Cayston

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Cayston 75 mg powder and solvent for nebuliser solution. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains aztreonam lysine equivalent to 75 mg aztreonam.  After reconstitution the nebuliser 
solution contains 75 mg aztreonam. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for nebuliser solution. 
 
White to off-white powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Cayston is 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. 
 
4.2 Posology and method of administration 
 
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. 
 



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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. 
Currently available data are described in section 5.1 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 eFlow rapid Control Unit.  For instructions on reconstitution of the 
medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
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. 
 



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Bronchospasm 
 
Bronchospasm (an acute reduction of ≥ 15% in FEV1) is a complication associated with nebulised 
therapies.  Bronchospasm has been reported after Cayston administration (see section 4.8).  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.  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 (see section 5.1).  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. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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. 
 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no data from the use of aztreonam in pregnant women.  Animal studies do not indicate direct 
or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 
 
Systemic concentration of aztreonam following inhaled administration of Cayston is low compared to 
a standard dose of aztreonam for injection (approximately 1% of the concentration resulting from a 
dose of 500 mg aztreonam for injection). 
 
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. 
 
Fertility 
 
Non-clinical data for aztreonam for injection about fertility do not indicate any adverse effects. 
 
4.7 Effects on ability to drive and use machines 
 
Cayston has no or negligible influence on the ability to drive or use machines. 
 
4.8 Undesirable effects 
 
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.   
In the two Phase 3 placebo-controlled clinical studies where patients received Cayston for 28 days, 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%). 
 
An acute reduction of ≥ 15% in FEV1 is a complication associated with nebulised therapies, including 
Cayston (see section 4.4). 
 
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). 
 



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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).  Refer to section 4.4. 
 
Haemoptysis 
 
Inhalation of nebulised solutions may induce a cough reflex which could aggravate underlying 
conditions (see section 4.4). 
 
Allergic reactions 
 
Rash has been reported with the use of Cayston and may be indicative of an allergic reaction to 
aztreonam (see section 4.4). 
 
Lung function test decreased 
 
Lung function test decreased has been reported with use of Cayston, but was not associated with a 
sustained decrease in FEV1 (see section 5.1).  
 
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.  It 
allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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4.9 Overdose 
 
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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antibacterials for systemic use, other beta-lactam antibacterials, 
ATC code: J01DF01 
 
Mechanism of action 
 
Aztreonam exhibits activity in vitro against gram-negative aerobic pathogens, including 
P. aeruginosa.  Aztreonam binds to penicillin-binding proteins of susceptible bacteria, which leads to 
inhibition of bacterial cell wall synthesis, followed by filamentation and cell lysis. 
 
Mechanisms of resistance 
 
Loss of susceptibility to aztreonam in CF patients with P. aeruginosa occurs either through selection 
of strains with mutations located on the chromosome or rarely through acquisition of plasmid/integron 
mediated genes. 
 
Known mechanisms of resistance to aztreonam mediated by mutation of chromosomal genes include: 
hyperexpression of the Class C beta-lactamase AmpC and up-regulation of the efflux pump 
MexAB-OprM.  The known mechanism of resistance to aztreonam mediated by acquisition of genes 
involves acquisition of extended spectrum beta-lactam enzymes (ESBLs) that hydrolyse the four-
member, nitrogen-containing ring of aztreonam. 
 
ESBLs from Class A, B and D beta-lactamases may have activity against aztreonam.  Class A beta-
lactamases reported to hydrolyse aztreonam include the VEB type (primarily Southeast Asia), 
PER type (Turkey), and GES and IBC types (France, Greece, and S. Africa).  There are rare reports of 
organisms with metallo-beta-lactamases (MBLs), Class B, that are resistant to aztreonam, VIM-5 
(K. pneumoniae and P. aeruginosa - Turkey), VIM-6 (P. putida - Singapore) and VIM-7 
(P. aeruginosa - United States), however, it is possible that these organisms were expressing multiple 
resistance mechanisms and thus a MBL was not responsible for the observed resistance to aztreonam.  
There are rare reports of Class D beta-lactamases from clinical isolates of P. aeruginosa, OXA-11 
(Turkey) and OXA-45 (United States) that hydrolyse aztreonam. 
 
Microbiology 
 
A single sputum sample from a CF patient may contain multiple isolates of P. aeruginosa and each 
isolate may have a different level of in vitro susceptibility to aztreonam.  The in vitro antimicrobial 
susceptibility test methods used for parenteral aztreonam therapy can be used to monitor the 
susceptibility of P. aeruginosa isolated from CF patients. 
 
In the Phase 3 placebo-controlled studies of Cayston, local aztreonam concentrations generally 
exceeded aztreonam MIC values for P. aeruginosa, regardless of the level of P. aeruginosa 
susceptibility. 
 
