Dosage & Administration
Recommendations Prior to ELELYSO Treatment :
Recommended Dosage in Patients 4 Years and Older :
Preparation and Administration :
Elelyso Prescribing Information
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)].
ELELYSO is indicated for the treatment of patients 4 years of age and older with a confirmed diagnosis of Type 1 Gaucher disease.
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)].
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.
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 reconstitution, mix vials gently. DO NOT SHAKE.
- (2)
- Prior to further dilution, visually inspect the reconstituted solution in the vials for particulate matter and discoloration. The solution should be clear and colorless. Discard if particulate matter is present or the solution is discolored.
- d.
- Withdraw the calculated dose of drug from the appropriate number of vials and dilute with 0.9% Sodium Chloride Injection, USP, to a final volume of 100 to 200 mL. Discard any unused reconstituted solution.
- (1)
- For pediatric patients 4 years of age and older, use a final volume of 100 to 120 mL.
- (2)
- For adult patients, may use a final volume of 130 to 150 mL. However, if the volume of reconstituted product alone is equal to or greater than 130 to 150 mL, then the final volume should not exceed 200 mL.
- e.
- Mix the diluted solution gently. DO NOT SHAKE. Since this is a protein solution, slight flocculation (described as translucent fibers) occurs occasionally after dilution.
- f.
- Discard any unused diluted solution.
Storage and Handling of the Reconstituted and Diluted Solution
- •
- If the reconstituted ELELYSO vial is not used immediately, refrigerate at 2 °C to 8 °C (36 °F to 46 °F) for up to 24 hours (under protection from light) or store at controlled room temperature at 20 °C to 25 °C (68 °F to 77 °F) for up to 4 hours (without protection from light).
- •
- If the diluted solution is not administered immediately, refrigerate at 2 °C to 8 °C (36 °F to 46 °F) for up to 24 hours (under protection from light).
- •
- The total storage time for the reconstituted and diluted solution should not exceed 24 hours. Discard the unused reconstituted or diluted solution after 24 hours from the start of preparation.
- •
- Do not freeze.
Administration Instructions
After reconstitution and dilution, administer via intravenous infusion over a minimum of 60 minutes and with an in‑line low protein-binding 0.2 micron filter.
- •
- For pediatric patients who weigh (based on actual body weight):
- o
- Less than 30 kg use an infusion rate of 1 mL/minute.
- o
- Greater than or equal to 30 kg, use an initial infusion rate of 1 mL/minute. After tolerability to ELELYSO is established, may increase the infusion rate to a maximum of 2 mL/minute.
- •
- For adult patients, use an initial infusion rate of 1.2 mL/minute. After tolerability to ELELYSO is established, may increase the infusion rate to a maximum of 2.2 mL/minute.
For injection: 200 units white to off-white lyophilized powder in a single-dose vial for reconstitution.
Pregnancy
Risk Summary
The limited available data on ELELYSO use in pregnant women are not sufficient to inform a drug-associated risk. However, there are clinical considerations (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 estimated background risk of major birth defects and miscarriage for the indicated population(s) are 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 surface area) did not show any embryo-fetal toxicity.
Lactation
Risk Summary
There are no data on the presence of taliglucerase alfa in human milk, the effects on the breast fed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ELELYSO and any potential adverse effects on the breastfed child from ELELYSO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of ELELYSO for the treatment of pediatric patients 4 years of age and older with a confirmed diagnosis of Type 1 Gaucher disease has been established. The use of ELELYSO for this indication is supported by evidence of effectiveness from adequate and well-controlled trials of ELELYSO in adults, with additional pharmacodynamic data from 5 pediatric patients and pharmacokinetic data from 9 pediatric patients who participated in clinical trials [see Clinical Studies (14.1, 14.2), Clinical Pharmacology (12.3)]. Data from 14 pediatric patients were included in the safety evaluation [see Adverse Reactions (6.1)]. The safety and effectiveness of ELELYSO has not been established in patients less than 4 years of age.
Pediatric patients experienced a higher frequency of vomiting during ELELYSO treatment (4 of 9 treatment-naïve patients) than adult patients, and this may be a symptom of hypersensitivity reaction. The frequencies of other adverse reactions were similar between pediatric and adult patients treated with ELELYSO [see Adverse Reactions (6.1)].
Geriatric Use
During clinical trials, 8 patients aged 65 or older were treated with ELELYSO. Clinical trials of ELELYSO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
None.