INTENDED FOR UK AND IRELAND HEALTHCARE PROFESSIONALS Patient InformationHomePrescribing information

For the management of chronic pulmonary infection due to Pseudomonas aeruginosa in patients with cystic fibrosis aged
6 years and older. 1

Inspiration for the lungs
ABOUT BRAMITOB
Bramitob
  • Bramitob (tobramycin) is an effective, unique formulation of inhaled tobramycin to treat chronic Pseudomonas aeruginosa pulmonary infection in patients with cystic fibrosis from the age of 6 years 1,2
  • Bramitob is tobramycin 300 mg in 4 ml of preservative-free saline 0.45% solution 2,3
  • Bramitob was formulated to be almost isotonic and is designed for the CF airway 2,3,4
Bramitob – designed with tolerability in mind
  • Bramitob has a 3 month shelf life out of the fridge (up to 25°C), which is 2 months longer than Tobramycin 300 mg / 5 ml.1,9,10
  • Bramitob comes in 4 vial foils1 – easy to store and take on travels.

References:

  1. Bramitob. Summary of Product Characteristics. Chiesi Limited.
  2. Chuchalin A et al. A formulation of aerosolized tobramycin (Bramitob®) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection. A double-blind, placebo-controlled, multicenter study. Pediatr Drug 2007;9(Suppl 1):21–31.
  3. Chuchalin A et al. Tobramycin for inhalation in cystic fibrosis: beyond respiratory improvements. Pulm Pharmacol Therap 2009;22:526–532.
  4. Poli G et al. Clinical pharmacology study of Bramitob®, a tobramycin solution for nebulization, in comparison with Tobi®. Pediatr Drugs 2007;9(Suppl 1):3–9.
  5. Thompson J, Lawrence D. A practical guide to contemporary pharmacy practice. 2nd Ed. Lippincott Williams and Wilkins 2003.
  6. Troy D, Beringer P. The science and practice of Pharmacy. Ch 18, page 252, 21st Ed. Lippincott Williams and Wilkins 2005.
  7. European patent specification 01116071.0, 2003.
  8. European patent specifications EP 0 734 249 B1, 1996.
  9. Tobi. Summary of Product Characteristics, Mylan.
  10. Tymbrineb. Summary of Product Characteristics, Teva UK Limited.
Dosing and Storage
  • Bramitob is a 28 day treatment, followed by 28 days off treatment.1
  • A 300 mg / 4 ml dose (one container) is taken twice a day.1
  • Bramitob is licensed for use with a PARI LC PLUS® reusable nebuliser connected to a PARI TurboBOY® compressor.1
  • It takes approximately 15 minutes to nebulise each dose through a PARI LC PLUS® nebuliser.1
  • Bramitob is a refrigerated product which can be stored out of the fridge (up to 25°C) for up to 3 months.1
  • Containers should be kept in their foil until use to protect Bramitob from light.1

Reference:

  1. Bramitob. Summary of Product Characteristics. Chiesi Limited.
KEY DATA
Phase III efficacy and safety study (8 weeks) – Lenoir G et al.
Efficacy, Safety, and Local Pharmacokinetics of Highly Concentrated Nebulized Tobramycin in Patients with Cystic Fibrosis Colonized with Pseudomonas aeruginosa Pediatr Drugs. 2007;9 Suppl. 1:11–20.1
Study aim Investigate the efficacy and safety of a highly concentrated (300 mg / 4 ml) tobramycin solution for inhalation (Bramitob) in patients with cystic fibrosis and Pseudomonas aeruginosa infection
Study design Phase III, prospective, randomised (tobramycin:placebo), double-blind, placebo-controlled, parallel-group, multinational clinical trial
Age > 6 years
Primary endpoint Change in FEV1 % predicted at week 4
Secondary endpoints FVC and FEF25-75% predicted, P. aeruginosa susceptibility, minimum concentration required inhibit 90% of strains (MIC90), safety
FEV1 % predicted vs placebo at weeks 2 and 41
Study overview
Study CT011
Bramitob n=29
Placebo n=30
Study drug Bramitob (300 mg / 4 ml; inhaled), BID
Comparator Placebo (PBO)
Pulmonary function Primary endpoint: Significant improved increase in FEV1 % predicted vs PBO (p≤0.003 at weeks 2 and 4)   

