Alglucosidase alfa

Alglucosidase alfa
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sree Teja Yelamanchili, MBBS [2]

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Black Box Warning

WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, AND RISK OF CARDIORESPIRATORY FAILURE See full prescribing information for complete Boxed Warning. * Life-threatening anaphylactic reactions and severe hypersensitivity reactions, presenting as respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria, have occurred in some patients during and after alglucosidase alfa infusions. Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following alglucosidase alfa treatment. Closely observe patients during and after alglucosidase alfa administration and be prepared to manage anaphylaxis and hypersensitivity reactions. Inform patients of the signs and symptoms of anaphylaxis, hypersensitivity reactions, and immune-mediated reactions and have them seek immediate medical care should signs and symptoms occur. Infantile-onset Pompe disease patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload, and require additional monitoring.

Overview

Alglucosidase alfa is an enzyme replacement therapy that is FDA approved for the treatment of patients with Pompe disease (GAA deficiency-Glycogen storage disease-type II). There is a Black Box Warning for this drug as shown here. Common adverse reactions include {{{adverseReactions}}}.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Alglucosidase alfa FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Alglucosidase alfa in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Alglucosidase alfa in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Indications

Hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (acid α-glucosidase (GAA) deficiency)

Dosage

Recommended Dose

• The recommended dosage of alglucosidase alfa is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion.
• For injection: 50 mg of alglucosidase alfa as lyophilized powder in a single-use vial for reconstitution

Instructions for Use

• Alglucosidase alfa does not contain any preservatives. Vials are single-use only. Discard any unused product.
• The total volume of infusion is determined by the patient's body weight and should be administered over approximately 4 hours.
• Infusions should be administered in a step-wise manner using an infusion pump.
• The initial infusion rate should be no more than 1 mg/kg/hr.
• The infusion rate may be increased by 2 mg/kg/hr every 30 minutes, after patient tolerance to the infusion rate is established, until a maximum rate of 7 mg/kg/hr is reached.
• Vital signs should be obtained at the end of each step.
• If the patient is stable, alglucosidase alfa may be administered at the maximum rate of 7 mg/kg/hr until the infusion is completed.
• The infusion rate may be slowed or temporarily stopped in the event of mild to moderate hypersensitivity reactions.
• In the event of anaphylaxis or severe hypersensitivity reaction, immediately discontinue administration of alglucosidase alfa, and initiate appropriate medical treatment.
• See TABLE below for the rate of infusion at each step, expressed as mL/hr based on the recommended infusion volume by patient weight.

Reconstitution, Dilution, and Administration

• Alglucosidase alfa should be reconstituted, diluted and administered by a healthcare professional.
• Use aseptic technique during preparation. Do not use filter needles during preparation.
• Determine the number of vials to be reconstituted based on the individual patient's weight and the recommended dose of 20 mg/kg.
• Patient weight (kg) × dose (mg/kg) = patient dose (in mg)
• Patient dose (in mg) divided by 50 mg/vial = number of vials to reconstitute. If the number of vials includes a fraction, round up to the next whole number.

• Example: Patient weight (68 kg) × dose (20 mg/kg) = patient dose (1,360 mg)

 1,360 mg divided by 50 mg/vial = 27.2 vials; therefore, 28 vials should be reconstituted.

