Monitoring Patients

Because of the multisystemic aspects of Fabry disease, coordination of care among the treating physician and specialists is essential for comprehensive treatment and monitoring of patients on Fabrazyme^® (agalsidase beta).

To connect with physicians with experience in treating Fabry disease, please contact Genzyme at 617-768-9000 or toll-free 800-745-4447, option 2.

Comprehensive Annual Evaluations ^[1]

In a 2003 publication, a consensus panel of physicians with experience in treating Fabry disease recommended the following:

• Annual assessments, including physical examination and routine hematology, chemistry, and urinalysis
• Annual urinary protein (including protein to creatinine ratio) and creatinine clearance assessments to determine renal function
• Echocardiogram and EKG at least every 2 years to detect and monitor cardiac abnormalities
• For female carriers, a complete baseline examination as described above. Symptomatic carriers may be followed annually.
• Baseline MRIs of kidney, heart, and brain to document disease progression and assess the effect of treatment.
• Abnormal findings may be monitored more frequently as indicated.

^{Fabry Registry}

While physicians determine the actual frequency of necessary assessments according to a patient's individualized need for medical care and routine follow-up, Genzyme’s Fabry Registry provides a recommended Schedule of Assessments, which may be useful as a guideline. These guidelines have been developed based on the input of physicians from the international medical community with experience in the care of patients with Fabry disease.

In order to better understand the variability and progression of Fabry disease in the population as a whole and in women, and to monitor and evaluate long-term treatment effects of Fabrazyme, the Fabry Registry has been established. The Registry will also monitor the effect of Fabrazyme on pregnant women and their offspring, and determine if Fabrazyme is excreted in breast milk. Patients should be informed of the Fabry Registry and encouraged to participate. They should be advised that their participation is voluntary and may involve long-term follow-up.

Physicians can monitor their patients’ disease status by utilizing Fabry Registry’s patient-specific reports, by exchanging clinical data among physicians to facilitate clinical decision-making, and accessing information on current treatment guidelines and practice patterns. Patient and physician identifiable information submitted to the Fabry Registry is maintained as confidential.

For more information visit Genzyme’s www.fabryregistry.com website or call 617-591-5500 or toll-free 800-745-4447, ext. 15500.

Indications and Usage Fabrazyme (agalsidase beta) is indicated for use in patients with Fabry disease. Fabrazyme reduces globotriaosylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types. The reduction of GL-3 inclusions suggests that Fabrazyme may ameliorate disease expression; however, the relationship of GL-3 inclusion reduction to specific clinical manifestations of Fabry disease has not been established. Important Safety Information Life-threatening anaphylactic and severe allergic reactions have been observed in patients during Fabrazyme infusions. In clinical trials and postmarketing safety experience, approximately 1% of patients developed anaphylactic or severe allergic reactions during Fabrazyme infusions. Reactions have included localized angioedema (including swelling of the face, mouth, and throat), bronchospasm, hypotension, generalized urticaria, dysphagia, rash, dyspnea, flushing, chest discomfort, pruritus, and nasal congestion. Interventions have included cardiopulmonary resuscitation, oxygen supplementation, IV fluids, hospitalization, and treatment with inhaled beta-adrenergic agonists, antihistamines, epinephrine, and IV corticosteroids. If severe allergic or anaphylactic reactions occur, immediately discontinue administration of Fabrazyme and provide necessary emergency treatment. Because of the potential for severe allergic reactions, appropriate medical support measures should be readily available when Fabrazyme is administered. In patients experiencing infusion reactions, pretreatment with an antipyretic and antihistamine is recommended. Infusion reactions occurred in some patients after receiving pretreatment with antipyretics, antihistamines, and oral steroids. If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administrating additional antipyretics, antihistamines, and/or steroids may ameliorate the symptoms. If severe infusion reactions occur, immediate discontinuation of the administration of Fabrazyme should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen when clinically indicated. Because of the potential for severe infusion reactions, appropriate medical support measures should be readily available when Fabrazyme is administered. Re-administration of Fabrazyme to patients who have previously experienced severe or serious allergic reactions to Fabrazyme should be done only after careful consideration of the risks and benefits of continued treatment, and only under the direct supervision of qualified personnel and with appropriate medical support measures readily available. The most common adverse reactions reported are infusion reactions, some of which were severe. Infusion reactions occurred in approximately 50-55% of patients during Fabrazyme administration in clinical trials. Serious and/or frequently occurring (≥ 5% incidence) related adverse reactions consisted of one or more of the following: chills, fever, 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. 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. Other serious adverse events reported in clinical studies 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. Severe and serious infusion related reactions have been reported in postmarketing experience, some of which were life threatening including anaphylactic shock. In addition to the above adverse reactions, the following have been reported during postmarketing use of Fabrazyme: arthralgia, asthenia, erythema, hyperhidrosis, infusion site reaction, lacrimation increased, leukocytoclastic vasculitis, lymphadenopathy, hypoesthesia, oral hypoesthesia, palpitations, rhinorrhea, oxygen saturation decreased and hypoxia. Adverse reactions (regardless of relationship) resulting in death reported in the postmarketing setting with Fabrazyme treatment included cardiorespiratory arrest, respiratory failure, cardiac failure, sepsis, cerebrovascular accident, myocardial infarction, renal failure, and pneumonia. Some of these reactions were reported in Fabry disease patients with significant underlying disease. The safety and efficacy in patients younger than 8 years of age have not been evaluated. Most patients who develop IgG antibodies do so within the first three months of exposure.  IgG seroconversion in pediatric patients was associated with prolonged half-life of Fabrazyme, a phenomenon rarely observed in adult patients. In clinical trials, a few 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 antibodies. Fabrazyme is available by prescription only. Side effects should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. To learn more, please see the full Prescribing Information (PDF) or contact Genzyme at 1-800-745-4447.

^References

1. Desnick RJ, Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, Grabowski G, Packman S, Wilcox WR. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003;138:338-346.