Secondary endpoint: Significant differences in favour of Bramitob in FVC and FEF25-75% vs PBO (p=0.017 and p=0.004 respectively)

Microbiology Significantly better outcome in Bramitob vs PBO in microbiologic testing after 4 weeks (p=0.033)
Adverse events Significantly fewer AEs reported in Bramitob vs PBO (p=0.026)   

No signs or renal or auditory toxicity

A serious adverse event was observed in one patient in the tobramycin group and in three patients in the placebo group; these three patients discontinued due to worsening of pulmonary symptoms

AE, adverse event; FEF25-75%, forced expiratory flow at 25-75%; FEV1 forced expiratory volume in 1 second; FVC, forced vital capacity; PBO, placebo

Reference:

  1. Lenoir G, et al. Efficacy, Safety, and Local Pharmacokinetics of Highly Concentrated Nebulized Tobramycin in Patients with Cystic Fibrosis Colonized with Pseudomonas aeruginosa Pediatr Drugs. 2007;9 Suppl. 1:11–20.
Phase III efficacy and safety study (24 weeks) – Chuchalin A, et al.
A formulation of aerosolized tobramycin (Bramitob®) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection. A double-blind, placebo-controlled, multicenter study. Pediatr Drug 2007;9(Suppl 1):21–31.1
Study aim Assess efficacy and tolerability of tobramycin highly concentrated solution for inhalation (300 mg /4 ml) (Bramitob), when added to other anti-pseudomonal therapies in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection
Study design Phase III, double-blind, randomised 2:1, placebo-controlled, multi-centre, 24-week study period with three 4-week treatment periods and three 4-week off periods in an alternating cycle
Age > 6 years
Primary endpoint Change in FEV1 % predicted at week 20
Secondary endpoints FVC and FEF25-75% predicted, P. aeruginosa susceptibility, minimum concentration required inhibit 90% of strains (MIC90), rates of P. aeruginosa-negative culture, P. aeruginosa persistence and superinfection, pulmonary exacerbations, need for hospitalisation and parenteral antipseudomonal antibiotics, loss of school/working days due to the disease, and nutritional status (bodyweight and body mass index)
Change from baseline in mean FEV1% predicted at each timepoint1
FVC and FEF25-75% – change from baseline to study endpoint1
Pulmonary parameter Bramitob Placebo
FVC percent predicated
Patients (n) 161 84
Baseline 70.8 ± 13.8 73.6 ± 13.1
Endpoint 76.7 ± 18.8* 74.9 ± 18.9
Mean ± SD change 5.9 ± 14.2 1.3 ± 13.3
95% CI 3.7, 8.1 -1.6, 4.2
FEF25-75% percent predicated
Patients (n) 158 80
Baseline 41.8 ± 23.7 43.9 ± 25.8
Endpoint 50.5 ± 30.2** 44.6 ± 29.0
Mean ± SD change 8.8 ± 17.3 0.7 ± 19.0
95% CI 6.0, 11.5 -3.6, 4.9
* p=0.022, **p=0.001 vs placebo
Microbiologic assessment outcomes a, 1
Category Bramitob Placebo
Week 4
Patients (n) 159 84
Negative culture [no. (%)] 49 (30.8) 12 (14.3)
Persistence [no. (%)] 85 (53.5) 51 (60.7)
Superinfection [no. (%)] 25 (15.7) 21 (25.0)
p=0.011
Week 8
Patients (n) 159 83
Negative culture [no. (%)] 23 (14.5) 10 (12.1)
Persistence [no. (%)] 76 (47.8) 46 (55.4)
Superinfection [no. (%)] 38 (23.9) 22 (26.5)
Reinfection [no. (%)] 20 (12.6) 4 (4.8)
Not available/assessed [no. (%)] 2 (1.3) 1 (1.2)
p=0.27
Week 20
Patients (n) 156 79
Negative culture [no. (%)] 52 (33.3) 13 (16.5)
Persistence [no. (%)] 69 (44.2) 41 (51.9)
Superinfection [no. (%)] 25 (16.0) 21 (26.6)
Reinfection [no. (%)] 7 (4.5) 2 (2.5)
Not available/assessed [no. (%)] 3 (1.9) 2 (2.5)
p=0.024
Week 24
Patients (n) 153 78
Negative culture [no. (%)] 38 (24.9) 17 (21.8)
Persistence [no. (%)] 67 (43.8) 42 (53.8)
Superinfection [no. (%)] 27 (17.6) 14 (17.9)
Reinfection [no. (%)] 17 (11.1) 3 (3.8)
Not available/assessed [no. (%)] 4 (2.6) 2 (2.6)
p=0.44

