Anaphylaxis and severe allergic reactions have been observed in patients during or up to 3 hours after
ALDURAZYME infusions. Some of these reactions were life-threatening and included respiratory failure, respiratory
distress, stridor, tachypnea, bronchospasm, obstructive airways disorder, hypoxia, hypotension, bradycardia, and
urticaria. If anaphylactic or other severe allergic 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.
Interventions have included resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization,
and treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.
In clinical studies and postmarketing safety experience with ALDURAZYME, approximately 1% of patients
experienced severe or serious allergic reactions. In patients with MPS I, pre-existing upper airway obstruction may
have contributed to the severity of some reactions. Due to the potential for severe allergic reactions, appropriate
medical support should be readily available when ALDURAZYME is administered. Because of the potential for
recurrent reactions, some patients who experience initial severe reactions may require prolonged observation.
The risks and benefits of re-administering ALDURAZYME following an anaphylactic or severe allergic 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 with an acute febrile or respiratory illness at the time of ALDURAZYME infusion may be at greater risk for
infusion reactions. Careful consideration should be given to the patient’s clinical status prior to administration of
ALDURAZYME and consider delaying ALDURAZYME infusion.
Sleep apnea is common in MPS I patients. Evaluation of airway patency should be considered prior to initiation of
treatment with ALDURAZYME. 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.
Caution should be exercised when administering ALDURAZYME to patients susceptible to fluid overload or patients
with an acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid
restriction is indicated. These patients may be at risk of serious exacerbation of their cardiac or respiratory status
during infusions. Appropriate medical support and monitoring measures should be readily available during
ALDURAZYME infusion, and some patients may require prolonged observation times that should be based on the
individual needs of the patient.
Because of the potential for infusion reactions, patients should receive antipyretics and/or antihistamines prior to
infusion. If an infusion-related reaction occurs, regardless of pre-treatment, decreasing the infusion rate, temporarily
stopping the infusion, or administering additional antipyretics and/or antihistamines may ameliorate the symptoms.
The most serious adverse reactions reported with ALDURAZYME treatment during clinical trials were anaphylactic
and allergic reactions.
In a 26-week, placebo-controlled clinical trial in patients 6 years and older, the most commonly reported infusion
reactions regardless of treatment group were flushing, pyrexia, headache, and rash. Flushing occurred in 5 patients
(23%) receiving ALDURAZYME; the other reactions were less frequent. Less common infusion reactions included
angioedema (including face edema), hypotension, paresthesia, feeling hot, hyperhidrosis, tachycardia, vomiting,
back pain, and cough. Other reported adverse reactions included bronchospasm, dyspnea, urticaria, and pruritus.
In the open-label, uncontrolled extension phase of this clinical trial, the infusion reactions were similar, but also
included abdominal pain or discomfort and injection site reaction. Less commonly reported infusion reactions
included nausea, diarrhea, feeling hot or cold, vomiting, pruritus, arthralgia and urticaria. Additional common
adverse reactions included, back pain and musculoskeletal pain.
In an open-label, uncontrolled clinical trial in patients 6 years and younger who received ALDURAZYME treatment
for up to 52 weeks, the most commonly reported serious adverse events (regardless of relationship) in patients 6
years and younger, were otitis media (20%), and central venous catherization required for ALDURAZYME infusion
(15%). The most commonly reported adverse reactions in patients 6 years and younger were infusion reactions
reported in 35% (7 of 20) of patients and included pyrexia (30%), chills (20%), blood pressure increased (10%), tachycardia (10%),
and oxygen saturation decreased (10%). Other commonly reported infusion reactions occurring
in ≥5% of patients were pallor, tremor, respiratory distress, wheezing, crepitations (pulmonary), pruritus, and rash.
In postmarketing experience with ALDURAZYME, severe and serious infusion reactions have been reported, some
of which were life-threatening, including anaphylactic shock. Adverse reactions resulting in death reported in the
postmarketing setting with ALDURAZYME treatment included cardio-respiratory arrest, respiratory failure, cardiac
failure, and pneumonia. These events have been reported in MPS I patients with significant underlying disease.
Additional common adverse reactions included erythema and cyanosis. There have been a small number of reports
of extravasation in patients treated with ALDURAZYME. There have been no reports of tissue necrosis associated
with extravasation. Because these reactions are reported voluntarily from a population of uncertain size, it is not
always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
In clinical trials, 99 of 102 patients (97%) treated with ALDURAZYME were positive for IgG antibodies to
ALDURAZYME. In the 2 trials of patients 6 years and older, 9 patients who experienced severe infusion reactions
were tested for ALDURAZYME-specific IgE antibodies and complement activation. One of the nine patients had an
anaphylactic reaction consisting of urticaria and airway obstruction and tested positive for both
ALDURAZYME-specific IgE binding antibodies and complement activation. In the postmarketing setting,
approximately 1% of patients experienced severe or serious infusion-allergic reactions and tested positive for IgE.
Of these IgE-positive patients, some have discontinued treatment, but some have been successfully re-challenged.
The clinical significance of antibodies to ALDURAZYME, including the potential for product neutralization, is not
known.
ALDURAZYME is available by prescription only. Please see the Full Prescribing Information including Boxed Warning (PDF).
