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Imiglucerase

Pronunciation

(i mi GLOO ser ace)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

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Solution Reconstituted, Intravenous:

Cerezyme: 200 units (1 ea); 400 units (1 ea)

Brand Names: U.S.

  • Cerezyme

Pharmacologic Category

  • Enzyme

Pharmacology

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: 0.09-0.15 L/kg

Excretion

Clearance: 9.8-20.3 mL/minute/kg

Onset of Action

Significant improvement in symptoms: Hepatosplenomegaly and hematologic abnormalities: Within 6 months; Improvement in bone mineralization: Noted at 80-104 weeks of therapy

Half-Life Elimination

3.6-10.4 minutes

Use: Labeled Indications

Gaucher disease:

U.S. 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

U.S. labeling: There are no known contraindications in the manufacturer’s labeling.

Canadian labeling: Severe hypersensitivity to imiglucerase or any component of the formulation

Dosage

Gaucher disease, type 1: Children ≥2 years, Adolescents, and Adults: IV (dose is individualized): 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 30-60 units/kg every 2 weeks (Charrow, 2004).

Gaucher disease, type 3 (Canadian labeling; not in U.S. labeling): Children ≥2 years, Adolescents, and Adults: IV (dose is individualized): 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.

Dosage adjustment in renal impairment: No dosage adjustment provided in the manufacturer’s labeling.

Dosage adjustment in hepatic impairment: No dosage adjustment provided in the manufacturer’s labeling.

Reconstitution

Reconstitute 200 unit vial with 5.1 mL SWFI or 400 unit vial with 10.2 mL SWFI. Withdraw appropriate volume of reconstituted solution and further dilute in NS to a final volume of 100-200 mL.

Administration

IV: Infuse over 1-2 hours; may use an in-line, low protein-binding 0.2 micron filter during infusion. The Canadian labeling recommends a maximum infusion rate of 1 unit/kg/minute. Infusion times <1 hour are not recommended (Martins, 2009).

Storage

Prior to reconstitution, store at 2°C to 8°C (36°F to 46°F). Reconstituted solution is stable for 12 hours at 25°C (77°F) and at 2°C to 8°C (36°F to 46°F) resulting in a concentration of 40 units/mL. Slight flocculation (thin translucent fibers) may appear; however, do not use if discolored or contains opaque particles. Solution diluted for infusion further diluted in NS is stable for up to 24 hours when stored at 2°C to 8°C (36°F to 46°F). Contains no preservatives; reconstituted vials should not be stored for future use.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

1% to 10%:

Cardiovascular: Tachycardia (<2%)

Central nervous system: Chills (<2%), dizziness (<2%), fatigue (<2%), fever (<2%), headache (<2%)

Dermatologic: Pruritus (<2%), rash (<2%)

Gastrointestinal: Abdominal discomfort (<2%), diarrhea (<2%), nausea (<2%), vomiting (<2%)

Neuromuscular & skeletal: Backache (<2%)

Miscellaneous: Hypersensitivity reaction (7%; symptoms may include pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis, hypotension,paresthesia)

<1% (Limited to important or life-threatening): Anaphylactoid reactions; cyanosis, injection site burning, swelling, or sterile abscess; peripheral edema, pneumonia, pulmonary hypertension, rigors

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic 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 physician: Should be administered under the supervision of a physician 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 ~every 3 months during the first year and at ~18 months), chitotriodase, angiotensin-converting enzyme, acid phosphatase (AP), iron, iron-binding capacity, ferritin, vitamin B12; MRI or CT of liver and spleen, skeletal x-rays; ECG, chest x-ray and doppler echocardiogram in patients >18 years of age; physical exam every 12 months

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted; however, imiglucerase has been used safely during pregnancy based on available data (Sherer, 2003; 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 injection site irritation. Have patient report immediately to prescriber angina, tachycardia, dyspnea, excessive weight gain, edema of extremities, flushing, severe dizziness, syncope, 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.

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