Fabrazyme Side Effects
Generic Name: agalsidase beta
Please note - some side effects for Fabrazyme may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).
Side Effects of Fabrazyme - for the Consumer
Fabrazyme
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Fabrazyme:
Seek medical attention right away if any of these SEVERE side effects occur when using Fabrazyme:Dizziness; headache; nausea; runny or stuffy nose; sore throat; stomach upset.
TopSevere allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bone pain; chest pain or tightness; chills; confusion; decreased hearing or hearing loss; decreased or painful urination; fainting; fast, slow, or irregular heartbeat; fever; joint pain; loss of coordination; mental or mood changes (eg, anxiety, depression); muscle pain or weakness; numbness or pain of an arm or leg; one-sided weakness; severe headache, dizziness, or nausea; shortness of breath; slurred speech; stomach pain; sudden vision changes; swelling (eg, hands, legs, feet, lips, ears); throat tightness; unusual tiredness or weakness; unusually pale skin; vomiting.
Fabrazyme Side Effects - for the Professional
Fabrazyme
6.1 Adverse Reactions in Clinical Studies
The most serious adverse reactions reported with Fabrazyme treatment during clinical trials were anaphylactic and allergic reactions [see Warnings and Precautions (5.1)].
The most common adverse reactions reported with Fabrazyme are infusion reactions, some of which were severe [see Warnings and Precautions (5.1) and (5.2)]. Serious and/or frequently occurring (≥5% incidence) related adverse reactions consisted of one or more of the following: chills, pyrexia, feeling hot or cold, dyspnea, nausea, flushing, headache, vomiting, paresthesia, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, back pain, pallor, bradycardia, urticaria, hypotension, face edema, rash, and somnolence. The occurrence of somnolence can be attributed to clinical trial specified pretreatment with antihistamines. Most infusion-related reactions requiring intervention were ameliorated with slowing of the infusion rate, temporarily stopping the infusion, and/or administration of antipyretics, antihistamines, or steroids.
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 80 patients, ages 16 to 61 years, to 1 mg/kg Fabrazyme every two weeks in two separate double-blind, placebo-controlled clinical trials, for periods ranging from 1 to 35 months (mean 15.5 months). All 58 patients enrolled in one of the two studies continued into an open-label extension study of Fabrazyme treatment for up to 54 additional months. Patients were treated with antipyretics and antihistamines prior to the infusions.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in patients in clinical practice.
Table 2 enumerates treatment-emergent adverse reactions (regardless of relationship) that occurred during the double-blind treatment periods of the two placebo-controlled trials (Study 1 and Study 2) [see Clinical Studies (14)]. Reported adverse reactions have been classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology System Organ Class and Preferred Term.
|
MedDRA System Organ Class/ Preferred Term |
Fabrazyme n=80 (%) |
Placebo n=60 (%) |
| Cardiac Disorders | ||
| Tachycardia | 7 (9) | 2 (3) |
| Ventricular wall thickening | 4 (5) | 1 (2) |
| Ear and Labyrinth Disorders | ||
| Tinnitus | 6 (8) | 2 (3) |
| Hypoacusis | 4 (5) | 0 |
| Gastrointestinal Disorders | ||
| Toothache | 5 (6) | 2 (3) |
| Dry mouth | 3 (4) | 0 |
| General Disorders and Administration Site Conditions | ||
| Chills | 34 (43) | 7 (12) |
| Pyrexia | 31 (39) | 13 (22) |
| Fatigue | 19 (24) | 10 (17) |
| Edema peripheral | 17 (21) | 4 (7) |
| Pain | 13 (16) | 8 (13) |
| Feeling cold | 9 (11) | 1 (2) |
| Adverse event | 8 (10) | 3 (5) |
| Chest discomfort | 4 (5) | 1 (2) |
| Infections and Infestations | ||
|
Upper respiratory tract infection |
35 (44) | 18 (30) |
|
Lower respiratory tract infection |
14 (18) | 4 (7) |
| Sinusitis | 7 (9) | 2 (3) |
| Pharyngitis | 5 (6) | 1 (2) |
| Fungal infection | 4 (5) | 0 |
| Viral infection | 4 (5) | 0 |
| Localized infection | 3 (4) | 0 |
| Injury, Poisoning and Procedural Complications | ||
| Procedural pain | 20 (25) | 12 (20) |
| Post procedural complication | 8 (10) | 1 (2) |
| Excoriation | 7 (9) | 1 (2) |
| Fall | 5 (6) | 2 (3) |
| Contusion | 3 (4) | 0 |
| Thermal burn | 3 (4) | 0 |
| Investigations | ||
| Blood creatinine increased | 7 (9) | 3 (5) |
| Musculoskeletal and Connective Tissue Disorders | ||
| Pain in extremity | 15 (19) | 5 (8) |
| Back pain | 13 (16) | 6 (10) |
| Myalgia | 11 (14) | 3 (5) |
| Muscle spasms | 4 (5) | 1 (2) |
| Nervous System Disorders | ||
| Headache | 31 (39) | 17 (28) |
| Paresthesia | 25 (31) | 11 (18) |
| Dizziness | 17 (21) | 5 (8) |
| Burning sensation | 5 (6) | 0 |
| Psychiatric Disorders | ||
| Anxiety | 5 (6) | 2 (3) |
| Depression | 5 (6) | 1 (2) |
| Respiratory, Thoracic and Mediastinal Disorders | ||
| Cough | 26 (33) | 15 (25) |
| Nasal congestion | 15 (19) | 9 (15) |
| Dyspnea | 6 (8) | 1 (2) |
| Respiratory tract congestion | 6 (8) | 1 (2) |
| Wheezing | 5 (6) | 0 |
| Skin and Subcutaneous Tissue Disorders | ||
| Rash | 16 (20) | 6 (10) |
| Pruritus | 8 (10) | 2 (3) |
| Vascular Disorders | ||
| Hypertension | 11 (14) | 3 (5) |
| Hot flush | 4 (5) | 0 |
Observed adverse reactions in the Phase 1/2 study and the open-label treatment period for the extension study following the controlled study were not different in nature or intensity.
