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Elosulfase Alfa

Class: Enzymes
Molecular Formula: C5020H7588N1364O1418S34
CAS Number: 9025-60-9
Brands: Vimizim

Warning(s)

  • Risk of Anaphylaxis
  • Risk of life-threatening anaphylactic reactions.1 (See Hypersensitivity Reactions under Cautions.) Appropriate medical support should be readily available.1 Observe patients closely during and after infusion.1

  • Patients with acute febrile or respiratory illness may be at increased risk of serious acute exacerbation of their respiratory compromise due to hypersensitivity reactions; may require additional monitoring.1 (See Acute Respiratory Complications under Cautions.)

Introduction

Biosynthetic (recombinant DNA origin) form of human N-acetylgalactosamine-6-sulfatase (GALNS).1 3 4 5 8

Uses for Elosulfase Alfa

Mucopolysaccharidosis IVA

Replacement therapy in patients with mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome);1 3 4 5 8 designated an orphan drug by FDA for this use.2

Shown to improve endurance (as indicated by increases in walking distance).1 3 8

Elosulfase Alfa Dosage and Administration

General

  • Prepare and administer under supervision of a clinician capable of managing medical emergencies.1

  • To minimize risk of hypersensitivity reactions, administer an antihistamine (with or without an antipyretic) 30–60 minutes prior to each infusion.1 3

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1

Administer using a low-protein-binding infusion set equipped with a low-protein-binding 0.2-mcm inline filter.1

Contains no preservatives; discard partially used vials.1

Do not infuse through the same IV tubing with other drugs.1

Dilution

Must dilute commercially available elosulfase alfa concentrate prior to administration.1 Dilute appropriate volume that will provide the recommended dose with 0.9% sodium chloride injection to a final volume of 100 mL (for patients weighing <25 kg) or 250 mL (for patients weighing ≥25 kg).1 Gently rotate infusion bag to mix; avoid shaking or agitation.1

Diluted solutions should be clear to slightly opalescent and colorless to pale yellow.1 Discard solution if discolored or particulate matter other than slight flocculation (e.g., thin translucent fibers) is present.1

Use immediately after dilution.1 If immediate use not possible, may store diluted solution at recommended conditions, but administration should be completed within 48 hours from the time of dilution.1 (See Storage under Stability.)

Rate of Administration

Administer over a minimum of 3.5–4.5 hours, depending on total infusion volume.1

Patients weighing <25 kg receiving total infusion volume of 100 mL: Infuse at a rate of 3 mL/hour for the first 15 minutes; if tolerated, may increase to 6 mL/hour for the next 15 minutes.1 If patient continues to tolerate the infusion, may increase incrementally by 6 mL/hour every 15 minutes up to a maximum rate of 36 mL/hour.1 Administer total volume over ≥3.5 hours.1

Patients weighing ≥25 kg receiving total infusion volume of 250 mL: Infuse at a rate of 6 mL/hour for the first 15 minutes; if tolerated, may increase to 12 mL/hour for the next 15 minutes.1 If patient continues to tolerate the infusion, may increase incrementally by 12 mL/hour every 15 minutes up to a maximum rate of 72 mL/hour.1 Administer total volume over ≥4.5 hours.1

Observe patients closely for anaphylaxis during and following administration.1 If a hypersensitivity reaction occurs, reduce infusion rate, temporarily interrupt infusion, or discontinue infusion for that visit.1 If a severe hypersensitivity reaction occurs, immediately discontinue infusion and initiate appropriate treatment.1 (See Hypersensitivity Reactions under Cautions.)

