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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Alglucosidase alfa: Drug information

Alglucosidase alfa: Drug information
(For additional information see "Alglucosidase alfa: Pediatric drug information" and see "Alglucosidase alfa: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Risk of hypersensitivity reactions:

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 if signs and symptoms occur.

Risk of cardiorespiratory failure:

Infantile-onset Pompe disease patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of cardiac or respiratory compromise due to fluid overload and require additional monitoring.

Brand Names: US
  • Lumizyme
Brand Names: Canada
  • Myozyme
Pharmacologic Category
  • Enzyme
Dosing: Adult
Pompe disease

Pompe disease: Noninfantile, late-onset: IV: 20 mg/kg every 2 weeks

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Pediatric

(For additional information see "Alglucosidase alfa: Pediatric drug information")

Note: Patients with infantile-onset Pompe disease should have a cross-reactive immunological material (CRIM) assessment early in their disease course and be managed by a clinical specialist knowledgeable in immune tolerance induction.

Pompe disease, infantile-onset

Pompe disease, infantile-onset: Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 2 weeks.

Pompe disease, late-onset; noninfantile

Pompe disease, late-onset; noninfantile: Children and Adolescents: IV: 20 mg/kg/dose every 2 weeks.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in pediatric patients and adults unless otherwise specified.

>10%:

Cardiovascular: Flushing (≤13%)

Dermatologic: Skin rash (infants and children: 18%; adolescents and adults: ≥3%), urticaria (8% to 13%)

Hypersensitivity: Hypersensitivity reaction (including severe hypersensitivity reaction and type III hypersensitivity reaction)

Immunologic: Development of IgG antibodies (infants and children: 89%; adolescents and adults: 100%; may affect efficacy)

Miscellaneous: Fever (infants and children: 15%; adolescents and adults: ≥3%)

1% to 10%:

Cardiovascular: Chest discomfort (adolescents and adults: 7%), hypertension (infants and children: 10%), increased blood pressure (adolescents and adults: 5%), peripheral edema (adolescents and adults: 3%), tachycardia (infants and children: 8%)

Dermatologic: Erythema of skin (infants and children: 5%), hyperhidrosis (adolescents and adults: 8%), pallor (infants and children: 5%), papular rash (adolescents and adults: 3%), pruritus (adolescents and adults: 3%)

Gastrointestinal: Nausea (≥3%), vomiting (5%)

Hypersensitivity: Anaphylaxis (adolescents and adults: 7%)

Nervous system: Agitation (infants and children: 5%), fatigue (≥3%), feeling hot (≤5%), rigors (infants and children: 5%), tremor (infants and children: 5%)

Neuromuscular & skeletal: Muscle twitching (adolescents and adults: 7%), myalgia (adolescents and adults: 5%)

Respiratory: Cough (infants and children: 8%), cyanosis (infants and children: 5%), oxygen saturation decreased (infants and children: 8%), pharyngeal edema (adolescents and adults: 3%), tachypnea (infants and children: 8%)

Frequency not defined:

Cardiovascular: Atrioventricular nodal arrhythmia, bradycardia, livedo reticularis, ventricular premature contractions

Hypersensitivity: Angioedema

Neuromuscular & skeletal: Arthropathy

Postmarketing:

Cardiovascular: Heart failure

Dermatologic: Skin necrosis (lesions)

Endocrine & metabolic: Hyperparathyroidism, hypervolemia

Genitourinary: Proteinuria

Hypersensitivity: Anaphylactic shock

Renal: Membranous glomerulonephritis, nephrotic syndrome

Respiratory: Flu-like symptoms, respiratory failure

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to alglucosidase alfa or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity/Anaphylactoid reactions: [US Boxed Warning]: Life-threatening anaphylactic reactions and severe hypersensitivity reactions, some of which were IgE mediated, may occur; immediate medical support should be readily available. Reactions may occur during and up to 3 hours after infusion. Patients who develop IgE antibodies to alglucosidase alfa may be at a higher risk; monitor these patients closely during administration. Consider testing for IgG titers in patients who develop allergic reactions; may also test for IgE antibodies or other mediators of anaphylaxis. Consider risks/benefits of readministration following an anaphylactic or severe allergic reaction; some patients have been rechallenged under close clinical supervision; appropriate resuscitation measures should be available.

• IgG antibody formation: The presence of IgG antibodies has been observed within 3 months from the onset of therapy in the majority of patients. Patients with high and sustained IgG antibody titers, including cross-reactive immunologic material (CRIM)-negative patients, may result in reduced efficacy of alglucosidase alfa (eg, loss of motor function, ventilator dependence, death).

