Budgetary Implications of Introducing the GSK Ellipta Portfolio for COPD in the UK

Transcription

1 Budgetary Implications of Introducing the GSK Ellipta Portfolio for COPD in the UK Poster No. PRS20 Harding T 1, Thompson G 1, Mulley P 2 1 Health Outcomes, UK Pharma, GlaxoSmithKline, Stockley Park, UK 2 Global Market Access, GlaxoSmithKline, Brentford, UK Aims The GSK Ellipta portfolio contains three once-daily products (Relvar Ellipta, Anoro Ellipta and Incruse Ellipta) licensed for the treatment of COPD in the UK. A budget impact model (BIM) was designed to explore the financial implications of prescribing the GSK Ellipta portfolio for new and/or existing COPD patients. The number of patients who experience symptoms of breathlessness or have an exacerbation are estimated using Clinical Practice Research Datalink (CPRD) data. The model also demonstrates the budget impact of moving a proportion of non-symptomatic patients estimated to be using non-licensed therapies or multiple inhaler devices to matched Ellipta products. The model does not explore differences in patient outcomes, efficacy or safety; it explores drug acquisition costs alone. The predicted impact of prescribing the GSK Ellipta portfolio as a treatment option in these dynamic patients is investigated in an average local health economy in the UK. The model can be amended to represent any local data. This analysis was conducted using dispensing data (PACT) from December and prices were correct and up to date in August Methods This is a one-year economic model exploring the potential budget impact of managing a modelled COPD patient population with an Ellipta based strategy compared to the range of existing treatments used in a local health economy. The model does not explore differences in outcomes, efficacy or safety; it explores drug acquisition cost alone. Model flow can be seen in Figure 1. The model utilises local dispensing information obtained from prescribing analysis and cost tabulation (PACT) 1 data and drug prices from MIMS 2 (Figure 2) as the basis of estimating the size of the local treated COPD population. The PACT data includes sales for both asthma and COPD. A Cegedim Strategic Data (CSD) national patient level data 3 report gives an estimate for the proportion of inhaler sales allocated to COPD and an average patient annual pack collection rate. A further CSD analysis 4 gives an estimate of the proportions of COPD patients using inhaled agents alone or in combinations to generate baseline cohorts of monotherapy, dual therapy and triple therapy patients, giving a means of avoiding double counting patients. In this data, a diagnosis of COPD takes precedence over a diagnosis of asthma. GSK cannot guarantee that this estimate is accurate and representative for all regions as this is based on national figures calculated from a subset of GP practices. Users may input their own estimate if alternative data is available. General Medical Services (GMS) data is used to identify a cohort of new incident COPD patients who enter the model having had no prior treatment. This model uses a Clinical Practice Research Database (CPRD) 5 data to give proportions of COPD patients who experience symptoms of moderate breathlessness (28.84%) or who might experience 1 exacerbations in a 12 months period (26.68%). A proportion of these dynamic patients will have their treatment intensified by adding a appropriate therapy in to their baseline regimen. A proportion of dynamic patients who do not have treatment intensified are moved to an Ellipta that matches their baseline treatment regimen, to factor in potential benefits from the once daily regimens and ease of device use that Ellipta offers. For new patients, the CPRD 5 data places proportions into cohorts with symptoms of mild breathlessness; moderate breathlessness or COPD exacerbation to allow an appropriate therapy to be allocated. Users have the option of overriding any of the proportions of patients who are symptomatic; who are progressed; or receive Ellipta rather than existing treatment options. The model allows the user to specify the progression routes of patients from a baseline treatment to an intensified regiment based on the symptoms that the patient is experiencing. This allows the modelling of guidelines based on COPD phenotypes with inhaled steroid-based treatment being targeted at patients with symptoms of COPD exacerbation. For patients who are not in the dynamic population, the model offers medicines optimisation with proportions to be moved to a matched Ellipta regimen. The default setting of the model target this intervention to patients who are estimated to