Medicines Management of Chronic Obstructive Pulmonary Disorder (COPD)

Medicines Management of Chronic Obstructive Pulmonary Disorder (COPD) Guidelines for Primary Care Guideline Authors: Shaneez Dhanji (NHS Wandsworth) and Reena Rabheru-Dodhy (NHS Sutton & Merton) Date Prepared: May 2010 Date Approved: August 2010 Date Updated: February 2012 Date Approved: Date for Review: February 2014

Medicines Management of Chronic COPD All COPD patients still smoking, regardless of age, should be encouraged to stop, and offered help (including drug therapy) to do so, at every opportunity. Contact the Stop Smoking Service on 020 8812 7794 for NHS Wandsw orth or 0800 652 8019 for NHS Sutton & Merton This algorithm outlines the treatment pathway for symptoms of COPD. (Refer to Wandsworth COPD Pathway for other management of COPD) Patients should have a diagnosis of COPD, confirmed by post-bronchodilator spirometry. The choice of drug should take into account the patient s response to a trial of the drug, side effects, patient preference, potential to reduce exacerbations and cost. Some patients may require unlicensed doses and devices and this should be decided on an individual basis, with specialist input. It is good practice to review all new treatment intitated and check inhaler technique regularly. Add Long Acting Beta Agonist (LABA) Formoterol 12mcg BD( 24.80) OR Salmeterol 50mcg BD ( 29.26) Continue SABA or SAMA prn FEV 1 > 50% Exacerbations or Persistent breathlessness FEV 1 < 50% or Add Long Acting Muscarinic Antagonist (LAMA) Tiotropium Handihaler 18mcg OD ( 34.87) Continue SABA prn. Discontinue SAMA If the patient does not demonstrate satisfactory technique, consider Tiotropium Respimat 2.5mcg; 2 puffs OD. Use with caution in patients with known cardiac rhythm disorders MHRA advice (see Appx 1) Exacerbations or Persistent breathlessness LABA + Inhaled Corticosteroid (ICS) in a combination inhaler Fluticasone/Salmeterol (Seretide ) 500mcg/50mcg Accuhaler: 1 puff BD( 40.92) OR Budesonide/Formoterol (Symbicort ) Turbohaler: 200mcg/6mcg: 2 puffs BD or 400mcg/12mcg: 1 puff BD ( 38.00) If ICS declined or not tolerated, consider LABA + LAMA Breathlessness and/or Exercise limitation Assess symptoms, severity and disability and manage as below Short-acting beta agonist (SABA)- Salbutamol 100mcg; 2 puffs PRN ( 1.50) AND / OR Short-acting muscarinic antagonist (SAMA) Ipratropium 20mcg; 2 puffs PRN ( 5.05) If patient does not demonstrate satisfactory technique, add spacer device or change device Be aware of the potential risk of developing side effects (including non-fatal pneumonia) in people with COPD treated with high-dose inhaled corticosteroids. Note: Seretide Evohaler is not licensed in COPD. However, if this is the most suitable device for the patient, consider using a spacer Continual exacerbations or persistent COPD symptoms, irrespective of FEV 1 Chronic cough / Sputum production: Consider a trial of carbocisteine capsules 750mg tds for 6-8 weeks then 750mg bd if there is an improvement in sputum production and reduction in viscosity. For futher information, see Appendix 2. Consider theophylline in certain situations (see additional information). Caution in elderly patients and smokers due to pharmacokinetic Produced for use differences. in NHS Wandsworth Prescribe only by brand name only. Monitor plasma levels and drug interactions (check BNF). Pneumococcal vaccination and annual influenza vaccination should be offered to all patients with COPD.. LAMA + LABA + Inhaled Corticosteroid (ICS) in a combination inhaler

