Fabrazyme Warnings, Precautions, Pregnancy, Nursing, Abuse - Agalsidase Beta

Fabrazyme Warnings, Precautions, Pregnancy, Nursing, Abuse - Agalsidase Beta

WARNINGS

Infusion reactions occurred in many patients treated with Fabrazyme^Ò (see ADVERSE REACTIONS). 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 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^Ò is administered.

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 WARNINGS). Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme^Ò.

Most patients develop IgG antibodies to Fabrazyme^Ò (see ADVERSE REACTIONS:

Immunogenicity). Some patients developed IgE or skin test reactivity specific to Fabrazyme^Ò. Physicians should consider testing for IgE (see Laboratory Tests) in patients who experienced suspected allergic reactions and consider the risks and benefits of continued treatment in patients with anti- Fabrazyme^Ò IgE.

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), 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^Ò 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. For more information visit www.fabryregistry.com or call (800) 745-4447.

There are no marketed tests for antibodies against Fabrazyme^Ò. If testing is warranted, contact your local Genzyme representative or Genzyme Corporation at 800-745-4447.

There are no animal or human studies to assess the carcinogenic or mutagenic potential of Fabrazyme^Ò. There are no studies assessing the potential effect of Fabrazyme^Ò on fertility in humans.

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^Ò. There are, however, no adequate and well-controlled studies in pregnant women. 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 PRECAUTIONS: Information for Patients).

It is not known whether Fabrazyme^Ò is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fabrazyme^Ò is administered to a nursing woman.

Nursing mothers should be encouraged to enroll in the Fabry registry (see PRECAUTIONS: Information for Patients).

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. Generally, the rates of progression of organ impairment are slower than in male Fabry disease patients and severity of signs and symptoms is variable.

Two women were enrolled in the clinical studies with Fabrazyme^Ò. 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.

The safety and effectiveness of Fabrazyme^Ò in pediatric patients have not been established.

Clinical studies of Fabrazyme^Ò did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.