Bronchitol-Pharmaxis (Powder) Instructions for Use

Marketing Authorization Holder

Gen İlaç Ve Sağlık Ürünleri San. Ve Tic., A.Ş. (Turkey)

Manufactured By

Arna Pharma, Pty. Ltd. (Australia)

ATC Code

R05CB16 (Mannitol)

Active Substance

Mannitol (BP British Pharmacopoeia)

Dosage Form

Bronchitol-Pharmaxis

Powder for inhalation, metered-dose 40 mg: caps. 10 pcs. with 1 inhaler, caps. 280 pcs. with 2 inhalers

Dosage Form, Packaging, and Composition

Powder for inhalation, metered-dose in hard gelatin capsules No. 3; the capsule body and cap are transparent and almost colorless; there are inscriptions in black ink: on the body – “40 mg”, on the cap – “PXS”; the capsule contents are a white or almost white powder.

Excipients:
Capsule shell composition:
Capsule body gelatin – 100%.
Capsule cap gelatin – 100%.

Composition of black ink shellac, ethanol, isopropanol, butanol, propylene glycol, purified water, concentrated ammonia solution, potassium hydroxide, black iron oxide dye (E172).

10 pcs. – blister packs (1) in a set with 1 inhaler – cardboard packs.
10 pcs. – blister packs (28) in a set with 2 inhalers – cardboard packs.

Clinical-Pharmacological Group

Mucolytic drug used in cystic fibrosis

Pharmacotherapeutic Group

Mucolytic expectorant

Pharmacological Action

Osmotic diuretic. Mannitol in the form of inhalations (in the appropriate dosage form) is intended to improve pulmonary hygiene by correcting the impaired mucociliary clearance characteristic of cystic fibrosis. Although the exact mechanism of action is unknown, it is assumed that when mannitol is administered by inhalation, the viscoelastic properties of sputum are altered, the hydration of the periciliary fluid layer is increased, and mucociliary and cough clearance are increased.

Pharmacokinetics

The absolute bioavailability of mannitol after inhalation compared to intravenous administration is 0.59±0.15. The rate and extent of absorption of mannitol after inhalation were very close to the rate and extent of absorption after oral administration. T_max after inhalation was 1.5±0.5 h.

Lung deposition studies demonstrated 24.7% deposition of inhaled mannitol, confirming its distribution to the target organ. Preclinical toxicological studies show that Mannitol reaching the lungs is absorbed into the blood; with C_max in serum reached within 1 h. After intravenous administration of a 500 mg dose, V_d was 34.3±13.8 L. There is no evidence that Mannitol accumulates in the body, so the distribution of inhaled mannitol was not studied in pharmacokinetic studies.

Mannitol is metabolized after oral administration (by intestinal microflora), but no significant metabolism is observed after intravenous administration. A small percentage of systemically absorbed mannitol is metabolized in the liver to form glycogen and carbon dioxide.

The cumulative volume of mannitol entering the urine over a 24-hour period was close to the volume entering the urine after inhalation (55%) and oral administration (54%) of mannitol. When administered intravenously, Mannitol is excreted almost unchanged by glomerular filtration. 87% of the dose is excreted in the urine within 24 h. The mean terminal T_1/2 in adults from serum was about 4-5 h, from urine – about 3.6 h.

Indications

Treatment of cystic fibrosis in children over 6 years of age and adults in addition to the use of dornase alfa, as well as in patients with intolerance or ineffectiveness of dornase alfa.

ICD codes

Dosage Regimen

It is administered by inhalation in the appropriate dosage form.

Before starting treatment, all patients should be assessed for bronchial hyperreactivity to inhaled mannitol upon receiving the initial dose. Patients for whom spirometry is contraindicated and who for this reason cannot undergo assessment upon taking the initial dose should not be prescribed Mannitol for inhalation use.

The therapeutic dose regimen should not be prescribed until the initial dose assessment has been performed.

The recommended dose is 400 mg twice daily.

Adverse Reactions

Infections and parasitic diseases uncommon – oral candidiasis, staphylococcal infection.

Metabolism and nutrition disorders common – decreased appetite.

Nervous system disorders common – headache; uncommon – dizziness.

Ear and labyrinth disorders uncommon – ear pain.

Respiratory, thoracic and mediastinal disorders very common – cough; common – hemoptysis, bronchospasm, wheezing, bronchial asthma, deterioration of condition, pharyngolaryngeal pain, productive cough, chest discomfort, infected sputum; uncommon – positive fungal test in sputum, airway flooding syndrome, throat irritation, rhinorrhea.

Gastrointestinal disorders common – vomiting, post-tussive vomiting; uncommon – gastroesophageal reflux disease, glossalgia.

Skin and subcutaneous tissue disorders uncommon – acne, pruritus, rash, cold sweat.

Musculoskeletal and connective tissue disorders uncommon – arthralgia, joint stiffness, musculoskeletal chest pain.

Renal and urinary disorders uncommon – urinary incontinence.

General disorders and administration site conditions: uncommon – hernia sac pain.

Contraindications

Hypersensitivity to mannitol, bronchial hyperreactivity to inhaled mannitol.

Use in Pregnancy and Lactation

Since the consequences of a possible hyperreactivity reaction on the mother and/or fetus are unknown, caution should be exercised when using mannitol by inhalation during pregnancy if necessary.

It is not known whether Mannitol is excreted in human breast milk. The excretion of mannitol into milk in animals has not been studied. The decision to continue (discontinue) breastfeeding or to continue (discontinue) treatment with mannitol for inhalation should be made taking into account the benefits of breastfeeding for the child and the benefits of this treatment for the woman.

Use in Hepatic Impairment

There are no dose recommendations for these patient groups.

Use in Renal Impairment

There are no dose recommendations for these patient groups.

Pediatric Use

The use of Mannitol by inhalation in children under 6 years of age is not recommended due to insufficient data on safety and efficacy.

Geriatric Use

There are no recommendations for use in elderly patients.

Special Precautions

Patients with bronchial asthma should be carefully monitored for worsening of asthma symptoms after inhalation of the initial dose.

Bronchospasm may develop upon inhalation of mannitol even in patients who did not show hyperreactivity to the initial dose inhalation.

The safety and efficacy of inhaled mannitol have not been established in patients with FEV1 less than 30% of normal.

Patients with a history of hemoptysis should be carefully monitored.

Drug Interactions

When mannitol is used concomitantly with cardiac glycosides, an increase in their toxic effect associated with hypokalemia is possible.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°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.