WARNINGS
Approximately 13% of patients treated clinically and tested to date have developed IgG antibody to Ceredase® during the first year of therapy. It appears that patients who will develop IgG antibody are most likely to do so within 6 months of treatment and will rarely develop antibodies to Ceredase® after 12 months of therapy. Approximately 25% of patients with detectable IgG antibodies experienced symptoms of hypersensitivity.
Thus, patients with antibody to Ceredase® have a higher risk of hypersensitivity reaction. Conversely, not all patients with symptoms of hypersensitivity have detectable antibody and further evaluation of their antibody isotypes and mechanisms is continuing. It is suggested that patients be monitored periodically for IgG antibody formation.
At present, should a patient experience a reaction with symptoms suggestive of hypersensitivity, it is recommended that a serum sample for tryptase levels and complement activation be drawn within two hours of the event after appropriate treatment of the symptoms. Subsequent serum for testing antibody to Ceredase® would be helpful. Decreased efficacy has been noted in less than 0.5% of treated patients due to antibodies to Ceredase® .
PRECAUTIONS
General
Therapy with Ceredase® (alglucerase injection) should be directed by physicians knowledgeable in the management of patients with Gaucher disease. Treatment with Ceredase® should be approached with caution in patients who have exhibited symptoms of hypersensitivity to the product. Pretreatment with antihistamines has allowed continued use of Ceredase® in some patients (see ADVERSE REACTIONS ). Ceredase® should also be used with caution in patients with androgen sensitive malignancies, e.g., prostate cancer and patients with known prior allergies to hCG.
Ceredase® is prepared from pooled human placental tissue that may contain the causative agents of some viral diseases. Manufacturing steps have been designed to reduce the risk of transmitting viral infectious agents. These steps have demonstrated in vitro inactivation of a panel of model viruses, including human immunodeficiency virus (HIV-1). The risk of contamination from slowly acting or latent viruses, including the Creutzfeldt-Jacob disease agent, is believed to be remote but has not been tested. Accordingly, the benefits and the risks of treatment with this product should be assessed prior to use.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies have not been conducted to assess the potential effects of Ceredase® on carcinogenesis or mutagenesis. Histopathology studies using hCG-reduced Ceredase® to detect effects on spermatogenesis in rats have revealed no testicular changes.
Pregnancy Category C
Animal reproductive studies have not been conducted with Ceredase® . It is also not known whether Ceredase® can cause fetal harm when administered to a pregnant woman, or can affect reproductive capacity. Ceredase® should be given to a pregnant woman only if clearly needed.
Nursing Mothers
Since Ceredase® may be excreted in human milk, caution should be exercised when Ceredase® is administered to a nursing woman.
Pediatric Use
The safety and effectiveness of Ceredase® (alglucerase injection) have been established in patients between 2 and 16 years of age. Use of Ceredase® in this age group is supported by evidence from adequate and well-controlled studies of Ceredase® and Cerezyme® (imiglucerase for injection) in adults and pediatric patients, with additional data obtained from the medical literature and from long-term postmarketing experience. Ceredase® has been administered to patients younger than 2 years of age, however the safety and effectiveness in patients younger than 2 have not been established.
As hCG has been detected in Ceredase® , physicians should be alert for signs of early virilization in males under the age of ten. One case of precocious puberty has been reported to date, however due to the recent introduction of manufacturing steps designed to reduce the level of hCG in Ceredase® , the likelihood of this occurrence is reduced.
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