Medicines Management of Chronic Obstructive Pulmonary Disease (COPD) For the management of COPD, this fact sheet must be read in conjunction with NICE guidelines 1 and Wandsworth COPD Pathway 2. The main treatment goals are to reduce exacerbations, reduce hospital admissions and to improve patient s quality of life. All patients who smoke should be encouraged to stop smoking and offered help at every opportunity as smoking cessation is one of the most important components of their treatment 1. For further information regarding smoking cessation services, contact the local Stop Smoking Services. Key Messages Inhaled short acting beta-2 agonists (SABA) or short acting muscarinic antagonists (SAMA) should be used as required for the relief of breathlessness in mild COPD. A combination of both can be used if the patient remains symptomatic on single therapy. Long acting beta-2 agonists (LABA) or long acting muscarinic antagonists (LAMA) should be used to control symptoms in patients with stable COPD who remain breathless or have exacerbations despite using short acting bronchodilators as necessary with an FEV 1 of 50% or greater.(once daily LAMA usage is recommended in preference to four-times-daily SAMA usage in patients with stable COPD. Discontinue SAMA if using LAMA refer to Tiotropium guidelines Appendix 1 for further information 4 ) Remember Inhaled inhaler corticosteroid technique (ICS) needs with to be LABA checked combination regularly and inhaler spacers should prescribed used with to control metered symptoms dose inhalers patients 2. with stable COPD who remain breathless or have exacerbations, with an FEV 1 of less than 50% despite therapy with a SABA, SAMA or LAMA. A combination of an ICS + LABA inhaler and a LAMA inhaler is recommended for patients with continual exacerbations or persistent COPD symptoms, irrespective of FEV1. 1 Care must be taken regarding potential risk of developing side effects (including non-fatal pneumonia) in patients treated with high dose inhaled corticosteroids the risks should be discussed with the patient. Additional information: The choice of drug(s) should take into account the patient s response to a trial of the drug, the drug s side effects, patient preference and cost. Patients should have their inhaler technique reviewed by a competent healthcare professional to ensure they are using it correctly. 1 Other treatments: Prednisolone (oral corticosteroid) 30mg daily for 7-14 days 3 is recommended in the treatment of COPD exacerbations for all patients with significant increase in breathlessness and all hospital admitted patients, unless contraindicated 1. Maintenance use of oral corticosteroids is not normally recommended. In cases where maintenance therapy is appropriate, the lowest possible dose should be used. Patient response to oral corticosteroids cannot be used to predict response to inhaled corticosteroid therapy, and should not be used to identify patients suitable for inhaled corticosteroids. Osteoporosis prophylaxis should be considered for patients requiring frequent courses or a maintenance dose of oral corticosteroids. e.g. Adcal D3. Theophylline has a limited place in therapy and should only be used after a trial of SABA and LABA inhalers or in patients who are unable to use inhaled therapies. Theophylline levels need to be monitored at least annually or more often if toxicity is suspected. Levels should be between 10-20mg/litre. Common signs of toxicity include tachycardia, palpitations, nausea and headache. Particular caution should be taken in the elderly as the plasma theophylline concentration is increased in this group of patients. Mucolytics (e.g. carbocysteine) can be considered in patients with a chronic productive cough of sputum. Treatment should only be continued if there is symptomatic improvement (e.g. reduction in cough frequency or sputum). Mucolytics should not be routinely used as prevention of an exacerbation in patients with stable COPD. For further information see Appendix 2 5. Pneumococcal vaccination and an annual influenza vaccination should be offered to all patients with COPD 1. Oral antibiotics are recommended for exacerbations causing purulent sputum. Prophylactic antibiotics is not recommended in the management of stable COPD 3. For further information refer to WPCT Primary Care antibiotic guidelines. Roflumilast is recommended by NICE, only in the context of research as part of a clinical trial for adults with severe COPD (FEV 1 post-bronchodilator < 50% predicted) associated with chronic bronchitis with a history of frequent exacerbations as an add-on to bronchodilator treatment 6. Long-term, short-term and ambulatory oxygen therapy is also recommended for patients meeting necessary criteria 1 - Refer to the Community Respiratory Nurse Specialist.

Combination Therapy Corticosteroids Anticholinergic Beta2-agonists Table 1: Cost comparison of 30 days of treatment of beta 2 agonists, corticosteroid, anticholinergic and combination inhalers Salbutamol 100mcg MDI Inhaler Salbutamol 200mcg Accuhaler Terbutaline 500mcg Turbohaler Formoterol Fumarate 12mcg Turbohaler Salmeterol 50mcg Accuhaler Salmeterol 25mcg MDI Inhaler 1.50 4.92 6.92 24.80 29.26 29.26 Ipratropium 20mcg MDI Inhaler Tiotropium 18mcg Inhaled Capsules 5.05 34.87 Fluticasone 100mcg Accuhaler Budesonide 200mcg Turbohaler Budesonide 400mcg Turbohaler Fluticasone 125mcg Evohaler Fluticasone 250mcg Accuhaler Fluticasone 250mcg Evohaler Fluticasone 500mcg Accuhaler 8.93 11.84 13.86 21.26 21.26 36.14 36.14 Fluticasone and Salmeterol 100/50 Accuhaler Fluticasone and Salmeterol 250/50 Accuhaler Fluticasone and Salmeterol 125/25 Evohaler Budesonide and Formoterol Turbohaler 400/12 Budesonide and Formoterol Turbohaler 200/6 Fluticasone and Salmeterol 500/50 Accuhaler Fluticasone and Salmeterol 250/25 Evohaler 18.00 35.00 35.00 38.00 38.00 40.92 59.48 0 10 20 30 40 50 60 70 Drug Tariff Feb 2012 (prices are subject to change) References: 1. National Institute for Health and Clinical Excellence. Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care (partial update). Clinical Guideline No. 101 June 2010 2. NHS Wandsw orth COPD pathw ay 3. WPCT Primary Care Antibiotic Guidelines 2008 4. Guidance on the use of Tiotropium in patients w ith COPD. May 2010 (Appendix 1) 5. Guidance on the use of Mucolytics in patients w ith COPD. May 2010 (Appendix 2) 6. National Institute for Health and Clinical Excellence. Roflumilast for the management of severe chronic obstructive pulmonary disease. Technology Appraisal Guidance 244. January 2012

