Components:
Method of action:
Treatment option:
Medically reviewed by Militian Inessa Mesropovna, PharmD. Last updated on 22.03.2022
Attention! Information on this page is intended only for medical professionals! Information is collected in open sources and may contain significant errors! Be careful and double-check all the information on this page!
Top 20 medicines with the same components:
Cayston 75 mg powder and solvent for nebuliser solution.
Each vial contains aztreonam lysine equivalent to 75 mg aztreonam. After reconstitution the nebuliser solution contains 75 mg aztreonam.
Powder and solvent for nebuliser solution.
White to off-white powder.
WHAT AZACTAM IS AND WHAT IT IS USED FOR
Azactam is an antibiotic of the monobactam group.
Antibiotics are used to treat bacterial infections and are not used to treat viral infections such as flu or cold.
It is important that you follow the instructions regarding the dose, the interval of administration and the duration of treatment indicated by your doctor.
Do not store or reuse this medicine. If after the end of the treatment you have any antibiotic left, return it to the pharmacy for proper disposal. You should not throw medicines down the drain or into the trash.
HOW TO TAKE AZACTAM
Follow exactly the instructions for Azactam given by your doctor. Consult your doctor or pharmacist if you have any doubts.
Azactam is administered by intramuscular injection, and intravenously. For preparation instructions, see Section 6 below.
Intravenous use is recommended in patients requiring unit doses greater than 1 g or suffering from bacterial sepsis, localized parenchymal abscesses (e.g. intra-abdominal abscesses), peritonitis and other serious or life-threatening systemic infections. Due to the serious nature of infections caused by Pseudomonas aeruginosa, in systemic infections produced by this microorganism a dose of 2 g is recommended every 6 or 8 hours, at least at the beginning of treatment.
Your doctor will tell you the duration of your treatment. Do not stop treatment without consulting your doctor first.
Your doctor will determine the appropriate dose and frequency of Azactam depending on the severity of your infection.
In adults the usual dosing guidelines are:
| Type of infection | Dose* | Frequency (hours) |
| Urinary tract infections | 500 mg or 1 g | 8 or 12 |
| Moderately severe systemic infections | 1 g or 2 g | 8 or 12 |
| Serious or life-threatening systemic infections | 2 g | 6 or 8 |
* The maximum recommended dose in adults is 8 g per day.
A single dose of 1 g administered intramuscularly is effective in the treatment of uncomplicated acute gonorrhea and uncomplicated acute cystitis.
If you have kidney failure or are an elderly patient, your doctor will adjust the dose based on the creatinine clearance value.
In patients with transient or persistent renal impairment, following a normal initial dose, the maintenance dose of Azactam should be halved in patients with an estimated creatinine clearance between 10 and 30 ml / min / 1.73 m2.
In patients with severe renal impairment, with creatinine clearance values less than 10 ml/min/1.73 metro2 (for example, patients undergoing haemodialysis), normal doses should be given initially. Maintenance doses should be one quarter of the initial dose, administered at fixed intervals of 6, 8 or 12 hours. In severe or life-threatening infections, one-eighth of the initial dose should be given after each haemodialysis in addition to the designated maintenance doses.
If you suffer from chronic liver disease with cirrhosis your doctor may recommend a dose reduction of 20-25%, especially in cases of alcoholic cirrhosis and when kidney function is also impaired.
Paediatric population
In children, the usual dosage in patients older than 1 Week is 30 mg/kg every 6 to 8 hours. To treat severe infections in patients 2 years of age or older, a dose of 50 mg / kg each 6 a 8 hours. The recommended dose for all pediatric patients in the treatment of infections caused by P. aeruginosa is 50 mg/kg each 6 a 8 hours. The maximum daily dose should not exceed the maximum dose recommended for adults.
If you think the action of Azactam is too strong or weak, tell your doctor or pharmacist.
If you use more Azactam than you should
If you receive more than the prescribed dose of Azactam, and despite the fact that you are unlikely to suffer severe poisoning, go to the doctor as soon as possible or contact the Emergency Department of the nearest Hospital. If necessary, aztreonam can be removed from the serum by haemodialysis and/or peritoneal dialysis.
