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Imiglucerase
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30 to 60 units/kg/dose IV every 2 weeks, initially.[33013] [49245] [69534] Premedicate patients with hypersensitivity reactions with antihistamines and/or corticosteroids. The FDA-approved labeling recommends a dosage range of 2.5 units/kg/dose IV infused 3 times per week to 60 units/kg/dose IV infused once every 2 weeks.[49245] Individualize maintenance dosages according to patient goals and response; doses more than 60 units/kg/dose every 2 weeks are rarely needed. Although an every 2-week regimen is the most commonly studied schedule, some data suggest that the dosage interval may be extended to every 3 or 4 weeks for certain patients with non-severe GD1.[56815] [56816]
30 to 60 units/kg/dose IV every 2 weeks, initially; children at highest risk for complications should receive 60 units/kg/dose IV every 2 weeks initially.[33013] [49245] [69534] Premedicate patients with hypersensitivity reactions with antihistamines and/or corticosteroids. The FDA-approved labeling recommends a dosage range of 2.5 units/kg/dose IV infused 3 times per week to 60 units/kg/dose IV infused once every 2 weeks.[49245] Individualize maintenance dosages according to patient goals and response; doses more than 60 units/kg/dose IV every 2 weeks are rarely needed. Assess the need for dosage adjustments frequently to maintain a constant dose/kg body weight.[33013] [69534]
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 indication
Imiglucerase is an intravenous enzyme replacement therapy indicated for the long term management of adult and pediatric patients 2 years and older with type 1 Gaucher disease and who have at least one of the following conditions: anemia, thrombocytopenia, bone disease, hepatomegaly, or splenomegaly. Imiglucerase is a hydrolytic lysosomal glucocerebrosidase-specific enzyme, an analogue of the human enzyme beta-glucocerebrosidase.[49245] In type 1 Gaucher disease, a genetic disease found most commonly among Ashkenazi Jews, patients are deficient in the enzyme glucocerebrosidase, which is responsible for degradation of glucosylceramide. Glucosylceramide arises mainly from the breakdown of red and white blood cells and turnover of lipids during CNS myelin sheath formation. As evident in type 1 Gaucher disease, excess storage of glucosylceramide occurs within the macrophage lysosome, leading to progressive organ enlargement (liver, spleen, bone marrow), thrombocytopenia, anemia, recurrent infection, and skeletal weakening (e.g., osteonecrosis, osteopenia).[27584] Imiglucerase is able to break down glucocerebrosidase into its more basic elements, glucose and ceramide, thereby reducing the build up of waste products in cells. Monitor patients closely during administration for hypersensitivity reactions including anaphylaxis and infusion-related reactions. Resuscitative equipment should be readily available during administration. Imiglucerase was FDA-approved in 1994.[49245]
For storage information, see the specific product information within the How Supplied section.
Reconstitution
Dilution
Intravenous infusion
Serious hypersensitivity reactions or anaphylaxis have been reported in patients treated with enzyme replacement therapy, including imiglucerase. Anaphylaxis and anaphylactoid reactions have occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Signs and symptoms observed concomitantly with hypersensitivity and infusion-related reactions include pruritus, flushing, urticaria, rash, angioedema, chest pain (unspecified), dyspnea, cough, cyanosis, sinus tachycardia, and hypotension. Approximately 15% of patients receiving imiglucerase develop IgG antibody formation during the first year of treatment. In most patients, the development of antibodies does not prohibit continued drug administration. Antibodies are most likely to develop within the first 6 to 12 months of treatment. While patients with IgG antibodies are at higher risk of developing imiglucerase hypersensitivity, the development of antibodies is not necessary for a hypersensitivity reaction to occur. Approximately 46% of patients with detectable IgG antibodies experience symptoms of hypersensitivity. If a severe hypersensitivity reaction occurs, discontinue imiglucerase and initiate appropriate medical treatment, including the use of epinephrine. Consider the risk and benefit of readministering treatment. If the decision is made to readminister imiglucerase, consider pretreatment with antihistamines and/or corticosteroids and a reduced rate of infusion and monitor patients for the occurrence of new signs and symptoms of a severe hypersensitivity reaction.[49245]
Injection site reactions have been reported during imiglucerase treatment and may present as infusion-site burning, infusion-site discomfort, or infusion-site swelling.[49245]
General adverse reactions reported during imiglucerase treatment include dizziness, headache, fatigue, fever, chills, and back pain.[49245]
Nausea, vomiting, abdominal pain, and diarrhea have been reported during imiglucerase treatment.[49245]
Pneumonia and pulmonary hypertension have been reported during imiglucerase treatment.[49245]
The use of imiglucerase requires an experienced clinician knowledgeable in the management of Gaucher's disease.[49245]
Imiglucerase is associated with a risk of serious hypersensitivity reactions or anaphylaxis and infusion-related reactions. 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. Signs and symptoms observed concomitantly with hypersensitivity reactions or infusion-related reactions include pruritus, flushing, urticaria, rash, angioedema, chest pain, dyspnea, cough, cyanosis, tachycardia, hypotension, angioedema, chest discomfort, chills, fatigue, infusion-site reaction (burning, swelling, discomfort). If a severe hypersensitivity reaction or anaphylaxis occurs, immediately discontinue imiglucerase infusion and initiate appropriate medical treatment, including use of epinephrine. Observe patients closely during and after the infusion. 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. Monitor patients for occurrence of new hypersensitivity reactions. Patients with antibody formation to imiglucerase have a higher risk of hypersensitivity reactions. However, not all patients with symptoms of hypersensitivity have detectable IgG antibody. Consider periodic monitoring of patients during the first year of treatment for IgG antibody formation.[49245]
