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Taliglucerase Alfa
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General Dosing Information
NOTE: Taliglucerase alfa is designated as an orphan drug by the FDA for this indication.
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]
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]
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.
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.
† Off-label indicationTaliglucerase alfa is an enzyme replacement therapy used in the treatment of adult and pediatric patients 4 years and older with a confirmed diagnosis of Type I Gaucher 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. Patients must be monitored closely during administration for hypersensitivity reactions including anaphylaxis. Premedication with antihistamines and/or corticosteroids may be considered to reduce the risk of hypersensitivity reactions. Resuscitative equipment should be readily available during administration and patients observed closely for 3 hours after the start of each infusion.[49908] Taliglucerase alfa was FDA-approved in May 2012.
For storage information, see the specific product information within the How Supplied section.
Reconstitution and Dilution
Intravenous Infusion
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]
Serious hypersensitivity reactions or anaphylaxis have been reported in patients treated with enzyme replacement therapy. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. 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, ensure appropriate medical support is readily available during administration and patients are observed for at least 3 hours after administration. If a severe reaction occurs, immediately discontinue taliglucerase and initiate appropriate medical treatment, including the use of epinephrine. 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]
Taliglucerase alfa is associated with a risk of serious hypersensitivity reactions or anaphylaxis. Anaphylaxis has occurred during the early course of therapy and after extended duration of therapy. The initiation of therapy requires a specialized care setting where appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, are available. Administration should be supervised by a health care provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Monitor patient for 3 hours after the start of every infusion. Signs and symptoms observed concomitantly with hypersensitivity reactions include urticaria, hypotension, flushing, wheezing, chest tightness, nausea, vomiting, dizziness, pruritus, angioedema, erythema, rash, cough, and throat irritation. If a severe hypersensitivity reaction or anaphylaxis occurs, immediately discontinue taliglucerase alfa infusion and initiate appropriate medical treatment, including use of epinephrine. Inform patients and/or caregivers of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should signs and symptoms occur. The management of hypersensitivity reactions should be based on the severity of the reaction and may include temporary interruption of the infusion, treatment with antihistamines, antipyretics, and/or corticosteroids, or discontinuation of the infusion. To reduce the risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or steroids. Consider the risks and benefits of readministering taliglucerase alfa to a patient who has experienced a severe hypersensitivity reaction. Patients receiving taliglucerase have developed anti-drug antibodies (ADA) to the product. Patients with ADA may be at increased risk for hypersensitivity reactions.[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]
Taliglucerase alfa substitutes for the deficient enzyme glucosylceramidase in patients with Gaucher disease. Gaucher 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: 07/24/2024, 09:08:23 AMTaliglucerase 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 to 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 to 28.7 minutes for both adult dose groups.[49908]
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 2,007 and 6,459 ng x hour/mL after 30 and 60 units/kg doses, respectively, in adult patients.[49908]
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 to 17 years) with Gaucher disease Type 1 were treated with taliglucerase 30 units/kg or 60 units/kg for 10 to 27 months. The median volume of distribution at steady state (Vss) ranged from 8.8 to 14.9 L. Median AUC values were 1,416 and 2,984 ng x hour/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 to 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]
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]
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