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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].
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].
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].
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 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. Nephrotic syndrome secondary to membranous glomerulonephritis was observed in a few Pompe patients treated with alglucosidase alfa and who had persistently positive anti-rhGAA IgG antibody titers [see ADVERSE REACTIONS]. In these patients renal biopsy was consistent with immune complex deposition. Patients improved following treatment interruption. It is therefore recommended to perform periodic urinalysis.
Patients should be monitored for the development of systemic immune 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.
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
Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness. Therefore, caution should be used when administering general anesthesia for the placement of a central venous catheter intended for MYOZYME infusion. Ventricular arrhythmias 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 during general anesthesia for central venous catheter placement.
Infusion reactions occurred in 20 of 39 (51%) patients treated with MYOZYME in clinical studies [see ADVERSE REACTIONS]. 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.
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.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with MYOZYME.
MYOZYME at intravenous doses up to 40 mg/kg, administered every other day (plasma AUC of 64.6 mg•min/mL, 0.4 times the human steady-state exposure at the recommended bi-weekly dose) had no effect on fertility and reproductive performance in mice.
Use In Specific Populations
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 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 INFORMATION].
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 INFORMATION].
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.
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].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/5/2016
Additional Myozyme Information
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