English
Taliglucerase Alfa
Indications/Dosage
Labeled
- Gaucher disease
Off-Label
For replacement therapy of glucosylceramidase in confirmed (type 1) Gaucher disease:
NOTE: Taliglucerase alfa is designated as an orphan drug by the FDA for this indication.
Intravenous dosage
Adults
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.[49908]
Children and Adolescents 4 to 17 years
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.[49908]
Therapeutic Drug Monitoring
Maximum Dosage Limits
- Adults
60 units/kg/dose IV every 2 weeks.
- Geriatric
60 units/kg/dose IV every 2 weeks.
- Adolescents
60 units/kg/dose IV every 2 weeks.
- Children
4 to 12 years: 60 units/kg/dose IV every 2 weeks.
1 to 3 years: Safety and efficacy have not been established.
- Infants
Safety and efficacy have not been established.
- Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
† Off-label indicationReferences
How Supplied
Taliglucerase alfa Lyophilisate for solution for injection
Elelyso 200unit Powder for Injection (00069-0106) (Pfizer Injectables) nullDescription/Classification
Description
Taliglucerase alfa is an enzyme used in the treatment of patients with Gaucher's disease. Taliglucerase alfa replaces the endogenous enzyme beta-glucocerebrosidase. Taliglucerase alfa is produced by recombinant DNA technology using plant cell culture (carrot), making it the first plant-made pharmaceutical. This process is beneficial because it eliminates the threat of viruses and other pathogens that can contaminate mammalian stocks. Taliglucerase differs from the endogenous metabolic enzyme by two amino acids at the N terminal and up to 7 amino acids at the C terminal.[49908] Treatment with taliglucerase alfa is indicated for adults and children >= 4 years with a confirmed diagnosis of Type I Gaucher's disease. The FDA approved taliglucerase alfa under orphan status in May 2012.
Classifications
- Alimentary Tract and Metabolism
- Metabolic Disorder Agents
- Lysosomal Storage Disorder Agents
- Gauchers Disease Agents
- Lysosomal Storage Disorder Agents
- Metabolic Disorder Agents
References
Administration Information
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
- 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.[49908]
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.[49908]
Clinical Pharmaceutics Information
From Trissel's 2‚Ñ¢ Clinical Pharmaceutics DatabaseTaliglucerase alfa
pH Range
Approximately pH 6.0 after reconstitution.Stability
Taliglucerase alfa injection in intact vials stored as directed by the manufacturer are stable until the labeled expiration date. The manufacturer states that reconstituted taliglucerase alfa should be used immediately after reconstitution. If that is not possible, the manufacturer states that the drug may be stored for up to 24 hours under refrigeration at 2 to 8 degree C and protected from exposure to light or for 12 hours at controlled room temperature not protected from exposure to light. The manufacturer further notes that the total time from reconstitution and dilution until use must be no more than 24 hours. Taliglucerase alfa is provided in single-use vials with no preservative present in the formulation. The manufacturer directs that any reconstituted solution remaining in the vial after preparation of the dilution must be discarded. Infusion Solutions: Taliglucerase alfa is to be diluted in 100 to 200 mL of sodium chloride 0.9% for intravenous administration. This protein solution may develop slight flocculation that is described as translucent fibers after dilution. The manufacturer states that taliglucerase alfa contains no preservatives and should be used immediately. If that is not possible, the manufacturer states that the drug may be stored for up to 24 hours under refrigeration at 2 to 8 degree C and protected from exposure to light or for 12 hours at controlled room temperature not protected from exposure to light. The manufacturer further notes that the total time from reconstitution and dilution until use must be no more than 24 hours.Light Exposure
Intact vials of taliglucerase alfa should be protected from exposure to light during storage. The manufacturer states that the drug may be stored for up to 24 hours under refrigeration at 2 to 8 degree C and protected from exposure to light or for 12 hours at controlled room temperature not protected from exposure to light.Freezing
Taliglucerase alfa should be protected from freezing.Filtration
The manufacturer states that taliglucerase alfa should be administered using a low-protein-binding administration set equipped with a low-protein-binding 0.2-micron inline filter.Sorption Leaching
The manufacturer states that taliglucerase alfa should be prepared for administration using a low-protein-binding container and administered using a low-protein-binding administration set equipped with a low-protein-binding 0.2-micron inline filter. Taliglucerase alfa contains a small amount of the polysorbate 80 in the formulation. While surfactants have the potential to leach plasticizers from some plastics, the very small amount in this formulation is not likely to result in the leaching of meaningful amounts.Stability Max
Maximum reported stability period: In NS- 24 hours refrigerated and protected from light and 12 hours at room temperatureReferences
Adverse Reactions
Moderate
- antibody formation
- erythema
- hypotension
- infusion-related reactions
- wheezing
Mild
- abdominal pain
- arthralgia
- back pain
- cough
- diarrhea
- dizziness
- fatigue
- flushing
- headache
- nausea
- pruritus
- rash
- throat irritation
- urticaria
- vomiting
Severe
- anaphylactoid reactions
- angioedema
Headache (13% to 19%), arthralgia (13%), extremity pain (10%), and fatigue (9%) were among the most common adverse reactions reported during clinical trials with taliglucerase (n = 72). Back pain has been reported in post-marketing surveillance.[49908]
