Ceredase Warnings, Precautions, Pregnancy, Nursing, Abuse - Alglucerase

Ceredase Warnings, Precautions, Pregnancy, Nursing, Abuse - Alglucerase

WARNINGS

Approximately 14% of 538 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. Pre-treatment with antihistamines has allowed continued use of Ceredase in some patients. (See ADVERSE REACTIONS). As hCG has been detected in Ceredase physicians should be alert for signs of early virilization in males under the age of ten, although no cases of precocious puberty have been reported to date. 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, mutagenesis, or impairment of fertility in animals or man.

Pregnancy Category C

Animal reproductive studies have not been conducted with C 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 C Ceredase may be excreted in human milk, caution should be exercised when Ceredase is administered to a nursing woman.

ANIMAL TOXICOLOGY

A 3 month toxicity study in rats revealed testicular changes of focal atrophy and necrosis of seminiferous tubules consistent with currently known effects of hCG, which is present in Ceredase. Current experience suggests these testicular effects are specific to rats and unlikely to occur in humans.