Colobreathe · 4.3 Contraindications · 1

HOS-155027 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The safety of Colobreathe has been assessed in a total of 237 subjects (225 cystic fibrosis patients and 12 healthy volunteers). Of these, 187 patients aged 6 years and above were exposed to Colobreathe one capsule twice daily in a 24-week, phase 3 comparative study. There were 32 patients aged 6-12 years, 41 patients aged 13-17 years and 114 patients aged 18 years and older. The most commonly reported adverse reactions as a percent of all Colobreathe treated patients were: unpleasant taste (62%), cough (59.4%), throat irritation (43.9%), dyspnoea (16.6%) and dysphonia (10.7%). Inhalation may induce coughing or bronchospasm which may be controlled by pre-treatment with inhaled beta2 agonists. Sore throat or mouth has been reported with nebulised colistimethate sodium and may occur with Colobreathe. This may be related to Candida albicans infection or hypersensitivity. Skin rash may also indicate hypersensitivity and if this occurs treatment should be withdrawn. Tabulated list of adverse reactions In the 24 week clinical study, the following adverse reactions were observed across all ages. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare ((≥1/10,000 to <1/1,000), very rare <1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. System Organ Class Very Common Common Uncommon Immune system Drug disorders hypersensitivity Metabolism and Weight fluctuation, nutrition disorders decreased appetite Psychiatric disorders Anxiety Nervous system Balance disorder, Convulsions, disorders headache somnolence Ear and labyrinth Tinnitus Ear congestion disorders Respiratory, thoracic Dyspnoea, Haemoptysis, Chest pain, and mediastinal cough, bronchospasm, dyspnoea disorders dysphonia, asthma,

Auszug; vollständigen Abschnitt im Original lesen.

HOS-155023 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance, colistin sulphate or polymyxin B.

HOS-155022 · has-indication-information · PDF-Seite 2

Colobreathe is indicated for the management of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF) aged 6 years and older (see section 5.1). Consideration should be given to official guidance on the appropriate use of antibacterial active substances.

HOS-155025 · has-interaction-information · PDF-Seite 4

There is no experience of using Colobreathe concurrently with other inhaled antibacterial agents. Caution should be taken with concomitant use with other formulations of colistimethate sodium as there is little experience and there is a possibility of summative toxicity. No in-vivo interaction studies have been performed. Colistimethate sodium and colistin have been investigated in vitro to determine the effects on the expression of cytochrome P450 (CYP) enzymes on treating primary cultures of fresh human hepatocytes. Treatment with colistimethate sodium or colistin did not induce the activity of any enzyme tested (CYP1A2, 2B6, 2C8, 2C9, 2C19 and 3A4/5). Concomitant use of inhaled colistimethate sodium with other medicinal products that are potentially nephrotoxic or neurotoxic, such as aminoglycosides, or neuromuscular blocking products, such as curariform agents should be undertaken with caution. Co-treatment with colistimethate sodium and macrolides such as azithromycin and clarithromycin, or fluoroquinolones such as norfloxacin and ciprofloxacin should be undertaken with caution in patients with myasthenia gravis (see section 4.4).

HOS-155026 · has-pregnancy-information · PDF-Seite 4

Pregnancy There are no or limited amount of data from the use of inhaled colistimethate sodium in pregnant women. Studies in animals using parenteral administration have shown reproductive toxicity (see section 5.3). Single dose intravenous studies in human pregnancy show that colistimethate sodium crosses the placenta and consequently there is potential for foetal toxicity if administered during pregnancy. Colistimethate sodium is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding Physico-chemical data suggest excretion of colistimethate sodium in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from colistimethate sodium therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman. Fertility 4 Colistimethate sodium has no notable effects on fertility in male or female rats or mice.

HOS-155024 · has-warning-information · PDF-Seite 3

Bronchospasm and coughing Bronchospasm or coughing may occur on inhalation. These reactions usually disappear or significantly diminish with continued use and may be ameliorated by appropriate treatment with beta2- agonists prior to or following dry powder colistimethate sodium inhalation. If bronchospasm or coughing remain problematic, withdrawal of treatment should be considered. Haemoptysis Haemoptysis is a complication in cystic fibrosis and is more frequent in adults. The use of colistimethate sodium in patients with clinically significant haemoptysis should be undertaken or continued only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage. Acute respiratory exacerbation If acute respiratory exacerbations develop additional intravenous or oral antibacterial agent therapy should be considered. Oral fungal super-infection After each inhalation of Colobreathe, the mouth should be rinsed with water. The rinse should not be swallowed. Rinsing may reduce the risk of developing oral fungal super-infection during treatment and may also reduce the unpleasant taste associated with colistimethate sodium. Nephrotoxicity/neurotoxicity There is very low transpulmonary absorption of colistimethate after inhalation of Colobreathe (see section 5.2). Care should still be taken in administering Colobreathe to patients who are known to have a propensity for nephrotoxic or neurotoxic events. Caution should be taken with concomitant use of Colobreathe and parenteral or nebulised colistimethate sodium. Caution should be taken with concomitant use of colistimethate sodium and potential nephrotoxic or neurotoxic medicinal products, including non-depolarising muscle relaxants (see section 4.5). 3 Other Colobreathe should be used with extreme caution in patients with myasthenia gravis because of potential for drug induced neuromuscular blockade. Colistimethate sodium should be used with extreme caution in patients with porphyria. Safety and efficacy have been assessed in controlled studies for up to 24 weeks. (see section 5.1). Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.