INTENDED FOR UK AND IRELAND HEALTHCARE PROFESSIONALS Patient InformationHomePrescribing information

For the treatment of cystic fibrosis in
adults aged 18 years and above as an
add-on therapy to best standard of care 1

Clarity for the lungs
About Bronchitol
Bronchitol
  • Bronchitol (mannitol) is licensed for adults with CF as an add-on therapy to best standard of care.1
  • Bronchitol is an osmotic mucociliary clearance agent in capsule form, delivered via a small-sized dry powder inhaler.1
  • Bronchitol offers a time-efficient and effective mucolytic treatment, which helps clear mucus build-up from the lungs.1-3
  • Bronchitol has a compact design4 so it is easy to carry and convenient to use.
  • Bronchitol does not need refrigeration or a power supply.1
  • No cleaning or disinfection is needed for Bronchitol – after 7 days’ treatment patients simply swap to a new inhaler.4
  • The portability and convenience of Bronchitol could fit well into the lives of people with CF.
 
  • A Bronchitol Initiation Dose Assessment (BIDA) must be performed before starting Bronchitol.1
  • FEV1 response to Bronchitol at 6 weeks is highly predictive of long-term efficacy.5
  • Recommended follow-up is after 6 weeks of Bronchitol treatment.1

References:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
  2. NICE Technology Appraisal Guidance, Mannitol dry powder for inhalation for treating cystic fibrosis TA266. 28 November 2012.
  3. Aitken M et al. Long-term inhaled dry powder mannitol in cystic fibrosis. An international randomized study. Am J Respir Crit Care Med 2012;185(6):645–652.
  4. Bronchitol. Patient Information Leaflet, Pharmaxis Europe Limited.
  5. Flume PA et al. Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe 2015;11(1):39–48.
Dosing
 
  • Bronchitol is twice a day continuous treatment and is provided in 2 week packs, one inhaler is provided per week of Bronchitol medication.1
  • The full 400 mg Bronchitol dose is delivered with 10 capsules, this takes around 5 minutes or with practice 2–3 minutes.2,3

References:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
  2. Flume PA et al. Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe 2015;11(1):39–48.
  3. NICE Technology Appraisal Guidance, Mannitol dry powder for inhalation for treating cystic fibrosis TA266. 28 November 2012.
Bronchitol patient case studies
 

Bronchitol real-world evidence – A patient case study1

About the patient
  • Aged between 18-29 years.
  • University student with a busy schedule.
  • Active and regularly went to the gym (trained 4-5 times a week at a competitive level).
  • Found it difficult to adhere to airways clearance therapy (ACT).
  • Acknowledged they didn’t feel they cleared their chest effectively with their current therapy.
  • Baseline FEV1 81% predicted but was slowly declining with lung function in the last 6 months not being above 75%.
A thorough assessment of the patient’s current treatment revealed
  • Patient had relatively good adherence to their treatment regime apart from Hypertonic Saline (HTS) and ACT.
  • This is because she found them both time consuming and ineffective.
Rationale for treatment with Bronchitol:
  • No obvious sign of infection that would cause a drop in lung function.
  • Imaging wasn’t convincing of an increase in disease progression, but there was:
    • a slow decline in lung function.
    • subjective reports of sputum retention.
    • some audible peripheral secretions which were difficult to shift with current regime.
  • Patient had difficulties fitting treatments into her busy lifestyle and had lost confidence in her current treatment so was non-adherent.
  • Bronchitol could provide a simple treatment option which could be added to her current regime and easily fit in with her lifestyle.
Clinical Outcomes as a result of treatment with Bronchitol:
  • FEV1 increased back to baseline in next clinic review.
  • Patient subjectively reported improved adherence to mucolytic therapy (Bronchitol) and ACT.
  • Reported less audible secretions (confirmed with physiotherapy assessment) during autogenic drainage sessions.
  • Although only still doing autogenic drainage if she does not exercise on a day, she finds the combination of exercise and Bronchitol very effective and is more understanding of doing ACT if she is not exercising.

Summary of key points in this patient case study

  • Bronchitol improved adherence to mucolytic therapy.
  • Bronchitol used in conjunction with exercise was successful in achieving airways clearance.
  • Bronchitol was perceived as less effort and more effective for moving sticky peripheral secretions.

