Taliglucerase Alfa
FDA Drug Information • Also known as: Elelyso
- Brand Names
- Elelyso
- Dosage Form
- LIQUID
- Product Type
- DRUG FOR FURTHER PROCESSING
⚠ Boxed Warning (Black Box)
WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life‑threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life‑threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ] . WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning.
Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. ( 5.1 ) Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. ( 5.1 ) If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine. ( 5.1 )Description
11 DESCRIPTION Taliglucerase alfa is a hydrolytic lysosomal glucocerebroside-specific enzyme produced by recombinant DNA technology using plant cell culture (carrot). Taliglucerase alfa is a monomeric glycoprotein enzyme containing 4 N-linked glycosylation sites (kDa=60.8). Taliglucerase alfa differs from native human glucocerebrosidase by 2 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. A unit is the amount of enzyme that catalyzes the hydrolysis of 1 micromole of the synthetic substrate para-nitrophenyl-β-D-glucopyranoside ( p NP-Glc) per minute at 37 °C. ELELYSO (taliglucerase alfa) for injection is supplied as a sterile, preservative-free, lyophilized powder for reconstitution and dilution prior to intravenous infusion. Each single-dose vial contains 200 units of taliglucerase alfa and D-mannitol (206.7 mg), polysorbate 80 (0.56 mg), and sodium citrate (30.4 mg). Citric acid may be added to adjust the pH at the time of manufacture. After reconstitution with 5.1 mL Sterile Water for Injection, USP, taliglucerase alfa concentration is 40 units/mL [see Dosage and Administration (2) ] . Reconstituted solutions have a pH of approximately 6.0.
What Is Taliglucerase Alfa Used For?
1 INDICATIONS AND USAGE ELELYSO is indicated for the treatment of patients 4 years of age and older with a confirmed diagnosis of Type 1 Gaucher disease. ELELYSO is a hydrolytic lysosomal glucocerebroside-specific enzyme indicated for the treatment of patients 4 years and older with a confirmed diagnosis of Type 1 Gaucher disease ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Recommendations Prior to ELELYSO Treatment ( 2.1 ):
Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Recommended Dosage in Patients 4 Years and Older ( 2.2 ): Treatment-naïve : 60 units/kg administered every other week as a 60- to 120-minute intravenous infusion. Patients switching from imiglucerase : Initiate ELELYSO intravenous treatment (60- to 120-minute infusion) with the same units/kg imiglucerase dosage and subsequently administer ELELYSO every other week. Dosage adjustments can be based on achievement and maintenance of each patient’s therapeutic goals. Preparation and Administration ( 2.3, 2.4, 2.5 ): Reconstitute, dilute and administer under the supervision of a healthcare professional. See Full Prescribing Information for complete instructions. 2.1 Recommendations Prior to ELELYSO Treatment Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1) ] . Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1) ] . To reduce the risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or corticosteroids [see Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage in Patients 4 Years and Older Treatment-Naïve Patients 4 Years of Age and Older The recommended dosage of ELELYSO is 60 units/kg (based on actual body weight) administered every other week as a 60- to 120-minute intravenous infusion. Patients 4 Years of Age and Older Switching from Imiglucerase If it is acceptable to switch from a stable imiglucerase dosage to ELELYSO, initiate ELELYSO intravenous treatment (60- to 120-minute infusion) with the same units/kg imiglucerase dosage and subsequently administer ELELYSO every other week. Dosage adjustments can be made based on achievement and maintenance of each patient's therapeutic goals. 2.3 Preparation Instructions ELELYSO should be reconstituted, diluted, and administered under the supervision of a healthcare professional. Prepare ELELYSO according to the following steps using aseptic technique: a. Determine the number of vials to be reconstituted based on the patient's weight in kg and the recommended dose [see Dosage and Administration (2.2) ] . Round the number of vials up to the next whole number. b. Remove the required number of vials from the refrigerator. Do not leave these vials at room temperature longer than 24 hours prior to reconstitution. Do not heat or microwave these vials. c. Reconstitute each vial of ELELYSO with 5.1 mL of Sterile Water for Injection, USP to yield a reconstituted product with a concentration of 40 units/mL and an extractable volume of 5 mL. (1) Upon...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reactions are:
