Glurazyme (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Generium-Next, LLC (Russia)

Manufactured By

Generium, JSC (Russia)

Packaging and Quality Control Release

Generium, JSC (Russia)

Or

Generium-Next, LLC (Russia)

ATC Code

A16AB02 (Imiglucerase)

Active Substance

Imiglucerase (Rec.INN registered by WHO)

Dosage Form

Glurazyme

Lyophilisate for preparation of solution for infusion 400 IU: vial.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for infusion in the form of an amorphous mass from white to white with a slight yellowish tint.

Each ml of the reconstituted solution contains 40 IU of imiglucerase.

Excipients: mannitol, sodium citrate dihydrate, citric acid monohydrate, polysorbate 80.

400 IU – vials (1) – cardboard packs.

* International Unit (IU) denotes the amount of enzyme (imiglucerase) that catalyzes the hydrolysis of 1 μmol of the synthetic substrate para-nitrophenyl β-D-glucopyranoside (pNP-Glc) per minute at a temperature of (37±0.2)°C.

Clinical-Pharmacological Group

Enzyme preparation

Pharmacotherapeutic Group

Other agents for the treatment of gastrointestinal diseases and metabolic disorders; enzymes

Pharmacological Action

Recombinant macrophage-targeted beta-glucocerebrosidase – an analogue of human lysosomal beta-glucocerebrosidase. Purified Imiglucerase is a monomeric glycoprotein consisting of 497 amino acid residues and an oligosaccharide component. Gaucher disease is characterized by a functional deficiency of beta-glucocerebrosidase enzymatic activity, leading to the accumulation of the lipid glucocerebroside in macrophages, which become engorged and are called “Gaucher cells”. Gaucher cells are typically found in the liver, spleen, bone marrow, and sometimes in the lungs, kidneys, and intestines. Secondary hematological manifestations include severe anemia and thrombocytopenia, which are combined with characteristic progressive hepatosplenomegaly. Bone changes are common and often the most debilitating and disabling consequences of Gaucher disease. These include: osteonecrosis, osteopenia with secondary pathological fractures, inadequate remodeling, osteosclerosis. Imiglucerase compensates for the functional deficiency of beta-glucocerebrosidase enzymatic activity: it catalyzes the hydrolysis of the lipid glucocerebroside, resulting in the formation of glucose and ceramide (according to the normal pathway of fat degradation).

After intravenous administration over 1 hour of 4 doses (7.5, 15, 30, 60 IU/kg) of imiglucerase, a steady-state increase in enzymatic activity is reached by 30 minutes. After the infusion is completed, plasma enzymatic activity decreases rapidly.

Pharmacokinetics

V_d – 0.09-0.15 L/kg. T_1/2 – from 3.6 to 10.4 min. Clearance varies from 9.8 to 20.3 mL/min/kg.

Indications

Gaucher disease type I (for long-term enzyme replacement therapy in patients with a confirmed diagnosis who have clinically significant manifestations of this disease: anemia (after excluding other causes), thrombocytopenia; pathological bone changes (after excluding other causes such as vitamin D deficiency); hepatomegaly or splenomegaly).

ICD codes

Dosage Regimen

Given the heterogeneity and multisystemic nature of Gaucher disease, the dose is set individually after clinical assessment of all manifestations of the disease.

Administered intravenously by drip infusion.

The initial dose is 60 IU/kg once every 2 weeks (on average, after 6 months, an improvement in hematological parameters and symptoms from internal organs is noted). Continuation of treatment helps to halt the progression of the disease and reduce the severity of symptoms from the skeletal system. Use at a dose of 2.5 IU/kg 3 times a week or 15 IU/kg once every 2 weeks helps to improve hematological parameters, reduce the size of the liver and spleen, but does not affect symptoms from the skeletal system.

Follow-up examination of patients is recommended every 6-12 months.

The dose is recommended to be adjusted (increased or decreased) depending on the severity of symptoms.

Adverse Reactions

From the digestive system 10-16% – nausea, diarrhea, vomiting.

From the CNS 10-16% – headache, dizziness.

Dermatological reactions 10-16% – skin rash.

Allergic reactions 3% – generalized pruritus, angioedema, dyspnea, bronchospasm.

Local reactions discomfort, itching and burning of the skin, swelling at the venipuncture site.

Other 10-16% – increased body temperature, facial flushing.

Contraindications

Hypersensitivity to the active substance.

Use in Pregnancy and Lactation

Use with caution during pregnancy and lactation.

Pediatric Use

Use with caution in children.

Special Precautions

Periodic monitoring for the formation of IgG antibodies to imiglucerase is necessary. During the first year of therapy, IgG antibodies to imiglucerase are formed in approximately 15% of patients. The appearance of IgG antibodies most often occurs in the first 6 months of treatment and rarely after 12 months of therapy.

During treatment, the activity of acid phosphatase and ACE should be monitored every 2-3 months (as the duration of treatment increases, their activity should decrease). The effectiveness of therapy can also be monitored by the level of ALT, AST activity every 6-12 months (a decrease in their activity also indicates a positive clinical effect). Every 6-12 months, monitoring of bilirubin, Ca2+, creatinine, electrolytes and phosphorus concentrations is necessary.

To assess the effectiveness of therapy, the content of Hb and platelets should be monitored monthly (an increase in their number indicates the effectiveness of therapy). The size of the liver and spleen should be monitored every 6 months (they should decrease).

Every 1-2 years, patients are shown an MRI of the long bones (with a positive clinical effect, their characteristics should improve). In patients with antibodies to imiglucerase, hypersensitivity reactions occur more frequently. In such cases, premedication with antihistamines and/or corticosteroids is recommended, as well as a reduction in the frequency of infusions.

Use with caution in children.

Drug Interactions

Pharmaceutically incompatible with other drugs.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.