Overdose of this drug can cause encephalopathy, which can lead to confusion, loss of consciousness, epilepsy and movement disorders.
In case of overdose or accidental ingestion immediately consult your doctor or pharmacist or call the toxicological information service, telephone: 91 562 04 20, indicating the drug and the amount ingested.
If you forgot to use Azactam
A double dose should not be given to make up for forgotten doses.
Consult your doctor. The doctor will determine what will be the actions to follow.
If you have any other questions about the use of this product, ask your doctor or pharmacist.
POSSIBLE SIDE EFFECTS
Like all medicines, this medicine it can cause side effects, although not all people suffer from them.
Adverse effects are classified according to their frequency of appearance: very common (affect more than 1 in 10 people), common (may affect up to 1 in 10 people), uncommon (may affect up to 1 in 100 people), rare (may affect up to 1 in 1000 people), very rare (may affect up to 1 in 10,000 people) and not known (cannot be estimated from the available data).
Uncommon: increased blood creatinine.
Rare: vaginal infection, vaginal candidiasis (fungal infection), increase or decrease in the number of platelets and white blood cells, decrease in the number of red blood cells, increase in blood clotting time, Coombs test positive, seizures, paresthesia (tingling), dizziness, headache, confusion, lack of sleep, double vision, vertigo, ringing in the ears, a drop in blood pressure, bleeding, dyspnea (difficulty breathing), sneezing, nasal congestion, wheezing, gastrointestinal bleeding, pseudomembranous colitis (inflammation of the colon) with diarrhoea), bad breath, hepatitis (inflammation of the liver), jaundice (yellowing of the skin and mucous membranes), muscle pain, tenderness, fever, malaise, fatigue, chest pain, changes on the electrocardiogram.
Reporting of adverse effects
If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is possible side effects that are not listed in this leaflet. You can also communicate them directly through Spanish pharmacovigilance system for Medicinal Products for Human Use: www.notificaram.es. By reporting side effects you can help provide more information about the safety of this medicine.
BEFORE YOU TAKE AZACTAM
Do not use Azactam
If you are allergic (hypersensitive) to aztreonam or any of the other ingredients of Azactam.
Warnings and precautions
If you are allergic to penicillins, cephalosporins and/or carbapenems, you should only use Azactam with extreme caution, in the event that the expected benefit justifies the risk of a hypothetical serious allergic reaction. In case you notice any allergic reaction, you should stop taking Azactam and consult your doctor, as certain measures may need to be taken.
You should tell your doctor if you have impaired kidney or liver function, as you will need adequate follow-up during treatment. If Azactam is given to elderly people, who often have renal impairment, the doctor will conduct the necessary studies to determine the appropriate dose.
You should tell your doctor if you experience significant blood or skin changes during treatment with Azactam, as it may be necessary to stop it.
In some rare cases, seizures have been reported during treatment with aztreonam, which usually reverse during treatment. If you experience seizures during treatment with aztreonam, consult your doctor.
If you suffer from diarrhea during treatment or up to two months later, you should also inform your doctor, who will take appropriate measures.
If you are taking oral anticoagulants, tell your doctor, as some adjustments in the dose of these oral anticoagulants may be necessary. Some cases of increased activity of oral anticoagulants have been reported in patients treated with antibiotics. In connection with this, the presence of severe inflammation or infection, age and general condition of the patient appear to be risk factors.
If you are using an aminoglycoside antibiotic during treatment with this medicine, your doctor will monitor your kidney function, due to the possible toxicity to the kidneys and ears of these antibiotics.
The use of beta-lactam antibiotics, such as this drug, can lead to a risk of encephalopathy that can lead to confusion, loss of consciousness, epilepsy and movement disorders, especially in patients with renal insufficiency and in case of overdose.(see Sections 3 and 4).