Treatment with up to nine 28-day courses of 75 mg 3 times a day Cayston therapy resulted in 
clinically important improvements in respiratory symptoms, pulmonary function, and sputum 
P. aeruginosa CFU density; no increases in P. aeruginosa MIC50 (± 2 dilution change) were observed, 



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whereas MIC90 increased intermittently to 4 times the initial MIC.  In a 24-week active-controlled 
study of Cayston therapy, no increases in P. aeruginosa MIC50 (± 2 dilution change) were observed, 
whereas MIC90 increased to 4 times the initial MIC.  At the end of the study, the percentage of patients 
with aztreonam MIC for P. aeruginosa above the parenteral breakpoint (> 8 µg/ml) increased from 
34% at baseline to 49%, the percentage of patients with P. aeruginosa resistant to at least 1 beta-
lactam antibiotic increased from 56% at baseline to 67%, and the percentage of patients with 
P. aeruginosa resistant to all 6 beta-lactam antibiotics tested increased from 13% at baseline to 18%.  
There is a risk that P. aeruginosa isolates may develop resistance to aztreonam or other beta-lactam 
antibiotics in patients treated with Cayston.  The emergence of parenteral P. aeruginosa resistance to 
aztreonam and other beta-lactam antibiotics may have potential consequences for the treatment of 
acute pulmonary exacerbations with systemic antibiotics.  However, similar improvements in lung 
function were seen after treatment with Cayston among patients with aztreonam susceptible or 
resistant P. aeruginosa isolates. 
 
In studies of up to nine 28-day courses of Cayston therapy, no increases of clinical significance were 
observed in the treatment-emergent isolation of other gram-negative bacterial respiratory pathogens 
(Burkholderia species, Stenotrophomonas maltophilia and Alcaligenes species).  During the 6-month 
randomised phase of study GS-US-205-0110, treatment-emergent isolation of MSSA and MRSA was 
observed more commonly among aztreonam-treated patients than Tobramycin Nebuliser Solution 
(TNS)-treated patients.  The majority of the treatment-emergent isolations were intermittent.  
Treatment-emergent persistent isolation (defined as absent at screening/baseline then present at 3 or 
more subsequent consecutive visits) of MSSA occurred in 6% of aztreonam-treated patients compared 
to 3% of TNS-treated patients.  Treatment-emergent intermittent isolation of MRSA occurred in 7% of 
aztreonam-treated patients compared to 1% of TNS-treated patients and treatment-emergent persistent 
isolation of MRSA occurred in 3% of aztreonam-treated patients compared to no TNS-treated patients.  
An association between persistent isolation of MRSA and more severe disease and increased mortality 
has been reported in the literature.  During clinical studies of Cayston, isolation of MRSA did not 
result in worsening of lung function. 
 
Clinical efficacy and safety 
 
Cayston was compared to TNS over three 28-day courses of treatment in a randomised, active-
controlled, multicenter study (GS-US-205-0110).  Patients participating in this study in Europe who 
completed at least 1 course of Cayston or TNS during the randomised phase could subsequently 
receive up to three 28-day courses of Cayston in an open-label extension phase.  Entry criteria 
included CF, FEV1 ≤ 75% predicted, stable pulmonary disease, a recent positive sputum culture for 
P. aeruginosa, and previous treatment with aerosolised antibiotics without demonstration of drug 
intolerance. 
 
Cayston was evaluated over a period of 28-days of treatment (one course) in two randomised, double-
blind, placebo-controlled, multicentre studies (CP-AI-005 and CP-AI-007).  Patients participating in 
these studies could subsequently receive multiple courses of Cayston in an open-label follow-on study 
(CP-AI-006).  Entry criteria included CF, baseline FEV1 between 25% and 75% predicted, and chronic 
P. aeruginosa lung infection.   
 
Overall, 539 patients (78% adults) were treated in these studies.  Studies were conducted using the 
Altera Nebuliser System to administer Cayston. 
 
GS-US-205-0110 
 
In GS-US-205-0110, 268 patients with CF and chronic P. aeruginosa lung infection were randomised 
and received Cayston (n = 136) or TNS (n = 132).  Fifty-nine paediatric patients aged 6 to 17 years 
were included in the study.  Patients were randomised in a 1:1 ratio to receive either aztreonam 
(75 mg) administered by inhalation 3 times a day or TNS (300 mg) administered 2 times a day.  
Treatments were administered for three cycles of 28 days on therapy followed by 28 days off therapy.  
The co-primary endpoints were non-inferiority of Cayston to TNS in relative change from baseline to 
Day 28 in FEV1 % predicted and superiority of Cayston to TNS in actual change from baseline in 



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FEV1 % predicted across 3 treatment courses (the average of the actual change in FEV1 % predicted 
observed at the end of each treatment course). 
 
The adjusted mean percent change from baseline to Day 28 in FEV1 % predicted was 8.35 and 0.55 in 
the Cayston and TNS groups, respectively (treatment difference: 7.80; p = 0.0001; 95% CI: 3.86, 
11.73).  The adjusted mean actual change from baseline in FEV1 % predicted across 3 treatment 
courses was 2.05 and -0.66 in the Cayston and TNS groups, respectively (treatment difference: 2.70; 
p = 0.0023; 95% CI: 0.98, 4.43).  Patients treated with aztreonamexperienced a longer time to need for 
i.v. antipseudomonal antibiotics related to respiratory events compared to TNS-treated patients 
(p = 0.0025).  The Kaplan-Meier estimates for this event rate at week 24 were 36% in aztreonam-
treated patients and 54% in TNS-treated patients.  Additionally, aztreonam-treated patients had fewer 
hospitalisations due to respiratory events (40 versus 58, p = 0.044) and fewer respiratory events 
requiring the use of i.v. or inhaled antipseudomonal antibiotics (84 versus 121, p = 0.004) than TNS-
treated patients.  Aztreonam-treated patients also demonstrated larger mean improvements in CFQ-R 
respiratory symptoms scores compared to TNS-treated patients across 3 treatment courses (6.30 versus 
2.17, p = 0.019). 
 