Reference:

  1. Chiesi Data on File. Bronchitol real world evidence – A patient case study.
How Bronchitol works

Bronchitol is thought to increase hydration, making mucus easier to clear1

  • An imbalance between mucus volume and airways surface liquid results in mucus turning increasingly thick and sticky.2
  • Ciliary function is also compromised, making it harder for patients to clear the mucus, so it becomes stagnated.2
  • Inhaled dry powder mannitol is thought to increase the hydration of the airways surface liquid, improving the consistency of the mucus and making it easier for patients to clear.1

References:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
  2. Daviskas E & Anderson SD. Inhaled Mannitol as a Therapeutic Medication. Clin Pulm Med 2016; 23(5): 197-202.
Lung deposition of mannitol

Precision engineering is used to arrange the naturally irregular structure of mannitol into 3-micron diameter spheres. This helps to improve its deposition once inhaled correctly.1

Deposition with 3 microns
(image taken from a healthy subject)

Deposition with 4 microns
(image taken from a healthy subject)

Reproduced from Glover W et al. Int J Pharm 2008: 349; 314-322. Coronal slices from the SPECT images obtained after inhalation of the radio-labelled mannitol powders in one of the subjects.

Reference:

  1. Glover W, et al. Effect of particle size of dry powder mannitol on the lung deposition in healthy volunteers. Int J Pharm 2008: 349; 314–322.
Recommended Treatment Order
 
For CF patients receiving several respiratory therapies, the recommended order is:1
 

Evening dose of Bronchitol should be taken 2-3 hours before bedtime1

Reference:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
KEY DATA
Pooled analysis of adult data from two phase III efficacy and safety studies in CF populations – Flume PA, et al. 2015

Overview of Bronchitol registration studies in adults:

Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe 2015;11(1):39–48.1
Study aim To present pooled data specific to adult patients, distinct from the paediatric subjects who were included in previous publications.
Study design Integrated data analysis of two Phase III, randomised 3:2, double-blind with open-label extension studies with nearly identical protocols (CF301 and CF302).
Age Subgroup analysis of adult population ≥18 years.
Primary endpoint Mean absolute change in FEV1 from baseline compared with control over 26 weeks of treatment.
Secondary endpoints include: FVC, pulmonary exacerbations, safety, post-dose sputum weight.
Change in FEV1 from baseline in ITT population in adults ≥ 18 years (CF301 & CF302)

Adapted from Flume PA, et al. Breathe (Sheff) 2015; 11:39-481

Change in FEV1 from baseline in adults ≥ 18 years (CF301 & CF302)

Adapted from Altken M, et al. ECFS Dublin 2012 (Abstract #47).2

Mean weight change in sputum (grams) 30 mins after administration in adults ≥ 18 years (CF301 & CF302)

Adapted from Altken M, et al. ECFS Dublin 2012 (Abstract #47).2

Study overview
Study Flume PA, et al 1
(pooled analysis CF301 and CF302)
n=390
ITT=341
Study drug Bronchitol 400 mg (inhaled), BID.
Comparator Mannitol 50 mg (inhaled), BID
Concomitant medication Continuation of all approved CF therapies asside from hypertonic saline was permitted.
Pulmonary function Primary endpoint: Significant improvement in FEV1 vs control, irrespective of rhDNase, tobramycin or colistin use.
Adverse events Discontinuation due to AEs: 15.9% (33) vs 9.0% (12) (Bronchitol vs control group, respectively)
Treatment-related serious adverse events: 3.4% vs 1.5% (Bronchitol vs control group, respectively).

BID, twice daily; CI, confidence interval; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; rhDNase, dornase alfa; HTS, hypertonic saline

References:

  1. Flume PA et al. Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe 2015;11(1):39–48.
  2. Aitken M et al. Bronchitol (inhaled dry powder mannitol) in adult patients with cystic fibrosis. ECFS Dublin 2012; Abstract #47.
STARTING BRONCHITOL
What comes in a box of Bronchitol?
  • 28 blister packs, containing 10 x 40 mg capsules in each, for two weeks of treatment.1
  • 2 x Bronchitol inhalers, 1 for each week of treatment.1

For the Bronchitol Initiation Dose Assessment (BIDA) a BIDA pack can be purchased separately, this will contain 1 inhaler and 10 capsules of Bronchitol.

Reference:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
Initiation of Bronchitol
  • The Bronchitol Initiation Dose Assessment (BIDA) must be undertaken for each patient and passed before starting Bronchitol.1
  • The BIDA is to assess for any bronchial hyperresponsiveness to inhaled mannitol.1
  • In phase 3 clinical trials, over 90% of adults passed the BIDA.1
  • UK healthcare professionals should also refer to the Risk Minimisation Material and can download our UK Electronic BIDA Sheet.

Patients must be pre-medicated with a bronchodilator 5-15 minutes before the BIDA is started but after the baseline FEV1 and SpO2 (Oxygen saturation in the blood) measurement.

The BIDA must be given under the supervision and monitoring of an experienced cystic fibrosis healthcare professional trained and equipped to:

  • Monitor oxygen saturation (SpO2).
  • Perform spirometry.
  • Manage acute bronchospasm including appropriate use of resuscitation equipment.

