Reasons for adding or updating:

• Change to section 2 - Qualitative and quantitative composition
• Change to section 3 - Pharmaceutical form
• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.7 - Effects on ability to drive and use machines
• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 5.3 - Preclinical safety data
• Change to section 6.5 - Nature and contents of container
• Change to section 9 - Date of first authorisation/renewal of the authorisation
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 01-May-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



·         Section 2

o   Qualitative & Quantitative text reduced

·         Section 3

o   ‘lyphilised’ removed

·         Section 4.2

o   Inclusion of sentence describing dosing for children 6 years and older which is the same as adults

o   Text describing the paediatric population re-worded

o   The word ‘Elderly’ replaces ‘Older people’ throughout the SmPC

·         Section 4.4 & 4.5

o   In some cases, Cayston is replaced with aztreonam. This occurs throughout the SmPC

 

·         Section 4.7

o   Wording has been reduced and simply says ‘Cayston has no or negligible influence on the ability to drive or use machines’

·         Section 4.8

o   Removal of text describing the patient population & dosing regimen in the  Phase 3 trials

o   In some cases, Cayston is replaced with aztreonam. This occurs throughout the SmPC

 

·         Section 4.8

o   In some cases, Cayston is replaced with aztreonam. This occurs throughout the SmPC

·         Section 5.1, 5.2, 5.3, 6.5

o   In some cases, Cayston is replaced with aztreonam. This occurs throughout the SmPC

·         Section 9

o   Date of latest renewal updated

 

·         Section 10

o   Date of revision updated

Reasons for adding or updating:

• Change to section 6.3 - Shelf life
• Change to section 7 - Marketing authorisation holder
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 03-Aug-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

• Section 6.3: Shelf life reduced from 4 to 3 years for the solvent ampoule
• Section 7: Minor correction of the name of the marketing authorisation holder (MAH)
• Section 10: Change to the date of revision to August 2015

Reasons for adding or updating:

• Change to section 6.5 - Nature and contents of container
• Change to section 6.6 - Special precautions for disposal and other handling
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 03-Nov-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

• Sections 6.5 & 6.6: Addition of an alternative flip tear-off seal for drug product vials

• Section 10: Change to the date of revision to November 2014

Reasons for adding or updating:

• Change to section 5.2 - Pharmacokinetic properties

Date of revision of text on the SPC: 02-Jun-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

- Minor amendment to section 5.2; which now states that protein binding of aztreonam in plasma is approximately 77% within the clinical dose range at clinically relevant plasma concentrations.

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 02-Jun-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

• Deletion of the marked text below in sections 4.4 and 4.8 of the SmPC:

“The following rare and severe adverse reactions have not been observed to date with Cayston, but have been reported after parenteral use of other aztreonam containing products: toxic epidermal necrolysis, anaphylaxis, purpura, erythema multiforme, exfoliative dermatitis, urticaria, petechiae, pruritus, diaphoresis.”

• Change to the date of revision to June 2014 in section 10

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 01-May-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

• Update of the SmPC sections 4.2, 4.4, 4.8, 5.1 and 5.2 in order to reflect study results obtained in open-label phase 2 trial GS-US-205-0162 [to evaluate the safety and efficacy of aztreonam 75 mg powder in paediatric patients with Cystic Fibrosis (CF) and new onset lower respiratory tract culture positive for Pseudomonas aeruginosa (PA)]

• Change to the date of revision to May 2014

Reasons for adding or updating:

• Change to section 5.2 - Pharmacokinetic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 03-Mar-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 5.2: Inclusion of the following protein binding data in section 5.2 of the SmPC (Distribution): “The protein binding of aztreonam in plasma is approximately 77% at clinically relevant plasma concentrations.”
Section 10: Date changed for the date of revision.

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.8 - Undesirable Effects
• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 5.2 - Pharmacokinetic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Jul-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



- Section 4.1 - Indication change to include paediatric patients aged 6 years and older

- Section 4.2 – For multiple inhaled therapies, the recommended order of administration is 1. bronchodilator, 2. mucolytics, 3. Cayston

- Section 4.2 – Inclusion of statement that Cayston may be taken in repeated cycles of 28 days on therapy followed by 28 days off Cayston therapy

- Section 4.2 – Amendment in the paediatric population section to now state that Cayston is indicated in children aged 6 years and older. The safety and efficacy of Cayston in children younger than 6 years of age has not been established. The dosing in children aged 6 years and older is the same as for adults. Dosage is not based on weight or adjusted for age

- Section 4.2 – For the method of administration, 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

