ADVERSE REACTIONS
The most serious and most common adverse reactions reported with Fabrazyme® are infusion reactions. Serious and/or frequently occurring infusion reactions consisted of one or more of the following: tachycardia, hypertension, throat tightness, chest pain/tightness, dyspnea, fever, chills/rigors, abdominal pain, pruritus, urticaria, nausea, vomiting, lip or ear edema, and rash (see WARNINGS: Infusion Reactions). Infusion reactions declined in frequency with continued use of Fabrazyme®. However, serious infusion reactions may occur after extended durations of Fabrazyme® treatment.
Other reported serious adverse events included stroke, pain, ataxia, bradycardia, cardiac arrhythmia, cardiac arrest, decreased cardiac output, vertigo, hypoacousia, and nephrotic syndrome. These adverse events also occur as manifestations of Fabry disease; an alteration in frequency or severity cannot be determined from the small numbers of patients studied.
The data described below reflect exposure of 29 patients to 1.0 mg/kg Fabrazyme® every two weeks for 5 months in a placebo-controlled study. All 58 patients continued into an open-label extension study of Fabrazyme® treatment for up to 30 additional months. An additional 28 patients received open-label treatment. All patients were treated with antipyretics and antihistamines prior to the infusions.
Because clinical trials are conducted under widely varying and controlled conditions, the observed adverse reaction rates may not predict the rates observed in patients in clinical practice.
Table 2 enumerates adverse events and selected laboratory abnormalities that occurred during the placebo-controlled trial in at least 2 patients more in the Fabrazyme® group than was observed in the placebo group. Reported adverse events have been classified by organ system. Observed adverse events in the Phase 1/2 study and the open-label treatment period following the controlled study were not different in nature or severity.
Table 2
Incidence (%) of Adverse Events Occurring in the
Placebo-Controlled Study
| Adverse Event |
Placebo
(n = 29)
|
Fabrazyme®
(n = 29)
|
|
Body as a Whole
|
|
Chest pain
|
3 (10) |
5 (17) |
|
Fever
|
5 (17) |
14 (48) |
|
Pain
|
3 (10) |
6 (21) |
|
Pallor
|
1 (3)
|
4 (14) |
|
Rigors
|
4 (14) |
15 (52) |
Temperature changed
sensation
|
1 (3)
|
5 (17) |
|
Cardiovascular
|
|
Cardiomegaly
|
1 (3)
|
3 (10) |
|
Hypertension
|
0
|
3 (10) |
|
Hypotension
|
2 (7)
|
4 (14) |
|
Edema dependent
|
1 (3)
|
6 (21) |
|
Central and Peripheral Nervous System
|
|
Dizziness
|
2 (7)
|
4 (14) |
|
Headache
|
11 (38) |
13 (45) |
|
Paraesthesia
|
2 (7)
|
4 (14) |
|
Gastro-Intestinal System
|
|
Dyspepsia
|
1 (3)
|
3 (10) |
|
Nausea
|
4 (14) |
8 (28) |
|
Musculo-Skeletal System
|
|
Arthrosis
|
0
|
3 (10) |
|
Skeletal pain
|
0
|
6 (21) |
|
Psychiatric
|
|
Anxiety
|
5 (17) |
8 (28) |
|
Depression
|
1 (3)
|
3 (10) |
|
Reproductive, Male
|
|
Testicular pain
|
0
|
2 (7)
|
|
Respiratory System
|
|
Bronchitis
|
1 (3)
|
3 (10) |
|
Bronchospasm
|
0
|
2 (7)
|
|
Laryngitis
|
0
|
2 (7)
|
|
Pharyngitis
|
2 (7)
|
8 (28) |
|
Rhinitis
|
7 (24) |
11 (38) |
|
Sinusitis
|
0
|
2 (7)
|
|
IMMUNOGENICITY
Sixty-three of 71 (89%) patients in the clinical studies treated with Fabrazyme® have developed antibodies to Fabrazyme®. Most patients who develop antibodies do so within the first 3 months of exposure. Antibodies to Fabrazyme® were purified from 15 patients with high antibody titers (>/= 12,800) and studied for inhibition of in vitro enzyme activity. Under the conditions of this assay, most of these 15 patients had inhibition of in vitro enzyme activity ranging between 14-74% at one or more timepoints during the study. No general pattern was seen in individual patient reactivity over time. The clinical significance of binding and/or inhibitory antibodies to Fabrazyme® is not known. In patients followed in the open-label study, reduction of GL-3 in plasma and GL-3 inclusions in superficial skin capillaries was maintained after antibody formation.
The data reflect the percentage of patients whose test results were considered positive for antibodies to Fabrazyme® using an ELISA and radioimmunoprecipitation (RIP) assay for antibodies. These results are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibodies in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Fabrazyme® with the incidence of antibodies to other products may be misleading.
|
REPORTS OF SUSPECTED FABRAZYME SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Fabrazyme. The information is not vetted and should not be considered as verified clinical evidence.
Possible Fabrazyme side effects / adverse reactions in 56 year old male
Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2011-10-05
Patient: 56 year old male
Reactions: Left Ventricular Dysfunction, Sudden Death
Adverse event resulted in: death
Suspect drug(s):
Fabrazyme
Possible Fabrazyme side effects / adverse reactions in 73 year old male
Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2011-10-05
Patient: 73 year old male
Reactions: Renal Impairment, Troponin T Increased, Cardiac Failure Congestive
Adverse event resulted in: death
Suspect drug(s):
Fabrazyme
Possible Fabrazyme side effects / adverse reactions in 27 year old male
Reported by a consumer/non-health professional from Korea, Republic of on 2011-10-06
Patient: 27 year old male weighing 77.6 kg (170.7 pounds)
Reactions: Road Traffic Accident, Skull Fracture
Adverse event resulted in: hospitalization
Suspect drug(s):
Fabrazyme
Dosage: 70 mg, unk
End date: 2010-03-04
Fabrazyme
Dosage: 35 mg, unk
Indication: Fabry's Disease
Start date: 2010-03-01
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