Reference:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
Inhaler technique

Correct inhaler technique is key to long-term treatment success

The BIDA also creates an opportunity to teach patients the correct inhaler technique and how to identify a productive cough, which can contribute to sputum clearance.1,2

  • A productive cough which helps patients to clear their lungs is desirable, and a feature of Bronchitol treatment.
  • Inhalation of dry powder can cause an irritant cough but can be minimised with good technique.

3 top tips for inhalation success:

1. Angle of inhalation:
Tilting the head back
opens the airways.3

2. Timing: The contents of the
capsules should be inhaled
closely together.3

3. Water between capsules:
Sipping water between capsules
helps to clear the throat.3

References:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
  2. Bilton D, et al. Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study Eur Respir J 2011; 38: 1071-1080.
  3. Flume PA et al. Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe 2015;11(1):39–48.
What your patients need to know before starting Bronchitol

Cough

  • Cough is a possible side effect with Bronchitol and patients should know this before starting treatment.1
  • Productive cough is considered part of the therapeutic effect and can happen quickly after taking Bronchitol.2
  • Irritant cough is a sign that inhaler technique should be revisited and patients advised to slow down the speed of inhaling each capsule and take sips of water between capsules.2

Haemoptysis

  • Haemoptysis has been commonly reported with Bronchitol in clinical studies.1
  • A 5-year safety study found no increase in haemoptysis in the Bronchitol-exposed population compared to a control population.3

Patients can use the following step-by-step guide to assist them in taking Bronchitol

1. TAKE OFF THE CAP

  • Using both hands, hold the inhaler upright and take off the cap.

2. OPEN THE INHALER

  • Hold the bottom of inhaler firmly with one hand, making sure you don’t press piercing buttons
  • Open by turning mouth-piece in direction of arrow on inhaler

3. PUT IN THE CAPSULE

  • First, make sure your hands are dry
  • Then remove capsule from blister just before use
  • Put the capsule into capsule-shaped space at bottom of inhaler

4. CLOSE THE INHALER

  • Keep inhaler in an upright position
  • Twist mouth-piece into closed position – when it is closed you will hear a ‘click’

5. MAKE A HOLE IN THE CAPSULE

  • Hold inhaler upright and fully press both ‘piercing’ buttons on the sides at the same time, then release (this allows the powder in the capsule to be released when you breathe in).
  • Only do this once

6. PREPARE FOR INHALATION

  • Tilt inhaler so mouth-piece faces slightly downward, which allows capsule to drop forward into spinning chamber
  • Keep inhaler tilted in this way and breathe out completely away from inhaler

7. INHALE

  • Tilt your head back slightly
  • Put downward-tilted inhaler in mouth and close lips tightly
  • Take steady, deep breath in, fill lungs – hold for 5 seconds

8. BREATHE OUT

  • Take inhaler away from mouth
  • Breathe out, and then breathe normally again

9. CHECK THE CAPSULE

  • Look to see if capsule is empty – the capsule must spin in inhaler in order to empty
  • If the capsule is not empty, you may need to repeat steps 6, 7 and 8

10. TAKE OUT THE USED CAPSULE

  • Turn the inhaler upside down, tap the bottom and throw the empty capsule away

11. REPEAT STEPS 3 TO 10 FOR EACH CAPSULE

  • Perform these steps for each of the 10 capsules
  • To get the best results from Bronchitol, inhale each capsule one after another

Twice-daily dosage each delivered in approximately 5 minutes, following training.2

Demonstration inhalers with empty capsules can be used for training purposes.

Contact your Chiesi CF Hospital Specialist for more information and support.

References:

  1. Bronchitol. Summary of Product Characteristics. Pharmaxis Europe Limited.
  2. Flume PA et al. Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe 2015;11(1):39–48.
  3. Carr SB et al. Five Year Post Authorisation Safety Study of Bronchitol® (inhaled mannitol) in the UK. Poster presented at NACFC 2018.
RESOURCES

In this section you will find Bronchitol materials which can be downloaded.

Materials
  •  
    Bronchitol Key Takeaways Booklet (UK)
    This booklet gives a summary of information about Bronchitol for UK CF Healthcare Professionals.
  •  
    UK Electronic BIDA Sheet (UK)
    An electronic version of our Bronchitol Initiation Dose Assessment sheet which can be filled in on a computer, for UK CF Healthcare Professionals.

If you would like to provide the information below to your patients, please direct them to the Bronchitol patient section of this website.

  •  
    Bronchitol Patient Support Leaflet
    This leaflet provides patients prescribed Bronchitol with a summary of information about the product.
  1. Bronchitol Summary of Product Characteristics. Pharmaxis Europe Limited.

IE-BRO-2000011 | Oct 2020

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