Dosage

Dosage is expressed in terms of mg.1 The specific activity of elosulfase alfa is 2.6–6 units/mg; 1 unit is defined as the amount of enzyme that results in the conversion of 1 mcmol of sulfated monosaccharide substrate D-galactopyranoside-6-sulfate to desulfated-galactose and free sulfate per minute at 37°C.1

Pediatric Patients

Mucopolysaccharidosis IVA
IV

Children ≥5 years of age: 2 mg/kg by IV infusion once weekly.1

Adults

Mucopolysaccharidosis IVA
IV

2 mg/kg by IV infusion once weekly.1

Prescribing Limits

Pediatric Patients

Mucopolysaccharidosis IVA
IV

Children ≥5 years of age: Maximum infusion rate of 36 mL/hour for patients receiving total infusion volume of 100 mL or 72 mL/hour for those receiving total infusion volume of 250 mL.1

Adults

Mucopolysaccharidosis IVA
IV

Maximum infusion rate of 36 mL/hour for patients receiving total infusion volume of 100 mL or 72 mL/hour for those receiving total infusion volume of 250 mL.1

Special Populations

No special population dosage recommendations at this time.1

Cautions for Elosulfase Alfa

Contraindications

  • None.1

Warnings/Precautions

Warnings

Hypersensitivity Reactions

Hypersensitivity reactions, including life-threatening anaphylaxis, reported.1 3 5 7 (See Boxed Warning.) Manifestations have included cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and GI symptoms (e.g., nausea, abdominal pain, retching, vomiting) in conjunction with urticaria.1 Can occur at any time (as early as 30 minutes to as late as several days after the start of infusion) and after any infusion, regardless of course of treatment.1

Closely observe patients during and after administration; ensure that appropriate medical support is readily available.1 Additional monitoring may be required in patients with certain underlying conditions (e.g., acute febrile or respiratory illness).1 (See Acute Respiratory Complications under Cautions.)

To minimize risk of hypersensitivity reactions, premedicate with antihistamines (with or without antipyretics).1 (See General under Dosage and Administration.)

Manage hypersensitivity reactions based on severity.1 If a mild reaction occurs, reduce infusion rate, interrupt infusion, and/or administer additional antihistamines, antipyretics, and/or corticosteroids.1 If a severe reaction occurs, immediately discontinue infusion and initiate appropriate treatment.1 Consider risks and benefits of retreatment following a severe hypersensitivity reaction.1

Other Warnings/Precautions

Acute Respiratory Complications

Patients with acute febrile or respiratory illness may be at increased risk of life-threatening complications from hypersensitivity reactions.1 (See Hypersensitivity Reactions under Cautions.) Carefully consider patient's clinical status prior to infusion; a delay in therapy may be required.1

Sleep apnea is common in patients with MPS IVA; consider evaluating airway patency prior to initiating therapy.1 Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have those treatments readily available during elosulfase alfa infusion in the event of an acute reaction or antihistamine-induced episode of extreme drowsiness or sleep.1

Spinal or Cervical Cord Compression

Spinal or cervical cord compression, a known serious complication of MPS IVA, reported.1 Monitor for signs and symptoms (e.g., back pain, paralysis of limbs below the level of compression, urinary or fecal incontinence) and provide appropriate treatment if needed.1

Antibody Formation

Development of antibodies to elosulfase alfa reported in all patients receiving the drug in clinical studies.1 4 5 In addition, neutralizing antibodies that interfere with appropriate cellular uptake of the drug also detected.1 4 5

Effect of antibodies on efficacy and safety (e.g., risk of anaphylaxis or other hypersensitivity reaction) not known.1

Specific Populations

Pregnancy

Category C.1

No adequate and well-controlled studies in pregnant women; use during pregnancy only if potential benefits justify potential risks to the fetus.1

The Morquio A Registry collects data on pregnant women with MPS IVA who are treated with elosulfase alfa.1 For additional information or to enroll, call 800-983-4587 or contact MARS@bmrn.com.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Consider known benefits of breastfeeding, mother's clinical need for the drug, and any potential adverse effects of the disease or drug on the infant.1 Use with caution.1

The Morquio A Registry collects data on nursing women with MPS IVA who are treated with elosulfase alfa.1 For additional information or to enroll, call 800-983-4587 or contact MARS@bmrn.com.1