• Immune-mediated adverse effects: [US Boxed Warning]: Severe immune-mediated reactions (eg, necrotizing skin lesions, nephrotic syndrome secondary to membranous glomerulonephritis, proteinuria, inflammatory arthropathy) may occur; immediate medical support should be readily available. Reactions have occurred up to 3 years after initiation of therapy. Monitor urinalysis periodically. Monitor for immune-mediated reaction development. Consider testing for IgG titers in patients who develop immune-mediated reactions; may also test for IgE antibodies. Consider risks/benefits of readministration; some patients have been successfully rechallenged under close clinical supervision; immune tolerance induction administered in conjunction with alglucosidase alfa may aid tolerability of alglucosidase alfa in pediatric Pompe disease.

• Infusion reactions: Infusion-related reactions are common and may occur during and up to 2 hours after infusion. Appropriate medical support for the management of infusion reactions should be readily available. Discontinue immediately for severe hypersensitivity or anaphylactic reaction; mild to moderate reactions may be managed by reducing the infusion rate and/or administering antihistamines and/or antipyretics. Use caution with subsequent infusions; infusion reactions have occurred despite premedication with antihistamines, antipyretics, and/or corticosteroids. Patients with acute underlying illness are at greater risk for infusion reactions, including cardiorespiratory failure; monitor closely during infusion. Although less common, delayed-onset (within 48 hours after administration) infusion reactions have also occurred.

Disease-related concerns:

• Cardiovascular disease: [US Boxed Warning]: Use with caution in patients with compromised cardiac function; risk of acute cardiorespiratory failure secondary to infusion-related reactions or fluid overload may be increased. Additional monitoring is warranted. Cardiorespiratory failure has been observed in patients with cardiac hypertrophy up to 72 hours after infusion; ventricular arrhythmias and bradycardia have also been observed in patients with cardiac hypertrophy.

• Respiratory disease: [US Boxed Warning]: Use with caution in patients with compromised respiratory function; risk of acute cardiorespiratory failure secondary to infusion-related reactions or fluid overload may be increased. Additional monitoring is warranted.

• Sepsis: Patients with sepsis may be at increased risk for cardiorespiratory failure during infusions.

Special populations:

• Infantile-onset Pompe disease: Patients with infantile-onset Pompe disease should have a CRIM assessment early in their disease course and be managed by a clinical specialist knowledgeable in immune tolerance induction. Immune tolerance induction administered prior to and in conjunction with initiation of alglucosidase alfa has been reported to aid tolerability of alglucosidase alfa in CRIM-negative patients (CRIM-negative patients with infantile-onset Pompe disease treated with alglucosidase alfa have shown poorer clinical response in the presence of high sustained IgG antibody titers and positive inhibitory antibodies compared to CRIM-positive infants).

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Anesthesia: Use of general anesthesia for catheter placement for alglucosidase alfa infusions may be complicated by the presence of cardiac and skeletal (including respiratory) muscle weakness in patients with Pompe disease; use general anesthesia with caution. Ventricular arrhythmias and bradycardia, resulting in cardiac arrest or death or requiring cardiac resuscitation or defibrillation, have been observed in patients with cardiac hypertrophy.

• Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (1-800-745-4447).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Lumizyme: 50 mg (1 ea) [contains polysorbate 80]

Generic Equivalent Available: US

No

Pricing: US

Solution (reconstituted) (Lumizyme Intravenous)

50 mg (per each): $1,157.32

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Myozyme: 50 mg (1 ea) [contains polysorbate 80]

Administration: Adult

IV: Infuse through a separate line via an inline, low-protein-binding, 0.2 micron filter. Infuse over ~4 hours; initiate at 1 mg/kg/hour. If tolerated, increase by 2 mg/kg/hour every 30 minutes to a maximum rate of 7 mg/kg/hour. For mild to moderate infusion reactions, decrease rate or temporarily hold; for severe hypersensitivity reactions or anaphylaxis, discontinue immediately and initiate appropriate medical treatment. Monitor vital signs prior to each rate increase.

Administration: Pediatric

Parenteral: IV: Infuse through a low protein-binding, 0.2 micron in-line filter. Do not administer products with visualized particulate matter. Administer as weight-based IV infusion over ~4 hours: initiate at ≤1 mg/kg/hour, then increase by 2 mg/kg/hour every 30 minutes as tolerated to a maximum rate of 7 mg/kg/hour. Decrease rate or temporarily hold for mild to moderate infusion reactions; for severe hypersensitivity reactions or anaphylaxis, discontinue immediately and initiate appropriate medical treatment. Monitor vital signs prior to each rate increase. Protect from light.

