VERDICT & SUMMARY Erdosteine (Erdotin®▼)

For acute exacerbations of chronic bronchitis

Committee’s Verdict: Category D BNF: 3.7 Erdosteine is not considered suitable for prescribing. Current clinical evidence for the efficacy of erdosteine for its licensed indication is weak, with no evidence for improved clinical outcomes or quality of life. Its place in therapy for acute exacerbations of chronic bronchitis is unclear. NICE guidelines recommend the use of mucolytic drugs for longer-term use in stable chronic obstructive pulmonary disease. Mucolytic drugs are not mentioned for the treatment of acute exacerbations. Category D: cannot be recommended for prescribing because of inadequate evidence for efficacy and/or safety

MTRAC reviewed this drug because it is a newly licensed drug with potential for prescribing in primary care. Licensed indication • give oral antibiotics if the sputum is purulent As an expectorant. For the symptomatic treatment of • give prednisolone 30 mg daily for 7 to 14 days for acute exacerbations of chronic bronchitis in adults.1 all patients with significant increase in breathlessness, and all patients admitted to Background information hospital, unless contraindicated. Chronic bronchitis is defined as the presence of Most patients with an exacerbation can be managed chronic productive cough for three months in each of at home but a few need hospital treatment (e.g. those two successive years in a patient in whom other showing cyanosis, an impaired level of consciousness, those confined to bed or unable to causes of chronic cough such as tuberculosis, 6 carcinoma of the lung and heart failure have been cope alone). 2 excluded. Individuals with chronic bronchitis may The NICE guideline recommended a trial of mucolytic suffer recurrent, infective exacerbations with an therapy only in patients with stable COPD and a increase in volume or purulence of sputum. These chronic productive cough.5 exacerbations contribute to morbidity and poorer health as well as to increased healthcare costs. Erdosteine is a mucolytic drug licensed for short-term Chronic bronchitis is one of the main contributing use as an expectorant for the treatment of acute conditions in chronic obstructive pulmonary disease exacerbations of chronic bronchitis. (COPD), a disease characterised by airflow limitation Clinical efficacy that is not fully reversible.2 Eight randomised controlled trials (RCTs) were Nearly 900,000 people in the UK have been identified that evaluated erdosteine in patients with diagnosed with COPD, and about 1,500,000 may be 3 chronic bronchitis. Five of the trials did not evaluate living with undiagnosed COPD. In patients admitted erdosteine for its licensed indications and were to hospital in the UK with an exacerbation of COPD, a excluded from this review. retrospective audit of 1,400 admissions showed that 34% were re-admitted, and 14% died within three The included trials were three double-blind RCTs that months of admission.4 compared erdosteine with placebo in combination with amoxicillin,7 ciprofloxacin8 or unspecified antibiotics9 In 1999, there were approximately 30,000 deaths due 3 in 465 patients experiencing an acute exacerbation of to COPD in the UK, representing 5% of all deaths. chronic bronchitis. The patients received seven to ten Five-year survival from diagnosis is 78% in men and days’ drug treatment. 72% in women with mild disease, but falls to 30% in men and 24% in women with severe disease.3 The outcome measures in two of the studies7,8 were the changes from baseline to the end of treatment in The National Institute for Health and Clinical scores relating to the severity of six symptoms of Excellence (NICE) produced a clinical guideline for exacerbated chronic bronchitis: appearance and the management of COPD in adults in primary and 5 viscosity of sputum, difficulty in expectorating, catarrh secondary care in 2004. According to this guideline, at auscultation, cough, and intensity of dyspnoea. initial management of an exacerbation should include These two studies reported the change in average or the following: total scores for the six symptoms. • increase the frequency of bronchodilator use and The third study reported the percentage reduction in consider giving via a nebuliser scores for a similar set of symptoms individually:

