Elelyso

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

• 200 units/vial

Gaucher Disease

Indicated for enzyme replacement in patients with confirmed diagnosis of type 1 (non-neuropathic) Gaucher disease

60 units/kg IV q2weeks initially

Administration

Reconstitute, dilute and administer under the supervision of a healthcare professional

Infuse IV over 1-2 hr

Adjust dose based on achievement and maintenance of each patient’s therapeutic goals; clinical trials have evaluated doses ranging from 11-73 units/kg every other week

Patients on a stable dose of imiglucerase can be switched to taliglucerase alfa at that same dose

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

• 200 units/vial

Gaucher Disease

Indicated for enzyme replacement in patients with confirmed diagnosis of type 1 (non-neuropathic) Gaucher disease

<4 years: Safety and efficacy not established

≥4 years: 60 units/kg IV q2weeks initially

Administration

Infuse IV over 1-2 hr

Adjust dose based on achievement and maintenance of each patient’s therapeutic goals; clinical trials have evaluated doses ranging from 11-73 units/kg every other week

Patients on a stable dose of imiglucerase can be switched to taliglucerase alfa at that same dose

>10%

Vomiting, pediatrics (44%)

Hypersensitivity reactions (29%)

Headache (19%)

Arthralgia (13%)

1-10%

Fatigue (9%)

Nausea (9%)

Dizziness (9%)

Abdominal pain (6%)

Pruritus (6%)

Flushing (6%)

Vomiting (6%)

Urticaria (6%)

Serious hypersensitivity reactions, including anaphylaxis (2.8%)

Postmarketing Reports

Gastrointestinal disorders: Diarrhea

Immune system disorders: Type III immune-mediated fixed drug eruption

Musculoskeletal and connective tissue disorders: Back pain

Taliglucerase alfa, a hydrolytic lysosomal glucocerebroside-specific enzyme for intravenous infusion, is a recombinant active form of the lysosomal enzyme, β-glucocerebrosidase, which is expressed in genetically modified carrot plant root cells cultured in a disposable bioreactor system (ProCellEx®). β-Glucocerebrosidase (β-D-glucosyl-Nacylsphingosine glucohydrolase, E.C. 3.2.1.45) is a lysosomal glycoprotein enzyme that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide.

ELELYSO is produced by recombinant DNA technology using plant cell culture (carrot). Purified taliglucerase alfa is a monomeric glycoprotein containing 4 N-linked glycosylation sites (Mr = 60,800). Taliglucerase alfa differs from native human glucocerebrosidase by two amino acids at the N terminal and up to 7 amino acids at the C terminal. Taliglucerase alfa is a glycosylated protein with oligosaccharide chains at the glycosylation sites having terminal mannose sugars. These mannose-terminated oligosaccharide chains of taliglucerase alfa are specifically recognized by endocytic carbohydrate receptors on macrophages, the cells that accumulate lipid in Gaucher disease.

ELELYSO is supplied as a sterile, non-pyrogenic, lyophilized product. The quantitative composition of each 200 unit vial is D-mannitol (206.7 mg), polysorbate 80 (0.56 mg), sodium citrate (30.4 mg), and taliglucerase alfa (212 units). Citric acid may be added to adjust the pH at the time of manufacture.

A Unit is the amount of enzyme that catalyzes the hydrolysis of 1 micromole of the synthetic substrate paranitrophenyl-β-D-glucopyranoside (pNP-Glc) per minute at 37°C. After reconstitution with Sterile Water for Injection, taliglucerase alfa concentration is 40 units/mL [see DOSAGE AND ADMINISTRATION]. Reconstituted solutions have a pH of approximately 6.0.

Elelyso is a prescription medication used to treat Type 1 Gaucher disease. Elelyso belongs to a group of drugs called enzymes. These work by acting like the enzyme glucocerebrosidase. This enzyme does not work well in people with Type 1 Gaucher disease.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional. 

Common side effects of Elelyso include headache, joint pain, and lack of energy.

Elelyso can also cause dizziness. Do not drive or operate heavy machinery until you know how Elelyso affects you.

Serious side effects have been reported with Elelyso. See the "Drug Precautions" section.

Common side effects of Elelyso include the following:

• heachache
• joint pain
• lack of energy
• nausea
• dizziness
• stomach pain
• itching
• flushing
• vomiting
• hives

This is not a complete list of Elelyso side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Elelyso crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Elelyso.