Treatment-Naïve Adults (≥5%): headache, arthralgia, fatigue, nausea, dizziness, abdominal pain, pruritus, flushing, vomiting, urticaria ( 6.1 ). Patients who Switched from Imiglucerase, after 9 Months on Treatment (≥10%): arthralgia, headache, pain in extremity ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions from Clinical Trials of ELELYSO as Initial Therapy Clinical Trial in Adult Patients The safety of ELELYSO at dosages of either 30 units/kg (n=16) (50% of the recommended dosage) [see Dosage and Administration (2.1) ] or 60 units/kg (n=16) administered intravenously every other week was assessed in 32 adult treatment-naïve patients (aged 19 to 74 years) with Type 1 Gaucher disease in a 9-month double-blind, randomized clinical trial (Trial 1) [see Clinical Studies (14) ] . Table 1 presents the adverse reactions that occurred in these ELELYSO-treated patients. Table 1: Adverse Reactions in ≥5% of Treatment-Naïve Adult Patients Treated with ELELYSO Preferred Term Treatment-Naïve Adults (N=32) n (%) Headache 6 (19) Arthralgia 4 (13) Fatigue 3 (9) Nausea 3 (9) Dizziness 3 (9) Abdominal pain 2 (6) Pruritus 2 (6) Flushing 2 (6) Vomiting 2 (6) Urticaria 2 (6) Clinical Trial in Pediatric Patients 16 Years of Age and Younger The safety of ELELYSO at dosages of either 30 units/kg (n=4) (50% of the recommended dosage) [see Dosage and Administration (2.1) ] or 60 units/kg (n=5) administered intravenously every other week was assessed in 9 pediatric treatment-naïve patients (aged 2 to 13 years) with Type 1 Gaucher disease in a 12-month randomized clinical trial (Trial 2) [see Clinical Studies (14) ] . The most common adverse reaction (≥10%) was vomiting, which occurred in 4 of 9 patients. Two patients developed hypersensitivity reactions; 1 patient experienced severe vomiting and gastrointestinal inflammation, and 1 experienced mild throat irritation and chest discomfort. Both patients responded to treatment with antihistamines and continued ELELYSO treatment. Adverse Reactions in a Clinical Trial in Patients Who Switched from Imiglucerase to ELELYSO The safety of ELELYSO was assessed in 31 patients (26 adult and 5 pediatric patients), ages 6 to 66 years old, with Type 1 Gaucher disease who had previously been receiving imiglucerase treatment for a minimum of 2 years (Trial 3). ELELYSO was administered intravenously every other week for 9 months at the same number of units as each patient's previous imiglucerase dose. Table 2 presents the adverse reactions in these ELELYSO-treated patients. Table 2: Adverse Reactions in ≥10% of ELELYSO-Treated Patients Who Switched from Imiglucerase to ELELYSO (after 9 months on treatment) Preferred Term Adult and Pediatric Patients Switched from Imiglucerase (N=31) n (%) Arthralgia 4 (13) Headache 4 (13) Pain in extremity 3 (10) Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions Trials 1, 2, and 3 evaluated ELELYSO enzyme replacement therapy (ERT)-naïve and ERT-experienced adult and pediatric patients with Gaucher disease [see Clinical Studies (14.1, 14.2) ] . In patients with Type 1 Gaucher disease, hypersensitivity reactions occurred in 36% (9/25) of ELELYSO-treated patients who developed ADA during the treatment period and in 15% (6/41) of ELELYSO-treated patients who did not develop ADA during the treatment period [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.6) ] . Of the 9 ELELYSO-treated patients who tested positive for ADA and who developed hypersensitivity reactions, 2 patients had anaphylaxis and 1...Contraindications
4 CONTRAINDICATIONS None. None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data, including data from a product registry and pharmacovigilance reports, have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes in pregnant women exposed to ELELYSO. Additionally, there are risks associated with untreated symptomatic Type I Gaucher disease in pregnant women ( see Clinical Considerations ). In animal reproduction studies when pregnant rats and rabbits were administered taliglucerase alfa at intravenous doses up to 5 times the recommended human dose (RHD), there was no evidence of embryo-fetal toxicity ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Women with Type 1 Gaucher disease have an increased risk of spontaneous abortion if disease symptoms are not treated and controlled pre-conception and during a pregnancy. Pregnancy may exacerbate existing Type 1 Gaucher disease symptoms or result in new disease manifestations. Type 1 Gaucher disease manifestations may lead to adverse pregnancy outcomes, including hepatosplenomegaly which can interfere with the normal growth of a fetus and thrombocytopenia which can lead to increased bleeding and possible postpartum hemorrhage requiring transfusion. Data Animal Data Reproduction studies have been performed with taliglucerase alfa administered during the period of organogenesis in rats and rabbits. In rats, intravenous doses up to 55 mg/kg/day (about 5 times the RHD of 60 units/kg based on the body surface area) did not cause any adverse effects on embryo-fetal development. In rabbits, intravenous doses up to 27.8 mg/kg/day (about 5 times the RHD of 60 units/kg based on the body...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING ELELYSO (taliglucerase alfa) for injection is supplied as a sterile, preservative-free, white to off-white lyophilized powder in a single-dose vial. Each vial of ELELYSO contains 200 units of taliglucerase alfa. Each carton contains one vial (NDC 0069-0106-01). Refrigerate ELELYSO at 2 °C to 8 °C (36 °F to 46 °F) in the original carton to protect from light. Do not freeze.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.