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Serious hypersensitivity reactions, including anaphylactic reactions, have been reported during MYOZYME infusion, some of which were IgE mediated. Some reactions were life-threatening. Reactions generally occurred shortly after initiation of the infusion. A small number of patients (< 1%) in clinical trials and in the commercial setting developed anaphylactic shock and/or cardiac arrest during MYOZYME infusion that required life-support measures. Patients presented with a constellation of signs and symptoms, primarily respiratory, cardiovascular, edematous and/or cutaneous in nature. (Please see WARNINGS section of the full prescribing information.)
There is a risk of cardiac arrhythmia and sudden cardiac death during general anesthesia for central venous catheter placement 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.
There is a risk of acute cardiorespiratory failure. One such event requiring intubation and inotropic support has been observed after infusion with Myozyme in one infantile-onset Pompe disease patient with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of Myozyme. (See full prescribing information for information on appropriate infusion volumes.)
The most common adverse reactions requiring intervention were infusion-related reactions which occurred in 20 of 39 (51%) of patients treated with Myozyme in clinical studies. Some reactions were severe. Severe infusion reactions reported in more than one patient in clinical studies and the expanded access program included pyrexia, decreased oxygen saturation, tachycardia, cyanosis, and hypotension. Other infusion reactions reported as mild to moderate in more than one patient in clinical studies and the expanded access program included rash, flushing, urticaria, pyrexia, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure, cyanosis, hypertension, irritability, pallor, pruritus, retching, rigors, tremor, hypotension, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, lacrimation increased, 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 two hours after, the infusion of Myozyme, and are more likely with higher infusion rates.
Infusion-related reactions reported from worldwide post-marketing sources have included cardiac arrest, bradycardia, angioneurotic edema, pharyngeal edema, edema peripheral, chest pain, chest discomfort, dyspnea, muscle spasm, fatigue, respiratory distress, throat tightness and conjunctivitis. Severe reactions included cardiac arrest, bradycardia, chest pain, and dyspnea. The majority of patients continued to receive treatment with Myozyme, some under close clinical supervision.
Patients with an acute underlying illness at the time of Myozyme infusion appear to be at greater risk for infusion reactions. Careful consideration should be given to the patient’s clinical status prior to administration of Myozyme.
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.
If an infusion reaction occurs, regardless of pre-treatment, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion reactions occur, immediate discontinuation of the administration of Myozyme should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylactic reaction and cardiac arrest, epinephrine and/or cardiopulmonary resuscitation measures have been administered. Early detection of signs and symptoms of hypersensitivity or anaphylactic reactions may assist in effective management of patients and prevent possible significant or irreversible outcomes. Because of the potential for severe infusion reactions, appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when Myozyme is administered. Patients who have experienced infusion reactions should be treated with caution when readministered Myozyme.
The effect of antibody development on the long term efficacy of Myozyme is not fully understood. There is an observation that some patients who develop high and sustained anti-alglucosidase alfa antibody titers, including those who possess two null mutations, have a poorer clinical response. The cause of a poorer clinical response in some of these patients is thought to be multi-factorial.
Some IgG positive patients in clinical trials and on commercial therapy who were evaluated for the presence of inhibitory antibodies tested positive for inhibition of enzyme activity and/or uptake in in vitro assays.
Patients in clinical trials, expanded access programs and on commercial therapy have undergone testing for MYOZYME-specific IgE antibodies. Testing was performed for infusion reactions, especially moderate to severe or recurrent reactions, for which mast-cell activation was suspected. A small number of these patients tested positive for MYOZYME specific IgE binding antibodies, some of whom experienced an anaphylactic reaction. Some patients have been successfully rechallenged using a slower infusion rate at lower initial doses and have continued to receive treatment with Myozyme under close clinical supervision.
Myozyme is available by prescription only.
Side effects should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. To learn more, please see the full prescribing information or contact Genzyme Medical Information at 1-800-745-4447.
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