Included as part of the PRECAUTIONS section.
Anaphylaxis And Allergic Reactions
Anaphylaxis and severe allergic reactions have been
observed in patients during and up to 24 hours after NAGLAZYME infusion. Some
of the reactions were life-threatening and included anaphylaxis, shock,
respiratory distress, dyspnea, bronchospasm, laryngeal edema, and hypotension.
If anaphylaxis or other severe allergic reactions occur, NAGLAZYME should be
immediately discontinued, and appropriate medical treatment should be
initiated. In patients who have experienced anaphylaxis or other severe
allergic reactions during infusion with NAGLAZYME, caution should be exercised
upon rechallenge; appropriately trained personnel and equipment for emergency
resuscitation (including epinephrine) should be available during infusion [see
Type III immune complex-mediated reactions, including
membranous glomerulonephritis have been observed with NAGLAZYME, as with other
enzyme replacement therapies. If immune-mediated reactions occur,
discontinuation of the administration of NAGLAZYME should be considered, and
appropriate medical treatment initiated. The risks and benefits of
re-administering NAGLAZYME following an immune-mediated reaction should be
considered. Some patients have successfully been rechallenged and have
continued to receive NAGLAZYME under close clinical supervision [see ADVERSE
Risk Of Acute Cardiorespiratory Failure
Caution should be exercised when administering NAGLAZYME
to patients susceptible to fluid volume overload; such as in patients weighing
20 kg or less, patients with acute underlying respiratory illness, or patients
with compromised cardiac and/or respiratory function, because congestive heart
failure may result. Appropriate medical support and monitoring measures should
be readily available during NAGLAZYME infusion, and some patients may require
prolonged observation times that should be based on the individual needs of the
patient [see ADVERSE REACTIONS].
Acute Respiratory Complications Associated With Administration
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
(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.
Consider delaying NAGLAZYME infusions in patients who
present with an acute febrile or respiratory illness because of the possibility
of acute respiratory compromise during infusion of NAGLAZYME.
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 33 of 59 (56%) patients treated with NAGLAZYME. Serious
adverse reactions during infusion included laryngeal edema, apnea, pyrexia,
urticaria, respiratory distress, angioedema, and anaphylactoid reaction. Severe
adverse reactions included urticaria, chest pain, rash, dyspnea, apnea,
laryngeal edema, and conjunctivitis [see ADVERSE REACTIONS].
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. Twenty-three of 33 patients (70%)
experienced recurrent infusion reactions during multiple infusions though not
always in consecutive weeks.
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
If severe infusion reactions occur, immediately
discontinue the infusion of NAGLAZYME 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.
Spinal Or Cervical Cord Compression
Spinal or cervical cord compression (SCC) with resultant
myelopathy is a known and serious complication of MPS VI. SCC is expected to
occur in the natural history of the disease, including in patients on
NAGLAZYME. There have been post-marketing reports of patients treated with
NAGLAZYME who experienced the onset or worsening of SCC requiring decompression
surgery. Patients with MPS VI should be monitored for signs and symptoms of
spinal/cervical cord compression (including back pain, paralysis of limbs below
the level of compression, urinary and fecal incontinence) and given appropriate
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate carcinogenic
potential or studies to evaluate mutagenic potential have not been performed
Galsulfase at intravenous doses up to 3.0 mg/kg (about
0.5 times the recommended human dose of 1 mg/kg based on body surface area) was
found to have no effect on the fertility and reproductive performance of male
and female rats.
Use In Specific Populations
Pregnancy Category B
Adequate and well-controlled studies have not been
conducted with NAGLAZYME in pregnant women. Reproduction studies have been
performed in rats at intravenous doses up to 3 mg/kg/day (about 0.5 times the
recommended human dose of 1 mg/kg based on the body surface area) and in
rabbits at intravenous doses up to 3 mg/kg/day (about 0.97 times the
recommended human dose of 1 mg/kg based on the body surface area) and have
revealed no evidence of impaired fertility or harm to the fetus due to
NAGLAZYME. NAGLAZYME should be used during pregnancy only if clearly needed.
Pregnant women with MPS VI who are treated with NAGLAZYME
should be encouraged to enroll in the MPS VI Clinical Surveillance Program at
800-983-4587 [see PATIENT INFORMATION].
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 mother. Nursing mothers with MPS VI
who are treated with NAGLAZYME should be encouraged to enroll in the MPS VI
Clinical Surveillance Program at 800-983-4587 [see PATIENT INFORMATION].
Clinical studies with NAGLAZYME were conducted in 56
patients, ages 5 to 29 years, with the majority of these patients in the
pediatric age group [see Clinical Studies]. In addition, an open-label
study was conducted in four infants (3 months to 12.7 months) treated with 1
mg/kg (n = 2) or 2 mg/kg (n = 2) of NAGLAZYME. Safety results in infants were
consistent with results observed in patients 5 to 29 years old [see ADVERSE
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.