Dosage Forms
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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 0.09 to 0.15 L/kg
Excretion
Clearance: 9.8 to 20.3 mL/minute/kg
Half-Life Elimination
3.6 to 10.4 minutes
Use: Labeled Indications
Gaucher disease:
US labeling: Long-term enzyme replacement therapy for patients with type 1 Gaucher disease that results in at least one of the following: anemia, bone disease, hepatomegaly or splenomegaly, and thrombocytopenia
Canadian labeling: Long-term enzyme replacement therapy for patients with type 1 Gaucher disease or patients with type 3 Gaucher disease who display non-neurological manifestations (anemia, bone disease, hepatomegaly or splenomegaly, and thrombocytopenia) of the disease.
Contraindications
There are no known contraindications listed in the US manufacturer's labeling.
Canadian labeling: Severe hypersensitivity to imiglucerase or any component of the formulation
Dosage and Administration
Dosing: Adult
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.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Dose should be individualized.
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; based on risk for complications (Andersson 2005; Baldellou 2004; Charrow 2004); failure to respond to treatment within 6 months may indicate the need for a higher dosage (Baldellou 2004); doses >60 units/kg/dose are rarely needed (Charrow 2004)
High risk for complications: Initial dose: IV: 60 units/kg every 2 weeks. High risk is defined as one or more of the following: Symptomatic disease including manifestations of abdominal or bone pain, fatigue, exertional limitations, weakness, and cachexia; growth failure; evidence of skeletal involvement; platelet count ≤60,000 mm3 and/or documented abnormal bleeding episode(s); Hgb ≥2.0 g/dL below lower limit for age and sex; impaired quality of life (Andersson 2005)
Maintenance: Limited data available: Assess calculated dose and patient growth (weight) frequently to maintain consistent dosage per kg body weight (Baldellou 2004). The appropriate dose to prevent long-term complications in pediatric patients is unknown; after therapeutic goals 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 (Canadian labeling): Children ≥2 years and Adolescents: Initial range: 2.5 units/kg 3 times weekly, up to 60 units/kg every 2 weeks; individualize dose based on patient response; doses up to 120 units/kg every 2 weeks have been described (ages not specified for higher dosing)
Reconstitution
Reconstitute 400 unit vial with 10.2 ml SWFI resulting in a 40 units/mL concentration. Slight flocculation (thin translucent fibers) may appear after dilution; do not use if discolored or opaque particles appear. Withdraw appropriate volume of reconstituted solution and further dilute in NS to a final volume of 100 to 200 mL.
Administration
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).
Storage
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.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
>10%:
Immunologic: Development of IgG antibodies (15%)
1% to 10%:
Cardiovascular: Chest discomfort (<2%), flushing (<2%), hypotension (<2%), tachycardia (<2%)
Central nervous system: Chills (<2%), dizziness (<2%), fatigue (<2%), headache (<2%)
Dermatologic: Pruritus (<2%), skin rash (<2%), urticaria (<2%)
Gastrointestinal: Abdominal pain (<2%), diarrhea (<2%), nausea (<2%), vomiting (<2%)
Hypersensitivity: Hypersensitivity reaction (7%), angioedema (<2%)
Neuromuscular & skeletal: Back pain (<2%)
Respiratory: Cough (<2%), cyanosis (<2%), dyspnea (<2%)
Miscellaneous: Fever (<2%)
<1%, postmarketing, and/or case reports: Burning sensation at injection site, discomfort at injection site, injection site pruritus, nonimmune anaphylaxis, pneumonia, pulmonary hypertension, sterile abscess at injection site, swelling at injection site
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylactoid reactions: Have been reported (<1%). Most patients have continued treatment with pretreatment (antihistamines and/or corticosteroids) and a slower rate of infusion. Discontinue immediately for severe reactions and initiate appropriate medical treatment. Use caution in patients with previous hypersensitivity to, previously treated with, or have developed antibodies to alglucerase. Canadian labeling contraindicates use in patients with severe hypersensitivity to imiglucerase.
- 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.
Disease-related concerns:
- Pulmonary hypertension/pneumonia: Has been observed during treatment; causal relationship has not been established as this is a complication of Gaucher disease. Afebrile patients with respiratory symptoms should be assessed for pulmonary hypertension.
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).
Monitoring Parameters
CBC, platelets, liver function tests, IgG antibody formation periodically during the first year of treatment (Canadian labeling recommends antibody testing approximately every 3 months during the first year and at ~18 months), chitotriosidase, angiotensin-converting enzyme (ACE), acid phosphatase (AP), iron, iron-binding capacity, ferritin, vitamin B12; MRI or CT scan (liver and spleen volume), skeletal x-rays, DXA; pulmonary function tests; ECG/echocardiography; growth in pediatric patients
Pregnancy
Pregnancy Considerations
Animal reproduction studies have not been conducted; however, imiglucerase has been used safely during pregnancy based on available data (Sherer 2002; Zimran 2009). Doses of imiglucerase should be based on prepregnancy weight and adjusted as clinically indicated (Granovsky-Grisaru 2011).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, diarrhea, loss of strength and energy, headache, or back pain. Have patient report immediately to prescriber difficulty breathing, chest pain, fast heartbeat, shortness of breath, excessive weight gain, swelling of arms or legs, flushing, cough, severe dizziness, passing out, chills, or skin discoloration (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