Biosynthetic (recombinant DNA origin) form of human β-glucocerebrosidase (glucosylceramidase).1 3 4

General

• Prepare and administer under supervision of a clinician.1

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1

Administer using an inline, low-protein-binding 0.2-mcm filter.1

Contains no preservatives; use immediately following preparation.1 (See Storage under Stability.) Discard any unused portions.1

Reconstitute using proper aseptic technique.1

Determine number of vials to be reconstituted based on patient’s weight and recommended dose of 60 units/kg.1

Remove required number of vials from refrigerator prior to reconstitution; do not leave vials at room temperature for >24 hours and do not heat vials (e.g., in a microwave).1

Reconstitute each vial containing 200 units of taliglucerase alfa with 5.1 mL of sterile water for injection to provide a solution containing 40 units/mL.1 Mix gently; do not shake.1

Withdraw appropriate dose from reconstituted vials and dilute with 0.9% sodium chloride injection to yield a final volume of 100–200 mL.1 For pediatric patients, dilute to final volume of 100–200 mL.1 For adults, may dilute to final volume of 130–150 mL; however, if volume of reconstituted drug alone is equal to or greater than this amount, do not exceed final volume of 200 mL.1 Mix gently; do not shake.1

Slight flocculation (described as translucent fibers) occurs occasionally after dilution.1

Administer over 1–2 hours.1 In pediatric patients, initial infusion rate of 1 mL/minute recommended; if tolerated, may increase up to a maximum rate of 2 mL/minute.1 In adults, an initial infusion rate of 1.2 mL/minute recommended; if tolerated, may increase up to a maximum rate of 2.2 mL/minute.1 Administer total volume over a period of ≥1 hour.1

Dosage

Pediatric Patients

Pediatric patients ≥4 years of age: 60 units/kg every 2 weeks.1

Adjust dosage based on achievement and maintenance of the patient's therapeutic goals.1

Patients currently receiving imiglucerase can be switched to taliglucerase alfa at the same dosage.1

Adults

60 units/kg every 2 weeks.1

Adjust dosage based on achievement and maintenance of the patient's therapeutic goals.1

Patients currently receiving imiglucerase can be switched to taliglucerase alfa at the same dosage.1

Special Populations

No special population dosage recommendations at this time.1

Storage

Parenteral

2–8°C. Protect from light.1

Following reconstitution, 2–8°C for up to 24 hours if protected from light or up to 4 hours at 20–25°C without protection from light.1

Following dilution, may store at 2–8°C for up to 24 hours; protect from light.1 Do not freeze.1

Compatibility

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

Parenteral

Elelyso is injected into a vein through an IV. A healthcare provider will give you this injection.

You may be given other medications to prevent certain side effects of Elelyso.

Elelyso is usually given every other week. Follow your doctor's dosing instructions very carefully.

Your doctor may occasionally change your dose to make sure you get the best results.

Summary of Use during Lactation

No information is available on the clinical use of taliglucerase alfa during breastfeeding. Taliglucerase alfa is a biosynthetic synthetic enzyme closely related to beta-glucocerebrosidase, which is a normal component of human milk. Because it is a large protein molecule with a molecular weight of about 61,000, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant's gastrointestinal tract.[1][2] A limited amount of data support the safety of breastfeeding with alglucerase (the placenta-derived form of the enzyme) and imiglucerase (another biosynthetic form of the enzyme). An international panel of clinicians from 9 centers that treat Gaucher's disease reported that, breastfeeding complications were less frequent in mothers who were treated with alglucerase or imiglucerase postpartum than in untreated mothers with Gaucher's disease. Consider limiting the duration of breastfeeding to about 6 months to avoid excessive bone loss in the nursing mother.[2][3]

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

References

1. Belmatoug N. Considerations for pregnant patients with Gaucher disease: challenges for the patient and physician. Clin Ther. 2009;31 (Suppl C):S192-3. DOI: doi:10.1016/S0149-2918(09)80019-2

2. Zimran A, Morris E, Mengel E et al. The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause). Blood Cells Molec Dis. 2009;43:264-88. PMID: 19502088

3. Granovsky-Grisaru S, Belmatoug N, vom Dahl S. The management of pregnancy in Gaucher disease. Eur J Obstet Gynecol Reprod Biol. 2011;156:3-8. PMID: 21269752