Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Hyperresponsiveness to mannitol
Patients must be monitored for bronchial hyperresponsiveness to inhaled mannitol during their initiation dose assessment before commencing the therapeutic dose regimen of Bronchitol. If unable to perform spirometry patients cannot undergo the initiation dose assessment and must not be prescribed Bronchitol. The usual precautions regarding bronchial hyperresponsiveness monitoring apply (see section 4.2). Hyperresponsive patients should not be prescribed the therapeutic dose regimen of Bronchitol (see section 4.3).

A patient is defined as hyperresponsive to inhaled mannitol and must not be prescribed the therapeutic dose regimen if they experience any of the following:

-     ≥10% fall from baseline in SpO 2 at any point of the assessment; -     FEV 1 fall from baseline is ≥20% at 240 mg cumulative dose;
-     FEV 1 has fallen 20-<50% (from baseline) at the end of the assessment and does not return to <20% within 15 minutes;
-     FEV 1 has fallen ≥50% (from baseline) at the end of the assessment.

If a therapy induced hyperresponsive reaction is suspected, Bronchitol should be discontinued.

Bronchospasm
Bronchospasm can occur with inhalation of medicinal product and has been reported with Bronchitol in clinical studies, even in patients who were not hyperresponsive to the initiation dose of inhaled mannitol (see section 4.8). Bronchospasm should be treated with a bronchodilator or as medically appropriate.

If there is evidence of therapy induced bronchospasm, the physician should carefully evaluate whether the benefits of continued use of Bronchitol outweigh the risks to the patient.

All patients should be formally reviewed after approximately six weeks of Bronchitol treatment to assess for signs and symptoms suggestive of drug induced bronchospasm. The initiation dose assessment described in section 4.2 should be repeated if uncertainty exists.

Asthma
The safety/efficacy of mannitol in patients with asthma has not been properly studied. Patients with asthma must be carefully monitored for worsening signs and symptoms of asthma after the initiation dose of Bronchitol.

Patients must be advised to report worsening signs and symptoms of asthma during therapeutic use to their physician. If there is evidence of therapy induced bronchospasm, the physician should carefully evaluate whether the benefits of continued use of Bronchitol outweigh the risks to the patient. Bronchospasm should be treated with a bronchodilator or as medically appropriate.

Haemoptysis
Haemoptysis has been commonly reported with Bronchitol in clinical studies. Bronchitol has not been studied in patients with a history of significant episodes of haemoptysis (>60 ml) in the previous three months. As a consequence, these patients should be carefully monitored, and Bronchitol should be withheld in the event of massive haemoptysis. A massive/serious haemoptysis is considered to be: • acute bleeding ≥240 ml in a 24-hour period 3
• recurrent bleeding ≥100 ml/day over several days
The reinstitution or withholding of Bronchitol following smaller episodes of haemoptysis should be based on clinical judgement.

Cough
Cough was very commonly reported with use of Bronchitol in clinical studies (see section 4.8).
Patients should be trained to practice correct inhaler technique during treatment and advised to report persistent cough with the use of Bronchitol to their physician.

Impaired lung function
Safety and efficacy have not been demonstrated in patients with a FEV 1 of less than 30% of predicted (see section 5.1). The use of Bronchitol is not recommended in these patients.

Non-CF Bronchiectasis
Efficacy and safety have not been established in non-CF bronchiectasis patients. Therefore, treatment with Bronchitol is not recommended.

Effects on Driving

4.7   Effects on ability to drive and use machines

Bronchitol has no or negligible influence on the ability to drive and use machines.