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Common adverse reactions observed in > 1% of subjects in clinical studies were dysgeusia, pain in extremity, and positive furin antibody test.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
During clinical development, in a combined trial, 99 male previously treated patients (PTPs; exposed to a factor IX-containing product for ≥ 150 days) received at least one infusion of RIXUBIS as part of either on-demand treatment of bleeding episodes, perioperative management of major and minor surgical, dental, or other invasive procedures, routine prophylaxis, or pharmacokinetic evaluation of RIXUBIS. Eleven subjects (11.1%) were < 6 years of age, 12 (12.1%) were 6 to < 12 years of age, 3 (3%) were adolescents (12 to < 16 years of age), and 73 (73.7%) were adults (16 years of age and older). The subjects received a total of 14,018 infusions with a median of 163 infusions of RIXUBIS (range 8 to 327 infusions), for a median of 156 exposure days (range 8 to 316 days).
A total of 337 adverse events were reported in 80 (80.8%) of the 99 subjects. Adverse reactions that occurred in > 1% of subjects are shown in Table 3.
Table 3 : Summary of Adverse Reactions
|System Organ Class||Adverse Reactions (AR)||Number of ARs (N)||Number of Subjects
(N=99) n (%)
|Percent per Infusion
|Nervous System Disorders||Dysgeusia||2||1 (1.01%)||0.014%|
|Musculoskeletal and Connective Tissue Disorders||Pain in extremity||1||1 (1.01%)||0.007%|
|Investigations||Positive furin antibody testa||2||2 (2.02%)||0.014%|
|a See Immunogenicity.|
All 99 subjects were monitored for inhibitory and binding antibodies to factor IX, and binding antibodies to CHO protein and furin, at the following time points: at screening, at 72 hours following the first infusion of RIXUBIS and the commercial recombinant factor IX product in the crossover portion of the pharmacokinetic trial, after 5 and 13 weeks following first exposure to RIXUBIS, and thereafter every 3 months. Antibodies against furin were tested by an in-house enzyme-linked immunosorbent assay (ELISA). A titer of 1:20 or 1:40 was considered to be indeterminate for the above validated assay, as these titers were too low to be verified by the confirmatory assay.
No subjects developed neutralizing antibodies to factor IX. Low-titer, non-neutralizing antibodies against factor IX were observed in 21 (21.2%) subjects at one or more time points. Three of these 21 subjects were found to have these antibodies at screening, prior to receiving RIXUBIS. Six of the 21 subjects were pediatric (2 subjects in < 6 years of age cohort, 4 subjects in 6 to < 12 years age cohort). No clinical adverse findings were observed in any of these 21 subjects.
Nineteen subjects (19.2%) had signals for antibodies against furin (indeterminate specificity). Five of these 19 subjects expressed signals for antibodies at screening, prior to RIXUBIS treatment. One subject had an antibody signal after treatment with the comparator product and prior to RIXUBIS treatment. Two additional subjects had a positive titer of 1:80 that was not present when checked at a later time point and therefore considered transient. Two of the 19 subjects were pediatric (6 to < 12 years age cohort). All post-treatment antibody titer increases in these two pediatric subjects were < 2 dilution steps and therefore considered unrelated to treatment. No clinical adverse findings were observed in any of these 19 subjects.
In a trial of 500 normal volunteers, using the same assay as in the clinical trial, 7% had titers of 1:20 or 1:40 and 1.2% had higher titers ranging from 1:80 to 1:320. These antibodies are thought to be part of a natural immune system response. To date, these antibodies have not been associated with any clinical adverse findings.
The detection of antibody formation is dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
There was no clinical evidence of thromboembolic complications in any of the subjects. Out-of-range values for thrombogenicity markers (thrombin-antithrombin III, prothrombin fragment 1.2, and D-dimer), determined during the pharmacokinetic portion of the combined trial, did not reveal any pattern indicative of clinically relevant thrombogenicity with either RIXUBIS or a comparator factor IX-containing product.
Because the following reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders
Skin and Subcutaneous Tissue Disorders
Read the Rixubis (coagulation factor ix (recombinant) for intramuscular injection) Side Effects Center for a complete guide to possible side effects
No information provided.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 2/29/2016
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