be using ICS/LABA combination therapy that is not licensed in COPD or those using two different inhaler devices. Seretide Evohaler 250/25 mcg Flutiform MDI 250/10 mcg Seretide Accuhaler 500/50 mcg Symbicort Turbohaler 400/12 mcg Symbicort Turbohaler 200/6 mcg Duoresp 320/9 Spiromax mcg Duoresp 160/4.5 Spiromax mcg Fostair MDI 100/6 mcg Flutiform MDI 125/5 mcg Relvar Ellipta 92/22 mcg Ultibro Breezehaler Duaklir Genuair Anoro Ellipta 55/22 mcg Spiriva Handihaler [refill] 18 mcg Spiriva Respimat 2.5 mcg Eklira Genuair 322 mcg Seebri Breezhaler 50 mcg Incruse Ellipta 55 mcg Onbrez Breezhaler 300 mcg Onbrez Breezhaler 150 mcg Serevent Evohaler 25 mcg Striverdi Respimat 2.5 mcg Oxis Turbohaler 12 mcg Foradil 12 mcg Atimos Modulite 12 mcg Easyhaler Formoterol 12 mcg Figure 2. Drug Costs Off-licence ICS/LABA combinations (highlighted in grey) are included in the table below to reflect real world prescribing Results Treatment progression (814) A large proportion of COPD patients remain inadequately controlled on their current therapies. When these patients are moved to a GSK Ellipta Portfolio therapy as per clinical guideline recommendation there are budgetary implications. The BIM estimates that the average health economy (e.g. CCG) in the UK has 5518 COPD patients of whom 2753 are either new, breathless or exacerbating and therefore eligible to be progressed in their medication. Compared to baseline costs, use of current options to treat 100% of new and dynamic progressing patients would increase spend by 247,704 compared with an increase of 119,505 if matched Ellipta products were used instead. If the medicines optimisation options based on Ellipta treatment for non-dynamic patients are considered for 50% of eligible patients, prescribing costs would reduce by a further 251,614, giving a total estimated budget saving of 132,109 compared to baseline spend (Figure 3). Therefore the introduction of the GSK Ellipta portfolio in COPD has the potential to reduce the budget impact and total spend on COPD therapies by 379,812 in the average UK health economy compared to current patterns of prescribing. Conclusions The GSK Ellipta portfolio has the potential to reduce the budget impact of ICS/LABA initiation in appropriate patients compared to current prescribing patterns in the UK. The main limitation in the research is the attempt to look at an average health economy. Variability in prescribing patterns, levels of asthma control, population size, and other variables will have implications on the final budget figures when tailored for specific health regions. It is worth noting that the model does not account for the impact of the GSK Ellipta portfolio being a oncedaily dosing schedule (current alternatives are twice per day). The model assumes that patients maintain their adherence rates from their previous medication and therefore does not account for potential improvements in outcomes and control associated with one-per-day dosing of the Ellipta portfolio but also the potential increased drug acquisition cost associated with that improved adherence. References Breathless (1452) 1. Prescribing and cost tabulation (PACT) data MAT Dec Drug prices available at: [Accessed August 2015] 3. Cegedim Strategic Patient Data Report: Total Respiratory Market - Report 1 [GSK_1_001.DN2] Feb Cegedim Strategic Patient Data Report: Patient therapy combinations - Report AH [GSK7229_ADH.DN2] Feb GSK Data on File - UK/CPD/0001/14. February 2014 Acknowledgements The presenting author, Tara Harding, declares the following real or perceived conflicts of interest during the last 3 years in relation to this presentation. GSK employee and holds GSK stock. This study was funded by GSK Medicines Optimisation (637) Figure 1. Model Flow Symptomatic (2753) Patient cohort (4719) Treatment Progression (712) Exacerbating (1301) Asymptomatic (1966) Medicines Optimisation (590) No progression potential Medicines Optimisation (1966) Total number of pts is 5518, 4719 pts can be allocated to treatment specific cohorts, 159 new pts estimated to be managed on SABA alone and 640 could not be allocated to a drug specific cohort considered within the model Numbers on flow chart are subject to rounding Figure 3. COPD Budget Impact: current therapies vs. GSK Ellipta Portfolio Estimated spend ( ) 3,000,000 2,500,000 2,000,000 1,500,000 1,000, ,000 0 Average Local Health Economy Waterfall chart showing impact of current treatment options and the Ellipta portfolio on possible future spend 2,296,536 Baseline spend 247,704 Adoption using current treatment options 379,812 Adoption using Ellipta Portfolio 2,164,427 Estimated spend using Ellipta Portfolio Presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 18th Annual European Congress, Milan 9-11 Nov 2015

2 Relvar Ellipta (fluticasone furoate/ vilanterol [as trifenatate]) Prescribing information Relvar Ellipta (fluticasone furoate/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of fluticasone furoate (FF) 100 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of 92mcg FF and 22mcg VI. Each single inhalation of FF 200mcg and VI 25mcg provides a delivered dose of 184mcg of FF and 22mcg of VI. Indications: Asthma: Regular treatment of asthma in patients 12 years not adequately controlled on inhaled corticosteroids (ICS) and ''as needed short-acting inhaled β 2 -agonists, where a long-acting b 2 -agonist (LABA) and ICS combination is appropriate. COPD: Symptomatic treatment of adults with COPD with a FEV 1 <70% predicted normal (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy. Dosage and administration: Inhalation only. Asthma: Adults and adolescents 12 years: one inhalation once daily of: Relvar 92/22mcg for patients who require a low to mid dose of ICS in combination with a LABA. If patients are inadequately controlled then the dose can be increased to one inhalation once daily Relvar 184/22mcg. Relvar 184/22mcg can also be considered for patients who require a higher dose of ICS in combination with a LABA. Regularly review patients and reduce dose to lowest that maintains effective symptom control. COPD: one inhalation once daily of Relvar 92/22mcg. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate & magnesium stearate). Precautions: Pulmonary tuberculosis, severe cardiovascular disorders or heart rhythm abnormalities, thyrotoxicosis, uncorrected hypokalaemia, patients predisposed to low levels of serum potassium, chronic or untreated infections, diabetes mellitus. Paradoxical bronchospasm substitute alternative therapy if necessary. In patients with hepatic with moderate to severe impairment 92/22mcg dose should be used. Acute symptoms: Not for acute symptoms, use short-acting inhaled bronchodilator. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Therapy should not be abruptly stopped without physician supervision due to risk of symptom recurrence. Asthma-related adverse events and exacerbations may occur during treatment. Patients should continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Relvar. Systemic effects: Systemic effects of ICSs may occur, particularly at high doses for long periods, but much less likely than with oral corticosteroids. Possible Systemic effects include: Cushing s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract, glaucoma. More rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Increased incidence of pneumonia has been observed in patients with COPD receiving Relvar. Risk factors for pneumonia include: current smokers, patients with a history of prior pneumonia, patients with a body mass index <25 kg/m 2 and patients with a FEV 1 <50% predicted. If pneumonia occurs with Relvar treatment should be re-evaluated. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Relvar. Interactions with other medicinal products: Interaction studies have only been performed in adults. Avoid β-blockers. Caution is advised when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir). Concomitant administration of other sympathomimetic medicinal products may potentiate the adverse reactions of FF/VI. Relvar should not be used in conjunction with other long-acting β 2 - adrenergic agonists or medicinal products containing long-acting β 2 -adrenergic agonists. Pregnancy and breast-feeding: Experience limited. Balance risks against benefits. Side effects: Very Common ( 1/10): Headache, nasopharyngitis. Common ( 1/100 to <1/10): Candidiasis of the mouth and throat, dysphonia, pneumonia, bronchitis, upper respiratory tract infection, influenza, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, abdominal pain, arthralgia, back pain, fractures, pyrexia, muscle spasms. Other important side effects include: hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria. See SmPC for other adverse reactions. Legal category: POM. Presentation and Basic NHS cost: Relvar Ellipta. 1 inhaler x 30 doses. Relvar Ellipta 92/ Relvar Ellipta 184/ Marketing authorisation (MA) nos. 92/22mcg 1x30 doses [EU/1/13/886/002]; 184/22mcg 1x30 doses [EU/1/13/886/005]. MA holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS, UK. Last date of revision: March UK/FFT/0227/15(1). Relvar and Ellipta are registered trademarks of the GlaxoSmithKline group of companies. All rights reserved. Relvar Ellipta was developed in collaboration with Theravance Inc.

3 Anoro Ellipta (umeclidinium bromide/vilanterol [as trifenatate]) Prescribing information Anoro 55/22mcg (umeclidinium bromide /vilanterol [as trifenatate]) inhalation powder. Each single inhalation of umeclidinium (UMEC) bromide 62.5 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of UMEC 55mcg and VI 22mcg. Indications: Maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. Dosage and administration: Inhalation only. One inhalation once daily of Anoro. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate and magnesium stearate). Precautions: Anoro should not be used in patients with asthma. Treatment with Anoro should be discontinued in the event of paradoxical bronchospasm and alternative therapy initiated if necessary. Cardiovascular effects may be seen after the administration of muscarinic receptor antagonists and sympathomimetics therefore Anoro should be used with caution in patients with severe cardiovascular disease. Anoro should be used with caution in patients with urinary retention, narrow angle glaucoma, convulsive disorders, thyrotoxicosis, hypokalaemia, hyperglycaemia and severe hepatic impairment. No dosage adjustment is required in renal or mild to moderate hepatic impairment. Acute symptoms: Anoro is not indicated for acute episodes of bronchospasm. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken. Interactions with other medicinal products: Avoid β-blockers. Caution is advised when co-administering with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, itraconazole, ritonavir, telithromycin). Anoro should not be used in conjunction with other long-acting β 2 -adrenergic agonists or medicinal products containing long-acting muscarinic antagonists. Caution is advised with concomitant use with methylxanthine derivatives, steroids or non-potassiumsparing diuretics as it may potentiate possible hypokalaemic effect of β 2 -adrenergic agonists. Fertility, pregnancy, and breast-feeding: No available data. Balance risks against benefits. Side effects: Common ( 1/100 to <1/10): Urinary tract infection, sinusitis, nasopharyngitis, pharyngitis, upper respiratory tract infection, headache, cough, oropharyngeal pain, constipation and dry mouth. Other important side effects include: atrial fibrillation, supraventricular tachycardia, rhythm idioventricular, tachycardia, supraventricular extrasystoles, palpitations, and hypersensitivity reactions including rash (frequency uncommon, 1/1,000 to <1/100); hypersensitivity reactions including anaphylaxis, angioedema, and urticaria (frequency rare, 1/10,000 to <1/1,000); glaucoma (frequency not known ). See SmPC for other adverse reactions. Legal category: POM. Presentation and Basic NHS cost: Anoro Ellipta. 1 inhaler x 30 doses. Anoro Ellipta 55/22mcg Marketing authorisation (MA) no. 55/22mcg 1x30 doses [EU/1/14/898/002]; MA holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS, UK. Last date of revision: April UK/UCV/0095/15(1). Anoro and Ellipta are registered trademarks of the GlaxoSmithKline group of companies. All rights reserved. Anoro was developed in collaboration with Theravance, Inc.

4 Incruse Ellipta (umeclidinium bromide) Prescribing information Incruse Ellipta 55 (umeclidinium) inhalation powder. Each single inhalation provides a delivered dose (the dose leaving the mouthpiece of the inhaler) of 55 micrograms umeclidinium (equivalent to 65 micrograms of umeclidinium bromide). This corresponds to a pre-dispensed dose of 62.5 micrograms umeclidinium equivalent to 74.2 micrograms umeclidinium bromide. Indications: COPD: Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dosage and administration: Inhalation only. COPD: One inhalation once daily of Incruse Ellipta at the same time of the day each day. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate and magnesium stearate). Precautions: Incruse Ellipta should not be used in patients with asthma. Treatment with Incruse Ellipta should be discontinued in the event of paradoxical bronchospasm and alternative therapy initiated if necessary. Cardiovascular effects may be seen after the administration of muscarinic receptor antagonists, therefore Incruse Ellipta should be used with caution in patients with severe cardiovascular disorders, particularly cardiac arrhythmias. Incruse Ellipta should be used with caution in patients with urinary retention or narrow angle glaucoma. No dosage adjustment is required in renal or mild to moderate hepatic impairment. Acute symptoms: Incruse Ellipta is not indicated for acute episodes of bronchospasm. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken. Acute symptoms: Incruse Ellipta is not indicated for acute episodes of bronchospasm. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken. Interactions with other medicinal products: Co-administration of umeclidinium bromide with other long-acting muscarinic antagonists or medicinal products containing this active substance has not been studied and therefore, is not recommended. Fertility, pregnancy, and breast-feeding: No available human invivo data. Balance risks against benefits. Side effects: Common: nasopharyngitis, upper respiratory tract infection, headache, urinary tract infection, sinusitis, tachycardia and cough. Uncommon: pharyngitis, atrial fibrillation, supraventricular tachycardia, rhythm idioventricular, supraventricular extrasystoles, rash, dry mouth and constipation. Legal category: POM. Presentation and Basic NHS cost: Incruse Ellipta. 1 inhaler x 30 doses. Incruse Ellipta Marketing authorisation (MA) nos. 55mcg 1x30 doses [EU/1/14/922/002]; MA holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS, UK. Last date of revision: December UK/RESP/0122/14(2). Incruse and Ellipta are registered trademarks of the GlaxoSmithKline group of companies. All rights reserved.

5 Seretide Accuhaler and Evohaler (salmeterol xinafoate and fluticasone propionate) Prescribing Information (Please refer to the full Summary of Product Characteristics before prescribing) Seretide Accuhaler and Evohaler (salmeterol xinafoate and fluticasone propionate) Uses: Asthma: Regular treatment of asthma, where a long-acting β 2 agonist and inhaled corticosteroid is appropriate, i.e. patients uncontrolled on inhaled corticosteroids and 'as needed' short-acting inhaled bronchodilator or patients controlled on inhaled corticosteroid and long-acting β 2 agonist. Lowest strength Seretide (salmeterol 25mcg/fluticasone propionate 50 mcg and salmeterol 50mcg/fluticasone propionate 100 mcg) not appropriate in severe asthma. COPD: Symptomatic treatment of patients with COPD with a FEV1 <60% predicted normal (prebronchodilator) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy. Dosage and administration: Inhalation only. Asthma: Adults and adolescents 12 years and over: Seretide Accuhaler - one inhalation b.d. of: Seretide 100 (salmeterol 50 mcg/fluticasone propionate 100 mcg) or Seretide 250 (salmeterol 50 mcg/fluticasone propionate 250 mcg) or Seretide 500 (salmeterol 50 mcg/fluticasone propionate 500 mcg), Seretide Evohaler two puffs b.d. of: Seretide 50 (salmeterol 25 mcg/fluticasone propionate 50 mcg) or Seretide 125 (salmeterol 25 mcg/fluticasone propionate 125mcg) or Seretide 250 (salmeterol 25 mcg/fluticasone propionate 250 mcg). Children 4-11 years: Seretide 50 Evohaler (salmeterol 25 mcg/fluticasone propionate 50 mcg): two puffs b.d. Spacer recommended for co-ordination. Seretide 100 Accuhaler (salmeterol 50 mcg/fluticasone propionate 100 mcg) one inhalation b.d. Regularly review patients and reduce dose to lowest that maintains effective symptom control. Where the control of symptoms is maintained with the lowest strength of the combination, patients may be prescribed an inhaled corticosteroid alone, or if a long-acting β 2 agonist is required, Seretide may be given once daily. If rapid control of asthma in adults or adolescents with moderate persistent asthma (defined as patients with daily symptoms, daily