Patients treated with ALDURAZYME may develop infusion-related hypersensitivity reactions (see ADVERSE REACTIONS). In the clinical studies, one patient developed an anaphylactic reaction approximately three hours after the initiation of the infusion. The reaction consisted of urticaria and airway obstruction. Resuscitation required an emergency tracheostomy. This patient's pre-existing MPS I related upper airway obstruction may have contributed to the severity of this reaction (see ADVERSE REACTIONS: Infusion-Related Reactions and Immunogenicity).
Some infusion-related reactions may be ameliorated by slowing the rate of infusion or treatment with additional antipyretics and/or antihistamines. If severe hypersensitivity or anaphylactic reactions occur, immediately discontinue the infusion of ALDURAZYME and initiate appropriate treatment. Caution should be exercised if epinephrine is being considered for use in patients with MPS I due to the increased prevalence of coronary artery disease in these patients.
The risks and benefits of re-administering ALDURAZYME following a severe hypersensitivity or anaphylactic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
Patients should receive antipyretics and/or antihistamines prior to infusion (see WARNINGS and ADVERSE REACTIONS). If an infusion reaction occurs, regardless of pre-treatment, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of additional antipyretics and/or antihistamines may ameliorate the symptoms.
INFORMATION FOR PATIENTS
Patients should be informed that a registry for MPS I patients has been established in order to better understand the variability and progression of MPS I disease, and to continue to monitor and evaluate treatments. Patients should be encouraged to participate and advised that their participation may involve long-term follow-up. Information regarding the registry program may be found at www.MPSIregistry.com or by calling (800) 745-4447.
No formal drug interaction studies have been conducted.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Studies to assess the mutagenic and carcinogenic potential of ALDURAZYME have not been conducted.
Reproductive studies in rats have not demonstrated impairment of fertility (see PRECAUTIONS:Pregnancy).
PREGNANCY: CATEGORY B
Reproduction studies have been performed in male and female rats at doses up to 6.2 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ALDURAZYME. However, there are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ALDURAZYME should be used during pregnancy only if clearly needed.
It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ALDURAZYME is administered to a nursing woman (See PRECAUTIONS: Information for Patients regarding a registry program. Nursing women are encouraged to participate in this program.).
Patients younger than 5 were not included in the clinical studies because of inability to comply with efficacy outcome assessments. It is not known if children younger than 5 respond differently from older children.
Clinical studies of ALDURAZYME did not include patients aged 65 and over. It is not known whether they respond differently from younger patients.