Fabrazyme Special Precautions

Hypersensitivity Reactions Including Anaphylaxis: Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with enzyme replacement therapies, including FABRAZYME. In clinical trials and postmarketing safety experience with FABRAZYME, approximately 1% of patients developed anaphylaxis or severe hypersensitivity reactions. 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.
In clinical trials with FABRAZYME, 10 of 238 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.
Higher incidences of hypersensitivity reactions were observed in adult patients with persistent anti-FABRAZYME antibodies and in adult patients with high antibody titer compared to that in antibody-negative adult patients [see Adverse Reactions].
Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Administration of FABRAZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Prior to FABRAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Initiate FABRAZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment.
If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue FABRAZYME and immediately initiate appropriate medical treatment, including use of epinephrine. Consider the risks and benefits of re-administering FABRAZYME following severe hypersensitivity reactions (including anaphylaxis). Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.
Consider testing for IgE antibodies in FABRAZYME-treated patients who experienced severe hypersensitivity reactions, including anaphylaxis and consider the risks and benefits of continued treatment in patients with anti-FABRAZYME IgE antibodies. There are no marketed tests for antibodies against FABRAZYME. If testing is warranted, contact the local medical contact [see Adverse Reactions].
Patients who have had a positive skin test to FABRAZYME or who have tested positive for FABRAZYME-specific IgE antibodies have been rechallenged with FABRAZYME using a rechallenge protocol. Rechallenge of these patients should only occur under the direct supervision of qualified personnel with appropriate medical monitoring and support measures readily available [see Dosage & Administration and Adverse Reactions].
Infusion-Associated Reactions: In clinical trials of FABRAZYME,59% of patients experienced infusion-associated reactions (IARs) during FABRAZYME administration, some of which were severe. Infusion-associated reactions are defined as adverse reactions occurring on the same day as the infusion. The incidence of infusion-associated reactions was higher in patients who were positive for anti-FABRAZYME antibodies than in patients who were negative for anti-FABRAZYME antibodies [see Adverse Reactions].
Severe infusion-associated reactions experienced by more than one patient in clinical trials of FABRAZYME included chills, vomiting, hypotension, and paresthesia. Other infusion-associated reactions included pyrexia, feeling hot or cold, dyspnea, nausea, flushing, headache, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, urticaria, bradycardia, and somnolence [see Adverse Reactions].
Prior to FABRAZYME administration, consider pre-treatment with antihistamines, antipyretics, and/or corticosteroids to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur in patients after receiving pre-treatment. IARs tended to decline in frequency with continued use of FABRAZYME. However, IARs may still occur despite extended duration of FABRAZYME treatment. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily during FABRAZYME administration.
If a severe IAR occurs, discontinue FABRAZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering FABRAZYME following a severe IAR and monitor patients closely upon re-administration of FABRAZYME.
If a mild or moderate IAR occurs, consider temporarily holding the infusion, slowing the infusion rate, and/or reducing the FABRAZYME dosage.
Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from IARs. Closely monitor patients with compromised cardiac function if FABRAZYME is administered to these patients.
Use in Children: The safety and effectiveness of FABRAZYME have been established in pediatric patients based on adequate and well-controlled studies in adults, a single-arm, open-label study in 16 pediatric patients with Fabry disease aged 8 to 16 years [see Pharmacology and Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Patients younger than 8 years of age were not included in clinical studies. The safety and efficacy in patients younger than 8 years of age have not been evaluated.
Use in the Elderly: Clinical studies of FABRAZYME did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects.