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Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Anaphylaxis And Hypersensitivity Reactions

Anaphylaxis and hypersensitivity reactions have been observed in patients during and up to 3 hours after alglucosidase alfa infusion. Some of the reactions were life-threatening and included anaphylactic shock, cardiac arrest, respiratory arrest, respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria. Other accompanying reactions included chest discomfort/pain, wheezing, tachypnea, cyanosis, decreased oxygen saturation, convulsions, pruritus, rash, hyperhidrosis, nausea, dizziness, hypertension/increased blood pressure, flushing/feeling hot, erythema, pyrexia, pallor, peripheral coldness, restlessness, nervousness, headache, back pain, and paresthesia. Some of these reactions were IgE-mediated.

If anaphylaxis or severe hypersensitivity reactions occur, immediately discontinue administration of alglucosidase alfa, and initiate appropriate medical treatment. Severe reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylaxis, epinephrine has been administered. Appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when alglucosidase alfa is administered.

The risks and benefits of re-administering alglucosidase alfa following an anaphylactic or hypersensitivity reaction should be considered. Some patients have been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product [see ADVERSE REACTIONS].

Immune-Mediated Reactions

Immune-mediated cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions [see ADVERSE REACTIONS]. Systemic immune-mediated reactions, including possible type III immune-mediated reactions have been observed with alglucosidase alfa. These reactions occurred several weeks to 3 years after initiation of alglucosidase alfa infusions. Skin biopsy in one patient demonstrated deposition of anti-rhGAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with pyrexia and elevated erythrocyte sedimentation rate. Nephrotic syndrome secondary to membranous glomerulonephritis was observed in some Pompe disease patients treated with alglucosidase alfa who had persistently positive anti-rhGAA IgG antibody titers. In these patients, renal biopsy was consistent with immune complex deposition. Patients improved following treatment interruption. Therefore, patients receiving alglucosidase alfa should undergo periodic urinalysis [see ADVERSE REACTIONS].

Patients should be monitored for the development of systemic immune-mediated reactions involving skin and other organs while receiving alglucosidase alfa. If immune-mediated reactions occur, consider discontinuation of the administration of alglucosidase alfa, and initiate appropriate medical treatment. The risks and benefits of re-administering alglucosidase alfa following an immune-mediated reaction should be considered. Some patients have been able to be rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.

Risk Of Acute Cardiorespiratory Failure

Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during alglucosidase alfa infusion, and some patients may require prolonged observation times that should be individualized based on the needs of the patient. Acute cardiorespiratory failure has been observed in infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa [see DOSAGE AND ADMINISTRATION].

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

Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness. Therefore, caution should be used when administering general anesthesia. Ventricular arrhythmias and bradycardia, resulting in cardiac arrest or death, or requiring cardiac resuscitation or defibrillation have been observed in infantileonset Pompe disease patients with cardiac hypertrophy during general anesthesia for central venous catheter placement.

Risk Of Antibody Development

As with all therapeutic proteins, there is potential for immunogenicity. In clinical studies, the majority of patients developed IgG antibodies to alglucosidase alfa, typically within 3 months of treatment. There is evidence to suggest that some patients who develop high and sustained IgG antibody titers may experience reduced clinical efficacy to alglucosidase alfa treatment, such as loss of motor function, ventilator dependence, or death. The effect of antibody development on the long term efficacy of alglucosidase alfa is not fully understood.

Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop hypersensitivity reactions, other immune-mediated reactions, or lose clinical response. Patients who experience reduced clinical response may also be tested for inhibitory antibody activity. Patients who experience anaphylactic or hypersensitivity reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis [see ADVERSE REACTIONS].

There are currently no marketed tests for antibodies against alglucosidase alfa; however, a testing service is provided by Genzyme. Contact your local Genzyme representative or Genzyme Corporation at 1-800-745-4447 for information on testing and to obtain a sample collection box.

Nonclinical Toxicology

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 alglucosidase alfa.

Intravenous administration of alglucosidase alfa every other day in mice at doses up to 40 mg/kg (0.4 times the human AUC at the recommended bi-weekly dose) had no effect on fertility and reproductive performance.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There is a registry for Pompe disease patients that monitors the outcomes of women and their offspring exposed to alglucosidase alfa during pregnancy. Patients or their physicians should call 1-800-745-4447 or visit www.pomperegistry.com to enroll [see PATIENT INFORMATION].

Risk Summary

There are no studies of alglucosidase alfa in pregnant women. In animal reproduction studies, no effects on embryo-fetal development were observed in mice or rabbits given daily administration of alglucosidase alfa up to 0.4 or 0.5 times the human steady-state AUC (area under the plasma concentration-time curve), respectively, at the recommended human bi-weekly dose during the period of organogenesis. An increase in pup mortality was observed when alglucosidase alfa was administered every other day in mice during the period of organogenesis through lactation at a dose 0.4 times the human steady-state AUC at the recommended human bi-weekly dose. Alglucosidase alfa should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal Data

All reproductive studies included pre-treatment with diphenhydramine to prevent or minimize hypersensitivity reactions. The effects of alglucosidase alfa were evaluated based on comparison to a control group treated with diphenhydramine alone. Daily intravenous (IV) administration of alglucosidase alfa up to 40 mg/kg in mice and rabbits (0.4 and 0.5 times the human steady-state AUC, respectively, at the recommended bi-weekly dose) during the period of organogenesis had no effects on embryo-fetal development. Administration of 40 mg/kg IV every other day in mice (0.4 times the human steady-state AUC at the recommended bi-weekly dose) during the period of organogenesis through lactation produced an increase in mortality of offspring during the lactation period.

Nursing Mothers

Alglucosidase alfa is present in human milk. In one case report, the enzymatic activity of alglucosidase alfa was detected in the breast milk of a lactating woman up to 24 hours after the end of intravenous alglucosidase alfa administration. To minimize infant exposure to alglucosidase alfa, a nursing mother may temporarily pump and discard breast milk produced during the 24 hours after administration of alglucosidase alfa. Exercise caution when administering alglucosidase alfa to a nursing mother.

Pediatric Use

The safety and effectiveness of alglucosidase alfa have been established in pediatric patients with Pompe disease.

The safety and effectiveness of alglucosidase alfa were assessed in 57 treatment-naive infantileonset Pompe disease patients, aged 0.2 month to 3.5 years at first infusion, in three separate clinical trials [see Clinical Studies].

The safety and effectiveness of alglucosidase alfa were assessed in pediatric patients with late (noninfantile) onset Pompe disease in a randomized, double-blind, placebo-controlled study in 90 patients, including 2 patients 16 years of age or less [see Clinical Studies].

Anaphylaxis, hypersensitivity reactions, and acute cardiorespiratory failure have occurred in pediatric patients [see BOXED WARNING, WARNINGS AND PRECAUTIONS]. Additionally, cardiac arrhythmia and sudden cardiac death have occurred in pediatric patients during general anesthesia for central venous catheter placement [see WARNINGS AND PRECAUTIONS].

Geriatric Use

The randomized, double-blind, placebo-controlled study of alglucosidase alfa did not include sufficient numbers (n=4) of patients aged 65 years and over to determine whether they respond differently from younger patients [see Clinical Studies].

Last reviewed on RxList: 8/18/2014
This monograph has been modified to include the generic and brand name in many instances.

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