Pediatric Use

Safety and efficacy not established in children <5 years of age.1

Geriatric Use

No experience in patients ≥65 years of age; not known whether geriatric patients respond differently than younger patients.1

Common Adverse Effects

Pyrexia,1 3 vomiting,1 3 headache,1 3 nausea,1 abdominal pain,1 chills,1 fatigue.1

Interactions for Elosulfase Alfa

No formal drug interaction studies to date.1

Elosulfase Alfa Pharmacokinetics

Absorption

Bioavailability

Mean AUC and peak plasma concentrations increased by 2.8- and 2.9-fold, respectively, at 22 weeks compared with values obtained after the initial IV infusion in patients receiving once-weekly treatment with elosulfase alfa 2 mg/kg.1

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.1

Elimination

Half-life

8 minutes after initial infusion; 36 minutes after infusion at 22 weeks.1

Intracellular half-life in human Morquio A fibroblasts is approximately 5–7 days.4

Stability

Storage

Parenteral

Solution Concentrate for IV Infusion

2–8°C.1 Protect from light and freezing; do not shake.1 Vials are for single use only; discard any unused product.1

Diluted solutions: If not used immediately, may store at 2–8°C for up to 24 hours followed by up to 24 hours at 23–27°C during administration.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium chloride 0.9%.1

Actions

  • Biosynthetic (recombinant DNA origin) form of human N-acetylgalactosamine-6-sulfatase (GALNS), a lysosomal enzyme that catalyzes the hydrolysis of the glycosaminoglycans keratan sulfate and chondroitin-6-sulfate.1 3 4 5 8

  • Replaces the deficient GALNS enzyme in patients with MPS IVA.1 3 4 5

  • Cellular uptake into lysosomes is mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of the drug to mannose-6-phosphate receptors.1

Advice to Patients

  • Importance of encouraging patients to participate in the Morquio A Registry (800-983-4587 or MARS@bmrn.com).1 Importance of informing patients that participation is voluntary and may involve long-term follow-up.1

  • Risk of severe hypersensitivity reactions, including life-threatening anaphylaxis.1 Importance of informing patients of signs and symptoms of anaphylaxis and to seek immediate medical attention if hypersensitivity occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Elosulfase Alfa

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, concentrate, for IV infusion only

1 mg/mL (5 mg)

Vimizim

BioMarin

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.

References

1. BioMarin Pharmaceutical Inc. Vimizim (elosulfase alfa) injection prescribing information. Novato, CA; 2014 Feb.

2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website (http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm). Accessed 2015 Nov 11.

3. Hendriksz CJ, Burton B, Fleming TR et al. Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study. J Inherit Metab Dis. 2014; 37:979-90.

4. Qi Y, Musson DG, Schweighardt B et al. Pharmacokinetic and pharmacodynamic evaluation of elosulfase alfa, an enzyme replacement therapy in patients with Morquio A Syndrome. Clin Pharmacokinet. 2014; 53:1137-47. [PubMed 25234648]

5. Schweighardt B, Tompkins T, Lau K et al. Immunogenicity of elosulfase alfa, an enzyme replacement therapy in patients with Morquio A syndrome: results from MOR-004, a phase III trial. Clin Ther. 2015; 37:1012-21. [PubMed 25487082]

6. Harmatz P. Enzyme replacement therapies and immunogenicity in lysosomal storage diseases: is there a pattern? Clin Ther. 2015; 37:2130-4. [PubMed 26243075]

7. US Food and Drug Administration. Center for Drug Evaluation and Research. Summary Review: BLA# 125460. From FDA website.

8. Hendriksz CJ, Berger KI, Giugliani R et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015; 167A:11-25. [PubMed 25346323]

9. Hendriksz CJ, Harmatz P, Beck M et al. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013 Sep-Oct; 110:54-64. [PubMed 23665161]

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