Imiglucerase (Cerezyme) is an enzyme replacement therapy used for the treatment of Gaucher disease. Gaucher disease is a genetic disorder primarily caused by a deficiency of the enzyme acid β-glucosidase. Currently, imiglucerase has been marketed in China. This article provides a detailed explanation of imiglucerase's indications, usage and dosage, side effects, contraindications, clinical efficacy, etc.

(I) Indications

Imiglucerase for Injection (Cerezyme) is indicated for long-term enzyme replacement therapy in patients diagnosed with non-neuropathic (Type I) and chronic neuropathic (Type II) Gaucher disease who have significant clinical manifestations of non-neurological lesions.

The clinical manifestations of non-neurological lesions in Gaucher disease include one or more of the following conditions:

Anemia excluding other causes, such as iron deficiency anemia

Thrombocytopenia

Bone disease excluding other causes, such as vitamin D deficiency

Hepatomegaly or splenomegaly

(II) Usage and Dosage

Intravenous infusion, with an infusion time of 1-2 hours. The dosage should be adjusted according to the individual patient's condition. The initial dosage ranges from 2.5 U/kg three times a week to 60 U/kg once every two weeks. After 2 years, if the treatment target is achieved, the dosage can be adjusted to 45 U/kg. The dosage of 60 U/kg once every two weeks has the most available data. In severe cases, higher dosages or more frequent administrations may be required. The dosage should be adjusted based on each patient's individual situation, and comprehensive assessments of the patient's clinical manifestations should be conducted regularly to increase or decrease the dosage according to whether the treatment target is met.

Imiglucerase should be stored at 2-8°C (36-46°F). After reconstitution, it should be visually inspected before use. Since this product is a protein solution, slight flocculation (i.e., the formation of mild opaque fibers) may occasionally occur after dilution. During administration, the diluted solution can be filtered through a 0.2 μm filter membrane connected to the infusion tube (the filter membrane does not adsorb protein or adsorbs it to a very small extent). After reconstitution, if opaque particles or discoloration appear, it must not be used. The product must not be used after expiration.

On the day of administration, after determining the patient's dosage, take the corresponding number of vials and reconstitute with sterile water for injection according to the table below. The table shows the final concentration and administration volume:

Take 10.0 mL from each 400-unit vial and finally dilute it to 100-200 mL with 0.9% sodium chloride solution. Intravenous infusion should be performed over 1-2 hours under sterile conditions. Since this product does not contain any preservatives, it should be diluted immediately after preparation and must not be stored for later use. After preparation, the product is stable for 12 hours at room temperature (25°C) and 2-8°C. After dilution, it is stable for 12 hours at 2-8°C.

Imiglucerase has relatively low toxicity and a long duration of action, so minor dosage adjustments can be made occasionally to utilize the full amount in each vial and avoid drug waste, as long as the total monthly dosage remains basically unchanged.

(III) Target Population

Adults. Pregnant and lactating women, as well as elderly and pediatric patients, should use the drug under the guidance of a doctor.

(IV) Contraindications

The population using the drug in China and accumulated data are limited, and no known contraindications to the use of imiglucerase have been reported.

If there is clear clinical evidence of drug allergy, the treatment with imiglucerase should be carefully re-evaluated.

(V) Side Effects

Common side effects include dyspnea, cough, hypersensitivity reactions, urticaria/angioedema, pruritus, and rash.

Uncommon side effects include dizziness, headache, paresthesia, tachycardia, cyanosis, flushing, hypotension, vomiting, nausea, abdominal cramps, diarrhea, arthralgia, back pain, discomfort at the infusion site, burning pain at the infusion site, swelling at the infusion site, sterile abscess at the injection site, chest discomfort, fever, chills, and fatigue.

Rare side effects include rapid-like allergic reactions.

(VI) Precautions

General Precautions

(1) Pulmonary hypertension and pneumonia have occurred in less than 1% of patients during treatment with imiglucerase. Pulmonary hypertension and pneumonia are known complications of Gaucher disease and have been found in patients who have received or not received imiglucerase. The causal relationship between imiglucerase and these symptoms is unclear. Patients with or without febrile respiratory symptoms should be examined to determine the presence of pulmonary hypertension.

(2) Treatment with imiglucerase should be conducted under the guidance of doctors experienced in the treatment of Gaucher disease.

(3) Patients who have received Ceredase (alglucerase injection) and have developed antibodies against alglucerase injection or have had allergic reactions to alglucerase injection should use imiglucerase with caution.

Warnings

(1) To date, approximately 15% of patients have developed IgG antibodies against imiglucerase (imiglucerase for injection) during the first year of treatment. Most of these occur within the first 6 months of treatment, and the occurrence of anti-imiglucerase antibodies after 12 months of treatment is rare. Approximately 46% of patients with positive IgG antibodies experience allergic symptoms.

(2) Patients with anti-imiglucerase antibodies have a higher risk of allergic reactions. However, not all patients with allergic symptoms can be detected with IgG antibodies. It is recommended to regularly monitor the formation of IgG antibodies in patients during the first year of treatment.

(3) Patients who have had allergic symptoms to this product should use this product with caution during treatment.

(4) Rapid-like allergic reactions have been reported in less than 1% of patients. Caution should be exercised when further treatment with imiglucerase is administered. Most patients can successfully continue treatment after reducing the infusion rate and pre-treating with antihistamines and/or corticosteroids.

(VII) Therapeutic Efficacy

In clinical trials, imiglucerase for injection can improve anemia and thrombocytopenia, reduce hepatosplenomegaly, and improve cachexia, with clinical effects similar to alglucerase injection. Studies have shown that after 6 months of treatment with imiglucerase for Type I Gaucher disease, the number of patients reporting bone pain decreased by 37.5%, which can significantly improve patients' quality of life and growth and development. After 24 months of treatment with imiglucerase, the spleen volume was reduced by 50.9%, the liver volume by 30.8%, the average hemoglobin increased by 2.4 g/dL, and the average platelet count increased by 99.8%. The organ involvement and blood picture were significantly improved.

(VIII) Drug Interactions

There are no available experimental data or references. Currently, there are no known drug interactions.

(IX) Storage Conditions

Store and transport at 2-8°C away from light.