In guidance published today (27 March), NICE has recommended tobramycin (Tobi Podhaler, Novartis) and colistimethate sodium (Colobreathe, Forest Laboratories UK) dry powders for inhalation (DPI) as options for treating lung infections in people with cystic fibrosis in certain circumstances.

Tobramycin DPI is recommended as an option for treating chronic pulmonary infection caused by Pseudomonas aeruginosa in people with cystic fibrosis only if:

• nebulised tobramycin is considered an appropriate treatment, that is, when nebulised colistimethate sodium is contraindicated, not tolerated or has not produced an adequate clinical response, and
• the manufacturer provides tobramycin DPI with the discount agreed as part of the patient access scheme to primary, secondary and tertiary care in the NHS.

Colistimethate sodium dry powder for inhalation (DPI) is recommended as an option for treating chronic pulmonary infection caused by Pseudomonas aeruginosa in people with cystic fibrosis, only if:

• they would clinically benefit from continued colistimethate sodium but do not tolerate it in its nebulised form and thus tobramycin therapy would otherwise be considered and
• the manufacturer provides colistimethate sodium DPI with the discount agreed as part of the patient access scheme to primary, secondary and tertiary care in the NHS

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE said: “The primary cause of death in people with cystic fibrosis is respiratory failure resulting from chronic pulmonary infection caused by Pseudomonas aeruginosa. We are pleased to recommend both colistimethate sodium and tobramycin dry powders for inhalation as options for treating such infections in people with cystic fibrosis.”

Cystic fibrosis is one of the UK's most common life-threatening inherited diseases, and currently affects around 8,000 people. Over two million people in the UK carry the faulty gene that causes cystic fibrosis - around 1 in 25 of the population. For a baby to be born with cystic fibrosis, both parents must be carriers of the faulty gene. If two carriers have a child, the baby has a 1 in 4 chance of having cystic fibrosis. The condition affects the internal organs, especially the lungs and digestive system, by clogging them with thick, sticky secretions, making it hard to breathe and digest food. Symptoms of cystic fibrosis can include a troublesome cough, repeated chest infections, prolonged diarrhoea and poor weight maintenance.

The aim of treatment in adults with cystic fibrosis is to clear the respiratory secretions in order to maintain lung function, as well as to reduce inflammation and bacterial growth in the respiratory tract. Treatment includes regular physiotherapy, antibiotics, and inhaled mucolyticsi through a nebuliser. The main goal is to improve or maintain lung function.

Tobramycin DPI is inhaled using a breath activated, hand-held device and works by decreasing the amount of bacteria (Pseudomonas aeruginosa) in the lungs. Colistimethate sodium DPI is also inhaled with a breath activated, hand-held device. It works by disrupting the structure of bacterial cells, which kills the bacteria.

This is NICE's final guidance on these technologies and now replaces local recommendations across the country.

Ends

Notes to Editors

References and explanation of terms

i. Mucolytics dissolve thick mucus and help to relieve respiratory difficulties.

About the guidance

1. The final guidance can be found from 00:01 hrs on Wednesday 27 March on the NICE website.

2. Tobramycin DPI (TOBI Podhaler, Novartis). It acts primarily by disrupting protein synthesis leading to altered cell membrane permeability, progressive disruption of the cell envelope and eventual cell death. Tobramycin inhibits protein synthesis of many gram-negative bacteria and it is active against P. aeruginosa.

3. Tobramycin DPI is administered using a TOBI Podhaler device and is indicated for the suppressive treatment of chronic pulmonary infection caused by P. aeruginosa in adults and children aged 6 years and older with cystic fibrosis.

4. The recommended dosage for tobramycin DPI is 112 mg tobramycin (4×28-mg capsules), administered twice daily for 28 days using the TOBI Podhaler device in alternating cycles of 28 days on treatment followed by 28 days off treatment. The price for a pack of 56 ×28-mg capsules and 1 Podhaler device is £447.50 (excluding VAT; ‘British National formulary' [BNF] edition 62). The list price cost for 56 days of treatment is therefore £1790 excluding VAT. Costs may vary in different settings because of negotiated procurement discounts. The manufacturer of tobramycin DPI has agreed a patient access scheme with the Department of Health, details of which are confidential.

5. The results of the economic analysis showed that tobramycin DPI consistently dominated nebulised tobramycin with inclusion of the patient access scheme, that is, there was a cost saving and QALY gain (£42,500 and 0.34 QALYs respectively, in the base case) for tobramycin DPI compared with nebulised tobramycin.

6. Tobramycin dry powder is accepted for use within NHS Scotland.

7. Colistimethate sodium dry powder for inhalation (DPI), (Colobreathe, Forest Laboratories UK), is a formulation of colistimethate sodium supplied as hard capsules for use with an inhaler. It belongs to the polymixin class of antibacterials and works by disrupting the structure of the bacterial cell membrane, leading to bacterial death. It is active against aerobic gram-negative organisms including P. aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.

8. Colistimethate sodium DPI is administered using the ‘Turbospin' device, which is a breath-activated, reusable dry powder inhaler. Colistimethate sodium DPI is indicated for the management of chronic pulmonary infections caused by P. aeruginosa in patients with cystic fibrosis aged 6 years and older.

9. The recommended dosage for colistimethate sodium DPI is 1 capsule (approximately equal to 125 mg of colistimethate sodium) to be inhaled twice daily using the ‘Turbospin' inhaler device. The price for a 28-day pack is £968 (excluding VAT; price provided by the manufacturer). The list price cost for 56 days of treatment is therefore £1936 excluding VAT. Costs may vary in different settings because of negotiated procurement discounts. The manufacturer of colistimethate sodium DPI has agreed a patient access scheme with the Department of Health, details of which are confidential.

10. The results of the economic analysis showed a small quality-adjusted life year (QALY) loss (0.13 QALYs) for colistimethate sodium DPI compared with nebulised tobramycin but also a substantial cost saving (£37,946 with the list price for nebulised tobramycin); the ICER was £288,563 saved per QALY lost.

11. Colistimethate sodium dry powder for inhalation has not yet been appraised by the Scottish Medicines Consortium.

12. People with the cystic fibrosis are prone to lung infections caused by a range of pathogens including Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa and Burkholderia cepacia. This may be because the thick mucus caused by the condition makes it difficult for the body to clear inhaled bacteria, and because people with cystic fibrosis have an increased airway inflammatory response to pathogens. The condition can also lead to pulmonary disease as well as cystic fibrosis related diabetes, male infertility and it can cause the blockage of small ducts in the liver. At present, there is no cure.

Related NICE guidance

In November 2012, NICE recommended Mannitol dry powder for inhalation for treating cystic fibrosis.

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