Hunterase^® (Concentrate) Instructions for Use

Marketing Authorization Holder

NANOLEK LLC (Russia)

Manufactured By

GC Biopharma Corp. (Republic of Korea)

Or

NANOLEK LLC (Russia)

ATC Code

A16AB16 (Idursulfase beta)

Active Substance

Idursulfase beta (Rec.INN registered by WHO)

Dosage Form

Hunterase®

Concentrate for solution for infusion 2 mg/1 ml: fl. 3 ml 1 pc.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion as a clear or slightly opalescent colorless solution.

Excipients: sodium dihydrogen phosphate monohydrate – 6.75 mg, disodium hydrogen phosphate heptahydrate – 2.97 mg, sodium chloride – 24.00 mg, polysorbate 20 – 0.66 mg, water for injections – up to 3 ml.

3 ml – type I colorless glass vials with a volume of 6 ml (1) – cardboard packs.

Clinical-Pharmacological Group

Drug for the treatment of hereditary enzymatic deficiency

Pharmacotherapeutic Group

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

Pharmacological Action

Idursulfase beta is a purified form of the lysosomal enzyme iduronate-2-sulfatase – recombinant human iduronate-2-sulfatase (rhIDS). rhIDS is produced using recombinant DNA technology using a Chinese hamster ovary (CHO) cell line (host cell: CHO DG44/expression vector: ID pJK dhfr Or2).

Idursulfase beta is a glycoprotein with 525 amino acids and a molecular weight of about 78 kDa, which contains eight asparagine-linked glycosylation sites occupied by complex oligosaccharide structures and two disulfide bonds. The enzymatic activity of idursulfase beta depends on the post-translational modification of a specific cysteine to formylglycine.

Intravenous administration of idursulfase beta to patients with Hunter syndrome provides delivery of the exogenous enzyme to cellular lysosomes. The mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow the enzyme to specifically bind to M6P receptors on the cell surface, leading to internalization of the enzyme, targeting it to intracellular lysosomes, and subsequent catabolism of accumulated glycosaminoglycans (GAG).

Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is a rare X-linked recessive hereditary disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase in the patient’s body. Iduronate-2-sulfatase is involved in the first stage of the catabolism of GAGs – heparan and dermatan sulfate. As a result of insufficient activity of iduronate-2-sulfatase, accumulation of GAGs – heparan and dermatan sulfate – occurs in the lysosomes of almost all types of cells in various tissues and organs, leading to cellular overload, organomegaly, tissue destruction, and organ dysfunction.

Pharmacokinetics

Information on the pharmacokinetic parameters of idursulfase beta was obtained during a clinical study of patients with Hunter syndrome.

According to the analysis results, the serum concentration-time curve of idursulfase beta showed an apparent biphasic elimination pattern. The apparent terminal T_1/2 was 7.3-9.1 h. At a dose of 0.5 mg/kg, C_max was 1024.9 ng/ml, and AUC_last was 2724 ng×h/ml. At a dose of 1.0 mg/kg, C_max was 2045.2 ng/ml, and AUC_last was 7804 ng×h/ml.

Within the dose range of 0.5-1.0 mg/kg, C_max and AUC_last showed a trend towards increased exposure, while the apparent terminal T_1/2 (t_1/2, z) did not show significant differences.

Degradation of glycoproteins occurs through protein hydrolysis to form small peptide residues and amino acids, therefore, impaired renal or liver function does not affect the pharmacokinetic parameters of idursulfase beta.

Indications

Long-term treatment of patients with Hunter syndrome (mucopolysaccharidosis type II, MPS II).

ICD codes

Dosage Regimen

Administer intravenously as an infusion.

The recommended dose is 0.5 mg per kg of body weight.

Infuse this dose once every week.

Calculate the total volume to administer based on the patient’s body weight and the vial concentration of 2 mg/ml.

Dilute the calculated dose in 0.9% Sodium Chloride solution for infusion.

Use the final diluted solution immediately; do not store it.

Initiate the infusion at a rate of 2 ml per hour for the first 15 minutes.

