Version May 2024
Gaucher disease, type 1: Children and Adolescents: Limited data available for children <2 years:
Initial: IV: 30 to 60 units/kg/dose every 2 weeks; consider starting on higher end of range in patients with severe disease or at high risk for complications (Andersson 2005; Charrow 2004; Kaplan 2013); may increase dose in patients initiated at lower end of range if response inadequate (Kaplan 2013); doses >60 units/kg/dose are rarely needed (Charrow 2004).
Maintenance: IV: Limited data available: Assess calculated dose and patient growth (weight) frequently to maintain consistent dosage per kg body weight (Kaplan 2013). The appropriate dose to prevent long-term complications in pediatric patients is unknown; after therapeutic goals are achieved, any dose reduction should be considered with extreme caution and at intervals no more frequent than every 6 months; minimum dose: 30 units/kg/dose every 2 weeks (Andersson 2005; Baldellou 2004).
Gaucher disease, type 3: Limited data available: Note: In the management of type 3 Gaucher disease, enzyme replacement therapy is recommended to ameliorate visceral, skeletal, and hematologic manifestations; it has not been demonstrated to impact neurological manifestations.
Children and Adolescents: IV: Initial: 60 units/kg/dose every 2 weeks (Kaplan 2013; Vellodi 2009). Individualize dose based on patient response; doses up to 120 units/kg every 2 weeks have been described (Goker-Alpan 2008; Vellodi 2009).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Imiglucerase (glucocerebrosidase): Drug information")
Note: Dose should be individualized. IV:
Gaucher disease, type 1: Initial range: 2.5 units/kg 3 times weekly, up to 60 units/kg every 2 weeks. Note: Dosage adjustments are made based on assessment and therapeutic goals. Most benefits observed with doses of 30 to 60 units/kg every 2 weeks (Charrow 2004).
Gaucher disease, type 3 (Canadian labeling; not in US labeling): Initial range: 2.5 units/kg 3 times weekly, up to 60 units/kg every 2 weeks. Doses up to 120 units/kg every 2 weeks have been safely administered.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Immunologic: Development of IgG antibodies (15%)
Frequency not defined:
Cardiovascular: Tachycardia
Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction (including severe hypersensitivity reaction)
Local: Burning sensation at injection site, discomfort at injection site, swelling at injection site
Nervous system: Chills, dizziness, fatigue, headache
Neuromuscular & skeletal: Back pain
Respiratory: Pneumonia, pulmonary hypertension
Miscellaneous: Fever, infusion related reaction
There are no known contraindications listed in the US manufacturer's labeling.
Canadian labeling: Severe hypersensitivity to imiglucerase or any component of the formulation
Concerns related to adverse effects:
• Antibody formation: Development of IgG antibodies has been reported in ~15% of patients and has been observed within 6 months from the onset of therapy; antibody formation is rare after 12 months of therapy; may increase risk of hypersensitivity reactions.
• Hypersensitivity reactions: Hypersensitivity and other infusion-associated reactions, including anaphylaxis, angioedema, chest discomfort, cough, cyanosis, dyspnea, flushing, hypotension, pruritus, tachycardia, and urticaria, have been reported. Incidence is increased in patients with antibodies to imiglucerase. Discontinue treatment and institute appropriate therapy if hypersensitivity occurs. When retreating patients with prior hypersensitivity, administer antihistamine and/or corticosteroid premedications and decrease infusion rate.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
Other warnings/precautions:
• Experienced health care provider: Should be administered under the supervision of a health care provider experienced in treatment of Gaucher disease.
• Registry: A registry has been established and all patients with Gaucher disease, and physicians who treat Gaucher disease are encouraged to participate. Information on the International Collaborative Gaucher Group (ICGG) Gaucher Registry may be obtained at https://www.registrynxt.com, or by calling 1-800-745-4447 (ext.15500).
