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The most serious adverse reactions reported with MYOZYME (alglucosidase alfa) were cardiorespiratory failure, anaphylactic reactions, and cardiac arrest. Cardiorespiratory failure, possibly associated with fluid overload, was reported in one infantile-onset Pompe disease patient, and pre-existing cardiac hypertrophy likely contributed to the severity of the reaction (see WARNINGS: Risk of Acute Cardiorespiratory Failure). Anaphylactic reactions have been reported during MYOZYME infusion (see BOXED WARNING: Risk of Hypersensitivity Reactions, and WARNINGS: Hypersensitivity Reactions).

The most common serious treatment-emergent adverse events (regardless of relationship) observed in clinical studies with MYOZYME (alglucosidase alfa) were pneumonia, respiratory failure, respiratory distress, catheter-related infection, respiratory syncytial virus infection, gastroenteritis, and fever.

The most common treatment-emergent adverse events (regardless of relationship) were fever, diarrhea, rash, vomiting, cough, pneumonia, otitis media, upper respiratory tract infection, gastroenteritis and decreased oxygen saturation.

The most common adverse reactions requiring intervention were infusion-related reactions (see WARNINGS: Infusion Reactions). Twenty of 39 patients (51%) treated with MYOZYME (alglucosidase alfa) in clinical studies developed infusion reactions during the infusion or during the 2 hours following infusion. The majority of these reactions were mild to moderate. Infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included rash, flushing, urticaria, pyrexia, cough, tachycardia, decreased oxygen saturations, 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. Most infusion-related reactions requiring intervention were ameliorated with slowing of the infusion rate, temporarily stopping the infusion, and/or administration of antipyretics, antihistamines, or steroids.

The data described below reflect exposure of 39 Pompe disease patients to 20 or 40 mg/kg of MYOZYME (alglucosidase alfa) administered every other week in 2 separate clinical trials for periods ranging from 1 to 106 weeks (mean 61 weeks). Patients were ages 1 month to 3.5 years at first treatment. The population was nearly evenly distributed in gender (18 females and 21 males).

Because clinical trials are conducted under more controlled conditions, the observed adverse reaction rates may not predict the rates observed in patients in clinical practice.

Table 2 enumerates treatment-emergent adverse events (regardless of relationship) that occurred in at least 20% of patients treated with MYOZYME (alglucosidase alfa) in clinical trials described above. Reported frequencies of adverse events have been classified by MedDRA terms.

Five additional juvenile-onset Pompe disease patients were evaluated in a single-center, open-label, non-randomized, uncontrolled clinical trial. Patients were ages 5 to 15 years, ambulatory (able to walk at least 10 meters in 6 minutes), and not receiving invasive ventilatory support at study entry. All 5 patients received treatment with 20 mg/kg

Table 2: Summary of Adverse Events by System Organ Class and Preferred Term Occurring in at Least 20% of Patients Treated with MYOZYME (alglucosidase alfa) in Clinical Trials

MYOZYME (alglucosidase alfa) for 26 weeks. The most common treatment-emergent adverse events (regardless of causality) observed with MYOZYME (alglucosidase alfa) treatment in this study were headache, pharyngitis, upper abdominal pain, malaise, and rhinitis.

Significant hypersensitivity reactions have been reported from worldwide post-marketing sources in patients treated with MYOZYME (alglucosidase alfa) . Some of these patients experienced life-threatening anaphylactic reactions, including anaphylactic shock, some of which were IgE-mediated. Reactions generally occurred shortly after initiation of the infusion. Patients presented with a constellation of signs and symptoms, primarily respiratory, cardiovascular, edematous and/or cutaneous in nature.

Infusion-associated reactions (IARs) 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. Those IARs assessed as severe included cardiac arrest, bradycardia, chest pain, and dyspnea. The majority of patients continued to receive treatment with MYOZYME (alglucosidase alfa) , some under close clinical supervision.

Significant skin lesions (necrotizing inflammation) were reported in 1 patient following MYOZYME (alglucosidase alfa) treatment in a post-marketing setting. After temporary discontinuation of MYOZYME (alglucosidase alfa) treatment, lesions resolved and the patient was able to continue on therapy.

Immunogenicity

The majority of patients (34 of 38; 89%) in the two clinical trials tested positive for IgG antibodies to alglucosidase alfa. The data reflect the percentage of patients whose test results were considered positive for antibodies to alglucosidase alfa using an enzyme-linked immunosorbent assay (ELISA) and radioimmunoprecipitation (RIP) assay for alglucosidase alfa-specific IgG antibodies. Most patients who develop antibodies do so within the first 3 months of exposure. There is evidence to suggest that patients developing sustained titers ≥ 12,800 of anti-alglucosidase alfa antibodies may have a poorer clinical response to treatment, or may lose motor function as antibody titers increase. Treated patients who experience a decrease in motor function should be tested for neutralization of enzyme uptake or activity. Five patients with antibody titers ≥ 12,800 at Week 12 had an average increase in clearance of 50% from Week 1 to Week 12 (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

The effect of antibody development on the long-term efficacy of MYOZYME (alglucosidase alfa) 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.

Infusion reactions were reported in 20 of 39 patients (51%) treated with MYOZYME (alglucosidase alfa) in clinical studies and appear to be more common in antibody-positive patients: 8 of 15 patients with high antibody titers experienced infusion reactions whereas none of 3 antibody-negative patients experienced infusion reactions.

Patients in clinical trials, expanded access programs and on commercial therapy have undergone testing for MYOZYME (alglucosidase alfa) -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 (alglucosidase alfa) specific IgE binding antibodies, some of whom experienced an anaphylactic reaction (see WARNINGS: Hypersensitivity Reactions). Some patients have been successfully rechallenged using a slower infusion rate at lower initial doses and have continued to receive treatment with MYOZYME (alglucosidase alfa) under close clinical supervision.

No drug interaction studies have been performed.

Last reviewed on RxList: 2/2/2009
This monograph has been modified to include the generic and brand name in many instances.