In the limited subgroup of patients who received inhaled tobramycin for less than 84 days in the 
previous 12 months (n = 40), lung function improvements at Day 28 and across three 28-day treatment 
courses were numerically smaller among aztreonam-treated patients than TNS-treated patients.  
 
CP-AI-007 
 
CP-AI-007 enrolled 164 adult (predominantly) and paediatric patients randomised in a 1:1 ratio 
comparing Cayston 75 mg (80 patients) or placebo (84 patients) administered 3 times a day for 
28 days (one course).  Patients were required to have been off antipseudomonal antibiotics for at least 
28 days before treatment with study drug. 
 
Pulmonary function and respiratory symptoms significantly improved from baseline to Day 28 in 
patients treated with one course of Cayston. 
 
CP-AI-005 
 
CP-AI-005 enrolled 246 adult (predominantly) and paediatric patients.  All patients were treated with 
Tobramycin Nebuliser Solution (TNS) 300 mg, 2 times a day in the four weeks immediately prior to 
receiving Cayston or placebo either 2 or 3 times a day for 28 days.  Patients continued on their 
baseline medications, including macrolide antibiotics.  Patients were randomised in a 2:2:1:1 ratio to 
be treated with aztreonam 75 mg 2 or 3 times a day or volume-matched placebo 2 or 3 times a day for 
28 days immediately following the 28-day lead-in course of open-label TNS. 
 
Aztreonamtherapy resulted in significant improvements in pulmonary function and respiratory 
symptoms at Day 28 in the 66 patients treated with one course Cayston 75 mg 3 times a day. 
 
CP-AI-006 
 
CP-AI-006 was an open-label follow-on study to CP-AI-005 and CP-AI-007 evaluating the safety of 
repeated exposure to aztreonamand the effect on disease-related endpoints over multiple 28-day 
courses.  Patients received Cayston at the same frequency (2 or 3 times a day) as they took Cayston or 
placebo in the randomised studies.  Patients continued on their baseline medications and whenever 
indicated additional antibiotics were used in the majority of patients to treat exacerbations.  Each 
28-day course of Cayston was followed by a 28-day off drug period.  Over nine 28-day courses of 
therapy, measures of pulmonary function (FEV1), CFQ-R respiratory symptoms scores, and 
P. aeruginosa sputum density showed a trend to improvement while the patients were on treatment 
compared with off treatment.  However, due to the uncontrolled nature of the study and concomitant 
medications no conclusion can be drawn on the sustainability of the observed short term benefit over 
subsequent courses of treatment. 
 



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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.  Paediatric patients 
had clinical improvements with aztreonamas determined by an increase in FEV1, improvement in 
CFQ-R respiratory symptoms scores and decline in P. aeruginosa sputum density.  Cayston is 
indicated for use in paediatric patients aged 6 years and older with repeated cycles of 28 days on 
therapy followed by 28 days off Cayston therapy based on the above clinical experience. 
 
In a Phase 2 open-label study (GS-US-205-0162), 105 paediatric patients aged 3 months to < 18 years 
(24 patients aged 3 months to < 2 years; 25 patients aged 2 to < 6 years; 56 patients aged 6 to 
< 18 years) with CF and documented initial/new onset P. aeruginosa infection/colonisation received 
Cayston 3 times a day for a single course of 28 days. 
 
Of the 101 patients, all having a positive cultures for P. aeruginosa within 30 days of study enrolment, 
of whom 56 (55.4%) were free of P. aeruginosa at baseline who completed a 28-day treatment course 
89.1% (n = 90) were free of P. aeruginosa at the end of treatment (Day 28) and 75.2% (n = 76) were 
free of P. aeruginosa 1 month after the end of treatment (Day 56).  A total of 79 patients who 
completed a 28-day treatment course and who did not receive an additional antipseudomonal antibiotic 
during the treatment period were evaluable 6 months after the end of treatment; of these, 58.2% 
(n = 46) remained free of P. aeruginosa throughout this time period. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Cayston in one or more subsets of the paediatric population in cystic fibrosis patients with 
Pseudomonas aeruginosa pulmonary infection/colonisation (see section 4.2 for information on 
paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Sputum concentrations 
 
Individual patients’ sputum aztreonam concentrations exhibited considerable variability.  For the 
combined Phase 3 placebo-controlled studies, ten minutes following a single dose of 75 mg inhaled 
aztreonamon Days 0, 14, and 28, the mean sputum concentrations in 195 patients with CF were 
726 µg/g, 711 µg/g, and 715 µg/g, respectively, indicating no increased accumulation of aztreonam 
following repeated dosing. 
 
Plasma concentrations 
 
Individual patients’ plasma aztreonam concentrations exhibited considerable variability. 
 
One hour following a single dose of 75 mg inhaled aztreonam (at approximately peak plasma 
concentration), the mean plasma level in patients with CF was 0.59 µg/ml.  Mean peak plasma levels 
at Days 0, 14, and 28 of a course with 75 mg inhaled aztreonam 3 times a day were 0.55 µg/ml, 
0.67 µg/ml, and 0.65 µg/ml, respectively, indicating no systemic accumulation of aztreonam following 
3 times a day dosing.  In contrast, the serum concentration of aztreonam following administration of 
aztreonam for injection (500 mg) is approximately 54 µg/ml. 
 
