Myozyme Side Effects

Generic Name: alglucosidase alfa

Please note - some side effects for Myozyme may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Myozyme - for the Consumer

Myozyme

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Myozyme:

Constipation; diarrhea; heartburn; runny nose.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation, irritability, or restlessness; blue skin or nails; chest pain or tightness; chills; cold hands or feet; ear pain; excessive or cold sweat; fast, slow, or irregular heartbeat; feeling hot; fever; flushing; headache; increased tear production; nausea; pain, swelling, or redness at the injection site; pale skin; purplish skin discoloration; rapid or difficult breathing; severe headache or dizziness; stomach pain; swelling of the hands, legs, or feet; throat tightness; tremor; unexplained cough; unusual tiredness or weakness; vomiting; wheezing; white patches in the mouth.

Myozyme Side Effects - for the Professional

Myozyme

The most serious adverse reactions reported with Myozyme were anaphylactic reactions, acute cardiorespiratory failure, and cardiac arrest.

Anaphylactic reactions have been reported during and within 3 hours after Myozyme infusion.

Acute cardiorespiratory failure, possibly associated with fluid overload, has been reported in infantile-onset Pompe disease patients, and pre-existing cardiac hypertrophy likely contributed to the severity of the reaction.

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

The most common treatment-emergent adverse reactions (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 reactions.  Twenty of 39 patients (51%) treated with Myozyme in clinical studies developed infusion reactions during the infusion or during the 2 hours following infusion.  The majority of infusion reactions were mild to moderate.  Infusion reactions reported in more than 1 patient in clinical studies and the expanded access program include: rash, flushing, urticaria, fever, 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, increased lacrimation, livedo reticularis, nausea, periorbital edema, restlessness and wheezing.  Most infusion 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 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 reactions (regardless of relationship) that occurred in at least 20% of patients treated with Myozyme 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 Myozyme for 26 weeks.  The most common treatment-emergent adverse events (regardless of causality) observed with Myozyme treatment in this study were headache, pharyngitis, upper abdominal pain, malaise and rhinitis.

In postmarketing experience with Myozyme, severe and serious infusion reactions have been reported, some of which were life-threatening, including anaphylactic shock.  Acute cardiorespiratory failure, possibly associated with fluid overload, has been reported in infantile-onset Pompe disease patients with pre-existing hypertrophic cardiomyopathy.  In addition to the infusion reactions reported in clinical trials and expanded access programs, the following infusion reactions have been reported in patients during postmarketing use of Myozyme: cardiac arrest, pharyngeal edema, peripheral edema, chest pain, chest discomfort, muscle spasm, fatigue and conjunctivitis.  Systemic and cutaneous immune mediated reactions, including ulcerative and necrotizing skin lesions have been reported.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 

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.

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 2 null mutations, have a poorer clinical response.

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 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-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.

Side Effects by Body System

Hypersensitivity

Hypersensitivity side effects have been reported including anaphylactic reactions.

Some reactions were life-threatening. One patient developed anaphylactic shock during alglucosidase alfa infusion that required life-support measures.

Other

Other side effects including infections and infestations (95%) have been reported. These have included pneumonia (46%), otitis media (44%), upper respiratory tract infection (44%), gastroenteritis (41%), pharyngitis (36%), ear Infection (33%), oral candidiasis (31%), catheter related infection (28%), bronchiolitis (23%), and nasopharyngitis (23%).

General

General side effects including pyrexia (92%) and post procedural pain (26%) have been reported.

Immunologic

Immunologic side effects including the presence of IgG antibodies to alglucosidase alfa (89%) have been reported.

The data reflect the percentage of patients whose test results were considered positive for antibodies to alglucosidase alfa. Most patients who developed antibodies did so within the first three months of exposure. There is evidence to suggest that patients developing sustained titers greater than or equal to 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 greater than or equal to 12,800 at week twelve had an average increase in clearance of 50% from week one to week twelve.

Infusion reactions were reported in twenty of thirty nine patients treated with alglucosidase alfa in clinical studies and appear to be more common in antibody-positive patients. Eight of fifteen patients with high antibody titers experienced infusion reactions whereas none of the three antibody-negative patients experienced infusion reactions.

Testing was performed for infusion reactions, especially moderate to severe or recurrent reactions, for which mast cell activation was suspected. Three of these patients tested positive for alglucosidase alfa specific IgE binding antibodies, one of whom experienced an anaphylactic reaction.

Gastrointestinal

Gastrointestinal side effects including diarrhea (62%), vomiting (49%), gastroesophageal reflux disease (26%), and constipation (23%) have been reported.

Dermatologic

Dermatologic side effects including rash (54%), diaper dermatitis (36%), urticaria (21%), angioneurotic edema, erythema, periorbital edema, pruritus, hyperhidrosis, cold sweats, and livedo reticularis have been reported.

Respiratory

Respiratory side effects have been reported including cough (46%), decreased oxygen saturation (41%), respiratory distress (33%), respiratory failure (31%), rhinorrhea (28%), tachypnea (23%), wheezing/bronchospasm, rales, throat tightness, hypoxia, dyspnea, and respiratory tract irritation.

Hematologic

Hematologic side effects including anemia (31%) have been reported.

Cardiovascular

Cardiovascular side effects including tachycardia (23%), bradycardia (21%), flushing (21%), hypotension, cyanosis, hypertension, ventricular extrasystoles, pallor, nodal rhythm, and peripheral coldness have been reported. Cardiac arrhythmia, including ventricular fibrillation, ventricular tachycardia, and bradycardia, resulting in cardiac arrest or death, or requiring cardiac resuscitation or defibrillation have been reported 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 alglucosidase alfa infusion).

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.