a. Statistical analysis performed between groups

Additional secondary endpoints within the intention-to-treat population1
Outcome Bramitob Placebo p-value (between group comparison)
Patients (n) 161 84  
Pulmonary exacerbations [no. (%)] 64 (39.8) 43 (51.2) 0.09
Hospitalisations [no. (%)] 30 (18.6) 31 (36.9) 0.002
No. of school/working days lost (mean ± SD) 4.7 ± 9.1 10 ± 13.9 <0.001
Parenteral tobramycin [no. (%)] 10 (6.2) 14 (16.7) 0.009
Other antipseudomonal antibodies [no. (%)] 90 (55.9) 59 (70.2) 0.029
Study overview
Study ITT population
Bramitob n=161
Placebo n=84
Study drug Bramitob (300 mg / 4 ml, inhaled), BID
Comparator PBO
Pulmonary function Primary endpoint: Bramitob showed significantly greater increase in FEV1 from baseline vs PBO at all weeks, except week 8   

At week 24, statistical significance vs baseline (p=0.001)

Week 2 = p<0.001 vs PBO
Week 4 = p<0.001 vs PBO
Week 8 = no statistical significance
Week 12 = p<0.01
Week 16 = p<0.01
Week 20 = p<0.001 vs placebo
Week 24 = p<0.001 vs baseline

Secondary endpoints include: Clinically relevant improvement in FVC and FEF25-75% predicted vs PBO (p=0.022; p=0.001 respectively)

Exacerbation Lower number of patients experiencing at least one pulmonary exacerbation vs PBO (39.8% vs 51.2%, p=0.09)
Additional antibiotic use The need for parenteral tobramycin was significantly lower in the Bramitob group vs placebo (p=0.009)   

The need for other antipseudomonal antibiotics was also significantly lower in the Bramitob group vs placebo (p=0.029)

Adverse events Fewer AEs reported in Bramitob group vs PBO (p=0.028)   

Events considered treatment-related were reported by 16% of patients treated with Bramitob and 15% of patients receiving placebo

20 SAEs reported by 11% of Bramitob patients vs 27 SAEs reported by 26% of PBO patients

AE, adverse event; BID, twice daily; CI, confidence interval, FEF, forced expiratory flow; FEF25-75%, forced expiratory flow at 25-75%; FEV1 forced expiratory volume in 1 second; FVC, forced vital capacity; PBO, placebo; SAE, serious adverse event

Reference:

  1. Chuchalin A et al. A formulation of aerosolized tobramycin (Bramitob®) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection. A double-blind, placebo-controlled, multicenter study. Pediatr Drug 2007;9(Suppl 1):21–31.
Phase III efficacy and safety study (56 weeks) – Mazurek H, et al.
Long-Term Efficacy and Safety of Aerosolized Tobramycin 300 mg / 4 ml in Cystic Fibrosis. Pediatr Pulmonol. 2014;49:1076–89.1
Study aim Investigate the efficacy and safety of Bramitob compared to Tobramycin 300 mg/ 5ml (Mylan) in patients with cystic fibrosis and Pseudomonas aeruginosa infection and further investigation of long-term efficacy and safety of Bramitob in a subset of patients
Study design Phase III, prospective, randomised, 8 week open-label trial of Bramitob vs Tobramycin 300 mg/5ml (Mylan) (non-inferiority core study), followed by a 6 cycle, 48 week single-arm extension study evaluating the long-term safety and efficacy of Bramitob only
Age > 6 years
Primary endpoint Absolute change on FEV1 % predicted from baseline to week 4 (non-inferiority core study)   