Plasma aztreonam concentrations in paediatric patients aged 3 months to < 6 years are comparable to 
those observed for children > 6 years, adolescents and adults. 
 
Distribution 
 
The protein binding of aztreonam in plasma is approximately 77% at clinically relevant plasma 
concentrations. 



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Metabolism 
 
Aztreonam is not extensively metabolised.  The principal metabolite (SQ26,992) is inactive and is 
formed by opening of the beta-lactam ring due to hydrolysis.  Recovery data indicate that about 10% 
of the dose is excreted as this metabolite. 
 
Elimination 
 
The elimination half-life of aztreonam from serum is approximately 2.1 hours for inhalation 
administration, similar to what has been reported for aztreonam for injection.  Approximately 10% of 
the total inhaled aztreonamdose is excreted in the urine as unchanged drug, as compared to 60-65% 
following intravenous administration of aztreonam for injection.  Systemically absorbed aztreonam is 
eliminated about equally by active tubular secretion and glomerular filtration. 
 
Pharmacokinetics in special populations 
 
Age and gender 
 
There was no clinically relevant effect of age or sex on the pharmacokinetics of aztreonam. 
 
Renal and hepatic impairment 
 
Pharmacokinetic studies have not been performed in patients with renal or hepatic impairment. 
 
Pharmacokinetic properties for aztreonam for injection 
 
Peak levels of aztreonam are achieved at about one hour after i.m. administration.  After identical 
single i.m. or i.v. doses, the serum concentrations are comparable at 1 hour (1.5 hours from the start of 
i.v. infusion), with similar slopes of serum concentrations thereafter.  The serum half-life of aztreonam 
averaged 1.7 hours in subjects with normal renal function, independent of the dose and route.  In 
healthy subjects 60-70% of a single i.m. or i.v. dose was recovered in the urine by 8 hours, and urinary 
excretion was essentially complete by 12 hours. 
 
Paediatric population 
 
The Phase 2 and 3 placebo-controlled, registrational studies permitted comparison of plasma 
concentrations 1 hour post dose of Cayston by age (6 to 12 years, 13 to 17 years, and ≥ 18 years).  
Data from these studies revealed minimal differences in mean plasma aztreonam concentrations 
between age groups in patients receiving Cayston 3 times a day. 
 
Pooled sputum concentration data from the Phase 2 and 3 registrational studies revealed some 
evidence of lower mean sputum concentrations in patients aged 13 to 17 years following one dose of 
Cayston 3 times a day.  However, all mean sputum concentration values were associated with 
relatively large standard deviations.  
 
5.3 Preclinical safety data 
 
A 104-week rat inhalation toxicology study to assess the carcinogenic potential of ascending doses of 
aztreonamdemonstrated no drug-related increase in malignant tumours. 
 
Genotoxicity (Chromosomal aberration and mouse lymphoma mutation assay) studies with aztreonam 
were negative. 
 
Fertility, teratology, perinatal and postnatal studies were conducted with aztreonam for i.v. injection in 
rats at daily doses up to 750 mg/kg without adverse effects.  The survival rate during the lactation 
period was slightly reduced in the offspring of rats that received the highest dose. 



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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder  
 
L-Lysine 
 
Solvent  
 
Sodium chloride 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
Powder vial:  4 years. 
 
Solvent:  3 years. 
 
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. 
 
6.4 Special precautions for 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. 
 
For storage conditions of the reconstitued medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Powder vial: Type I amber glass vial with siliconised grey rubber stopper and aluminium tear off 
overseal with a blue cap. 
 
Solvent: 1 ml low density polyethylene ampoule. 
 
Each 28-day pack of Cayston contains 84 vials of lyophilised aztreonam and 88 solvent ampoules.  
The four additional solvent ampoules are provided in case of spillage. 
 
The following pack sizes are available: 
• 28-day pack of Cayston 
• Pack containing one 28-day pack of Cayston plus one Altera Nebuliser Handset 
 
Not all pack sizes may be marketed. 
 



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6.6 Special precautions for disposal and other handling 
 
Reconstitution 
 
Cayston should only be reconstituted with the solvent provided.  Following reconstitution, Cayston is 
a clear, colourless to slightly coloured solution. 
 
It is recommended that Cayston be administered immediately after reconstitution with solvent.  
Cayston should not be reconstituted until a dose is ready to be administered.  One glass vial containing 
Cayston is opened by carefully removing the blue cap and the metal ring, and then the grey rubber 
stopper.  The liquid is squeezed out of one solvent ampoule into the glass vial.  The vial is then gently 
swirled until contents have completely dissolved.  The reconstituted Cayston is then poured into the 
Altera Nebuliser Handset and the dose administered. 
 
Cayston is administered by inhalation over a 2 to 3 minute period, using a Cayston specific Altera 
Nebuliser Handset and Altera Aerosol Head connected to an eBase Controller or an eFlow rapid 
Control Unit.  Cayston should not be used with any other type of handset or aerosol head.  Cayston 
should not be mixed with any other medicinal products in the Altera Nebuliser Handset.  Do not put 
other medicinal products in the Altera Nebuliser Handset. 
 