Data on more than 500 pregnancies from the international Gaucher Disease registry, postmarketing reports, published observational studies, and case reports with imiglucerase during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal reproduction study data are not available.[49245] 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. No adverse effects on the fetus have been reported secondary to imiglucerase therapy.[49246] Imiglucerase has thus been suggested, based on the data available, as an agent for consideration for the treatment of Gaucher's disease during pregnancy.[56701] There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to imiglucerase; information about the registry can be obtained at www.registrynxt.com or by calling 1-800-745-4447, extension 15500.[49245]
Available literature suggests a small amount of imiglucerase is present in breast milk immediately following imiglucerase administration. Case reports and postmarketing reports have not reported adverse effects in breastfed infants due to imiglucerase exposure. No data are available on the effects of imiglucerase on milk production.[49245] Enzymes such as imiglucerase are likely to be degraded by the infant's digestive sytem 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. No adverse effects on the nursing infant were reported secondary to imiglucerase therapy. Consider reducing the duration of breast-feeding to avoid excessive bone loss in the mother.[49246] There are published reports of the successful use of imiglucerase in a pregnant, and subsequently lactating, patient. The case report stated a small amount of imiglucerase was found to be excreted into human breast milk, but only in the first milk produced after infusion, and the patient was able to successfully breast-feed the infant.[56702] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Encourage individuals who are breast-feeding while receiving imiglucerase to enroll in the Gaucher patient registry; information about the registry can be obtained at www.registrynxt.com or by calling 1-800-745-4447, extension 15500.[49245]
Imiglucerase substitutes for the deficient enzyme glucocerebrosidase in patients with Gaucher disease. Gaucher disease is characterized by a deficiency of glucocerebrosidase, a necessary catalyst for the hydrolysis of glucosylceramide, an endogenous, very insoluble glycolipid. Patients with this condition have a build-up of glucosylceramide 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 bone lesions. Treatment with imiglucerase results in hydrolysis of the accumulated glucosylceramide 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.[27584][49245]
Revision Date: 11/12/2024, 05:29:51 PMImiglucerase is administered by IV infusion. The volume of distribution corrected for weight ranged from 0.09 to 0.15 L/kg (mean +/- SD, 0.12 +/- 0.02 L/kg). The clearance of imiglucerase from plasma is reported to range from 9.8 to 20.3 mL/minute/kg (mean +/- SD, 14.5 +/- 4 mL/minute/kg). The enzymatic activity has a plasma half-life of approximately 3.6 to 10.4 minutes. These variables do not appear to be influenced by dose or duration of infusion. Patients who develop IgG antibodies to imiglucerase exhibit decreased volume of distribution and clearance and increased half-life compared to patients who do not develop these antibodies.[49245]
During 1-hour intravenous infusions of 4 doses (7.5, 15, 30, 60 units/kg) of imiglucerase, steady-state enzymatic activity was achieved by 30 minutes.[49245]
Data on more than 500 pregnancies from the international Gaucher Disease registry, postmarketing reports, published observational studies, and case reports with imiglucerase during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal reproduction study data are not available.[49245] 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. No adverse effects on the fetus have been reported secondary to imiglucerase therapy.[49246] Imiglucerase has thus been suggested, based on the data available, as an agent for consideration for the treatment of Gaucher's disease during pregnancy.[56701] There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to imiglucerase; information about the registry can be obtained at www.registrynxt.com or by calling 1-800-745-4447, extension 15500.[49245]
Available literature suggests a small amount of imiglucerase is present in breast milk immediately following imiglucerase administration. Case reports and postmarketing reports have not reported adverse effects in breastfed infants due to imiglucerase exposure. No data are available on the effects of imiglucerase on milk production.[49245] Enzymes such as imiglucerase are likely to be degraded by the infant's digestive sytem 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. No adverse effects on the nursing infant were reported secondary to imiglucerase therapy. Consider reducing the duration of breast-feeding to avoid excessive bone loss in the mother.[49246] There are published reports of the successful use of imiglucerase in a pregnant, and subsequently lactating, patient. The case report stated a small amount of imiglucerase was found to be excreted into human breast milk, but only in the first milk produced after infusion, and the patient was able to successfully breast-feed the infant.[56702] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Encourage individuals who are breast-feeding while receiving imiglucerase to enroll in the Gaucher patient registry; information about the registry can be obtained at www.registrynxt.com or by calling 1-800-745-4447, extension 15500.[49245]
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