The primary purpose of the extension phase was to assess the long-term safety of Bramitob

Absolute change in FEV1 % predicted during the core and extension phases from baseline

*Patients treated with TNS4 and TNS5 during the core phase of the study, n=100 and n=109 respectively

No assessments at weeks 20, 36 and 44

TNS4, Bramitob 300 mg / 4 ml; inhaled
TNS5, Tobramycin 300 mg / 5 ml (Mylan); inhaled

Bramitob was non-inferior to TNS5 at week 4, with a difference between groups of -0.5% (95% Cl: -2.6; 1.6)

P. aeruginosa bacterial load (Log10 colony-forming-units [CFU] per gram) in sputum by week; change from baseline

*Patients treated with TNS4 and TNS5 during the core phase of the study, n=100 and n=109 respectively

No assessments at weeks 20, 36 and 44

TNS4, Bramitob 300 mg / 4 ml; inhaled
TNS5, Tobramycin 300 mg / 5 ml (Mylan); inhaled

Study overview
Study Safety population (core phase)
Bramitob n=156
Tobramycin 300 mg / 5 ml (Mylan) n=168
Study drug TNS4; Bramitob (300 mg / 4 ml; inhaled), BID
Comparator TNS5; Tobramycin 300 mg / 5 ml (Mylan), BID
Pulmonary function Primary endpoint: Bramitob shown to be non-inferior to TNS5 at week 4 with a difference between groups of -0.5 (95% Cl: -2.6, 1.6)   

The lung function benefits observed during the 8-week core study were maintained throughout the extension phase, with minimal fluctuations between “on” and “off” drug periods

Exacerbation Infrequent with no difference between Bramitob (3.8%) and TNS5 (3.0%) in the core phase   

The incidence of pulmonary exacerbations increased during the extension phase occurring on average once during the 48 weeks in 24.9% of patients

Adverse events Similar percentages of reported AEs (Bramitob, 31.4%; TNS5, 28.0%; p=0.579) and 6 SAEs reported by 3.8% Bramitob patients vs 2 SAEs reported in 1.2% TNS5 patients (p=0.161) in the core phase   

During the extension phase, 148 (70.8%) patients reported AEs. The proportion of patients experiencing SAEs increased during the extension phase, occurring in 39 (18.7%) of patients

No events of bronchospasm were reported

AE, Adverse event; FEV1 forced expiratory volume in 1 second; PBO, placebo; SAE, serious adverse event.

Reference:

  1. Mazurek H, et al. Long-Term Efficacy and Safety of Aerosolized Tobramycin 300 mg/4 ml in Cystic Fibrosis. Pediatr Pulmonol. 2014;49:1076–89.
STARTING BRAMITOB
What comes in a box of Bramitob?
  • 56 doses of Bramitob 300 mg / 4 ml for 28 days’ treatment, packaged in 14 foils with 4 plastic ampoules in each1

Reference:

  1. Bramitob. Summary of Product Characteristics. Chiesi Limited.
Initiation of Bramitob
  • The first dose of Bramitob should be given under medical supervision.1
  • A pre-nebulisation bronchodilator should be used if this is already part of the patient’s current treatment.1
  • FEV1 (forced expiratory volume) should be measured before and after nebulisation.1­
  • Bronchospasm with Bramitob is rare.1
  • If a patient experiences bronchospasm after taking Bramitob and they have not pre-treated with a bronchodilator, the test should be repeated on a separate occasion, using a bronchodilator first.1
  • If the patient has pre-treated with a bronchodilator and they experience bronchospasm after taking Bramitob, this could indicate an allergic reaction.1
  • Bramitob should be discontinued if an allergic reaction is suspected.1
Challenge test packs
  • Challenge test packs contain 4 ampoules of Bramitob and are available free of charge to your CF Centre to allow you to supervise a patient’s first dose of Bramitob.
  • To order challenge test packs please send a free of charge purchase order to orders.uk@chiesi.com
    or fax to +44(0)161 332 6158.