Do not reconstitute or mix Cayston with any other solvent or medicinal product.  Do not reconstitute 
more than one dose at a time.  Any unused product or waste material should be disposed of in 
accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/543/001 
EU/1/09/543/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 September 2009 
Date of latest renewal: 26 May 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
 

http://www.ema.europa.eu/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



15 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Gilead Sciences Ireland UC 
IDA Business & Technology Park 
Carrigtohill 
County Cork 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 
 
 



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CAYSTON OUTER CARTON 
(With a Blue box - Not for co-packaging with the Altera Nebuliser Handset) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cayston 75 mg powder and solvent for nebuliser solution 
aztreonam 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each powder vial contains 75 mg aztreonam. 
After reconstitution, each ml of the nebuliser solution contains 75 mg aztreonam (as lysine). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder vial also contains L-Lysine 
 
Solvent ampoule contains sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for nebuliser solution 
 
84 single-use vials 
88 single-use 1 ml ampoules of solvent 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For inhalation use only.  Reconstitute before use. 
 
Powder should only be mixed with the solvent provided. 
 

 
Step A: With the blue cap tab facing toward you, place the vial on a flat surface. Using one hand to 
hold the vial steady, use the other hand to slowly flip up the blue cap 
 



19 

 
Step B: Pull the blue cap down to a flat (horizontal) position (where the bottom of the blue cap faces 
up), to prepare the metal seal for removal. Do not completely tear through the metal seal. 
 

 
Step C: While continuing to hold the vial steady with one hand, use the other hand to slowly pull the 
blue cap in a counterclockwise direction. Do not twist the blue cap. 
 

 
Step D: When the metal seal opens, continue to slowly pull on the blue cap in a counterclockwise 
direction until the metal seal is completely removed. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  May be stored outside a refrigerator but below 25°C for up to 28 days. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



20 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/543/001: 28-day pack of Cayston 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cayston 75 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 
 



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
(Outer carton containing one 28-day pack of Cayston and one Altera Nebuliser Handset with a 
Blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cayston 75 mg powder and solvent for nebuliser solution 
aztreonam 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each powder vial contains 75 mg aztreonam. 
After reconstitution, each ml of the nebuliser solution contains 75 mg aztreonam (as lysine). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder vial also contains L-Lysine 
 
Solvent ampoule contains sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for nebuliser solution 
 
84 single-use vials 
88 single-use 1 ml ampoules of solvent 
 
This pack contains one Altera Nebuliser Handset. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For inhalation use only.  Reconstitute before use. 
 
Powder should only be mixed with the solvent provided. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



22 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  May be stored outside a refrigerator but below 25°C for up to 28 days. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/543/002: 28-day pack of Cayston plus one Altera Nebuliser Handset 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cayston 75 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 



23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CAYSTON OUTER CARTON 
(No Blue box - for use only for co-packaging with Altera Nebuliser Handset) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cayston 75 mg powder and solvent for nebuliser solution 
aztreonam 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each powder vial contains 75 mg aztreonam. 
After reconstitution, each ml of the nebuliser solution contains 75 mg aztreonam (as lysine). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder vial also contains L-Lysine 
 
Solvent ampoule contains sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for nebuliser solution 
 
84 single-use vials 
88 single-use 1 ml ampoules of solvent 
 
This pack is not to be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For inhalation use only.  Reconstitute before use. 
 
Powder should only be mixed with the solvent provided. 
 

 
Step A: With the blue cap tab facing toward you, place the vial on a flat surface. Using one hand to 
hold the vial steady, use the other hand to slowly flip up the blue cap 
 



24 

 
Step B: Pull the blue cap down to a flat (horizontal) position (where the bottom of the blue cap faces 
up), to prepare the metal seal for removal. Do not completely tear through the metal seal. 
 

 
Step C: While continuing to hold the vial steady with one hand, use the other hand to slowly pull the 
blue cap in a counterclockwise direction. Do not twist the blue cap. 
 

 
Step D: When the metal seal opens, continue to slowly pull on the blue cap in a counterclockwise 
direction until the metal seal is completely removed. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  May be stored outside a refrigerator but below 25°C for up to 28 days. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



25 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/543/002: 28-day pack of Cayston plus one Altera Nebuliser Handset 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cayston 75 mg 



26 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CAYSTON INNER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cayston 75 mg powder and solvent for nebuliser solution 
aztreonam 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each powder vial contains 75 mg aztreonam. 
After reconstitution, each ml of the nebuliser solution contains 75 mg aztreonam (as lysine). 
 
 
3. LIST OF EXCIPIENTS 
 
Powder vial also contains L-Lysine 
 
Solvent ampoule contains sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for nebuliser solution 
 
42 single-use vials 
44 single-use 1 ml ampoules of solvent 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For inhalation use only.  Reconstitute before use. 
 
Powder should only be mixed with the solvent provided. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



27 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  May be stored outside a refrigerator but below 25°C for up to 28 days. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/543/001: 28-day pack of Cayston 
EU/1/09/543/002: 28-day pack of Cayston plus one Altera Nebuliser Handset 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cayston 75 mg 
 



28 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Cayston VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Cayston 75 mg powder for nebuliser solution 
aztreonam 
 
For inhalation use only. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
75 mg 
 
 
6. OTHER 
 
GILEAD 



29 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SOLVENT AMPOULE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Cayston 
Sodium Chloride 0.17% 
 
 
2. METHOD OF ADMINISTRATION 
 
Inhalation use only 
 
 
3. EXPIRY DATE 
 
 
4. BATCH NUMBER 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 
GILEAD SCIENCES 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



31 

Package leaflet: Information for the user 
 

Cayston 75 mg powder and solvent for nebuliser solution 
Aztreonam 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet.  You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only.  Do not pass it on to others.  It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist.  This includes any possible side 

effects not listed in this leaflet.  See section 4. 
 
