NAGLAZYME® (galsulfase) safety and tolerability
Safety and tolerability data were collected from 59 patients aged 3 months to 29 years in 4 open-label clinical trials and postmarketing surveys conducted in patients aged 3 months to 29 years. The mean exposure was 138 weeks. Two infants were exposed to 2 mg/kg of NAGLAZYME for 105 and 81 weeks, respectively.
The most common adverse events related to the use of NAGLAZYME occurred during administration of the drug through IV infusion.
Infusion Reactions
Despite routine pretreatment with antihistamines, infusion reactions, some severe, occurred in 33 of 59 patients treated with NAGLAZYME. The most common symptoms of drug-related infusion reactions were pyrexia, chills, rash, urticaria, dyspnea, nausea, vomiting, pruritis, erythema, abdominal pain, hypertension, and headache. Respiratory distress, chest pain, hypotension, angioedema, conjunctivitis, tremor, and cough were also reported. Infusion reactions began as early as week 1 and as late as week 146 of NAGLAZYME treatment.1
Symptoms typically abated with slowing or temporary interruption 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 NAGLAZYME administration, treatment with additional prophylactic antihistamines, and, in the event of a more severe reaction, treatment with prophylactic corticosteroids. Twenty-three of 33 patients (70%) experienced recurrent infusion reactions during multiple infusions, though not always in consecutive weeks.1
Adverse reactions
The most common serious adverse events related to the use of NAGLAZYME occurred during infusions and included apnea, pyrexia, and respiratory distress. Severe adverse reactions include chest pain, dyspnea, laryngeal edema, and conjunctivitis. The most common adverse reactions in clinical studies were rash, pain, urticaria, pyrexia, pruritus, chills, headache, nausea, vomiting, abdominal pain, and dyspnea. The most common adverse reactions requiring interventions are infusion-related reactions.
The table below enumerates adverse events reported during the 6-month placebo-controlled trial that occurred more frequently in the NAGLAZYME group than in the placebo group. Each event listed occurred in at least 2 more patients treated with NAGLAZYME than placebo-treated patients. Observed adverse events in the Phase 1, Phase 2, and open-label extension studies were not different in nature or severity.1
Type III immune complex–mediated reactions have been observed with NAGLAZYME, as with other enzyme replacement therapies. If immune-mediated reactions occur, initiate appropriate medical treatment and consider discontinuation of NAGLAZYME. The risks and benefits of re-administering NAGLAZYME following an immune-mediated reaction should be considered. Some patients have successfully continued to receive NAGLAZYME under close clinical supervision.1
Warnings and precautions
Life-threatening anaphylactic reactions have been observed in some patients during NAGLAZYME infusions and up to 24 hours after infusion. If anaphylaxis or other severe allergic reactions occur, immediately discontinue infusion and initiate appropriate treatment, which may include resuscitation, epinephrine, administering additional antihistamines, antipyretics, or corticosteroids.1
Caution should be exercised when administering NAGLAZYME to patients susceptible to fluid volume overload, because congestive heart failure may result. Appropriate medical support and monitoring measures should be readily available during NAGLAZYME infusion. Some patients may require prolonged observation times.1
Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of an apneic episode. Evaluation of airway patency should be considered prior to initiation of treatment. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) 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.1
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