Inspiration for the lungsBRAMITOB® – for the management of chronic pulmonary infection due to Pseudomonas aeruginosa in patients with cystic fibrosis aged 6 years and older.1

The most widely prescribed inhaled tobramycin in the UK2

Prescribing information and adverse event reporting information is available at the end of this booklet

Intended for CF healthcare professionals in the UK onlyReferences:1. Bramitob® Summary of Product Characteristics,

Chiesi Limited. 2. IQVIA in-market sales data, November 2020.

IQVIA in-market sales data, November 2020

Discover more at chiesicysticfibrosis.co.uk

Bramitob - convenience for your patients, reassurance for you

Bramitob has a two month longer shelf life out of the fridge than other TIS 1-3

How do patients store their medicine?

What do patients do with the unused vials?

Bramitob 300mg/4ml

1

Tobramycin 300 mg/5 ml Mylan and Teva UK Ltd

Bramitob has a 4 vial foil - easy to store

and take on travels1 Months at up to 25°C 1-3

References: 1. Bramitob® Summary of Product Characteristics, Chiesi Limited.2. Tobi Summary of Product Characteristics, Mylan.3. Tymbrineb Summary of Product Characteristics, Teva.

Bramitob - designed with tolerability in mind

Bramitob is tobramycin 300 mg in 4 ml of preservative-free saline 0.45% solution5,6

It has been specifically formulated to be almost isotonic, close to the physiological levels observed in the airway surface liquid of CF patients5-7

mO

sm/

l

Estimated isotonic reference range 1,2

Tobramycin 300 mg/5 ml (165-190 mOsm/l) *

360

340

320

300

280

260

240

220

200

180

160

140

120

100

80

60

40

20

0

Bramitob (280-350 mOsm/l) *

Mylan Pharmaceuticals UK (Ltd)

*Adapted from references 3 and 4

Bramitob is almost isotonic, and is designed for the CF airway5-7

References: 1. Thompson J, Lawrence D. A practical guide to contemporary pharmacy practice. 2nd Ed. Lippincott Williams and Wilkins 2003.2. Troy D, Beringer P. The science and practice of Pharmacy. Ch 18, page 252, 21st Ed. Lippincott Williams and Wilkins 2005.3. European patent specification 01116071.0, 2003.4. European patent specifications EP 0 734 249 B1, 1996.

5. 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.

6. Chuchalin A et al. Tobramycin for inhalation in cystic fibrosis: beyond respiratory improvements. Pulm Pharmacol Therap 2009;22:526–532.7. 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.

References: 1. Bramitob Summary of Product Characteristics, Chiesi Limited.2. European patent specification EP 01116071.0, 2003.3. European patent specification EP 0 734 249 B1, 1996.4. Tobi Summary of Product Characteristics, Mylan.

5. Thompson J, Lawrence D A practical guide to contemporary pharmacy practice. 2nd edition, Lippincott Williams & Wilkins 2003.

6. Troy D, Beringer P The Science and Practice of Pharmacy. Ch 18, page 252. 21st Ed. Lippincott Williams & Wilkins 2005.

How is Bramitob different?

Bramitob 300mg/4ml

Tobramycin 300mg/5ml (Mylan)

Tobramycin1,2 Antibiotic Tobramycin 3,4

280-350mOsm/l 2

(Almost isotonic 2,5,6) Osmolarity165-190mOsm/l 3

(Hypotonic5,6)

0.45%2 NaCI content 0.225%3

75mg/ml1,2 Concentration 60mg/ml3,4

≥ 6 years1 Patient age ≥ 6 years4

4 vials per foil56 vials in total per box 1 Packaging

14 vials per foil56 vials in total per box 4

Refrigeration and storage in foils to protect from light 1 Storage

Refrigeration and storage in foils to protect from light 4

Up to 3 months 1 Shelf life out of fridge Up to 28 days 4

Chiesi also provide a support package to help you and your patients that have been prescribed Bramitob. Please ask your representative for more details.