Appendix 1 Guidance on the use of Tiotropium in patients with Chronic Obstructive Pulmonary Disease (COPD) Introduction Tiotropium is a long-acting muscarinic antagonist (LAMA), recommended as a treatment option in people with stable COPD who remain breathless or have exacerbations despite using short-acting bronchodilators 1. Licensed Indication 2,3 Tiotropium is indicated as a maintenance bronchodilator treatment to relieve symptoms of patients with chronic obstructive pulmonary disease (COPD) It is not to be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy. Co-administration of tiotropium with other anticholinergics, e.g. ipratropium has not been studied and is therefore not recommended. Prescribing of Tiotropium (Refer to algorithm of chronic COPD) Stop Ipratropium in patients who are commenced on tiotropium. There is no data on the co-administration of tiotropium with other anticholinergics and therefore it is not recommended 1. Offer Tiotropium (LAMA) in addition to LABA, where ICS is declined or not tolerated 1. There is some evidence that suggests that inhaled anticholinergic drugs (e.g. tiotropium and ipratropium) increase the risk of cardiovascular (CV) events for patients with COPD compared with placebo or active comparators (inhaled ICS and β 2 -agonists). However the precise magnitude of this increase is uncertain. Bear this in mind when weighing up the benefits to risks of treatment 4. Recent data on the CV safety concerns about ipratropium (and to a lesser extent tiotropium) come from observational studies and retrospective pooled analyses of data. These have inherent limitations and only flag up potential safety issues, not confirm them. The UPLIFT trial and the recent report from the tiotropium trial database are reassuring about the safety of tiotropium. However, continued monitoring of both ipratropium and tiotropium is required 5. When decisions are made around which bronchodilator to use, NICE advises that choice in individual patients should take account of their response to a trial of the drug, the drug s side effects, patient preference and cost. This new safety data, as well as the potential benefits from treatment, should also feature in these decisions. However, the individual choice will probably depend more on whether they can use the inhaler device, tolerate the drug and how effective the medication is for their symptoms 5. The MHRA advises that Spiriva Respimat should be used with caution in patients with known cardiac rhythm disorders 6. Refer to the SPC for further information. Report suspected adverse reactions on a Yellow Card at www.yellowcard.gov.uk Choice of device This should be based on patient preference and ability to use the different devices. Handihaler -this device may be difficult for elderly and infirm patients to use. Could not find in SPC## Respimat - this device could be used in patients who have poor manual dexterity, and who have difficulty using the Handihaler device 4. A gentler longer inhalation is required, which may be difficult to manage by some patients. Therefore inhaler technique should be assessed.

Dose 2,3 (check BNF for latest dose) Handihaler - Adults over 18 years: one capsule (18mcg) is inhaled once daily at the same time of day. Refills are also available to prescribe. Respimat - Adults over 18 years: 2 puffs (5mcg) to be inhaled once daily at the same time of day. Monitoring Response in terms of symptomatic relief and quality of life are important. Patient s response should be reviewed after commencing tiotropium. Check any improvement in symptomatic control, wheezing and shortness of breath on exertion Any reduction in the use of short acting bronchodilators Check dose compliance and ability to use the device Patients who have not demonstrated an improvement, consider discontinuing treatment. Adverse Effects 2,3 (See SPC for full list) Dry mouth most common Pharyngitis - uncommon Atrial fibrillation - uncommon Palpitations - uncommon Special precautions 2,3 Patients using the Handihaler or Respimat should be advised to avoid getting the medication into their eyes as it may precipitate or worsen narrow angled glaucoma. Cautions and Contraindications 2,3 (see SPC for full list) Tiotropium should be used with caution in patients with narrow angle glaucoma, prostatic hyperplasia or bladder neck obstruction. Tiotropium is contraindicated in patients with hypersensitivity to either tiotropium bromide, atropine or its derivatives e.g. ipratropium or to the exipients. References 1. National Institute for Health and Clinical Excellence. Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care (partial update). Clinical Guideline No. 101 June 2010. 2. Spiriva 18mcg inhalation powder, hard capsules (tiotropium), SPC, updated 24/08/2010. [online] http://www.medicines.org.uk/emc/. Accessed 06/02/12. 3. Spriva Respimat 2.5mcg solution of inhalation (tiotropium), SPC, updated 18/08/2010. [online] http://www.medicines.org.uk/emc/. Accessed 06/02/12. 4. NPC MeReC Extra issue no.37. January 2009. Anticholinergics in COPD. [online] http://www.npc.co.uk/ebt/merec/resp/copd/merec_extra_no37.htm. Accessed 02/08/10 5. NPC MeReC Rapid Review. Cardiovascular safety of anticholinergics in COPD, 25 March 2010. [online] http://www.npci.org.uk/blog/?p=1214. Accessed 02/08/10 6. MHRA Drug Safety Update November 2011, Vol 4, Issue 4.

Appendix 2 Guidance on the use of Mucolytics in Chronic Obstructive Pulmonary Disorder (COPD) Introduction Consider mucolytic therapy for patients with a chronic cough productive of sputum, including COPD 1.Mucolytics can help increase the ability to expectorate sputum by reducing its viscosity. Treatment with mucolytic agents has shown a small but significant reduction in acute exacerbations and total number of days disability. It has been suggested if patients take mucolytics regularly through the winter months, it could result in a 20% reduction in exacerbations, which in turn may prevent hospitalisations. They are safe and well tolerated 2. Licensed Indications Mucolytics are used for adjunctive therapy for respiratory tract disorders characterised by excessive, vis cous mucus to help increase the ability to expectorate sputum by reducing its viscosity. Treatment should be continued if there is symptomatic improvement i.e. a reduction in frequency of cough and sputum production. Place in Therapy Patients should have a confirmed diagnosis of COPD with a chronic cough and sputum production Patients should have a cough and sputum on most days for 3 months in 2 consecutive years Patients should be in a chronic, stable, but symptomatic state Exclude differential diagnosis such as bronchiectasis, rhinitis, post nasal drip, lung cancer Dose 3 Carbocisteine is available in capsule and liquid preparations Initially 2250mg daily in divided doses (375mg capsules x 2 tds or 15mls liquid tds) and reducing to 1500mg daily in divided doses (375mg capsules x 1 qds or 10mls liquid tds) Monitoring Patients should be reviewed after one month of commencing treatment. Only continue with carbocisteine if there is a reported reduction in frequency of cough and sputum production and that the patient perceives a benefit in the mucolytic treatment 1. Do not routinely use for the prevention of exacerbations in stable COPD 1. References 1. National Institute for Health and Clinical Excellence. Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care (partial update). Clinical Guideline No. 101 June 2010. 2. The Cochrane Library 2006 Issue 3. Poole P and Black P. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease (review). The Cochrane Library Issue 3. 2006; Article No. CD001287.DOI:10.1002/14651858.CD001287.pub2. 3. Mucodyne capsules (carbocisteine), SPC, updated 20/04/2009. [online] http://www.medicines.org.uk/emc/. Accessed 02/08/10..

Acknowledgements Ioulia Mariaki Nikki Davies Vanessa Flagg Wendy Kong Dr Charlotte Levitt Louise Paterson Lisa Ronson David Tambyrajah Nick Beavon Pamela Nyatanga Samantha Prigmore Helen Parnell Dr Veronica Varney Anne Lowson Dr Simon Elliott Fiona White Sedina Agama Jan Walker Julia Russell Respiratory Clinical Nurse Specialist, NHSW Respiratory Clinical Nurse Specialist, NHSW Long Term Conditions Development Manager, NHSW Respiratory Clinical Nurse Specialist, NHSW GP, St Paul s Cottage Surgery & PBC rep NHSW Physiotherapist, Brysson Whyte Rehab Physio, St George s Hospital Community Pharmacy Lead, NHSW Chief Pharmacist, NHSW Respiratory Pharmacist, St George s Hospital Respiratory Nurse Consultant, St George s Hospital Respiratory Specialist Nurse, St Helier Respiratory Consultant, St Helier Hospital Formulary Pharmacist, St Helier Hospital GP, Robin Hood HealthCentre & GP Medicines Management Lead NHSSM Nurse Consultant in Primary Care, NHSSM Pharmaceutical Advisor, NHSSM Specialist Respiratory Nurse, NHSSM Specialist Respiratory Nurse, NHSSM