Tigeraza^® (Solution) Instructions for Use

Marketing Authorization Holder

Generium-Next, LLC (Russia)

Manufactured By

Generium, JSC (Russia)

Or

Pharmstandard-UfaVITA OJSC (Russia)

Labeled By

Pharmstandard-UfaVITA, OJSC (Russia)

Or

Moscow Endocrine Plant, FSUE (Russia)

Packaging and Quality Control Release

Generium, JSC (Russia)

Or

Generium-Next, LLC (Russia)

Or

Pharmstandard-UfaVITA, OJSC (Russia)

ATC Code

R05CB13 (Dornase alfa (deoxyribonuclease))

Active Substance

Dornase alfa (Rec.INN registered by WHO)

Dosage Form

Tigeraza®

Solution for inhalation 2.5 mg/2.5 ml: amp. 6 pcs.

Dosage Form, Packaging, and Composition

Solution for inhalation clear, colorless or yellowish in color.

* 1 mg of dornase alfa corresponds to 1000 IU.

Excipients : sodium chloride – 21.93 mg, calcium chloride dihydrate – 0.38 mg, water for injection – up to 2.5 ml.

2.5 ml – ampoules (6) – light-protective bags (1) – cardboard packs.

Clinical-Pharmacological Group

Mucolytic drug used in cystic fibrosis

Pharmacotherapeutic Group

Drugs used for cough and colds; expectorants, excluding combinations with antitussives; mucolytic agents

Pharmacological Action

Enzyme agent. It is a genetically engineered deoxyribonuclease – I – DNase. It cleaves extracellular DNA, which is present in large quantities in the viscous bronchial secretion that accumulates in the airways of patients with cystic fibrosis. It reduces the viscosity of sputum, thereby improving lung function and reducing the risk of infectious diseases in this category of patients.

Pharmacokinetics

Systemic absorption of dornase alfa after inhalation of the aerosol in humans is low.

Normally, DNase is present in human blood serum. Inhalation of dornase alfa in doses up to 40 mg for 6 days did not lead to a significant increase in serum concentration compared to normal endogenous levels. The serum concentration of DNase did not exceed 10 ng/ml. After administration at a dose of 2500 IU (2.5 mg) 2 times/day for 24 weeks, the mean serum concentrations of DNase did not differ from the mean pre-treatment values (3.5±0.1 ng/ml), indicating low systemic absorption or low accumulation.

Distribution. In patients with cystic fibrosis, the mean concentration of DNase in sputum 15 minutes after inhalation of a dose of 2500 IU (2.5 mg) is approximately 3.0 µg/ml. After inhalation, the concentration of DNase in sputum decreases rapidly.

Metabolism. Apparently, DNase is metabolized under the action of proteases present in biological fluids.

Excretion. After IV administration of DNase, T_1/2 is 3-4 hours.

Within 2 hours, the concentration of DNase in sputum decreases by more than 2 times compared to the value immediately after inhalation, but the effect on sputum rheology persists for more than 12 hours.

Indications

As part of the complex therapy of cystic fibrosis with a decrease in forced vital capacity of the lungs of no more than 40% of the physiological norm.

ICD codes

Dosage Regimen

Administer by inhalation only using a recommended jet nebulizer and compressor.

Use the single-dose ampoule entirely for one treatment; do not dilute or mix with other medications in the nebulizer.

The standard dose is 2.5 mg once daily.

In specific cases for patients over 21 years of age, a dose of 2.5 mg twice daily may be used under medical supervision.

Perform inhalation according to the device manufacturer’s instructions until the ampoule is empty and sputtering stops.

Store unused ampoules in the refrigerator at 2°C to 8°C; protect from light in the original packaging.

Discard any unused solution after opening the ampoule.

Adverse Reactions

From the organ of vision: conjunctivitis.

From the respiratory system: voice change, dyspnea, pharyngitis, laryngitis, rhinitis (all of non-infectious nature), respiratory tract infections, including those caused by Pseudomonas, increased bronchial secretion.

From the digestive system: dyspepsia.

From the skin and subcutaneous tissues: rash, urticaria.

From laboratory parameters: decrease in respiratory function indicators.

Other: chest pain (pleural/non-cardiac), pyrexia, headache.

Contraindications

Hypersensitivity to dornase alfa.

Use in Pregnancy and Lactation

During pregnancy and breastfeeding, it should be used only after consultation with a doctor, in cases where the intended benefit to the mother outweighs the potential risk to the fetus or infant.

Pediatric Use

It should be used with caution in children under 5 years of age. Dornase alfa should be prescribed to this age category of patients only in case of possible improvement in lung function or reduction in the risk of respiratory tract infections.

Special Precautions

When using dornase alfa, regular medical supervision of the patient and standard physiotherapy should be continued.

After starting therapy with dornase alfa, lung function may decrease somewhat, and sputum production may increase.

An exacerbation of an infectious disease during the use of dornase alfa is not a reason to discontinue therapy.

There are no data on the efficacy and safety of use in children under 5 years of age and/or in patients with a decrease in forced vital capacity of the lungs by more than 40%.

It should not be mixed in the inhaler with other medicines.

Drug Interactions

The product is compatible with standard drugs for the treatment of cystic fibrosis: antibiotics, bronchodilators, digestive enzymes, vitamins, inhaled and systemic corticosteroids and analgesics.

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.