What is in this leaflet: 
1. What Cayston is and what it is used for 
2. What you need to know before you take Cayston 
3. How to take Cayston 
4. Possible side effects 
5. How to store Cayston 
6. Contents of the pack and other information 
 
 
1. What Cayston is and what it is used for 
 
Cayston contains the active substance aztreonam. Caystonis an antibiotic used to suppress chronic 
lung infection caused by the bacteria Pseudomonas aeruginosa in patients aged 6 years and older with 
cystic fibrosis.  Cystic fibrosis, also known as mucoviscidosis, is a life-threatening inherited disease 
that affects the mucus glands of internal organs, especially the lungs, but also of the liver, pancreas, 
and the digestive system.  Cystic fibrosis in the lungs leads to clogging them with thick sticky mucus.  
This makes it hard to breathe. 
 
 
2. What you need to know before you take Cayston 
 
Do not take Cayston 
 
- if you are allergic to aztreonam or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
 
Talk to your doctor before taking Cayston: 
- if you are allergic to any other antibiotics (such as penicillins, cephalosporins, and/or 

carbapenems) 
- if you do not tolerate or have chest tightness from taking other inhaled medicines 
- if you have kidney problems 
- if you have ever coughed up any blood 
- if you have ever had low lung function tests. 
If any of these apply to you tell your doctor before using Cayston. 
 
As an inhaled medicine, Cayston could cause you to cough and this could lead to coughing up blood.  
If you have ever coughed up blood you should only use Cayston if your doctor thinks the benefit of 
taking this medicine outweighs the risk of coughing up blood. 
 
You may get a temporary lowering of lung function test result during treatment with Cayston, but this 
is typically not a lasting effect. 



32 

 
Children 
 
Cayston is not for use in children under the age of 6 years. 
 
Other medicines and Cayston 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
There are no clinical data on the use of Cayston in pregnant women, therefore you should not take 
Cayston during pregnancy unless specifically discussed with your doctor. 
 
If you plan to breast-feed ask your doctor for advice before taking Cayston.  You can breast-feed 
during treatment with Cayston because the amount of Cayston likely to be passed to your child during 
breast-feeding will be extremely small. 
 
Driving and using machines 
 
Cayston is not expected to affect your ability to drive or use machines. 
 
 
3. How to take Cayston 
 
Always take this medicine exactly as your doctor has told you.  Check with your doctor or pharmacist 
if you are not sure. 
 
The recommended dose is: 
 
- Take Cayston 3 times a day in repeated cycles of 28 days on therapy followed by 28 days 

off Cayston therapy.  Each of the three doses should be taken by inhalation at least four hours 
apart, using an Altera Nebuliser Handset.  You can use either an eBase Controller or an eFlow 
rapid Control Unit with the Altera Handset. 

 
- Each dose consists of one vial of Cayston mixed with one ampoule of solvent.  Cayston needs to 

be mixed with a solvent before being inhaled through the Altera Nebuliser. 
 
Put the prepared Cayston solution in the Altera Nebuliser Handset (see below).  Each treatment takes 
about 2 to 3 minutes to inhale. 
 
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. 
 
If you are using other inhaled therapies to treat cystic fibrosis, the recommended order of use is as 
follows: 
 
1. bronchodilator 
2. mucolytics (a medicine that helps to dissolve the thick mucous produced in the lungs) 
and finally: 
3. Cayston. 
 



33 

Do not mix Cayston with any other medicines in the Altera Nebuliser Handset. 
- Do not put other medicines in the Altera Nebuliser Handset. 
- Do not put the intravenous (injectable) form of aztreonam in the Altera Nebuliser Handset.  

Intravenous aztreonam is not suitable for inhalation. 
 
How to take Cayston using the Altera Nebuliser Handset 
 
You will need the following: 
 One amber-coloured vial of Cayston with a blue cap. 
 One plastic ampoule of solvent (0.17% w/v sodium chloride).  The information that appears on 

the solvent ampoule is provided in English only (see section 6). 
 An Altera Nebuliser Handset containing an Altera Aerosol Head connected to an eFlow Control 

Unit of the type 178 (eFlow rapid) or type 678 (eBase Controller). 
 
You must use the Cayston specific Altera Nebuliser Handset containing an Altera Aerosol Head.  
Do not try to take Cayston using any other type of nebuliser handset (including the eFlow rapid 
handset). 
 
Check that your nebuliser works properly before starting your treatment with Cayston.  Read the 
manufacturer’s instructions for use provided with your Altera Nebuliser System carefully. 
 
Preparing your Cayston for inhalation 
 
- Do not prepare Cayston until you are ready to administer a dose. 
- Do not use Cayston if you notice that the package has been tampered with. 
- Do not use Cayston if it has been stored outside a refrigerator for more than 28 days. 
- Do not use the solvent or prepared Cayston if it is cloudy or if there are particles in the solution. 
 
1. Take one amber vial of Cayston and one ampoule of solvent from the box.  Solvent ampoules 

must be separated by gently pulling them apart. 
 
2. Gently tap the amber vial containing the Cayston so that the powder settles at the bottom.  This 

helps to ensure that you get the proper dose of medicine. 
 
