Cerezyme Drug Information

is indicated for the treatment of non-central nervous system (CNS) manifestations of Type 1 or Type 3 Gaucher disease in adults and pediatric patients. CEREZYME is a hydrolytic lysosomal glucocerebrosidase-specific enzyme indicated for the treatment of non-central nervous system (CNS) manifestations of Type 1 or Type 3 Gaucher disease in adults and pediatric patients.

Clinical Trials and Postmarketing Experience

The following adverse reactions associated with the use of imiglucerase were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. See Table 2 for adverse reactions occurring in adults and pediatric patients treated with CEREZYME in clinical trials and the postmarketing setting.

Table 2: Adverse Reactions in Adults and Pediatric Patients Treated with CEREZYME Adverse Reactions Nervous system disorders dizziness, headache Cardiac disorders tachycardia Vascular disorders cyanosis, Signs and symptoms suggestive of hypersensitivity reactions including anaphylaxis and other infusion-associated reactions . flushing, hypotension, hypertension Respiratory, thoracic and mediastinal disorders cough, dyspnea, pneumonia, pulmonary hypertension Gastrointestinal disorders abdominal pain, diarrhea, nausea, vomiting Immune system disorders anaphylaxis, hypersensitivity Skin and subcutaneous tissue disorders angioedema, pruritus, rash, urticaria Musculoskeletal and connective tissue disorders back pain General disorders and administration site conditions chest discomfort, chills, fatigue, infusion-site burning, infusion-site discomfort, infusion-site swelling, pyrexia

Immunogenicity

The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of CEREZYME or of other imiglucerase products. Approximately 15% of patients treated and tested to date have developed IgG antibody to CEREZYME during the first year of therapy.

Patients who developed IgG antibody did so largely within 6 months of treatment and rarely developed antibodies to CEREZYME after 12 months of therapy. Approximately 46% of patients with detectable IgG antibodies experienced symptoms of hypersensitivity. Patients with antibody to CEREZYME have higher risk of hypersensitivity reaction . Patients who developed IgG antibody to CEREZYME had increased elimination half-life compared to patients without antibody .

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CEREZYME during pregnancy. Pregnant women exposed to CEREZYME and health care providers are encouraged to contact the Gaucher patient registry at 1-800-745-4447, extension 15500 or visit www.registrynxt.com. Risk Summary Available data on more than 500 pregnancies from the international Gaucher Disease registry, postmarketing reports, published observational studies and case reports with CEREZYME or non–US-licensed imiglucerase use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

There are risks associated with symptomatic Type I Gaucher disease in pregnancy (see Clinical Considerations ). No animal reproduction studies have been conducted with imiglucerase. The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnancy may exacerbate existing Type 1 Gaucher disease symptoms or result in new disease manifestations. Untreated symptomatic Type 1 Gaucher disease may lead to complications during pregnancy, including hepatosplenomegaly, which can interfere with the normal growth of a pregnancy and thrombocytopenia, which can lead to excessive bleeding.

Pediatric Use The safety and effectiveness of CEREZYME for the treatment of non-CNS manifestations of Type 1 or Type 3 Gaucher disease have been established in pediatric patients. Use of CEREZYME for the treatment of non-CNS manifestations of Type 1 Gaucher disease is supported by evidence from adequate and well-controlled trials in adults and pediatric patients 12 years of age and older and additional safety and efficacy data from an observational study of Type 1 Gaucher disease in pediatric patients . Use of CEREZYME for the treatment of non-CNS manifestations of Type 3 Gaucher disease is supported by evidence from adequate and well-controlled trials in adults and pediatric patients 12 years of age and older with Type I Gaucher disease and additional safety and efficacy data from an observational study of Type 3 Gaucher disease in adults and pediatric patients .