Fabrazyme (Page 2 of 6)

5.3 Compromised Cardiac Function

Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion-associated reactions [see Warnings and Precautions (5.1, 5.2)]. Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme.

5.4 Immunogenicity and Rechallenge

In clinical trials with Fabrazyme, a few patients developed IgE antibodies or skin test reactivity specific to Fabrazyme. Two of six patients in the rechallenge study discontinued treatment with Fabrazyme prematurely due to recurrent infusion-associated reactions. Four serious infusion-associated reactions occurred in three patients during Fabrazyme infusions, including bronchospasm, urticaria, hypotension, and development of Fabrazyme-specific antibodies. Other infusion-associated reactions occurring in more than one patient during the study included rigors, hypertension, nausea, vomiting, and pruritus. Physicians should consider testing for IgE antibodies in patients who experienced suspected allergic reactions and consider the risks and benefits of continued treatment in patients with anti-Fabrazyme IgE antibodies [see Warnings and Precautions (5.1)].

Patients who have had a positive skin test to Fabrazyme or who have tested positive for Fabrazyme-specific IgE antibody have been rechallenged with Fabrazyme using a rechallenge protocol [see Clinical Studies (14)]. Rechallenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available [see Dosage and Administration (2.1)].

5.5 Monitoring: Laboratory Tests

There are no marketed tests for antibodies against Fabrazyme. If testing is warranted, contact your local Genzyme representative or Genzyme Corporation at 1-800-745-4447.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in labeling:

6.1 Clinical Trials Experience

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.

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.

Most Common Adverse reactions

Table 2 enumerates adverse reactions that occurred during the double-blind treatment periods of the two placebo-controlled trials (Study 1 and Study 2) [see Clinical Studies (14)]. The most common adverse reactions reported with Fabrazyme were infusion-associated reactions, (Fabrazyme 59% vs placebo 27%) some of which were severe.

Common adverse reactions which occurred in ≥20% of patients treated with Fabrazyme and >2.5% compared to placebo are: upper respiratory tract infection, chills, pyrexia, headache, cough, paresthesia, fatigue, peripheral edema, dizziness and rash.

Table 2: Summary of Common Adverse Reactions * in Clinical Trials of Patients with Fabry Disease
Adverse Reaction Fabrazyme(n=80 )% Placebo(n=60)%
*
Reported at rate of at least 5% in Fabrazyme-treated patients and greater than 2.5% compared to placebo-treated patients.
Upper respiratory tract infection 44 30
Chills 43 12
Pyrexia 39 22
Headache 39 28
Cough 33 25
Paresthesia 31 18
Fatigue 24 17
Peripheral edema 21 7
Dizziness 21 8
Rash 20 10
Pain in extremity 19 8
Nasal congestion 19 15
Lower respiratory tract infection 18 7
Pain 16 13
Back pain 16 10
Myalgia 14 5
Hypertension 14 5
Feeling cold 11 2
Pruritus 10 3
Tachycardia 9 3
Sinusitis 9 3
Excoriation 9 2
Increased blood creatinine 9 5
Tinnitus 8 3
Dyspnea 8 2
Respiratory tract congestion 8 2
Toothache 6 3
Pharyngitis 6 2
Fall 6 3
Burning sensation 6 0
Anxiety 6 3
Depression 6 2
Wheezing 6 0
Hypoacusis 5 0
Chest discomfort 5 2
Fungal infection 5 0
Viral infection 5 0
Muscle spasms 5 2
Hot flush 5 0

Serious and/or frequently occurring (≥5% incidence) related adverse reactions based on a pooled analysis of 150 patients treated with Fabrazyme 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, 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.

Adverse Reactions in Pediatric Patients

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.

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