3. Follow Step A to D in Figure 1 below to open the amber vial: 
 

  

Step A: With the blue cap tab facing toward 
you, place the vial on a flat surface. Using one 
hand to hold the vial steady, use the other hand 
to slowly flip up the blue cap. 

Step B: Pull the blue cap down to a flat 
(horizontal) position (where the bottom of the 
blue cap faces up), to prepare the metal seal for 
removal. Do not completely tear through the 
metal seal. 



34 

  

Step C: While continuing to hold the vial 
steady with one hand, use the other hand to 
slowly pull the blue cap  in a counterclockwise 
direction. Do not twist the blue cap. 

Step D: When the metal seal opens, continue to 
slowly pull on the blue cap in a 
counterclockwise direction until the metal seal 
is completely removed. 

Figure 1 
 
4.   Safely dispose of the metal seal.  Carefully remove (but do not yet discard) the rubber stopper. 
 
5. Open the ampoule of solvent by twisting off the tip.  Squeeze out the contents completely into the 

vial (Figure 2).  Next, gently swirl the vial until the powder has completely dissolved and the liquid 
is clear. 

 
It’s best to use Cayston immediately after you have made up the solution.  But, if you cannot use 
the prepared dose straight away, replace the stopper in the vial and store in a refrigerator.  Use the 
prepared solution within 8 hours. 

 

 
Figure 2 

 
Preparing the Altera Nebuliser to take your Cayston 
 
1. Make sure the Altera Nebuliser Handset is on a flat, stable surface. 
 
2. Remove the medicine cap by twisting anticlockwise. 
 
3. Pour all of the prepared Cayston from the vial into the Altera Nebuliser Handset medicine 

reservoir (Figure 3a).  Be sure to completely empty the vial.  Gently tap the vial against the side of 
the medicine reservoir if necessary. 

 
4. Close the medicine reservoir by aligning the tabs of the medicine cap with the slots on the 

reservoir.  Press down and turn the cap clockwise as far as it will go (Figure 3b). 
 



35 

 
 

 
Using the Altera Nebuliser to take your Cayston 
 
1. Begin your treatment.  Sit in a relaxed, upright position.  Hold the handset level and place the 

mouthpiece in your mouth and close your lips around it (Figure 4). 
 

 
 

Keep the handset level. 
 
2. Press and hold the On/Off button on the Control Unit for a few seconds.  You will hear one 

“beep” and the status light will turn green. 
 

3. After a few seconds, an aerosol mist will begin to flow into the Aerosol Chamber of the Altera 
Nebuliser Handset.  If aerosol mist does not begin to flow, please refer to the Altera manual for 
information. 

 
4. Breathe normally (inhale and exhale) through the mouthpiece.  Avoid breathing through your 

nose.  Continue to inhale and exhale comfortably until the treatment is finished. 
 
5. When all of the medicine has been delivered, you will hear a tone that means “treatment 

complete” (2 beeps). 
 

Figure 4 
 

      Figure 3a      Figure 3b 



36 

6. When treatment is complete, open the medicine cap to ensure that all medicine has been used.  A 
few drops of medicine may remain in the reservoir at the end of treatment.  If there is more than a 
few drops of liquid left, replace the medicine cap and restart treatment. 

 
7. Once treatment is complete, disconnect the Control Unit and take apart the Altera Nebuliser 

Handset for cleaning and disinfecting.  For complete details on cleaning and disinfecting refer to 
the manufacturer’s instructions for use provided with your Altera Nebuliser Handset. 

 
What if I need to stop my treatment before I’ve finished? 

8. If for any reason you must stop the treatment before you have finished, press and hold the On/Off 
button for one full second.  To re-start the treatment, press and hold the On/Off button for one full 
second and then restart the treatment. 

 
Replacing the Altera Nebuliser Handset 
 
The Altera Nebuliser Handset is designed to last for three 28-day courses of Cayston when used as 
directed.  After this time replace your Altera Nebuliser Handset, including the aerosol head.  If you 
notice that the performance has changed before this time (for instance, if it takes longer to produce a 
mist, more than 5 minutes), please refer to the Altera Nebuliser instructions for use. 
 
If you take more Cayston than you should 
 
If you have taken more Cayston than you should, talk to a doctor or pharmacist immediately. 
 
If you forget to take Cayston 
 
If you miss a dose, you can still take all 3 daily doses as long as they are at least 4 hours apart.  If you 
can’t leave a gap of 4 hours just skip the missed dose. 
 
If you stop taking Cayston 
 
Do not stop taking Cayston without first talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you get a rash, tell your doctor immediately because this could mean that you have an allergic 
reaction to Cayston. 
 
Very common side effects (affects more than 1 user in 10) 
- Cough 
- Blocked nose 
- Wheezing 
- Sore throat 
- Shortness of breath 
- High temperature.  This may be more common in children than in adults. 
 
Common side effects (affects 1 to 10 users in 100) 
- Difficulty breathing 
- Chest discomfort 
- Runny nose 
- Coughing up blood 
- Rash 



37 

- Joint pain 
- Lower lung function test results 
 
Uncommon side effects (affects 1 to 10 users in 1000) 
- Joint swelling 
 
The following side effects have been observed after the use of aztreonam for injection, but not after 
taking Cayston: swelling of the face, lips, tongue and/or throat with difficulty in swallowing or 
breathing, sweating, skin irritation and flaking, itchy rash, flushing, small red spots and very rarely, 
blistering of the skin.  All these may be signs of an allergic reaction. 
 