Use: Labeled Indications

Pompe disease: For use in patients with Pompe disease (acid alpha-glucosidase [GAA] deficiency).

Medication Safety Issues
Sound-alike/look-alike issues:

Alglucosidase alfa may be confused with agalsidase alfa, agalsidase beta, alglucerase

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Reproductive Considerations

A registry has been established for patients diagnosed with Pompe disease; patients who may become pregnant are encouraged to enroll in the registry.

Pregnancy Considerations

Use of alglucosidase alfa in patients who continued enzyme replacement therapy throughout pregnancy is limited (de Vries 2011; Goker-Alpan 2020; Holbeck-Brendel 2017; Kłos 2017; Koyuncu 2017; Oliveira Santos 2018; Perniconi 2016; Van Houtte 2019; Zagnoli 2013); however, information related to Pompe disease in pregnancy is also limited (Karabul 2014).

Adverse events, such as worsening muscle weakness or decreased respiratory function, may be exacerbated by pregnancy and/or Pompe disease (Karabul 2014). The continuation of alglucosidase alfa during pregnancy may be considered (van der Ploeg 2017).

A registry has been established for patients diagnosed with Pompe disease; pregnant patients are encouraged to enroll in the registry (1-800-745-4447, extension 15500).

Breastfeeding Considerations

Acid alfa-glucosidase is endogenous to breast milk; concentrations are lower in women with Pompe disease.

Following an infusion of alglucosidase alfa in one woman with Pompe disease, maximum enzyme activity was found in breast milk 2.5 hours after the dose and was ~0.3% of the maternal peak plasma value. Activity in breast milk returned to baseline values within 24 hours after the infusion (de Vries 2011).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, benefits of breastfeeding to the infant, and benefits of treatment to the mother; exposure may be minimized by temporarily expressing and discarding breast milk for 24 hours after administration.

A registry has been established for patients with Pompe disease; patients who are breastfeeding are encouraged to enroll in the registry (1-800-745-4447, extension 15500)

Monitoring Parameters

Liver enzymes (baseline and periodically; elevation may be due to disease process); vital signs (prior to each infusion rate increase) during and following infusion; immune-mediated reactions involving skin and other organs; volume overload; urinalysis (periodically)

The manufacturer recommends monitoring for IgG antibody formation every 3 months for 2 years, then annually. Consider testing if patient develops allergic or other suspected immune-mediated reaction or experiences loss of clinical response. Testing services for antibodies are available through Genzyme Corporation at 1-800-745-4447. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.

Mechanism of Action

Alglucosidase alfa is a recombinant form of the enzyme acid alpha-glucosidase (GAA), which is required for glycogen cleavage. Due to an inherited GAA deficiency or absence, glycogen accumulates in the tissues of patients with Pompe disease, leading to progressive muscle weakness. In infantile-onset Pompe disease, glycogen accumulates in cardiac and skeletal muscles and hepatic tissue, leading to cardiomyopathy and respiratory failure. Juvenile- and adult-onset Pompe disease are limited to glycogen accumulation in skeletal muscle, leading to respiratory failure. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface, is internalized, and transported to lysosomes where it is activated for increased enzymatic glycogen cleavage.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vss: Infants 1 to 7 months: 96 ± 16 mL/kg