Based on postmarketing reporting, the most common reported adverse events in children 2 to 12 years include dyspnea, fever, nausea, flushing, vomiting, and coughing; for children ≥12 years and adolescents, the most common reported adverse events include headache, pruritus, and rash.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Cerezyme: 400 units (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Cerezyme Intravenous)
400 unit (per each): $2,060.35
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Cerezyme: 400 units (10.6 mL) [contains polysorbate 80]
Parenteral: IV: Infusion rate depends on weight; infuse as a diluted solution over 2 hours for patients <18 kg, and over 1 to 2 hours for patients ≥18 kg. A maximum infusion rate of 1 unit/kg/minute is described in Canadian labeling; infusion times <1 hour are not recommended (Martins 2009). May filter diluted solution through an in-line low-protein-binding 0.2 micron filter during administration. For patients who experience infusion-related reactions, start infusion very slowly and gradually increase rate; may also premedicate with an antihistamine or corticosteroid (Kaplan 2013).
IV: Infuse over 1 to 2 hours; may filter diluted solution through an in-line, low protein-binding 0.2-micron filter during administration. The Canadian labeling recommends a maximum infusion rate of 1 unit/kg/minute. Infusion times <1 hour are not recommended (Martins 2009). For patients who experience infusion-related reactions, reduce rate of infusion and premedicate with an antihistamine and/or corticosteroid.
Store intact vials at 2°C to 8°C (36°F to 46°F). Reconstituted solution is stable for 12 hours at 25°C (77°F) or 2°C to 8°C (36°F to 46°F). Solution diluted for infusion in NS is stable for up to 24 hours when stored at 2°C to 8°C (36°F to 46°F). Discard unused solution.
Long-term enzyme replacement therapy for patients with type 1 Gaucher disease (FDA approved in ages ≥2 years and adults); has also been used as enzyme replacement therapy for patients with type 3 Gaucher disease.
Cerezyme may be confused with Cerebyx, Ceredase
None known.
There are no known significant interactions.
Patients requiring treatment for type 1 Gaucher disease should continue imiglucerase while attempting to become pregnant to stabilize disease and achieve optimal health prior to pregnancy. Imiglucerase does not need to be initiated prior to conception in asymptomatic patients (Granovsky-Grisaru 2011).
An increased risk of adverse pregnancy outcomes has not been associated with maternal use of imiglucerase (Raynor 2019; Zimran 2009).
Pregnancy may exacerbate existing type 1 Gaucher disease or result in new symptoms. Patients with type 1 Gaucher disease have an increased risk of spontaneous abortion if disease is not well-controlled. Adverse events, including anemia, hepatosplenomegaly, and thrombocytopenia, may be exacerbated during pregnancy (Granovsky-Grisaru 2011). Based on available information, treatment with imiglucerase can reduce the risk of adverse pregnancy outcomes (Zimran 2009).
Patients requiring treatment for type 1 Gaucher disease should continue imiglucerase during pregnancy. Treatment may be initiated during pregnancy for symptomatic patients. Dosing should be based on prepregnancy weight and adjusted if clinically indicated (Granovsky-Grisaru 2011).
Data collection to monitor pregnancy and infant outcomes following exposure to imiglucerase is ongoing. Health care providers are encouraged to enroll patients exposed to imiglucerase during pregnancy in the Gaucher Patient Registry (1-800-745-4447, extension 15500 or https://www.registrynxt.com). Patients may also enroll themselves.
Monitor for achievement and maintenance of Gaucher disease treatment goals, including growth, physical exam, hematology tests (hemoglobin, platelets), biochemical markers, pulmonary function, visceral organ volumes, bone disease, pain, quality of life, and others as clinically appropriate. Management of Gaucher disease requires extensive monitoring; refer to current guidelines for additional guidance (Biegstraaten 2018; Kaplan 2013).
Drug-specific monitoring: Hypersensitivity; IgG antibody formation periodically during the first year of treatment (Canadian labeling suggests every 3 months and at 18 months after treatment initiation).
Imiglucerase is an analogue of glucocerebrosidase; it is produced by recombinant DNA technology using mammalian cell culture. Glucocerebrosidase is an enzyme deficient in Gaucher's disease. It is needed to catalyze the hydrolysis of glucocerebroside to glucose and ceramide.
Distribution: Vd: 0.09 to 0.15 L/kg
Half-life elimination: 3.6 to 10.4 minutes
Clearance: 9.8 to 20.3 mL/minute/kg
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