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.

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; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Myozyme:

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

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Myozyme Side Effects - for the Professional

Myozyme

Clinical Trial Experience

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. 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).

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 [see Boxed Warning and Warnings and Precautions (5.1)].

Acute cardiorespiratory failure has been observed in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa [see Boxed Warning  and Warnings and Precautions (5.2) and Instructions for Use (2.2)].

The most common serious treatment-emergent adverse reactions occurring in >10% of patients 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 adverse reactions requiring intervention in clinical trials were infusion reactions [see Warnings and Precautions (5.4)].  Twenty of 39 patients (51%) treated with Myozyme in clinical studies developed infusion reactions. Infusion reactions, defined as an adverse reaction occurring during the infusion or within 2 hours after completion of the infusion, that occurred 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.

The most common treatment-emergent adverse reactions occurring in ≥ 20% of patients were fever, diarrhea, rash, vomiting, cough, pneumonia, otitis media, upper respiratory tract infection, gastroenteritis and decreased oxygen saturation.

Table 2 enumerates treatment-emergent adverse reactions 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.

Table 2. Summary of Adverse Reactions by System Organ Class and Preferred Term Occurring in at Least 20% of Patients Treated with Myozyme® in Clinical Trials

System Organ Class             Preferred Term	Number of Patients (N=39) n (%)	Number of Adverse Events n
Any Adverse Events =	39 (100)	1859
General disorders and administration site conditions	38 (97)
Pyrexia	36 (92)	169
Respiratory, thoracic and mediastinal disorders	38 (97)
Cough	18 (46)	69
Respiratory distress	13 (33)	18
Respiratory failure	12 (31)	24
Rhinorrhea	11 (28)	16
Tachypnea	9 (23)	15
Infections and infestations	37 (95)
Pneumonia	18 (46)	43
Otitis media	17 (44)	35
Upper respiratory tract infection	17 (44)	39
Gastroenteritis	16 (41)	17
Pharyngitis	14 (36)	26
Ear infection	13 (33)	23
Oral candidiasis	12 (31)	20
Catheter-related infection	11 (28)	15
Bronchiolitis	9 (23)	10
Nasopharyngitis	9 (23)	25
Gastrointestinal disorders	32 (82)
Diarrhea	24 (62)	62
Vomiting	19 (49)	62
Gastroesophageal reflux disease	10 (26)	13
Constipation	9 (23)	14
Skin and subcutaneous tissue disorders	32 (82)
Rash	21 (54)	72
Diaper dermatitis	14 (36)	34
Urticaria	8 (21)	25
Investigations	28 (72)
Oxygen saturation decreased	16 (41)	44
Cardiac disorders	24 (62)
Tachycardia	9 (23)	31
Bradycardia	8 (21)	18
Injury, poisoning and procedural complications	22 (56)
Post procedural pain	10 (26)	20
Blood and lymphatic system disorders	17 (44)
Anemia	12 (31)	23
Vascular disorders	14 (36)
Flushing	8 (21)	15

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 reactions observed with Myozyme treatment in this study were headache (4.1%), pharyngitis (9.1%), upper abdominal pain (15.2%), malaise (6.1%) and rhinitis (6.1%).

Immunogenicity

As with all therapeutic proteins, there is potential for 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 (12.3)]. 

Some patients who developed IgG antibodies to alglucosidase alfa in clinical studies or in the postmarketing setting were evaluated for the presence of inhibitory antibodies and tested positive for inhibition of enzyme activity and/or uptake in in vitro assays.

The effect of antibody development on the long-term efficacy of Myozyme is not fully understood. However, CRIM negative infants have shown poorer clinical response in the presence of high sustained IgG antibody titers and positive inhibitory antibodies.

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 [see Warnings and Precautions (5.4)].

Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions [see Warnings and Precautions (5.1)]. Therefore, these patients should be monitored more closely during administration of Myozyme.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Myozyme. 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.

In postmarketing experience with Myozyme, severe and serious infusion reactions have been reported, some of which were life-threatening, including anaphylactic shock [see Boxed Warning and Warnings and Precautions (5.1)].  Acute cardiorespiratory failure, possibly associated with fluid overload, has been reported in infantile-onset Pompe disease patients with pre-existing hypertrophic cardiomyopathy [see Boxed Warning and Warning and Precautions (5.2)].  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, respiratory arrest, apnea, stridor, pharyngeal edema, peripheral edema, chest pain, chest discomfort, muscle spasm, fatigue and conjunctivitis [see Warnings and Precautions (5.1) and (5.4)]. Systemic and cutaneous immune mediated reactions, including ulcerative and necrotizing skin lesions have been reported [see Warnings and Precautions (5.5)].

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Side Effects by Body System - for Healthcare Professionals

General

Assessment of side effects is based on the exposure of 60 patients with late-onset Pompe disease to alglucosidase alfa. Serious side effects included anaphylaxis, supraventricular tachycardia, coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis, and dehydration. The most common side effects reported were infusion reactions. During postmarketing experience, deaths, and serious adverse reactions have been reported, including anaphylaxis.

Hypersensitivity

Anaphylaxis and severe allergic reactions have been reported during and up to 3 hours after alglucosidase alfa infusion. Some reactions were life-threatening. At least one patient developed anaphylactic shock during alglucosidase alfa infusion that required life-support measures.

Hypersensitivity side effects have included anaphylaxis (6.7%) and severe allergic reactions. Some reactions were life-threatening and included anaphylactic shock, cardiac arrest, respiratory arrest, apnea, dyspnea, bradycardia, tachycardia, and hypotension. Other accompanying reactions included chest discomfort/pain, throat tightness, bronchospasm, wheezing, tachypnea, cyanosis, decreased oxygen saturation/hypoxia, convulsions, angioedema (including tongue or lip swelling, periorbital edema, and face edema), pruritus, rash, urticaria, hyperhidrosis, nausea, dizziness, hypertension, flushing/erythema, fever, pallor, peripheral coldness, feeling hot, restlessness, nervousness, headache, back pain, and paresthesia. Anaphylactic reactions included angioedema, throat tightness, and chest pain/discomfort.

Other

Infusion reactions are defined as side effects occurring during or within 2 hours after completion of the infusion. Delayed onset infusion reactions are defined as side effects occurring within 48 hours after completion of the infusion.

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.

Other side effects have included infusion reactions, delayed onset infusion reactions, chest discomfort or pain (16.7%), peripheral edema (16.7%), procedural pain (15%), infusion site reactions (13.3%), ear discomfort or pain (11.7%), pain (8.3%), and malaise (5%). Infusion reactions (greater than or equal to 5%) have included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall, and chest discomfort. Additional infusion reactions have included respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor, and increased lacrimation. Delayed onset infusion reactions (greater than or equal to 3%) have included urticaria, dizziness, procedural pain, pharyngolaryngeal pain, malaise, muscle spasms, musculoskeletal pain, musculoskeletal weakness, musculoskeletal stiffness, neck pain, insomnia, and epistaxis. Adverse events resulting in death during postmarketing experience have included sepsis. Infusion reactions reported in at least 2 patients during postmarketing experience included dyspnea, respiratory failure, bronchospasm, stridor, decreased oxygen saturation/hypoxia, pharyngeal edema, chest discomfort, chest pain, hypotension, hypertension, erythema, flushing, lung infection, tachycardia, cyanosis, and hypersensitivity.

Immunologic

Immunologic side effects have included the presence of IgG antibodies to alglucosidase alfa. Systemic immune mediated reactions (including possible type III immune complex-mediated reactions) have been reported during postmarketing experience.

During one study, all 59 patients with available samples treated with alglucosidase alfa developed antibodies to alglucosidase alfa. All patients who developed IgG antibodies did so within the first 3 months of exposure. There was no apparent association between mean or peak IgG antibody titers and the occurrence of side effects.

Testing was performed in patients who experienced moderate to severe or recurrent infusion reactions, for which mast cell activation was suspected. Two of 10 patients evaluated tested positive for alglucosidase alfa specific IgE binding antibodies, both of whom experienced anaphylactic reactions.

Patients who develop IgE antibodies to alglucosidase alfa appear to be at greater risk for anaphylaxis and severe allergic reactions.

Cardiovascular

Cardiovascular side effects have included coronary artery disease. Supraventricular tachycardia was reported in a patient with a history of Wolff-Parkinson-White syndrome. Acute cardiorespiratory failure has been reported in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa. 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). Adverse events resulting in death during postmarketing experience have included cardiorespiratory arrest, cardiac failure, and aortic dissection.

Musculoskeletal

Musculoskeletal side effects have included musculoskeletal pain (36.7%), musculoskeletal stiffness or tightness (15%), muscle twitching (8.3%), and intervertebral disc protrusion.

Nervous system

Nervous system side effects have included hypoacusis (33.3%), vertigo (6.7%), tremor (6.7%), and somnolence (5%). Adverse events resulting in death during postmarketing experience have included cerebrovascular accident.

Gastrointestinal

Gastrointestinal side effects have included vomiting (21.7%), constipation (10%), gastroenteritis (10%), and dyspepsia (8.3%).

Respiratory

Respiratory side effects have included upper respiratory tract infection (18.3%), exertional dyspnea (6.7%), epistaxis (5%), respiratory tract infection (5%), and pneumonia. Adverse events resulting in death during postmarketing experience have included respiratory failure, hemothorax, and pneumothorax.

Dermatologic

Dermatologic side effects have included urticaria (10%), pruritus (10%), and hyperhidrosis (8.3%). Severe cutaneous reactions (including necrotizing skin lesions) have been reported during postmarketing experience. Adverse events resulting in death during postmarketing experience have included skin necrosis.

Hematologic

Hematologic side effects have included lymphadenopathy (8.3%).

Metabolic

Metabolic side effects have included hypokalemia (5%) and dehydration.

Ocular

Ocular side effects have included blurred vision (5%).

Renal

Renal side effects have included nephrolithiasis (5%).

Endocrine

Endocrine side effects have included at least 1 case of hyperparathyroidism during postmarketing experience.

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