Half-life elimination: Infants 1 to 7 months: 2.3 hours; Adults: 2.4 hours

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Antibody formation: Higher mean clearance (50%) was observed in patients who tested positive for antibodies to alglucosidase alfa.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Myozyme;
  • (AU) Australia: Myozyme;
  • (BE) Belgium: Myozyme;
  • (BG) Bulgaria: Myozyme;
  • (BR) Brazil: Myozyme;
  • (CH) Switzerland: Myozyme;
  • (CL) Chile: Myozyme;
  • (CO) Colombia: Myozyme;
  • (CZ) Czech Republic: Myozyme;
  • (DE) Germany: Myozyme;
  • (EE) Estonia: Myozyme;
  • (EG) Egypt: Myozyme;
  • (ES) Spain: Myozyme;
  • (FI) Finland: Myozyme;
  • (FR) France: Myozyme;
  • (GB) United Kingdom: Myozyme;
  • (GR) Greece: Myozyme;
  • (HR) Croatia: Myozyme;
  • (HU) Hungary: Myozyme;
  • (IE) Ireland: Myozyme;
  • (IT) Italy: Myozyme;
  • (JO) Jordan: Myozyme;
  • (JP) Japan: Myozyme;
  • (KR) Korea, Republic of: Myozyme;
  • (KW) Kuwait: Myozyme;
  • (LB) Lebanon: Myozyme;
  • (LT) Lithuania: Myozyme;
  • (LV) Latvia: Myozyme;
  • (MX) Mexico: Myozyme;
  • (NL) Netherlands: Myozyme;
  • (NZ) New Zealand: Myozyme;
  • (PE) Peru: Myozyme;
  • (PK) Pakistan: Myozyme;
  • (PL) Poland: Myozyme;
  • (PR) Puerto Rico: Lumizyme | Myozyme;
  • (PT) Portugal: Myozyme;
  • (PY) Paraguay: Myozyme;
  • (QA) Qatar: Myozyme;
  • (RO) Romania: Myozyme;
  • (RU) Russian Federation: Myozyme;
  • (SA) Saudi Arabia: Myozyme;
  • (SE) Sweden: Myozyme;
  • (SG) Singapore: Myozyme;
  • (SK) Slovakia: Myozyme;
  • (TH) Thailand: Myozyme;
  • (UA) Ukraine: Myozyme;
  • (UY) Uruguay: Myozyme;
  • (ZA) South Africa: Myozyme
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  3. de Vries JM, Brugma JD, Ozkan L, et al, "First Experience With Enzyme Replacement Therapy During Pregnancy and Lactation in Pompe Disease," Mol Genet Metab, 2011, 104(4):552-5. [PubMed 21967859]
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  5. Holbeck-Brendel M, Poulsen BK. Treatment with enzyme replacement therapy during pregnancy in a patient with Pompe disease. Neuromuscul Disord. 2017;27(10):956-958. doi: 10.1016/j.nmd.2017.06.556. [PubMed 28735900]
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  7. Karabul N, Berndt J, Kornblum C, et al. Pregnancy and delivery in women with Pompe disease. Mol Genet Metab. 2014;112(2):148-153. doi: 10.1016/j.ymgme.2014.03.010. [PubMed 24726296]
  8. Kłos J, Kwaśniak-Butowska M, Sławek J. Alglucosidase alfa therapy for Pompe disease in pregnancy - case report. J Neurol Sci. 2017;375:167-169. doi: 10.1016/j.jns.2017.01.068. [PubMed 28320122]
  9. Koyuncu K, Turgay B, Aytac R, Soylemez F. Delivery and postpartum management of a patient with Pompe disease: case report and review of the literature. Obstet Med. 2017;10(3):150-151. doi:10.1177/1753495X16688601 [PubMed 29051784]
  10. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  11. Lumizyme (alglucosidase alfa) [prescribing information]. Cambridge, MA: Genzyme Corp; May 2022.
  12. Lumizyme (alglucosidase alfa) [prescribing information]. Cambridge, MA: Genzyme Corp; May 2023.
  13. Myozyme (alglucosidase alfa) [prescribing information]. Cambridge, MA: Genzyme Corp; February 2020.
  14. Myozyme (alglucosidase alfa) [product monograph]. Mississauga, Ontario, Canada: Sanofi Genzyme; December 2016.
  15. Oliveira Santos M, Evangelista T, Conceição I. Enzyme replacement therapy with alglucosidase alfa in a late-onset Pompe disease patient during pregnancy. Neuromuscul Disord. 2018;28(11):965-968. doi: 10.1016/j.nmd.2018.08.002. [PubMed 30314719]
  16. Perniconi B, Vauthier-Brouzes D, Morélot-Panzini C, et al. Multidisciplinary care allowing uneventful vaginal delivery in a woman with Pompe disease. Neuromuscul Disord. 2016;26(9):610-613. [PubMed 27460347]
  17. Schoser B, Hill V, and Raben N, "Therapeutic Approaches in Glycogen Storage Disease Type II/Pompe Disease," Neurotherapeutics, 2008, 5(4):569-78. [PubMed 19019308]
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  20. Van Houtte J, De Bleecker JL. Two successfully completed pregnancies in adult onset Pompe disease, under continued treatment with alglucosidase alfa. Acta Neurol Belg. 2019;119(1):147-149. doi: 10.1007/s13760-019-01089-4. [PubMed 30715719]
  21. Zagnoli F, Leblanc A, Blanchard C. Pregnancy during enzyme replacement therapy for late-onset acid maltase deficiency. Neuromuscul Disord. 2013;23(2):180-181. [PubMed 23290485]
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