|
|
1 Reaction occurring within 72 hours after infusion.
|
|
2 Two subjects developed high titer inhibitor formation during treatment with BeneFIX® .
|
|
3 Relationship of HAV seroconversion to BeneFIX® is unknown. HAV seroconversion was noted on 2 occasions in a single patient but was negative at final visit. The patient had no laboratory or clinical findings associated with active infection.
|
|
4 Relationship of Parvovirus B19 seroconversion to BeneFIX® is unknown. It was unlikely that seroconversion was related to BeneFIX® due to the frequency of community acquired infection and viral safeguards built into the manufacturing process (See DESCRIPTION).
|
|
The following post-marketing adverse reactions have been reported for BeneFIX® , as well as for plasma-derived factor IX products: inadequate factor IX recovery, inadequate therapeutic response, inhibitor development (see CLINICAL PHARMACOLOGY), anaphylaxis (see WARNINGS), laryngeal edema, angioedema, cyanosis, dyspnea, hypotension, and thrombosis.
If any adverse 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.
|
REPORTS OF SUSPECTED BENEFIX SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Benefix. The information is not vetted and should not be considered as verified clinical evidence.
Possible Benefix side effects / adverse reactions in 29 year old male
Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2011-10-04
Patient: 29 year old male
Reactions: Arthritis Infective, Sepsis
Suspect drug(s):
Benefix
Possible Benefix side effects / adverse reactions in 24 year old male
Reported by a physician from Japan on 2011-10-05
Patient: 24 year old male weighing 7.5 kg (16.5 pounds)
Reactions: Drug Ineffective
Suspect drug(s):
Benefix
Possible Benefix side effects / adverse reactions in 29 year old male
Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2011-11-04
Patient: 29 year old male
Reactions: Arthritis Bacterial
Suspect drug(s):
Benefix
|