Tell your doctor if you have any of these effects. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist.  This includes any possible side effects 
not listed in this leaflet.  You can also report side effects directly via the national reporting system 
listed in Appendix V.  By reporting side effects you can help provide more information on the safety 
of this medicine. 
 
 
5. How to store Cayston 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the vial label, solvent ampoule and 
the carton.  The expiry date refers to the last day of that month. 
 
Powder vial and solvent ampoule: 
Store in a refrigerator (2°C - 8°C).  The unopened vials may also be stored outside the refrigerator but 
below 25°C for up to 28 days. 
 
Use this medicine immediately after preparation.  If not used immediately, the prepared solution must 
be stored at 2°C - 8°C and used within 8 hours.  Do not prepare more than one dose at a time. 
 
Do not use this medicine if you notice that the package has been tampered with. 
 
Do not use this medicine if it has been stored outside a refrigerator for more than 28 days. 
 
Do not throw away any medicines via wastewater or household waste.  Ask your pharmacist how to 
throw away medicines you no longer use.  These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Cayston and the solvent contain 
 
- The powder vial contains 75 mg aztreonam (as lysine). 
- The solvent ampoule contains water for injections and sodium chloride.  The ampoule is 

imprinted in English only.  The information that appears on the ampoule is presented below: 
 

Solvent for Cayston 
Sodium Chloride 0.17% 
Inhalation use only 
1 ml 
GILEAD SCIENCES 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


38 

What Cayston looks like and contents of the pack 
 
Cayston is a white to off-white powder and solvent for nebuliser solution. 
 
Cayston is contained in a 2 ml amber glass vial with a grey rubber stopper and aluminium tear-off 
overseal with a blue cap. 
 
The 1 ml solvent is contained in a plastic ampoule. 
 
Each 28-day pack of Cayston contains 84 vials of lyophilised Cayston and 88 solvent ampoules.  The 
four additional solvent ampoules are provided in case of spillage. 
 
The following pack sizes are available: 
• 28-day pack of Cayston 
• Pack containing one 28-day pack of Cayston plus one Altera Nebuliser Handset 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
Manufacturer: 
 
Gilead Sciences Ireland UC 
IDA Business & Technology Park 
Carrigtohill 
County Cork 
Ireland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Gilead Sciences Belgium SPRL-BVBA 
Tél/Tel: + 32 (0) 2 401 35 50 
 

Lietuva 
Gilead Sciences Poland Sp. z o.o. 
Tel: + 48 22 262 8702 
 

България 
Gilead Sciences Ireland UC 
Teл.:  + 353 (0) 1 686 1888 
 

Luxembourg/Luxemburg 
Gilead Sciences Belgium SPRL-BVBA 
Tél/Tel: + 32 (0) 2 401 35 79 
 

Česká republika 
Gilead Sciences s.r.o. 
Tel: + 420 910 871 986  
 

Magyarország 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

Danmark 
Gilead Sciences Sweden AB 
Tlf: + 46 (0) 8 5057 1849 
 

Malta 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

Deutschland 
Gilead Sciences GmbH 
Tel: + 49 (0) 89 899890-0 
 

Nederland 
Gilead Sciences Netherlands B.V. 
Tel: + 31 (0) 20 718 36 98 
 



39 

Eesti 
Gilead Sciences Poland Sp. z o.o. 
Tel: + 48 22 262 8702 
 

Norge 
Gilead Sciences Sweden AB 
Tlf: + 46 (0) 8 5057 1849 
 

Ελλάδα 
Gilead Sciences Ελλάς Μ.ΕΠΕ. 
Τηλ: +30 210 8930 100 
 

Österreich 
Gilead Sciences GesmbH 
Tel: + 43 1 260 830 
 

España 
Gilead Sciences, S.L. 
Tel: + 34 91 378 98 30 
 

Polska 
Gilead Sciences Poland Sp. z o.o. 
Tel: + 48 22 262 8702 
 

France 
Gilead Sciences 
Tél: + 33 (0) 1 46 09 41 00 
 

Portugal 
Gilead Sciences, Lda. 
Tel: + 351 21 7928790 
 

Hrvatska 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

România 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

Ireland 
Gilead Sciences Ireland UC 
Tel: +353 (0) 214 825 999 
 

Slovenija 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

Ísland 
Gilead Sciences Sweden AB 
Sími: + 46 (0) 8 5057 1849 
 

Slovenská republika 
Gilead Sciences Slovakia s.r.o 
Tel: + 421 232 121 210 
 

Italia 
Gilead Sciences S.r.l. 
Tel: + 39 02 439201 
 

Suomi/Finland 
Gilead Sciences Sweden AB 
Puh/Tel: + 46 (0) 8 5057 1849 
 

Κύπρος 
Gilead Sciences Ελλάς Μ.ΕΠΕ. 
Τηλ: + 30 210 8930 100 
 

Sverige 
Gilead Sciences Sweden AB 
Tel: + 46 (0) 8 5057 1849 
 

Latvija 
Gilead Sciences Poland Sp. z o.o. 
Tel: + 48 22 262 8702 
 

United Kingdom 
Gilead Sciences Ltd 
Tel: + 44 (0) 8000 113700 
 

 
This leaflet was last revised in . 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET