WARNINGS AND PRECAUTIONS
Anaphylaxis and Allergic Reactions (see Boxed Warning)
Anaphylaxis and severe allergic reactions have been
reported in some patients during and up to three hours after
MYOZYME infusion some of which were IgE-mediated.
Some of the reactions were life-threatening and included: anaphylactic shock, cardiac arrest,
respiratory distress, hypotension, bradycardia, hypoxia,
bronchospasm, throat tightness, dyspnea, angioedema, and
urticaria. Interventions have included:
cardiopulmonary resuscitation, mechanical ventilatory support,
oxygen supplementation, intravenous (IV) fluids,
hospitalization, treatment with inhaled beta-adrenergic
agonists, epinephrine, and IV corticosteroids.
[see
Adverse Reactions (6)
].
In clinical trials and postmarketing safety experience
with MYOZYME, approximately 1% of patients developed
anaphylactic shock and/or cardiac arrest during MYOZYME infusion
that required life-support measures. In clinical
trials and expanded access programs with MYOZYME, approximately
14% of patients treated with MYOZYME have developed
allergic reactions that involved at least 2 of 3 body systems,
cutaneous, respiratory or cardiovascular systems.
These events included: Cardiovascular: hypotension, cyanosis,
hypertension, tachycardia, ventricular extrasystoles,
bradycardia, pallor, flushing, nodal rhythm, peripheral
coldness; Respiratory: tachypnea,
wheezing/bronchospasm, rales, throat tightness, hypoxia,
dyspnea, cough, respiratory tract irritation, decreased oxygen
saturation; Cutaneous: angioedema, urticaria, rash, erythema,
periorbital edema, pruritus, hyperhidrosis, cold sweat, livedo
reticularis
[see
Adverse Reactions (6)
].
If anaphylactic or other severe allergic reactions occur,
immediate discontinuation of the administration of MYOZYME
should be considered, and appropriate medical treatment should
be initiated. Because of the potential for severe
allergic reactions, appropriate medical support measures,
including cardiopulmonary resuscitation equipment, should be
readily available when MYOZYME is administered.
The risks and benefits of re-administering MYOZYME
following an anaphylactic or severe allergic reaction should be
considered. Some patients have been
rechallenged and have continued to receive MYOZYME under close
clinical supervision. Extreme care should be exercised, with
appropriate resuscitation measures available, if the decision is
made to re-administer the product
[see
Adverse Reactions
]
.
Risk of Acute Cardiorespiratory Failure (see Boxed Warning)
Acute cardiorespiratory failure requiring intubation and
inotropic support has been observed up to 72 hours after
infusion with MYOZYME in infantile-onset Pompe disease patients
with underlying cardiac hypertrophy, possibly associated with
fluid overload with intravenous administration of
MYOZYME
[see
Instructions for Use
]
. Patients with acute underlying respiratory illness, compromised cardiac function and/or sepsis may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical
support and monitoring measures should be readily available
during MYOZYME infusion, and infants with cardiac dysfunction
may require prolonged observation times that should be
individualized based on the needs of the patient
[see
Dosage and Administration
].
Risk of Cardiac Arrhythmia and Sudden Cardiac Death During General Anesthesia for Central Venous Catheter Placement
Cardiac arrhythmia, including ventricular fibrillation,
ventricular tachycardia and bradycardia, resulting in cardiac
arrest or death, or requiring cardiac resuscitation or
defibrillation have been observed in infantile-onset Pompe
disease patients with cardiac hypertrophy, associated with the
use of general anesthesia for the placement of a central venous
catheter intended for MYOZYME infusion.
Caution should be used when administering general
anesthesia for the placement of a central venous catheter in
infantile-onset Pompe disease patients with cardiac
hypertrophy.
Infusion Reactions
Infusion reactions occurred in 20 of 39 (51%) of
patients treated with MYOZYME in clinical studies
[see
Adverse Reactions (6)
]
. Some reactions were severe.
Severe infusion reactions reported in more than 1 patient in
clinical studies and the expanded access program included:
fever, decreased oxygen saturation, tachycardia, cyanosis and
hypotension. Other infusion reactions reported in more
than 1 patient in clinical studies and the expanded access
program included: rash, flushing, urticaria, fever, cough,
tachycardia, decreased oxygen saturation, vomiting, tachypnea,
agitation, increased blood pressure/hypertension, cyanosis,
irritability, pallor, pruritus, retching, rigors, tremor,
hypotension, bronchospasm, erythema, face edema, feeling hot,
headache, hyperhidrosis, increased lacrimation, livedo
reticularis, nausea, periorbital edema, restlessness and
wheezing. Some patients were pre-treated with
antihistamines, antipyretics and/or steroids. Infusion
reactions occurred in some patients after receiving
antipyretics, antihistamines, or steroids. Infusion
reactions may occur at any time during, or up to 2 hours after,
the infusion of MYOZYME, and are more likely with higher
infusion rates.
Patients with advanced Pompe disease may have compromised
cardiac and respiratory function, which may predispose them to a
higher risk of severe complications from infusion
reactions. Therefore, these patients should be
monitored more closely during administration of
MYOZYME. Patients with an acute illness at the time of
MYOZYME infusion may be at greater risk for infusion
reactions. Careful consideration should be given to
the patient's clinical status prior to administration
of MYOZYME.
If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion or allergic reactions occur, immediate discontinuation of the administration of MYOZYME should be considered, and appropriate medical treatment should be initiated
[see
Adverse Reactions
]
. Severe infusion reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. Patients who have experienced infusion reactions should be treated with caution when they are re-administered MYOZYME.
Immune Mediated Reactions
Severe cutaneous and systemic immune mediated reactions
have been reported in postmarketing safety experience with
MYOZYME in at least 2 patients, including ulcerative and
necrotizing skin lesions, and possible type III immune
complex-mediated reactions
[see
Adverse Reactions
]
. These reactions occurred
several weeks to 3 years after initiation of MYOZYME
infusions. Skin biopsy in one patient demonstrated
deposition of anti-rh-GAA antibodies in the lesion.
Another patient developed severe inflammatory arthropathy in
association with fever and elevated erythrocyte sedimentation
rate. Patients should be monitored for the development
of systemic immune complex-mediated reactions involving skin and
other organs while receiving MYOZYME. If immune mediated reactions occur, discontinuation of the administration of MYOZYME should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune mediated reaction should be considered. Some patients have successfully been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.
Monitoring: Laboratory Tests
Patients should be monitored for IgG antibody formation
every 3 months for 2 years and then annually
thereafter. Testing for IgG titers may also be
considered if patients develop allergic or other immune mediated
reactions. Patients who experience anaphylactic or
allergic reactions may also be tested for IgE antibodies to
alglucosidase alfa and other mediators of anaphylaxis
.
There are no marketed tests for antibodies against
alglucosidase alfa. Contact your local Genzyme
representative or Genzyme Corporation at 1-800-745-4447 for
information on testing and to obtain a sample collection box.
Results from 2 intravenous repeated-dose animal
toxicology studies using doses of 100 or 200 mg/kg MYOZYME
(about 1.6 to 3.2 times the recommended human dose based on body
surface area) in Cynomolgus monkeys to evaluate the possibility
of liver accumulation over time showed GAA levels above
background in liver tissue several days following the last dose;
however, no concurrent changes in liver enzymes or
histopathology were observed. Liver enzymes should be evaluated prior to the initiation of MYOZYME
treatment and periodically thereafter.
USE IN SPECIFIC POPULATIONS
Pregnancy
Teratogenic Effects
Pregnancy Category B. Reproduction studies have been performed in pregnant mice at intravenous doses up to 40 mg/kg/day (plasma AUC of 64.6 mg•min/mL, 0.4 times the human steady-state exposure at the recommended bi-weekly dose) and pregnant rabbits at intravenous doses up to 40 mg/kg/day (plasma AUC of 85 mg•min/mL, 0.5 times the human steady-state exposure at the recommended bi-weekly dose) and have revealed no evidence of impaired fertility or harm to the fetus due to Myozyme. 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.
Women of childbearing potential are encouraged to
enroll in the Pompe Registry.
[see
Patient Counseling Information
].
Labor and Delivery
Information on the effect of MYOZYME on labor and
delivery is unknown. Pregnant women are encouraged to
enroll in the Pompe Registry
[see
Patient Counseling Information
].
Nursing Mothers
It is not known whether MYOZYME is excreted in human
milk. Because many drugs are excreted in human milk,
caution should be exercised when MYOZYME is administered to a
nursing woman.
Nursing women are encouraged to enroll in the Pompe
Registry
[see
Patient Counseling Information
].
Pediatric Use
Pediatric patients aged 1 month to 3.5 years at time of
first infusion have been treated with MYOZYME in clinical trials
[see
Clinical Studies
].
Other open-label clinical trials of MYOZYME
have been performed in older pediatric patients ranging from 2
to 16 years at the initiation of treatment (juvenile-onset Pompe
disease); however the risks and benefits of MYOZYME treatment
have not been established in the juvenile-onset Pompe disease
population.
Geriatric Use
Clinical studies did not include any subjects aged 65
years and older. It is not known whether they respond
differently than younger subjects.
[see
Clinical Studies
]
.
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