In clinical trials, 29% of patients experienced hypersensitivity and/or infusion-related reactions including pruritus, angioedema, flushing, erythema, rash, nausea, vomiting, cough, chest tightness, and throat irritation up to 3 hours after the start of infusion. Nausea (9%), dizziness (9%), abdominal pain (6%), pruritus (6%), flushing (6%), vomiting (6%), and urticaria (6%) were reported frequently during a 9-month clinical trial in adult treatment-naive patients (n = 32). During pediatric trials (n = 9), the most common adverse reaction 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 antihistamine treatment and continued taliglucerase treatment. Vomiting, diarrhea, and Type III immune-mediated fixed drug eruption have also been reported in postmarketing surveillance. Serious hypersensitivity reactions have also occurred; in clinical trials, 3% of patients experienced signs and symptoms consistent with anaphylaxis or anaphylactoid reactions (e.g., urticaria, hypotension, flushing, wheezing, chest tightness, nausea, vomiting, dizziness). For this reason, appropriate medical support should be readily available during administration and patients should be observed for an appropriate period after administration. If a severe reaction occurs, immediately discontinue taliglucerase and initiate appropriate medical treatment. For mild reactions, slow or temporarily interrupt the infusion and/or administer antihistamines, antipyretics, and/or corticosteroids. Pretreatment with antihistamines and/or corticosteroids may prevent subsequent reactions. Consider the risks and benefits of re-administration of taliglucerase in patients who have experienced a severe reaction; exercise great caution upon re-challenge.[49908]
As with all therapeutic proteins, anti-drug antibody formation (ADA) to taliglucerase may occur. During clinical trials, roughly 17 (53%) of 32 treatment-naive adult patients and 2 (22%) of 9 treatment-naive pediatric patients receiving taliglucerase alfa developed ADA, while 16% of adult and pediatric patients who were switched from imiglucerase to taliglucerase alfa developed ADA. Two adult patients (1 patient who developed ADA after the switch and 1 who was ADA positive at baseline) experienced hypersensitivity reactions. Neutralizing antibodies capable of inhibiting mannose receptor binding of taliglucerase were found in 19 (63%) of the 30 patients who had previously tested positive for ADA to taliglucerase. Of these 19 patients, 8 had neutralizing antibodies capable of inhibiting the enzymatic activity of taliglucerase. Nine (29%) of the 31 patients who were positive for ADA to taliglucerase also developed antibodies against plant-specific glycans in taliglucerase. In most patients, the development of antibodies does not prohibit the continued administration of the medication. However, the relationship between ADA and hypersensitivity reactions is not fully understood. Monitoring for ADA to taliglucerase may be useful in ADA positive patients or in patients who have experienced hypersensitivity reactions to enzyme replacement therapy.[49908]
References
Contraindications/Precautions
Absolute contraindications are italicized.
- breast-feeding
- children
- infants
- infusion-related reactions
- neonates
- pregnancy
Although there are no known contraindications, taliglucerase alfa should be used with caution in patients with a known hypersensitivity to other enzyme replacement therapies. Patients receiving taliglucerase have developed IgG antibodies to the product. In clinical studies, 29% of patients experienced hypersensitivity and/or infusion-related reactions. Serious hypersensitivity reactions, including anaphylactoid reactions and anaphylaxis, are possible and have occurred during and up to 3 hours after the start of taliglucerase infusion. For this reason, appropriate medical support should be readily available during administration. Observe patients closely for an appropriate period of time after administration. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical attention if such signs and symptoms occur. If a severe reaction occurs, immediately discontinue taliglucerase and initiate appropriate medical treatment. For mild reactions, slow or temporarily interrupt the infusion and/or administer antihistamines, antipyretics, and/or corticosteroids. Pretreatment with antihistamines and/or corticosteroids may prevent subsequent reactions. Consider the risks and benefits of re-administration of taliglucerase in patients who have experienced a severe reaction; exercise great caution upon re-challenge.[49908]
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.[49908] 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.[49246] 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.[49908] Imiglucerase has been suggested as an enzyme-replacement treatment option during pregnancy, based on limited data from case studies.[56701] [56702]
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.[49908] 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.[49246] Imiglucerase has been suggested as an enzyme-replacement treatment option, based on limited data from case studies and breast milk concentration data.[56701] [56702]
The safety and efficacy of taliglucerase alfa in children < 4 years, infants, or neonates have not been established.[49908]
References
Mechanism of Action
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.[49908] 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.
Revision Date: 05/04/2012, 01:14:59 PMReferences
Pharmacokinetics
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.[49908]
Affected cytochrome P450 isoenzymes and drug transporters: none
Route-Specific Pharmacokinetics
Intravenous Route
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.[49908]
Special Populations
Pediatrics
Clearance values of taliglucerase were similar and AUC values were lower in pediatric patients compared to adult patients during clinical pharmacokinetic trials. During these trials, 9 pediatric patients (age range: 4—17 years) with Gaucher disease Type 1 were treated with taliglucerase 30 units/kg or 60 units/kg for 10—27 months. The median volume of distribution at steady state (Vss) ranged from 8.8—14.9 L. Median AUC values were 1416 and 2984 ng x hr/ml, respectively; these values were lower than in adult patients due to weight-based dosing and lower body weights in pediatric patients (range: 16.5—71 kg). Median clearance values were 30.5 L/hour and 15.8 L/hour for the 30 units/kg and 60 units/kg dose groups, respectively. Median half-life values were 37.1 and 32.5 minutes, respectively.[49908]
References
Pregnancy/Breast-feeding
pregnancy
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.[49908] 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.[49246] 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.[49908] Imiglucerase has been suggested as an enzyme-replacement treatment option during pregnancy, based on limited data from case studies.[56701] [56702]
breast-feeding
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.[49908] 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.[49246] Imiglucerase has been suggested as an enzyme-replacement treatment option, based on limited data from case studies and breast milk concentration data.[56701] [56702]
References
Interactions
References
Monitoring Parameters
- laboratory monitoring not necessary
US Drug Names
- ELELYSO
