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Risk Of Hypersensitivity Reactions

(see BOXED WARNING)

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported during MYOZYME (alglucosidase alfa) infusion, some of which were IgE mediated. Some reactions were life-threatening. A small number of patients ( < 1%) in clinical trials and in the commercial setting developed anaphylactic shock and/or cardiac arrest during MYOZYME (alglucosidase alfa) infusion that required life-support measures (see ADVERSE REACTIONS).

In clinical trials and expanded access programs with MYOZYME (alglucosidase alfa) , 38 of 280 (approximately 14%) patients treated with MYOZYME (alglucosidase alfa) have developed infusion reactions that involved at least 2 of 3 body systems, cutaneous, respiratory or cardiovascular systems. These events included: Cardiovascular: hypotension, cyanosis, hypertension, tachycardia, ventricular extrasystoles, bradycardia, pallor, flushing, nodal rhythm, peripheral coldness; Respiratory: tachypnea, wheezing/bronchospasm, rales, throat tightness, hypoxia, dyspnea, cough, respiratory tract irritation, oxygen saturation decreased; Cutaneous: angioneurotic edema, urticaria, rash, erythema, periorbital edema, pruritus, hyperhidrosis, cold sweat, livedo reticularis (see ADVERSE REACTIONS). Of these cases, 8 patients experienced severe or significant hypersensitivity reactions.

If severe hypersensitivity or anaphylactic reactions occur, immediate discontinuation of the administration of MYOZYME (alglucosidase alfa) should be considered, and appropriate medical treatment should be initiated. Because of the potential for severe infusion reactions, appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when MYOZYME (alglucosidase alfa) is administered.

Risk Of Cardiac Arrhythima And Sudden Cardiac Death During General Anesthesia For Central Venous Catheter Placement

Cardiac arrhythmia, including ventricular fibrillation, ventricular tachycardia 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, associated with the use of general anesthesia for the placement of a central venous catheter intended for MYOZYME (alglucosidase alfa) infusion.

Caution should be used when administering general anesthesia for the placement of a central venous catheter in infantile-onset Pompe disease patients with cardiac hypertrophy.

Risk Of Acute Cardiorespiratory Failure

Acute cardiorespiratory failure requiring intubation and inotropic support has been observed after infusion with MYOZYME (alglucosidase alfa) in 1 infantile-onset Pompe disease patient with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of MYOZYME.

(See Instructions for Use: Reconstitution, dilution and administration for information on appropriate infusion volumes.)

Infusion Reactions

Infusion reactions occurred in 20 of 39 (51%) of patients treated with MYOZYME in clinical studies (see ADVERSE REACTIONS). Some reactions were severe. Severe infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included pyrexia, decreased oxygen saturation, tachycardia, cyanosis, and hypotension. Other 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 saturation, 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. Some patients were pre-treated with antihistamines, antipyretics and/or steroids. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines, or steroids. Infusion reactions may occur at any time during, or up to 2 hours after, the infusion of MYOZYME (alglucosidase alfa) , and are more likely with higher infusion rates.

Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from infusion reactions. Therefore, these patients should be monitored more closely during administration of MYOZYME (alglucosidase alfa) .

If an infusion reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion reactions occur, immediate discontinuation of the administration of MYOZYME (alglucosidase alfa) should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylactic reaction and cardiac arrest, epinephrine and/or cardiopulmonary resuscitation measures have been administered. Early detection of signs and symptoms of hypersensitivity or anaphylactic reactions may assist in effective management of patients and prevent possible significant or irreversible outcomes. Because of the potential for severe infusion reactions, appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when MYOZYME (alglucosidase alfa) is administered. Patients who have experienced infusion reactions should be treated with caution when readministered MYOZYME (alglucosidase alfa) .

General

Patients with an acute underlying illness at the time of MYOZYME (alglucosidase alfa) infusion appear to be at greater risk for infusion reactions. Careful consideration should be given to the patient's clinical status prior to administration of MYOZYME (alglucosidase alfa) .

Laboratory Tests

There are no marketed tests for antibodies against alglucosidase alfa. It is recommended that patients be monitored for IgG antibody formation every 3 months. Contact your local Genzyme representative or Genzyme Corporation at 1-800-745-4447 for information on testing and to obtain a sample collection box.

Results from 2 intravenous repeated-dose animal toxicology studies using doses of 100 or 200 mg/kg MYOZYME (alglucosidase alfa) (about 1.6 to 3.2 times the recommended human dose based on body surface area) in Cynomolgus monkeys to evaluate the possibility of liver accumulation over time showed GAA levels above background in liver tissue several days following the last dose; however, no concurrent changes in liver enzymes or histopathology were observed. It is suggested that liver enzymes be evaluated prior to the initiation of MYOZYME (alglucosidase alfa) treatment and periodically thereafter. Care should be exercised in interpreting these tests since aspartate aminotransferase and alanine aminotransferase levels may also be raised as a result of the muscle pathology in patients with Pompe disease.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with MYOZYME (alglucosidase alfa) .

MYOZYME (alglucosidase alfa) at intravenous doses up to 40 mg/kg, administered every other day (about 0.2 times the recommended human bi-weekly dose based on body surface area) had no effect on fertility and reproductive performance in mice.

Pregnancy: Teratogenic Effects: Pregnancy Category B.

A reproduction study has been performed in pregnant mice at doses up to 40 mg/kg/day (about 0.2 times the recommended human bi-weekly dose based on body surface area) and has revealed no evidence of impaired fertility or harm to the fetus due to MYOZYME (alglucosidase alfa) . There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Women of childbearing potential are encouraged to enroll in the Pompe patient registry (see PRECAUTIONS: PATIENT INFORMATION).

Nursing Mothers

It is not known whether MYOZYME (alglucosidase alfa) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when MYOZYME (alglucosidase alfa) is administered to a nursing woman (See PRECAUTIONS: PATIENT INFORMATION regarding a registry program. Nursing women are encouraged to participate in the registry program).

Pediatric Use

Pediatric patients aged 1 month to 3.5 years at time of first infusion have been treated with MYOZYME in clinical trials (see Clinical Studies). Other open-label clinical trials of MYOZYME (alglucosidase alfa) have been performed in older pediatric patients ranging from 2 to 16 years at the initiation of treatment (juvenile-onset Pompe disease); however, the risks and benefits of MYOZYME (alglucosidase alfa) treatment have not been established in the juvenile-onset Pompe disease population.

Geriatric Use

Clinical studies did not include any subjects aged 65 years and older. It is not known whether they respond differently than younger subjects.

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