Cayston

/ Gilead

Patients should use a bronchodilator before each dose of Aztreonam. 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 Aztreonam.
For patients taking multiple inhaled therapies, the recommended order of administration is as follows:
1. broncho-dilator
2. mucolytics
3. and lastly, Aztreonam.
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. Aztreonam may be taken in repeated cycles of 28 days on therapy followed by 28 days off Aztreonam therapy.
The dosing in children aged 6 years and older is the same as for adults.
Elderly: Clinical studies of Aztreonam did not include Aztreonam-treated patients aged 65 years and older to determine whether they respond differently from younger patients. If Aztreonam 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 Aztreonam 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 Aztreonam 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 Aztreonam 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.
Method of administration: For inhalation use. Aztreonam should only be used with the Altera Nebuliser Handset and Altera Aerosol Head connected to an eBase Controller or an eFlow rapid Control Unit.

Indicated for the suppressive therapy of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF) aged 6 years and older. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Hypersensitivity to the active substance or to any of the excipients.

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 Aztreonam 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.
Bronchospasm: Bronchospasm (an acute reduction of ≥ 15% in FEV1) is a complication associated with nebulised therapies. Bronchospasm has been reported after Cayston administration. Patients should use a bronchodilator before each dose of Aztreonam. 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 Aztreonam in paediatric CF patients has been associated with haemoptysis during treatment cycles and could have aggravated underlying conditions. Administration of Aztreonam 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. Aztreonam for injection has not been formulated for inhalation, and contains arginine, a substance known to cause pulmonary inflammation.
Resistance to aztreonam, other antibiotics and treatment-emergent microorganisms: The development of antibiotic-resistant P. aeruginosa and superinfection with other pathogens represent potential risks associated with antibiotic therapy. Development of resistance during inhaled aztreonam therapy could limit treatment options during acute exacerbations. A decrease in P. aeruginosa susceptibility to aztreonam and other beta-lactam antibiotics was observed in clinical studies of Cayston. In a 24-week active-controlled clinical study of Cayston therapy, increases were observed in the MIC90 for all P. aeruginosa isolates as well as in the percentages of patients with P. aeruginosa resistant (MIC above the parenteral breakpoint) to aztreonam, to at least 1 beta-lactam antibiotic, and to all 6 beta-lactam antibiotics tested. However, decreased P. aeruginosa susceptibility was not predictive of clinical efficacy of Cayston during the study.
Among patients with multidrug-resistant P. aeruginosa, improvements in respiratory symptoms and pulmonary function were observed following treatment with Cayston. The emergence of parenteral P. aeruginosa resistance to aztreonam or other beta-lactam antibiotics may have potential consequences for the treatment of acute pulmonary exacerbations with systemic antibiotics.
An increased prevalence of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), Aspergillus and Candida species was observed over time in patients treated with several Cayston treatment courses. An association between persistent isolation of MRSA and worse clinical outcome has been reported in the literature. During clinical studies of Cayston, isolation of MRSA did not result in worsening of lung function.

The most frequently occurring adverse reactions to Cayston were cough (58%), nasal congestion (18%), wheezing (15%), pharyngolaryngeal pain (13.0%), pyrexia (12%) and dyspnoea (10%).
See prescribing information for full details.

No interaction studies have been performed. However, no evidence of any drug interactions with aztreonam were identified from clinical studies in which Cayston was taken concomitantly with bronchodilators, dornase alfa, pancreatic enzymes, azithromycin, tobramycin, oral steroids (less than 10 mg daily/20 mg every other day) and inhaled steroids.

Pregnancy: Cayston should not be used during pregnancy unless the clinical condition of the woman requires treatment with aztreonam.
Breast-feeding: Following administration of aztreonam for injection, aztreonam is excreted in human milk at very low concentrations. Systemic concentration of aztreonam following inhaled administration of Cayston is approximately 1% of the concentration resulting from a standard dose of aztreonam for injection.
Therefore, and because of low oral absorption, aztreonam exposure in breast-fed infants due to mothers receiving Cayston is likely to be extremely low.
Cayston can be used during breast-feeding.
See prescribing information for full details.

Adverse reactions specifically associated with overdose of Cayston have not been identified. Since the plasma concentration of aztreonam following administration of Cayston (75 mg) is approximately 0.6 µg/ml, compared to serum levels of 54 µg/ml following administration of aztreonam for injection (500 mg), no safety issues associated with aztreonam overdose are anticipated.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage: Powder vial and solvent ampoule: Store in a refrigerator (2°C – 8°C). May be stored outside a refrigerator but below 25°C for up to 28 days.
Shelf life: After reconstitution, immediate use of Cayston is recommended. If not used immediately, the reconstituted solution must be stored at 2°C – 8°C and used within 8 hours.  In-use storage times and conditions prior to use are the responsibility of the user.