Bronchospasm was seen in 1 in 161 Bramitob patients taking part in a randomised, double-blind study: 1

Chuchalin A et al 1

Challenge testing

Bramitob Challenge Test Packs are provided free of charge

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.

Cost into context

Bramitob, the most widely prescribed inhaled tobramycin in the UK,1 is available to hospitals at a competitive price across all geographies:

England Commercial Medicines Unit (CMU) CM/PHG/17/5531

Scotland NP36120 - Antibiotic & Genito Urinary Medicines

Wales Generic Drugs - Topicals / Misc. Contract Ref. PAD-OJEU-37248

Northern Ireland Generic, Branded Generic & Proprietary Medicinal Products Group 2

Republic of Ireland Reimbursed through High Tech Scheme

Consistent and ReliableSince launch, the price of Bramitob has been consistently reduced.2

Chiesi supply is reliable, with 99% of orders placed delivered first time 3

References: 1. IQVIA in-market sales data, November 2020.2. Data on File. Bramitob Tender Summary.3. Data on File. Chiesi Supply Chain Data.

The right treatments at the right time protect patients’ lung function and extend their lives 1-5

Bramitob is almost isotonic and is designed for the CF airway 1,6,7

Bramitob has a 2 month longer shelf life out of the fridge than other TIS 8-10

Bramitob comes with a package of support

Summary

References: 1. Chuchalin A et al. Tobramycin for inhalation in cystic fibrosis: beyond respiratory improvements. Pulm Pharmacol Therap 2009;22:526–532.2. Geller DE et al. Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit

Care 2011;183:1510–16.3. Castellani C et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros 2018;17(2):153–178.4. Mogayzel PJ et al. Cystic Fibrosis Pulmonary Guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care

Med 2013;187(7):680–9.5. Antibiotic Treatment for Cystic Fibrosis. Cystic Fibrosis Trust. Third edition, 2009.

6. 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):21–31.7. Poli G et al. Clinical pharmacology study of Bramitob®, a tobramycin solution for nebulization, in comparison with Tobi®.

Pediatr Drugs 2007;9(Suppl 1):3–9.8. Bramitob Summary of Product Characteristics, Chiesi Limited.9. Tobi Summary of Product Characteristics, Mylan.

10. Tymbrineb Summary of Product Characteristics, Teva.

Bramitob Prescribing Information (UK)

Bramitob® 300mg/4ml Nebuliser Solution Prescribing InformationPlease refer to Summary of Product Characteristics (SPC) before prescribing. Presentation: Each Bramitob 4ml single-dose container contains tobramycin 300mg. Indication: Management of chronic pulmonary infection due to Pseudomonas aeruginosa in patients with cystic fibrosis aged 6 years and older. Dosage and administration: For inhalation use only. Consideration should be given to official guidance on appropriate use of antibacterial agents. Therapy should be initiated by physicians experienced in management of cystic fibrosis. Recommended dose for adults and children above 6 years is one single-dose container (300mg) twice daily (morning and evening) for 28 days. Dose interval should be as close as possible to 12 hours. After 28 days of therapy, patients should stop treatment for next 28 days. Alternate cycles of 28 days of active therapy followed by 28 days without treatment should be maintained. The efficacy and safety of Bramitob have not been demonstrated in patients less than 6 years of age. Tobramycin should be used with caution in elderly patients who may have reduced renal function. Tobramycin should be used with caution in patients with known or suspected renal dysfunction. Bramitob should be discontinued in the case of nephrotoxicity until serum concentration of tobramycin fall below 2 mcg/ml. No changes in Bramitob dose are required in hepatic insufficiency. Dosage is not adjusted for body weight. All patients should be administered one single-dose container of Bramitob twice daily. The contents of one single-dose container (300mg) emptied into the nebuliser should be administered by inhalation over approximately 15 minutes using a PARI LC PLUS reusable nebuliser equipped with PARI TURBO BOY compressor or PARI LC SPRINT equipped with compressor PARI BOY Sx. Patients receiving different respiratory therapies, it is recommended that they are taken in the following order: bronchodilator, respiratory physiotherapy, other inhaled medicinal products, and finally Bramitob. Bramitob should not be mixed with other inhalation medicinal products. Contraindications:

Hypersensitivity to tobramycin, any other aminoglycosides or any excipients. Contraindicated in patients receiving potent diuretics such as furosemide and ethacrynic acid which have proved to be ototoxic. Warnings and precautions: Use with caution in patients with known or suspected renal, auditory, vestibular or neuromuscular dysfunction, or with severe active haemoptysis. Renal and eighth cranial nerve function should be closely monitored in patients with known or suspected renal impairment. Bronchospasm in presence of bronchodilator therapy may indicate allergic reaction. The first dose of Bramitob should be given under medical supervision, using a pre-nebulisation bronchodilator if this is already part of the current treatment regimen for the patient. Use with great caution in patients with neuromuscular disorders including Parkinsonism and other conditions characterised by myasthenia. Monitor serum tobramycin concentrations in patients with known or suspected renal dysfunction after two to three doses to allow dose adjustment if necessary and also at three to four day intervals during therapy. Renal function should be assessed at baseline and thereafter periodically reassessed. If evidence of nephrotoxicity, therapy should be discontinued until drug minimum serum concentrations fall below 2mcg/ml. Monitor renal function in elderly patients and patients receiving parenteral aminoglycoside therapy. Patients should be monitored for ototoxicity throughout treatment period and have auditory function assessed. Use in patients with active, severe haemoptysis should only be undertaken if benefits outweigh risks. There is a theoretical risk that patients being treated with nebulised tobramycin may develop P. aeruginosa isolates resistant to intravenous tobramycin. Interactions: Concurrent and/or sequential use with other potentially nephrotoxic or ototoxic medicinal products should be avoided. Should not be administered concurrently with ethacrynic acid, furosemide, urea or intravenous and oral mannitol. Fertility, pregnancy and lactation: Not to be used during pregnancy or lactation unless benefits to the mother outweigh risks to the foetus or baby. If used during pregnancy,

or if patient becomes pregnant during therapy, patient should be informed of potential hazard to the foetus. It is unknown whether inhaled tobramycin is detectable in breast milk. Due to potential risk for ototoxicity and nephrotoxicity with tobramycin in infants, decision should be made whether to terminate nursing or discontinue Bramitob. Effects on driving and operating machinery: On basis of reported adverse drug reactions, presumed to be unlikely to affect the ability to drive and use machinery. Nevertheless, patients should be alerted that dizziness and/or vertigo may occur. Side effects: Common: cough, dysphonia. Uncommon: fungal infection, oral candidiasis, headache, vertigo, hypoacusis, deafness neurosensory, forced expiratory volume decreased, dyspnoea, rales, haemoptysis, oropharyngeal pain, productive cough, salivary hypersecretion, glossitis, abdominal pain upper, nausea, rash, asthenia, chest discomfort, mucosal dryness, transaminases increased, pharyngitis. Rare: laryngitis, anorexia, dizziness, aphonia, tinnitus, hearing loss, bronchospasm, chest discomfort, lung disorder, epistaxis, rhinitis, asthma, dysgeusia, mouth ulceration, vomiting, rash, pyrexia, chest pain, pain, pulmonary function test decreased. Very Rare: lymphadenopathy, hypersensitivity, somnolence, ear disorders, ear pain, hyperventilation, hypoxia, sinusitis, diarrhoea, abdominal pain, urticaria, pruritis, back pain, malaise (Refer to SPC for full list of side effects). Legal category: POM. Price and Pack: £1187.00 (1 x 56 single dose containers.) Marketing authorisation (MA) no: PL 8829/0155. MA holder: Chiesi Limited, 333 Styal Road, Manchester, M22 5LG. Date of Preparation: April 2019

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for

MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Chiesi

Limited on 0800 0092329 or PV.UK@Chiesi.com.

UK-BRA-2000012 December 2020