Safety Profile

^Warnings

Infusion reactions occurred in many patients treated with Fabrazyme^®(agalsidase beta). Some of the reactions were severe. Infusion reactions included fever, rigors, chest tightness, hypertension, hypotension, pruritis, myalgia, dyspnea, urticaria, abdominal pain, and headache. All patients in the phase 3 double blind study were pretreated with acetaminophen and an antihistamine. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines and oral steroids. Patients should be given antipyretics prior to infusion. If an infusion reaction occurs, regardless of pre-treatment, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of additional antipyretics, antihistamines and/or steroids may ameliorate the symptoms. Because of the potential for severe infusion reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.

^Precautions

Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion reactions. Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme. The safety and effectiveness of Fabrazyme in pediatric patients have not been established. Clinical studies of Fabrazyme did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

^{Treatment of Females}

Two women were enrolled in the clinical studies with Fabrazyme; therefore, no determination can be made whether symptomatic women respond to Fabrazyme differently than men. There is also insufficient information to determine whether the relationship between cellular histologic evaluations of biopsies and clinical manifestations differ between women and men. There are no adequate and well-controlled studies of Fabrazyme in pregnant women. Because animal reproduction studies are not always predictive of human response, Fabrazyme should be used during pregnancy only if clearly needed. Additionally, it is not known whether Fabrazyme is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fabrazyme is administered to a nursing woman.

^{Antibody Formation}

Most patients develop IgG antibodies to Fabrazyme (89% of patients in clinical trials). Some patients developed IgE or skin test reactivity specific to Fabrazyme. Physicians should consider testing for IgE in patients who experienced suspected allergic reactions and consider the risks and benefits of continued treatment in patients with anti-Fabrazyme IgE. There are no marketed tests for antibodies against Fabrazyme. If testing is warranted, please contact Genzyme Medical Information at 617-768-9000 or toll-free 800-745-4447. For information on immunogenicity, please see full prescribing information.

^{Adverse Reactions}

The most serious and most common adverse reactions reported with Fabrazyme are infusion reactions. The most 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. 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.

Table 1 below lists adverse events and selected laboratory abnormalities that occurred during the phase 3 placebo-controlled study in at least 2 patients more in the Fabrazyme group than was observed in the placebo group

Genzyme maintains a worldwide database of adverse events that have occurred in patients receiving Fabrazyme enzyme replacement therapy. To report an adverse event (infusion-related or otherwise), please contact Genzyme Medical Information at 617-768-9000 or toll-free 800-745-4447. In case of unexpected adverse events, a search for comparable events can be requested. This search may be helpful in the evaluation and management of unexpected events. Adverse events should be reported promptly to Genzyme Medical Information at 617-768-9000 or toll-free 800-745-4447 option 2.

Please see Full Prescribing Information for complete safety information.