- Section 4.4 – Inclusion of information on haemoptysis

- Section 4.4 – Addition of statement that efficacy has not been established in patients with FEV₁ >75% predicted

- Section 4.4 – Information on resistance to aztreonam, other antibiotics and treatment emergent microorganisms with data from the 24 week active controlled study of Cayston therapy

- Section 4.8 – Assessment of adverse reactions based on experience in four phase 3 clinical studies involving CF patients (n=539) and post marketing spontaneous reporting

- Section 4.8 – For the frequency of adverse reactions, dyspnoea listed as very common (≥1/10), haemoptysis, arthralgia and lung function test decreased listed as common (≥ 1/100 to ≤ 1/10) and joint swelling listed as uncommon (≥ 1/1000 to ≤ 1/100)

- Section 4.8 - Inclusion of information on haemoptysis as stated in section 4.4

- Section 4.8 – Lung function test decreased reported with the use of Cayston, but was not associated with a sustained decrease in FEV₁

- Section 4.8 – Paediatric information from the phase 2 and 3 clinical studies

- Section 5.1 - Inclusion of long term study information in the microbiology and clinical efficacy and safety sections

- Section 5.1- Addition of section on study GS-US-205-0110

- Section 5.1 – Minor amendments to information for study CP-AI-006

- Section 5.1 – Paediatric information from the phase 2 and 3 clinical studies as stated in section 4.8                       

- Section 5.2 – Additional information on metabolism

- Section 5.2 – In the elimination section, inclusion of information that approximately 10% of the total Cayston dose is excreted in the urine as unchanged drug, as compared to 60-65% following IV administration of aztreonam for injection

- Section 5.2 – Paediatric information from the phase 2 and 3 placebo-controlled, registrational studies

- Section 10 – Change to the date of revision

 

Reasons for adding or updating:

• Change to section 6. 3 - Shelf Life
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Mar-2012

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



• Section 6.3 - Powder shelf-life changed from 3 to 4 years

 

• Section 10 – Change to the date of revision

Reasons for adding or updating:

• Change to section 4.6 - Pregnancy and Lactation
• Change to section 4.8 - Undesirable Effects
• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Sep-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



• Section 4.6 – Inclusion of fertility statement ‘Non-clinical data for aztreonam for injection about fertility do not indicate any adverse effects’  

• Section 4.8 – Additional statements for the undesirable effects section - inclusion of paragraph describing frequently occurring adverse reactions in the two phase 3 placebo controlled clinical studies and also an acute reduction of ≥ 15% in FEV₁ is a complication associated with nebulised therapies, including Cayston

• Section 4.8 – The frequencies of the adverse reactions are tabulated

• Section 4.8- Addition of paragraph describing selected adverse reactions such as bronchospasm and allergic reactions

• Section 5.1 – Addition of statement from the EMA in the paediatric population section- ‘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)’

• Section 5.1- Removal of statement that Cayston has been authorised under a so called “conditional approval”

• Section 10 – Change to the date of revision

Reasons for adding or updating:

• Change to section 6. 3 - Shelf Life
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Jan-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Change to Section 6.3 - Shelf-life

Shelf-life for powder vial extended from 2 years to 3 years

Change to Section 10

Date of revision is 01/2011

Reasons for adding or updating:

• Change to section 5.3 - Preclinical Safety Data
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Nov-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Change to:

Section 5.3 - Preclinical Safety Data:

To align with the CHMP report; following assessment of the relevance of C-cell carcinoma using either nonclinical mechanistic studies or other relevant data. It was concluded that the clinical relevance of C-cell adenoma is likely to be low and is therefore deleted.

Section 10 - Date of Revision:

11/2010.

Reasons for adding or updating:

• Change to section 9 - Date of first Authorisation/renewal of the Authorisation
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Sep-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Section 9- Addition of the 21^st September 2010 as the latest authorisation renewal date

Section 10- Date of the revision of the test changed to 09/2010

Reasons for adding or updating:

• Change to section 6. 5 - Nature and Contents of Container
• Change to section 8 - MARKETING AUTHORISATION NUMBER(S)
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Mar-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Change to Section 6.5:

to include: 

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.

 

Update to Section 8:     Addition of a new MA number

 

Update to Section 10:    Date of revision to 03/2010

 

 

Reasons for adding or updating:

• Change to section 6. 3 - Shelf Life
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Oct-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Section 6.3

Shelf life of 2 years has been changed to:

Powder vial: 2 years
Solvent: 4 years


Section 10

Changed to from 09/2009 to 10/2009

Reasons for adding or updating:

• New SPC for new product

Legal Category:POM

Black Triangle (CHM): YES