If tolerated, gradually increase the infusion rate in a step-wise manner.

Complete the total infusion over approximately 3 hours.

Monitor the patient closely for infusion-associated reactions during and after administration.

Premedicate with antihistamines and/or corticosteroids prior to infusion if necessary.

Reduce the infusion rate, temporarily interrupt, or discontinue for severe reactions.

Adverse Reactions

Infections and infestations: very common – upper respiratory tract infections, bronchitis, sinusitis, middle ear otitis, pharyngotonsillitis; common – eye infection (stye), pneumonia (at a dose of 1.0 mg/kg).

Skin and subcutaneous tissue disorders: very common – urticaria, skin itching, dermatitis, fungal infections of the trunk; common – erythematous rash, atopic dermatitis, eczema, spots, fungal infections of the foot.

Respiratory system disorders: very common – cough, rhinorrhea, allergic rhinitis; common – rhinitis, bronchial asthma, epistaxis, productive cough (at a dose of 1.0 mg/kg), sleep apnea.

Gastrointestinal system disorders: very common – diarrhea, gastroenteritis, enteritis; common – nausea, vomiting, constipation, anal fissure, anorectal disorder, dyspepsia, stomatitis, dental disease.

Musculoskeletal and connective tissue disorders: common – muscle spasms, myalgia.

Eye disorders: common – conjunctivitis, dry keratoconjunctivitis (at a dose of 1.0 mg/kg).

Reproductive system and breast disorders: common – balanoposthitis (at a dose of 1.0 mg/kg).

General disorders and administration site conditions: very common – fever; common – malaise. The possibility of anaphylactic reactions cannot be ruled out. Patients with complete absence (deletion) or significant alteration of gene sequence (rearrangement) have an increased risk of developing infusion-associated reactions.

Administration site reactions: common – infusion site edema.

Contraindications

Clinically significant or life-threatening hypersensitivity to idursulfase beta in cases where symptoms are not controlled with appropriate treatment.

Pregnancy.

There is no clinical experience with the drug in patients with impaired liver or kidney function.

There is no experience with the drug in patients over 35 years of age.

There is no experience with the drug in children under 38 months of age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

There are no data on use during breastfeeding. It is unknown whether Idursulfase beta is excreted in breast milk. The risk to breastfed infants cannot be ruled out, so the decision to continue therapy with a drug containing idursulfase beta should be made considering the expected benefit of therapy for the mother and the potential risk for the breastfed infant.

Pediatric Use

There is no experience with drugs containing idursulfase beta in children under 38 months of age.

Geriatric Use

The drug is contraindicated for use in elderly patients.

Special Precautions

Use with caution in patients with severe concomitant respiratory diseases.

Patients receiving idursulfase beta may develop infusion-associated reactions, such as respiratory distress, hypoxia, hypotension, stroke, and/or angioedema. Adverse reactions can be managed by reducing the infusion rate, discontinuing the infusion, or administering antihistamines, corticosteroids.

Special precautions are necessary when administering the drug to patients with severe concomitant respiratory disease. Hospitalization of patients in a specialized unit for drug infusion and clinical monitoring may be required. The use of antihistamines or other sedatives in these patients should be limited or carefully monitored. In some cases, positive airway pressure support may be required.

Administration of the drug should be postponed if the patient develops an acute respiratory illness with fever. For patients using supplemental oxygen therapy, an oxygen supply should be available during drug administration in case of an adverse reaction.

Delayed signs of anaphylactic reactions may be observed even 24 hours after the initial reaction. If an anaphylactic reaction occurs, the infusion should be stopped immediately, and appropriate treatment and monitoring should be initiated. Current standards for emergency therapy should be followed. Patients with severe or refractory anaphylactic reactions may require prolonged clinical observation. Patients who have had anaphylactic reactions to the drug in the past should be re-administered the drug with caution; during drug administration, specially trained medical personnel and resuscitation equipment must be present. Severe and life-threatening hypersensitivity reactions in cases where the patient’s condition is uncontrollable are a contraindication for re-administration of the drug.

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.