Life-threatening anaphylactic reactions and severe allergic reactions have been observed in some patients during and up to three hours after Lumizyme® (alglucosidase alfa) infusions. Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions.1
Patients should be observed during and after the completion of each infusion by appropriate medical personnel familiar with Pompe disease and potential reactions to treatment. Some patients may require prolonged observation times. The appropriate length of post-infusion monitoring should be determined by the treating physician based on the individual patient’s clinical status and infusion history.
Following are some guidelines to follow during Lumizyme infusions:
If an infusion reaction occurs, temporarily stop the infusion, and/or administer antihistamines and/or antipyretics.
If anaphylaxis or other severe allergic reactions occur, immediate discontinuation of the administration of Lumizyme should be considered, and appropriate medical treatment should be initiated. In some cases of anaphylaxis, epinephrine has been administered. Appropriate medical treatment, may include administering antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated.
The risks and benefits of re-adminstering Lumizyme following an anaphylactic or severe allergic reaction should be considered. Some patients have been rechallenged and have continued to receive Lumizyme under close clinical supervision; however, extreme care should be exercised, with appropriate resuscitation measures available, if the product is re-administered.
Severe cutaneous and systemic immune-mediated reactions have been reported with Lumizyme treatment, occurring from several weeks to three years after infusions. Therefore patients receiving Lumizyme should be monitored for the development of systemic immune-mediated reactions involving skin and other organs.
Anaphylaxis and hypersensitivity reactions have been observed in patients during and up to 3 hours after alglucosidase alfa infusion. Some of the reactions were life-threatening and included anaphylactic shock, cardiac arrest, respiratory arrest, respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria. Other accompanying reactions included chest discomfort/pain, wheezing, tachypnea, cyanosis, decreased oxygen saturation, convulsions, pruritus, rash, hyperhidrosis, nausea, dizziness, hypertension/increased blood pressure, flushing/feeling hot, erythema, pyrexia, pallor, peripheral coldness, restlessness, nervousness, headache, back pain, and paresthesia. Some of these reactions were IgE-mediated.
If anaphylaxis or severe hypersensitivity reactions occur, immediately discontinue administration of alglucosidase alfa, and initiate appropriate medical treatment. Severe reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylaxis, epinephrine has been administered. Appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when alglucosidase alfa is administered. The risks and benefits of re-administering alglucosidase alfa following an anaphylactic or hypersensitivity reaction should be considered. Some patients have been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product .
Be sure to report any suspected adverse reactions to Sanofi Genzyme by calling, option 2
As with all therapeutic proteins, Lumizyme treatment poses potential for immunogenicity, so patients should be monitored regularly for antibody formation.
LUMIZYME® (alglucosidase alfa) is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (GAA deficiency).
WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, AND RISK OF CARDIORESPIRATORY FAILURE
Anaphylaxis and Hypersensitivity Reactions: Life-threatening anaphylaxis and hypersensitivity reactions have been observed in some patients during and after treatment with alglucosidase alfa. If anaphylaxis or severe hypersensitivity reactions occur, immediately discontinue infusion and institute appropriate medical treatment. Appropriate medical support and monitoring measures should be available during infusion.
Immune-Mediated Reactions: Monitor patients for the development of systemic immune-mediated reactions involving skin and other organs. If immune-mediated reactions occur, consider discontinuation of the administration of alglucosidase alfa, and initiate appropriate medical treatment.
Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function 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 alglucosidase alfa infusion, and some patients may require prolonged observation times that should be individualized based on the needs of the patient.
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. 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.
Risk of Antibody Development: Patients with infantile-onset Pompe disease should have a cross-reactive immunologic material (CRIM) assessment early in their disease course and be managed by a clinical specialist knowledgeable in immune tolerance induction in Pompe disease to optimize treatment. CRIM status has been shown to be associated with immunogenicity and patients’ responses to enzyme replacement therapies. There is evidence to suggest that some patients who develop high and sustained IgG antibody titers, including CRIM-negative patients, may experience reduced clinical alglucosidase alfa treatment efficacy.
Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter.
The most frequently reported adverse reactions (≥ 5%) in clinical trials were hypersensitivity reactions and included: anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia.
Please see the Full Prescribing Information for complete details, including boxed WARNING.