• Remove the required number of vials from the refrigerator and allow them to reach room temperature prior to reconstitution (approximately 30 minutes).
• Reconstitute each alglucosidase alfa vial by slowly injecting 10.3 mL of sterile water for Injection, USP to the inside wall of each vial. Each vial will yield a concentration of 5 mg/mL.
• The total extractable dose per vial is 50 mg per 10 mL.
• Avoid forceful impact of the water for injection on the powder and avoid foaming.
• This is done by slow drop-wise addition of the water for injection down the inside of the vial and not directly onto the lyophilized cake.
• Tilt and roll each vial gently. Do not invert, swirl, or shake.
• The reconstituted alglucosidase alfa solution should be protected from light.
• Perform an immediate visual inspection on the reconstituted vials for particulate matter and discoloration.
• If upon immediate inspection opaque particles are observed or if the solution is discolored do not use.
• The reconstituted solution may occasionally contain some alglucosidase alfa particles (typically less than 10 in a vial) in the form of thin white strands or translucent fibers subsequent to the initial inspection. This may also happen following dilution for infusion. These particles have been shown to contain alglucosidase alfa and may appear after the initial reconstitution step and increase over time. Studies have shown that these particles are removed via in-line filtration without having a detectable effect on the purity or strength.
• Alglucosidase alfa should be diluted in 0.9% Sodium Chloride for Injection, USP, immediately after reconstitution, to a final alglucosidase alfa concentration of 0.5 to 4 mg/mL.
• Slowly withdraw the reconstituted solution from each vial. Avoid foaming in the syringe.
• Remove airspace from the infusion bag to minimize particle formation due to the sensitivity of alglucosidase alfa to air-liquid interfaces.
• Add the reconstituted alglucosidase alfa solution slowly and directly into the sodium chloride solution. Do not add directly into airspace that may remain within the infusion bag. Avoid foaming in the infusion bag.
• Gently invert or massage the infusion bag to mix. Do not shake.
• Administer alglucosidase alfa using an in-line low protein binding 0.2 µm filter.
• Do not infuse alglucosidase alfa in the same intravenous line with other products.
• The reconstituted and diluted solution should be administered without delay. If immediate use is not possible, the reconstituted and diluted solution is stable for up to 24 hours at 2°C to 8°C (36°F to 46°F).
• Storage of the reconstituted solution at room temperature is not recommended.
• The reconstituted and diluted alglucosidase alfa solution should be protected from light.
• Do not freeze or shake.
• Alglucosidase alfa does not contain any preservatives. Vials are single-use only.
• Discard any unused product.

Dosage form and Strengths

For injection: 50 mg of alglucosidase alfa is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder in a single-use vial for reconstitution. After reconstitution, the resultant solution concentration is 5 mg/mL.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Alglucosidase alfa in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Alglucosidase alfa in pediatric patients.

Contraindications

None.

Warnings

WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, AND RISK OF CARDIORESPIRATORY FAILURE See full prescribing information for complete Boxed Warning. * Life-threatening anaphylactic reactions and severe hypersensitivity reactions, presenting as respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria, have occurred in some patients during and after alglucosidase alfa infusions. Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following alglucosidase alfa treatment. Closely observe patients during and after alglucosidase alfa administration and be prepared to manage anaphylaxis and hypersensitivity reactions. Inform patients of the signs and symptoms of anaphylaxis, hypersensitivity reactions, and immune-mediated reactions and have them seek immediate medical care should signs and symptoms occur. Infantile-onset Pompe disease patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload, and require additional monitoring.

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.

Immune-Mediated Reactions

• Immune-mediated cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions.
• 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.
• 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.

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 infantile-onset 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.
• There are currently no marketed tests for antibodies against alglucosidase alfa; however, a testing service is provided by Genzyme.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Alglucosidase alfa Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Alglucosidase alfa Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Alglucosidase alfa Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Alglucosidase alfa in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Alglucosidase alfa in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Alglucosidase alfa during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Alglucosidase alfa in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Alglucosidase alfa in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Alglucosidase alfa in geriatric settings.

Gender

There is no FDA guidance on the use of Alglucosidase alfa with respect to specific gender populations.

Race

There is no FDA guidance on the use of Alglucosidase alfa with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Alglucosidase alfa in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Alglucosidase alfa in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Alglucosidase alfa in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Alglucosidase alfa in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Alglucosidase alfa Administration in the drug label.

Monitoring

There is limited information regarding Alglucosidase alfa Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Alglucosidase alfa and IV administrations.

Overdosage

There is limited information regarding Alglucosidase alfa overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Alglucosidase alfa Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Alglucosidase alfa Mechanism of Action in the drug label.

Structure

There is limited information regarding Alglucosidase alfa Structure in the drug label.

Pharmacodynamics

There is limited information regarding Alglucosidase alfa Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Alglucosidase alfa Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Alglucosidase alfa Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Alglucosidase alfa Clinical Studies in the drug label.

How Supplied

There is limited information regarding Alglucosidase alfa How Supplied in the drug label.

Storage

There is limited information regarding Alglucosidase alfa Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Alglucosidase alfa Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Alglucosidase alfa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Alglucosidase alfa Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Alglucosidase alfa Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Alglucosidase alfa

Clinical data
ATC code	A16AB07 (WHO)
Identifiers
CAS Number	[1] 420794-05-0
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C4758H7262N1274O1369S35
Molar mass	105338

Alglucosidase alfa (Myozyme) is a drug used to treat Glycogen storage disease type II (Pompe's disease). It is an analogue of acid alpha-glucosidase.

Some health plans have refused to pay for Myozyme, because it costs $300,000 a year for adults, and has only been approved by the F.D.A. for use in infants.