Treatment with Azactam may interfere with some analytical determinations (increase in blood transaminases and false positive for glucose in urine), as well as positive results in a direct or indirect Coombs test (blood test used to detect some types of disease from the detection of the presence of antibodies).
Children and adolescents
The effectiveness and safety of Azactam in newborns less than 1 Week has not been established.
Other medicines and Azactam
Tell your doctor or pharmacist if you are using or have recently used other medicines, including those purchased without a prescription, as it may be necessary to stop treatment or adjust the dose of any of them.
In particular, you should tell your doctor if you are being treated with other antibiotics (used for the treatment of infections) oral gold anticoagulants.
Your doctor should monitor you appropriately when anticoagulants are administered concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the appropriate level of coagulation.
If you use an aminoglycoside antibiotic during treatment with Azactam, your doctor will monitor your kidney function, due to the possible toxicity to the kidneys and ears of these antibiotics.
Some antibiotics (such as cefoxitin and imipenem) counteract the effect of many beta-lactam antibiotics, including aztreonam, on the treatment of some bacteria.
Tell your doctor if you are taking probenecid (used to treat gout) or Furosemide (a diuretic used to treat hypertension) at the same time, as co-administration with these medicines may lead to an increase in aztreonam serum levels.Pregnancy, lactation and fertility
If you are pregnant or breastfeeding, think you may be pregnant or intend to become pregnant, see to your doctor or pharmacist before using this medicine. Tell your doctor if you are pregnant or plan to become pregnant. Azactam it should not be administered during pregnancy, unless the expected benefit justifies the possible risk.
Tell your doctor if you are breast-feeding. Aztreonam is excreted in very small amounts in human milk, accordingly, temporary cessation of lactation during treatment with this drug should be considered.
Driving and using machines
This medicine may have a significant influence on the ability to drive and use machinery, in particular due to the possible occurrence of encephalopathies (which can lead to confusion, seizures or abnormal movements) (see Sections 3-if you use more Azactam than you should and 4).
Azactam contains arginine.
Studies in infants born with low birth weight have shown that arginine given with this medicine may result in increases in insulin, indirect bilirubin and serum arginine.
The consequences of this component in newborns treated with aztreonam they have not been established with certainty. Therefore, use in newborns should be carefully evaluated
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.
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.
Cayston has no or negligible influence on the ability to drive or use machines.
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.
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).
|
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 c. 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).
Haemoptysis
Inhalation of nebulised solutions may induce a cough reflex which could aggravate underlying conditions.
Allergic reactions
Rash has been reported with the use of Cayston and may be indicative of an allergic reaction to aztreonam.
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.
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:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
or search for MHRA Yellow Card in the Google Play or Apple App Store
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: [email protected]
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal
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.
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, 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 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.
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).
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.
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.
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.
Powder
L-Lysine
Solvent
Sodium chloride
Water for injections
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
HOW TO STORE AZACTAM
Keep this medicine out of the sight and reach of children.
Before opening the vial: store in the original packaging. Do not store above 25 ° C.
Do not use this medicine after the expiration date which is stated on the carton.
After the first opening/reconstitution with the corresponding diluent: the solution is stable up to 48 hours at controlled room temperature (15ºC-30ºC) and for 7 days in a refrigerator (between 2ºC and 8ºC).
However, from a microbiological point of view, once opened, the product should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user.
The medicines should not be thrown down drains or into the trash. Ask your pharmacist how to get rid of the packaging and medicines that no longer need. In this way, it will help protect the environment.
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.
Powder vial: Type I amber glass vial with siliconised grey rubber stopper and aluminium tear off overseal with or without 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.
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 tearing and flipping up the blue cap or lifting up the metal flap, the metal ring is removed by carefully pulling the flap (tweezers or small pliers may be used to remove the metal ring if necessary) and the grey rubber stopper removed. 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.
Gilead Sciences Ireland UC
Carrigtohill
County Cork, T45 DP77
Ireland
EU/1/09/543/001
EU/1/09/543/002
Date of first authorisation: 21 September 2009
Date of latest renewal: 26 May 2016
05/2018
