Fabrazyme Special Precautions

Anaphylaxis and Allergic Reactions: Life-threatening anaphylactic and severe allergic reactions have been observed in patients 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, epinephrine, and IV corticosteroids.
In clinical trials and postmarketing safety experience with Fabrazyme, approximately 1% of patients developed anaphylactic or severe allergic reactions during Fabrazyme infusion.
If anaphylactic or severe allergic reactions occur, immediately discontinue the administration of Fabrazyme and initiate necessary emergency treatment. Because of the potential for severe allergic reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.
The risks and benefits of re-administering Fabrazyme following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate medical support measures readily available, if the decision is made to re-administer the product (see following text and Pharmacology: Clinical Studies under Action).
Infusion Reactions: In clinical trials with Fabrazyme, approximately 50-55% of patients experienced infusion reactions during Fabrazyme administration, some of which were severe (see following text). Severe infusion reactions experienced by more than one patient in clinical studies with Fabrazyme included chills, vomiting, hypotension, and paresthesia. Other infusion 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.
Most patients in clinical trials were pretreated with acetaminophen. 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. Infusion reactions tended to decline in frequency with continued use of Fabrazyme. However, infusion reactions may still occur despite extended duration of Fabrazyme treatment. 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. Patients who have experienced infusion reactions should be treated with caution when re-administering Fabrazyme.
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 reactions (see PRECAUTIONS). Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme.
Immunogenicity and Re-challenge: In clinical trials with Fabrazyme, a few patients developed IgE antibodies or skin test reactivity specific to Fabrazyme. Two of six patients in the re-challenge study discontinued treatment with Fabrazyme prematurely due to recurrent infusion reactions. Four serious infusion reactions occurred in three patients during Fabrazyme infusions, including bronchospasm, urticaria, hypotension, and development of Fabrazyme-specific antibodies. Other infusion-related 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 following text and DOSAGE & ADMINISTRATION).
Patients who have had a positive skin test to Fabrazyme or who have tested positive for Fabrazyme-specific IgE antibody have been re-challenged with Fabrazyme using a re-challenge protocol (see Pharmacology: Pharmacodynamics: CLINICAL STUDIES under Actions). Re-challenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available.
Labor and Delivery: There is no information on the effect of Fabrazyme during labor and delivery. Pregnant females are encouraged to enroll in the Fabry registry (see PATIENT COUNSELING INFORMATION).
Responses in Women: Fabry disease is an X-linked genetic disorder. However, some heterozygous women will develop signs and symptoms of Fabry disease due to the variability of the X-chromosome inactivation within cells.
A total of 12 adult female patients with Fabry disease were enrolled in two separate randomized, double-blind, placebo-controlled clinical studies with Fabrazyme, and two female pediatric patients with Fabry disease, ages 11 years, were evaluated in an open-label, uncontrolled pediatric study (see following text and Pharmacology: Clinical Studies under Actions). Although the safety and efficacy data available in female patients in these clinical studies are limited, there is no indication that female patients respond differently to Fabrazyme compared to males.
Use in Children: The safety and efficacy of Fabrazyme were assessed in a multinational, multicenter, uncontrolled, open-label study in 16 pediatric patients with Fabry disease (14 males, 2 females), ages 8 to 16 years (see 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 Elderly: Clinical studies of Fabrazyme did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.