Infusion Reactions

Because of the potential for infusion reactions, patients should receive antihistamines with or without antipyretics prior to infusion. Despite routine pretreatment with antihistamines infusion reactions, some severe, occurred in 30 of 55 patients treated with NAGLAZYME. Severe symptoms included angioneurotic edema, hypotension, dyspnea, bronchospasm respiratory distress, apnea, and urticaria. The most common symptoms of infusion reactions included fever, chils/rigors headache, rash, and mild to moderate urticaria. Nausea, vomiting, elevated blood pressure, retrostemal pain, abdominal pain, malaise, and joint pain were also reported. Initial reactions were observed as late as Week 55 of treatment.

Symptoms typically abated with slowing or temporary interrption of the infusion and administration of additional antihistamines antipyretics, and occasionally corticosteroids. Most patients were able to complete their infusions. Subsequent infusions were managed with a slower rate of NAG LAZY ME administration treatment with additional prophylactic antihistamines, and, in the event of a more severe reaction, treatment with prophylactic corti co steroids. Despite these measures, 13 of 30 patients had additional infusion reactions.

If severe infusion reactions occur, immediately discontinue the infusion of NAG LAZY ME and initiate appropriate treatment. The risks and benefits of re-administering NAGLAZYME following a severe reaction should be considered.

No factors were identified that predisposed patients to infusion reactions. There was no association between severity of infusion reactions and titer of anti-galsulfase antibodies.

General

Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apneic episodes. Evaluation of airway patency should be considered prior to initiation of treatment. Patients using supplemental oxygen or continuous positive airway pressure (CP AP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction, or extreme drowsiness/sleep induced by antihistamine use.

Consider delaying NAGLAZYME infusions in patients who present with an acute febrile or respiratory illness.

Carcinogenesis, Mutagenesis, Impairment of Fertilty

Studies to assess the mutagenic and carcinogenic potential of NAGLAZYME 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 rats at doses up to 3 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to NAGLAZYME. 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.

Nursing Mothers

It is not known whether NAGLAZYME is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NAGLAZYME is administered to a nursing woman. (See PRECAUTIONS: Information for Patients regarding the Clinical Surveilance Program. Nursing women are encouraged to participate in this program.

Pediatric Use

The majority of individuals in the clinical studies were pediatric patients; however, patients younger than 5 years of age were not included in the clinical studies. Safety and effcacy in patients younger than 5 years of age have not been evaluated.

Geriatric Use

Clinical studies of NAGLAZYME did not include patients older than 29 years of age. It is not known whether older patients respond differently from younger patients.

Bookmark this page: