Myozyme

What Is Myozyme?

Myozyme (alglucosidase alfa) contains an enzyme that is used to treat a glycogen storage disorder called Pompe disease, (also called GAA deficiency) in adults and children who are at least 8 years old.

What Are Side Effects of Myozyme?

Common side effects of Myozyme include:

• mild skin rash or itching
• diarrhea
• constipation
• stomach pain or upset
• vomiting
• sore throat
• neck pain
• pain or swelling in your arms or legs
• infusion site reactions (pain, swelling, burning, or irritation)
• fever
• cough
• runny nose
• pneumonia
• ear infection
• upper respiratory tract infection
• oral thrush
• gastroesophageal reflux disease (GERD)
• hives
• fast or slow heart rate
• anemia, or
• flushing

Dosage for Myozyme

The recommended dosage regimen of Myozyme is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion.

What Drugs, Substances, or Supplements Interact with Myozyme?

Myozyme may interact with other drugs. Tell your doctor all medications and supplements you use.

Myozyme During Pregnancy and Breastfeeding

Myozyme is not expected to harm a fetus. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is unknown if this drug passes into breast milk or if it could harm a nursing baby. Consult your doctor before breastfeeding.

Additional Information

Our Myozyme (alglucosidase alfa) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Myozyme Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some allergic reactions may occur during the injection, or as long as 3 hours afterward. Tell your caregivers or get emergency medical help right away if you have:

• a feeling like you might pass out, even while lying down;
• slow heart rate, weak pulse, fainting, slow breathing (breathing may stop);
• bronchospasm (wheezing, tight feeling in your chest or throat, trouble breathing);
• pale skin, cold or clammy skin, blue lips or fingernails, cold hands or feet;
• warmth, redness, numbness, or tingly feeling under your skin;
• rash, itching, sweating, fever;
• severe headache, nausea, feeling restless or nervous;
• seizure (convulsions); or
• fast heart rate, pounding in your neck or ears, anxiety, confusion.

Also call your doctor at once if you have:

• skin changes (sores, lesions, ulcers, discoloring); or
• puffy eyes, swelling in your ankles or feet, weight gain, urine that looks foamy.

Common side effects may include:

• hives; difficult breathing; swelling of your face, lips, tongue, or throat;
• pale skin, blue lips, feeling hot or feverish;
• skin rash, itching, flushing (warmth, redness, or tingly feeling);
• headache, dizziness, agitation, muscle twitching;
• fast heart rate, rapid breathing, chest discomfort, cough;
• increased blood pressure;
• nausea, vomiting;
• tremor, shaking, increased sweating; or
• muscle pain, tiredness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Myozyme (Alglucosidase Alfa)

 

Myozyme Professional Information

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed 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].

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, WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION].

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]. 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)
Postprocedural 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 detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other alglucosidase alfa products may be misleading.

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 alfaspecific 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 antialglucosidase alfa antibodies, including cross-reactive immunologic material (CRIM)–negative patients (i.e., patients in whom no endogenous GAA protein was detected by Western blot analysis and/or predicted based on the genotype) 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].

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.

CRIM-negative infants have shown poorer clinical response in the presence of high sustained IgG antibody titers and positive inhibitory antibodies [see WARNINGS AND PRECAUTIONS].

Immunogenicity data from clinical trials and published literature in CRIM-negative, infantile-onset Pompe disease patients suggest that the administration of an immune tolerance induction regimen individualized to alglucosidase alfa–naive patients may be effective in preventing or reducing the development of high sustained antibody titer against alglucosidase alfa.

Infusion reactions were reported in 20 of 39 CRIM-positive 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].

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]. Therefore, these patients should be monitored more closely during administration of MYOZYME.

Postmarketing Experience

The following adverse reactions have been identified during postapproval 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]. 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]. 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]. Additional adverse drug reactions included proteinuria and nephrotic syndrome [see WARNINGS AND PRECAUTIONS].

Recurrent reactions consisting of flu-like illness or a combination of events such as fever, chills, myalgia, arthralgia, pain, or fatigue occurring after completion of infusions and lasting for 1-3 days have been observed in some patients treated with alglucosidase alfa. The majority of patients were successfully rechallenged with alglucosidase alfa using lower doses and/or pretreatment with anti-inflammatory drugs and/or corticosteroids and were able to continue treatment under close clinical supervision.

Systemic and cutaneous immune-mediated reactions, including ulcerative and necrotizing skin lesions, and nephrotic syndrome secondary to membranous glomerulonephritis have been reported in postmarketing safety experience with alglucosidase alfa [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Myozyme (Alglucosidase Alfa)