Reference:

  1. Bramitob. Summary of Product Characteristics. Chiesi Limited.
Day to day use of Bramitob
  • Bramitob should be taken twice daily for 28 days, followed by 28 days off-treatment.1
  • It can be useful to work out in advance how taking Bramitob will fit in with your patient’s morning and evening routines, as this could aid adherence.
  • Bramitob is licensed for use with a PARI LC PLUS reuseable nebuliser with a PARI TURBO BOY compressor.1
  • A dose of Bramitob should take approximately 15 minutes to nebulise through the PARI LC PLUS nebuliser.1
  • Bramitob needs to be refrigerated, though patients can store Bramitob outside of the fridge for up to 3 months at not more than 25°C.1

    For downloadable Bramitob patient support information go to our resources section

References:

  1. Bramitob. Summary of Product Characteristics. Chiesi Limited.
  2. Tobi. Summary of Product Characteristics, Mylan.
  3. Tymbrineb. Summary of Product Characteristics, TEVA UK Limited.
Tolerability with Bramitob
  • Bramitob was specifically formulated to be almost isotonic, close to the physiological levels observed in the airway surface liquid of CF patients.1,2,3
  • A phase III study showed comparable incidence of adverse events between Bramitob (300 mg / 4 ml) and Tobramycin 300 mg / 5 ml (Mylan).4
  • Hearing loss and bronchospasm are rare with Bramitob.5
  • To see a full list of Bramitob adverse events, please see the UK Summary of Product Characteristics or the Ireland Summary of Product Characteristics

References:

  1. Chuchalin A et al. A formulation of aerosolized tobramycin (Bramitob®) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection. A double-blind, placebo-controlled, multicenter study. Pediatr Drug 2007;9(Suppl 1):21–31.
  2. Chuchalin A et al. Tobramycin for inhalation in cystic fibrosis: beyond respiratory improvements. Pulm Pharmacol Therap 2009;22:526–532.
  3. Poli G et al. Clinical pharmacology study of Bramitob®, a tobramycin solution for nebulization, in comparison with Tobi®. Pediatr Drugs 2007;9(Suppl 1):3–9.
  4. Mazurek H, et al. Long-Term Efficacy and Safety of Aerosolized Tobramycin 300 mg/4 ml in Cystic Fibrosis. Pediatr Pulmonol. 2014; 49:1076-89.
  5. Bramitob. Summary of Product Characteristics. Chiesi Limited.
Chiesi funded homecare delivery

In the UK we also offer Chiesi funded homecare delivery for Bramitob, with a choice of 3 providers, so patients can get their Bramitob delivered to them at home

Contact your Chiesi CF Hospital Specialist for more information and support

RESOURCES

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

Materials
  •  
    Bramitob Key Takeaways Booklet (UK)
    This booklet gives a summary of need to know information about Bramitob for UK CF Healthcare Professionals.
  •  
    Bramitob Key Takeaways Booklet (Ireland)
    This booklet gives a summary of need to know information about Bramitob for CF Healthcare Professionals in the Republic of Ireland.
  •  
    Bramitob Comparison with TIS 300 mg / 5 ml (UK)
    This resource gives a summary comparison of Bramitob (300 mg / 4 ml) and Tobramycin Inhaled Solution (300 mg / 5 ml) for UK CF Healthcare Professionals.
  •  
    Bramitob Comparison with TIS 300 mg / 5 ml (Ireland)
    This resource gives a summary comparison of Bramitob (300 mg / 4 ml) and Tobramycin Inhaled Solution (300 mg / 5 ml) for CF Healthcare Professionals in the Republic of Ireland.

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

  •  
    Bramitob Patient Support Leaflet
    This leaflet provides patients prescribed Bramitob with a summary of information about the product.
  •  
    Bramitob Patient Support Leaflet for children
    This leaflet provides paediatric patients prescribed Bramitob with colourful and easy to read information about Bramitob.
  •  
    7 Ways to Stay Well with CF – for Kids
    This guide shows 7 ways to stay well with CF in a cartoon format designed for children.
  1. Bramitob Summary of Product Characteristics. Chiesi Limited.

IE-BRA-2000028 | Dec 2020

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