ADVERSE REACTIONS
Adverse Reactions from Clinical Trials
During controlled clinical studies with RECOMBINATE enrolling 210 subjects, the most commonly reported adverse drug reactions were chills, flushing, rash and epistaxis..
System Organ Class (SOC)
|
Preferred MedDRA Term
|
Number of Subjects
|
Percent of Evaluable Subjects
|
GASTROINTESTINAL DISORDERS
|
Nausea |
1 |
0.48 |
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
|
Chills
Fatigue
Pyrexia |
3
1
1 |
1.43
0.48
0.48 |
INFECTIONS AND INFESTATIONS
|
Ear infections |
1 |
0.48 |
INVESTIGATIONS
|
Acoustic stimulation tests abnormal |
1 |
0.48 |
MUSCULOSKELETAL AND CONNECTIVE TISSUES DISORDERS
|
Pain in extremity |
1 |
0.48 |
NERVOUS SYSTEM DISORDERS
|
Dizziness
Tremors |
1
1 |
0.48
0.48 |
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
|
Pharyngolaryngeal pain |
1 |
0.48 |
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
|
Hyperhidrosis
Pruritus
Rash
Rash maculopapular |
1
1
2
1 |
0.48
0.48
0.95
0.48 |
VASCULAR DISORDERS
|
Epistaxis
Flushing
Hematoma
Hypotension
Pallor
Peripheral coldness |
1
2
1
1
1
1 |
0.48
0.95
0.48
0.48
0.48
0.48 |
During the Previously Treated Patients (PTP) study, none of the 71 subjects developed de novo evidence of Factor VIII inhibitor. However, during the phase II/III portion of the study, 1 subject with a history of inhibitors exhibited inhibitor activity at 6 months (0.8 Bethesda Units [BU]), which resolved by 9 months. One other subject in this study had detectable Factor VIII inhibitor at baseline (1.26 BU) and exhibited an anamnestic response at 6 months (10.3 BU). During a prospective pharmaco-surveillance study of subjects who received batches of RECOMBINATE containing modestly increased Chinese Hamster Ovary (CHO) cell protein levels, none of the 34 treated subjects developed a Factor VIII inhibitor.
During the Previously Untreated Patients (PUP) study, 22 of the 73 evaluable subjects developed inhibitors to Factor VIII. Of these, 13 subjects displayed no detectable Factor VIII inhibitors at study exit.
Post-Marketing Adverse Reactions
In addition to the adverse reactions noted in clinical trials, the following adverse reactions have been reported in the post-marketing experience. These adverse reactions are listed by MedDRA (version 12.1) System Organ Class (SOC), then by MedDRA coding system Preferred Term in order of severity.
BLOOD AND LYMPHATIC SYSTEM DISORDERS: Factor VIII inhibition
CARDIAC DISORDERS: Tachycardia, Cyanosis
GASTROINTESTINAL DISORDERS: Vomiting, Abdominal pain
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Malaise, Injection site reactions, Chest pain, Chest discomfort
IMMUNE SYSTEM DISORDERS: Anaphylactic reaction, Hypersensitivity
NERVOUS SYSTEM DISORDERS: Loss of consciousness, Headache, Paresthesia
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Dyspnea, Cough, Laryngeal edema
SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Angioedema, Urticaria, Erythema
|