Cayston

Posology Patients should use a bronchodilator before each dose of Cayston. Short acting bronchodilators can be taken between 15 minutes and 4 hours and long acting bronchodilators can be taken between 30 minutes and 12 hours prior to each dose of Cayston.

For patients taking multiple inhaled therapies, the recommended order of administration is as follows: 1. bronchodilator 2. mucolytics 3. and lastly, Cayston. Adults and children 6 years and older The recommended dose for adults is 75 mg three times per 24 hours for 28 days.

Doses should be taken at least 4 hours apart. Cayston may be taken in repeated cycles of 28 days on therapy followed by 28 days off Cayston therapy. The dosing in children aged 6 years and older is the same as for adults. 3 Elderly Clinical studies of Cayston did not include Cayston-treated patients aged 65 years and older to determine whether they respond differently from younger patients.

If Cayston is to be prescribed to the elderly then the posology is the same as for adults. Renal impairment Aztreonam is known to be excreted renally and therefore administration of Cayston in patients with renal impairment (serum creatinine > 2 times upper limit of normal) should be undertaken with caution.

No dose adjustment is necessary in cases of renal impairment since the systemic concentration of aztreonam following inhaled administration of Cayston is very low (approximately 1% of the concentration resulting from a dose of 500 mg aztreonam for injection).

Hepatic impairment There are no data on the use of Cayston in patients with severe hepatic impairment (ALT or AST greater than 5 times the upper limit of normal). No dose adjustment is necessary in cases of hepatic impairment. Paediatric population The safety and efficacy of Cayston in children younger than 6 years of age have not been established.

1 but no recommendation on posology can be given. Method of administration For inhalation use. Cayston should only be used with the Altera Nebuliser Handset and Altera Aerosol Head connected to an eBase Controller or an eTrack Controller.

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Summary of the safety profile Assessment of adverse reactions is based on experience in four Phase 3 clinical studies involving CF patients with chronic P. aeruginosa infection and post-marketing spontaneous reporting. 0%), pyrexia (12%) and dyspnoea (10%).

4). Tabulated summary of adverse reactions The adverse reactions considered at least possibly related to treatment from clinical study and post- marketing experience are listed below by body system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1000 to < 1/100).

6 Respiratory, thoracic and mediastinal disorders: Very common: cough, nasal congestion, wheezing, pharyngolaryngeal pain, dyspnoea Common: bronchospasm1, chest discomfort, rhinorrhoea, haemoptysis1 Skin and subcutaneous tissue disorders: Common: rash1 Musculoskeletal and connective tissue disorders: Common: arthralgia Uncommon: joint swelling General disorders and administration site conditions: Very common: pyrexia Investigations: Common: lung function test decreased1 1 See section Description of selected adverse reactions Description of selected adverse reactions Bronchospasm Nebulised therapies, including Cayston, may be associated with bronchospasm (an acute reduction of ≥ 15% in FEV1).

4. 4). 4). 1). The following rare and severe adverse reactions have been reported after parenteral use of other aztreonam containing products: toxic epidermal necrolysis, anaphylaxis, purpura, erythema multiforme, exfoliative dermatitis, urticaria, petechiae, pruritus, diaphoresis.

Paediatric population A total of 137 paediatric patients aged 6 to 17 years with chronic P. aeruginosa infection and FEV1 ≤ 75% predicted have received Cayston in Phase 2 and Phase 3 clinical studies (6-12 years, n = 35; 13-17 years, n = 102).

Pyrexia was observed at a higher incidence rate in paediatric patients aged 6 to 17 years compared to adults. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Allergic reactions If an allergic reaction to aztreonam does occur, stop administration of the medicinal product and initiate treatment as appropriate. The occurrence of rash may be indicative of an allergic reaction to aztreonam. Cross-reactivity may occur in patients with a history of allergy to beta-lactam antibiotics, such as penicillins, cephalosporins, and/or carbapenems.

Animal and human data demonstrate low risk of cross-reactivity between aztreonam and beta-lactam antibiotics. Aztreonam, a monobactam, is only weakly immunogenic. Caution is advised when administering Cayston to patients if they have a history of beta-lactam allergy.

The following rare and severe adverse reactions have been reported after parenteral use of other aztreonam containing products: toxic epidermal necrolysis, anaphylaxis, purpura, erythema multiforme, exfoliative dermatitis, urticaria, petechiae, pruritus, diaphoresis.

4 Bronchospasm Bronchospasm (an acute reduction of ≥ 15% in FEV1) is a complication associated with nebulised therapies. 8). Patients should use a bronchodilator before each dose of Cayston. If a case of bronchospasm is suspected to be part of an allergic reaction appropriate measures should be taken (see “allergic reactions” paragraph above).

Haemoptysis Inhalation of nebulised solutions may induce a cough reflex. The use of Cayston in paediatric CF patients has been associated with haemoptysis during treatment cycles and could have aggravated underlying conditions. Administration of Cayston in CF patients with active haemoptysis should be undertaken only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage.

Other precautions Efficacy has not been established in patients with FEV1 > 75% predicted. Patients with Burkholderia cepacia isolated from sputum within the previous 2 years were excluded from the clinical studies. Aztreonam for injection must not be used in the Altera or other nebulisers.

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