ELELYSO

Gauchers Disease Agents

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Administer via intravenous (IV) infusion only.
 
Reconstitution and Dilution
Each vial provides 200 units. Determine the number of vials that will be needed to provide the patient's dose; round up to the next whole vial.
Remove vials from refrigerator; do not leave them longer than 24 hours at room temperature. Do not heat.
Reconstitute each 200 unit vial with 5.1 mL Sterile Water for Injection. Mix gently; do not shake the vials. This yields a reconstituted product with a concentration of 40 units/mL and a withdrawal volume of 5 mL.
Do not use vials exhibiting opaque particles or discoloration to prepare the infusion.
Pediatric patients: Withdraw the calculated dose of drug from the appropriate number of vials and dilute with 0.9% Sodium Chloride Injection to a final volume of 100 to 120 mL. Mix gently and do not shake.
Adult patients: Withdraw the calculated dose of drug from the appropriate number of vials and dilute with 0.9% Sodium Chloride Injection. A final volume of 130 to 150 mL may be used; if the volume of reconstituted drug alone is equal to or greater than 130 to 150 mL, then do not exceed a maximum final volume of 200 mL. Mix gently and do not shake.
Being a protein solution, slight flocculation (described as thin translucent fibers) occurs occasionally after preparing the infusion.
Storage: Use solution promptly after dilution; do not store for later use. If immediate use is not possible, the reconstituted product is stable for 24 hours at 2 to 8 degrees C (36 to 46 degrees F) under protection from light or 4 hours at 20 to 25 degrees C (68 to 77 degrees F) without protection from light. After dilution, the infusion is stable up to 24 hours if stored at 2 to 8 degrees C (36 to 46 degrees F) under protection from light. Do not freeze.
 
Intravenous Infusion
During administration, filter the diluted solution through an in-line, low protein-binding, 0.2 micron filter over a minimum of 60 minutes.
Pediatric patients weighing less than 30 kg (based on actual body weight): Use an infusion rate of 1 mL/minute.
Pediatric patients weighing 30 kg or more (based on actual body weight): Begin with an initial infusion rate of 1 mL/minute; once tolerability is established, the rate may be increased to a maximum of 2 mL/minute.
Adult patients: Begin with an initial infusion rate of 1.2 mL/minute; once tolerability is established, the rate may be increased to a maximum of 2.2 mL/minute.

anaphylactoid reactions / Rapid / 3.0-3.0
angioedema / Rapid / Incidence not known

antibody formation / Delayed / 22.0-53.0
infusion-related reactions / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
erythema / Early / Incidence not known

headache / Early / 13.0-19.0
arthralgia / Delayed / 13.0-13.0
fatigue / Early / 9.0-9.0
nausea / Early / 9.0-9.0
dizziness / Early / 9.0-9.0
flushing / Rapid / 6.0-6.0
pruritus / Rapid / 6.0-6.0
urticaria / Rapid / 6.0-6.0
abdominal pain / Early / 6.0-6.0
vomiting / Early / 6.0
back pain / Delayed / Incidence not known
cough / Delayed / Incidence not known
throat irritation / Early / Incidence not known
diarrhea / Early / Incidence not known
rash / Early / Incidence not known

ELELYSO

Rx

Metabolic enzyme replacement.
Used in the treatment of patients with Gaucher's disease.
First plant-made recombinant pharmaceutical.

60 units/kg/dose (based on actual body weight) IV infusion once every 2 weeks. Patients with Type I Gaucher disease who are changing therapy from a dose of imiglucerase to taliglucerase should begin treatment with taliglucerase at that same dose. Titrate dose to individual patient response and therapeutic goals.

60 units/kg/dose (based on actual body weight) IV infusion once every 2 weeks. Patients with Type I Gaucher disease who are changing therapy from a dose of imiglucerase to taliglucerase should begin treatment with taliglucerase at that same dose. Titrate dose to individual patient response and therapeutic goals.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Taliglucerase Alfa products.

ELELYSO Intravenous Inj Pwd F/Sol: 200IU

60 units/kg/dose IV every 2 weeks.

60 units/kg/dose IV every 2 weeks.

60 units/kg/dose IV every 2 weeks.

4 to 12 years: 60 units/kg/dose IV every 2 weeks.
1 to 3 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Taliglucerase alfa substitutes for the deficient enzyme glucosylceramidase in patients with Gaucher's disease. Gaucher's disease is a congenital disorder of lipid metabolism. It results from a deficiency of glucosylceramidase, a necessary catalyst for the hydrolysis of glucosylceramide, an endogenous, very insoluble glycolipid. Patients with this condition have a build-up of this glycolipid in lysosomes of phagocytic cells, which are found in storage cells of the liver, spleen, and bone marrow as well as in the lung, kidney, and intestine. Clinically, this build-up is associated with splenomegaly, hepatomegaly, increased skin pigmentation, and lesions of bone.
 
Taliglucerase alfa is designed to be preferentially taken up by macrophages, the drug's site of action. Treatment with taliglucerase alfa results in hydrolysis of the accumulated glycolipid within macrophages and improvement in hemoglobin, hematocrit, and platelet counts, and a decrease in hepatomegaly and splenomegaly. Reductions in size of an enlarged liver and spleen correspond to hematological improvement and patients' subjective improvement. Treatment with taliglucerase alfa does not cure the underlying condition, but it does provide improvement. Continued use is required to maintain suppression of symptoms.

Taliglucerase alfa is administered by intravenous (IV) infusion because glycoproteins are destroyed in the gastrointestinal tract and cannot be administered orally. In adult clinical trials (n = 29), the median systemic clearance values were 30.5 L/hour and 18.5 L/hour for the 30 and 60 units/kg dose groups, respectively. The median volume of distribution at steady state (Vss) ranged from 10.7—11.7 L for both adult dose groups. At the end of the infusion, taliglucerase alfa serum concentrations decreased rapidly with a median terminal half-life of 18.9—28.7 minutes for both adult dose groups.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Taliglucerase alfa exhibits nonlinear pharmacokinetics with a greater than dose-proportional increase in exposure at the intravenous infusion doses studied. Median AUC values were 2007 and 6459 ng x hr/ml after 30 and 60 units/kg doses, respectively, in adult patients.

The limited available data on taliglucerase alfa use in pregnant women are not sufficient to inform a drug-associated risk. There are no adequate and well controlled studies in pregnant women. However, a report from a panel of clinicians that treat Gaucher's disease indicated that treatment with enzyme replacement therapy during pregnancy led to a reduced risk of spontaneous abortion and a reduced risk of Gaucher-related complications during delivery and during the postpartum period. Reproduction studies have been performed in pregnant rats and rabbits at taliglucerase alfa doses about 5 times the recommended human dose; results did not show impaired fertility or fetal harm. According to the manufacturer, because animal reproduction studies are not always predictive of human response, taliglucerase alfa should be used during pregnancy only if clearly needed. Imiglucerase has been suggested as an enzyme-replacement treatment option during pregnancy, based on limited data from case studies.

It is not known whether taliglucerase alfa is distributed into breast milk, the effects on the breast fed infant, or the effects on milk production. Enzymes such as taliglucerase alfa are likely to be degraded by the infant's digestive system and unlikely to reach the systemic circulation of a nursing infant. Limited data in a report from a panel of clinicians that treat Gaucher's disease indicated that breast-feeding complications were reduced in women treated with enzyme replacement therapy postpartum. Consider reducing the overall duration of breast-feeding to avoid excessive bone loss in the mother. Imiglucerase has been suggested as an enzyme-replacement treatment option, based on limited data from case studies and breast milk concentration data.