Fabrazyme Special Precautions

General: 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 Infusion Reactions under Warnings). Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme.
Immunogenicity and Rechallenge: In clinical trials wit 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 Dosage & Administration). 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 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.
Information for Patients: Patients should be informed that a Registry has been established in order to better understand the variability and progression of Fabry disease in the population as a whole and in women (see Responses in Women as follows), and to monitor and evaluate long-term treatment effects of Fabrazyme. 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 encouraged to participate and advised that their participation is voluntary and may involve long-term follow-up.
Laboratory Tests: There are no marketed tests for antibodies against Fabrazyme. If testing is warranted, contact the local Genzyme representative.
Interference with Laboratory Tests: There is no known interference by Fabrazyme with laboratory tests. Antibody samples should be collected prior to Fabrazyme infusions.
Carcinogenesis, Mutagenesis, & Impairment of Fertility: There are no animal or human studies to assess the carcinogenic or mutagenic potential of Fabrazyme. There are no studies assessing the potential effect of Fabrazyme on fertility in humans.
Pregnancy: Category B: There are no adequate and well-controlled studies of Fabrazyme use in pregnant women. Reproduction studies have been performed in rats at doses up to 30 times the human dose and have revealed no evidence of impaired fertility or negative effects on embryo fetal development due to Fabrazyme. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Women of childbearing potential should be encouraged to enroll in the Fabry patient registry (see Information for Patients in previous texts). The registry will monitor the effect of Fabrazyme on pregnant women and their offspring.
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 Information for patients as follows).
Nursing Mothers: 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.
Nursing mothers should be encouraged to enroll in the Fabry registry (see Information for Patients previously).
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 Pediatric Use as follows). 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 than do males.
Pediatric Use: The safety and efficacy of Fabrazyme were assessed in a multinational, multicenter, uncontrolled, open-label study to evaluate safety, pharmacokinetics, and pharmacodynamics in 16 pediatric patients with Fabry disease (14 males, 2 females) who were ages 8 to 16 years at first treatment (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.
Geriatric Use: Clinical studies of Fabrazyme did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.