November 2007 Page 1 of 2 cough intensity and frequency, catarrh, sputum • At current prices, ten days’ treatment with adhesiveness, purulence and volume. erdosteine costs £5. The two larger studies (n = 237, 200),7,8 reported a References significantly greater reduction in the average symptom score for patients treated with erdosteine in addition to 1. Galen Ltd. Erdotin 300 mg capsules. Summary of amoxicillin or ciprofloxacin than for patients treated Product Characteristics. 2007. http://www.emc.medicines.org.uk/ with the antibiotic alone (plus placebo). In one study,7 2. Poole PJ, Black PN. Mucolytic agents for chronic there was a 2-point greater reduction (on a scale of 0 bronchitis or chronic obstructive pulmonary disease. to 18) for the combination of erdosteine plus Cochrane Database of Systematic Reviews 2006. amoxicillin compared with amoxicillin plus placebo 3. National Collaborating Centre for Chronic Conditions. (reduction in sum of average symptom scores of 7.33 National Clinical Guideline on management of vs. 5.32 points for placebo, p < 0.01). The second chronic obstructive pulmonary disease in adults in study8 reported the average of the score variations for primary and secondary care: Introduction and the six symptoms to be 3.03 points for erdosteine preface. Thorax 2004;59:1-6. treatment vs. 2.33 points for placebo (p = 0.01). 4. Roberts CM, Lowe D, Bucknall CE et al. Clinical audit indicators of outcome following admission to There was insufficient description of the rating scale hospital with acute exacerbation of chronic used to enable determination of the score range and obstructive pulmonary disease. Thorax 2002;57:137- thus the magnitude of the results reported. 141. In the third study (n = 28),9 the percentage reduction 5. National Institute for Health and Clinical Excellence. CG12: Management of chronic obstructive pulmonary for cough intensity and frequency, catarrh and sputum disease in adults in primary and secondary care. adhesiveness was significantly greater for erdosteine NICE. 2004. http://guidance.nice.org.uk/CG12 (plus antibiotic) treatment than with antibiotic (plus 6. National Collaborating Centre for Chronic Conditions. placebo) treatment alone (percentage reductions National Clinical Guideline on management of ranged from 50 to 67% vs. 15 to 27%). There was no chronic obstructive pulmonary disease in adults in significant difference between treatment groups for primary and secondary care: Management of the other symptoms: sputum purulence or volume.9 exacerbations of COPD. Thorax 2004;59:131-156. 7. Marchioni CF, Polu JM, Taytard A et al. Evaluation Adverse effects of efficacy and safety of erdosteine in patients affected by chronic bronchitis during an infective The most commonly reported adverse events with exacerbation phase and receiving amoxycillin as erdosteine treatment were headache and basic treatment (ECOBES, European Chronic gastrointestinal disorders: epigastralgia, nausea and Obstructive Bronchitis Erdosteine Study). Int J Clin diarrhoea.7-9 Pharmacol Ther 1995;33:612-618. 8. Mohanty KC, et al. Evaluation of efficacy and safety Additional information of erdosteine in patients affected by exacerbation of chronic bronchitis and receiving ciprofloxacin as • The recommended dose of erdosteine is 300 mg basic treatment. J Clin Res 2001;4:35-39. twice daily for a maximum of ten days.1 9. Bisetti A, Mancini C. Mucolytic activity of erdosteine: double blind clinical trial vs placebo. Arch Med Interna 1995;47:89-97.

Launch date: November 2006 Manufacturer: Galen Ltd PL 14682/0012 WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics This guidance is based upon the published information available in English at the time the drug was considered. It remains open to review in the event of significant new evidence emerging. MTRAC can be contacted at the Dept. of Medicines Management, Keele University, Keele, Staffs ST5 5BG Tel: 01782 584131 Fax: 01782 713586 Email: [email protected] Web: www.mtrac.co.uk No guidance from NICE for erdosteine was available at the time of issue of this verdict Date: November 2007 ©Midlands Therapeutics Review & Advisory Committee VS07/22