The safety profile of Fabrazyme in pediatric Fabry disease patients, ages 8 to 16 years, was found to be consistent with that seen in adults [see Use in Specific Populations (8.4) and Clinical Studies (14)]. The safety of Fabrazyme in patients younger than 8 years of age has not been evaluated.
6.2 Immunogenicity
Ninety-five of 121 (79%) adult patients and 11 of 16 (69%) pediatric patients (106 of 137, 74% of all patients) treated with Fabrazyme in clinical studies have developed IgG antibodies to Fabrazyme. Most patients who develop IgG antibodies do so within the first 3 months of exposure. IgG seroconversion in pediatric patients was associated with prolonged half-life of Fabrazyme, a phenomenon rarely observed in adult patients [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.4)]. A possible cause for this prolongation likely pertains to the ability of antibodies to act as “carriers” for their antigens. Among the 14 female patients exposed to Fabrazyme in clinical studies, four (two adult and two pediatric patients) developed IgG antibodies to Fabrazyme.
IgG 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 21-74% at one or more time points during the study. Assessment of inhibition of enzyme uptake in cells has not been performed. 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 extension study, reduction of GL-3 in plasma and GL-3 inclusions in superficial skin capillaries was maintained after antibody formation.
As with all therapeutic proteins, there is a potential for immunogenicity. 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. The incidence of antibody formation is highly 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. For these reasons, comparison of the incidence of antibodies to Fabrazyme with the incidence of antibodies to other products may be misleading.
Testing for IgE was performed in approximately 60 patients in clinical trials who experienced moderate to severe infusion reactions or in whom mast cell activation was suspected. Seven of these patients tested positive for Fabrazyme-specific IgE antibodies or had a positive skin test to Fabrazyme. Patients who have had a positive skin test to Fabrazyme, or who have tested positive for Fabrazyme-specific IgE antibodies in clinical trials with Fabrazyme have been re-challenged [see Clinical Studies (14), Warnings and Precautions (5.4) and Dosage and Administration (2)].
6.3 Postmarketing Experience
In postmarketing experience with agalsidase beta, severe infusion-related reactions have been reported, some of which were life-threatening, including anaphylaxis [see Warnings and Precautions (5.1)]. Reactions have included localized angioedema (including auricular swelling, eye swelling, dysphagia, lip swelling, edema, pharyngeal edema, face swelling, and swollen tongue), generalized urticaria, bronchospasm, and hypotension.
In addition to adverse events reported in Adverse Reactions in Clinical Studies (6.1), the following adverse reactions have been reported during postmarketing use of agalsidase beta: arthralgia, asthenia, erythema, hyperhidrosis, infusion site reaction, lacrimation increased, leukocytoclastic vasculitis, lymphadenopathy, oral hypoesthesia, palpitations, and rhinorrhea. Because these 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.
TopSide Effects by Body System
General
In general, infusion-related side effects have been reported the most frequently. These have included tachycardia, hypertension, urticaria, chest pain, fever, and rigors. Temperature changed sensation and pallor have also been reported.
Cardiovascular
Cardiovascular side effects have included hypertension (greater than 10%), reports of cardiomegaly, hypotension, and edema.
Nervous system
Nervous system side effects including pain related to Fabry disease and headache have been reported in greater than 10% of patients. Cerebrovascular events (i.e., symptomatic stroke or transient ischemic attack) were reported in 9% of patients. Dizziness and paraesthesia have also been reported.
Gastrointestinal
Gastrointestinal side effects have included reports of dyspepsia and nausea.
Musculoskeletal
Musculoskeletal side effects have included reports of arthrosis and skeletal pain.
Psychiatric
Psychiatric side effects have included reports of anxiety and depression.
Respiratory
Respiratory side effects have included reports of bronchitis, bronchospasm, laryngitis, pharyngitis, rhinitis, and sinusitis.
Genitourinary
Genitourinary side effects reported by men involved in the placebo controlled study have included testicular pain.
Immunologic
Immunologic side effects have included reports of the development of antibodies to agalsidase beta. Most patients involved in clinical studies developed antibodies within the first 3 months of exposure.
The reported rates of IgG seroconversion during the clinical studies were 88 % and 89 %. There are reports of decrease in titers after 12 months of treatment and one case that became seronegative. Seroconversion did not affect the efficacy end points. The clinical significance of the antibodies to agalsidase beta is not yet known.
Other
Other side effects including chills have been reported in greater than 10% of patients.
TopMore Fabrazyme resources
- Fabrazyme Prescribing Information (FDA)
- Fabrazyme Consumer Overview
- Fabrazyme Advanced Consumer (Micromedex) - Includes Dosage Information
- Fabrazyme Medfacts Consumer Leaflet (Wolters Kluwer)
- Agalsidase Beta Professional Patient Advice (Wolters Kluwer)
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