rescue use and moderate to severe airflow limitation) is essential, an initial dose of two inhalations b.d of Seretide 50 Evohaler (salmeterol 25 mcg/fluticasone propionate 50 mcg) or one inhalation b.d of Seretide 100 Accuhaler (salmeterol 50 mcg/fluticasone propionate 100 mcg) may be considered on a shortterm basis. Once control of asthma is attained treatment should be regularly reviewed and stepped down. Doubling the dose of all strengths of Seretide may be considered when adult patients require additional short-term (up to 14 days) inhaled corticosteroid therapy but this causes a small increase in β-agonist-related adverse events. COPD: one inhalation b.d. of Seretide 500 Accuhaler (salmeterol 50mcg/fluticasone propionate 500 mcg). Contraindications: Hypersensitivity to the active ingredients or to any of the excipients. Precautions: Pulmonary tuberculosis, fungal, viral or other infections of the airway, severe cardiovascular disorders, heart rhythm abnormalities, diabetes mellitus, hypokalaemia and thyrotoxicosis. Increased reporting of pneumonia and bronchitis in patients with COPD receiving Seretide compared with placebo. If a patient with severe COPD has experienced pneumonia, treatment with Seretide should be re-evaluated. Paradoxical bronchospasm post dose. Severe unstable asthma: Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Consider increased inhaled/additional corticosteroid therapy. Acute symptoms: Not for acute symptoms. Use short-acting inhaled bronchodilator. Systemic effects: Systemic effects of inhaled corticosteroids may occur, particularly at high doses for prolonged periods, but much less likely than with oral corticosteroids. May include Cushing s syndrome, cushingoid features, adrenal suppression, adrenal crisis, growth retardation in children and adolescents, decrease in bone mineral density, cataract, glaucoma and, more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Monitor height of children on prolonged inhaled corticosteroid therapy. Tremor, palpitations and headache, have been reported with β 2 agonist treatment. In asthma, therapy should be down titrated under physician supervision to lowest effective dose and treatment should not be abruptly stopped due to risk of exacerbation. Serious asthma-related adverse events and exacerbations may occur during treatment with Seretide. Patients should not be initiated on Seretide during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Data from a large asthma trial suggested patients of black African or Afro-Caribbean ancestry were at increased risk of serious respiratory-related events or deaths when using salmeterol. All patients should continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen when initiated on Seretide or using Seretide. In COPD cessation of therapy may also be associated with decompensation and should be supervised by a physician. Transfer from oral steroids: Special care needed. Consider appropriate steroid therapy in stressful situations. Drug interactions: Avoid betablockers. Avoid concomitant administration of ketoconazole or other potent (e.g. itraconazole, telithromycin, ritonavir) and moderate (erythromycin) CYP3A4 inhibitors unless benefits outweigh potential risk. β 2 adrenergic blockers may weaken or antagonise the effect of salmeterol. ly serious hypokalaemia may result from β 2 agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics. Pregnancy and lactation: Experience limited. Balance risks against benefits. Side effects: Very Common: headache, nasopharyngitis. Common: candidiasis of the mouth and throat, hoarseness/dysphonia, throat irritation, pneumonia, bronchitis, hypokalaemia, sinusitis, contusions, traumatic fractures, arthralgia, myalgia, muscle cramps. Uncommon: respiratory symptoms (dyspnoea), anxiety, tremor, palpitations, tachycardia, angina pectoris, atrial fibrillation, cutaneous hypersensitivity reactions, hyperglycaemia, sleep disorders, cataract. Rare: angioedema, respiratory symptoms (bronchospasm), anaphylactic reactions including anaphylactic shock, Cushings syndrome, cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, oesophageal candidiasis, behavioural changes including psychomotor hyperactivity and irritability (predominately in children), glaucoma, cardiac arrhythmias and paradoxical bronchospasm. Not known: depression or aggression (particularly in children). Paradoxical bronchospasm: substitute alternative therapy. Legal category: POM. Presentation and Basic NHS cost: Accuhaler 60 inhalations. Seretide Seretide Seretide Evohaler 120 inhalations. Seretide Seretide Seretide Product Licence (PL) nos: 10949/ , 10949/ PL holder: Glaxo Welcome UK Limited, trading as GlaxoSmithKline UK, Stockley Park West, Uxbridge, UB11 1BT. Last date of revision: May 2015; UK/RESP/0333/14(1). Seretide, Accuhaler and Evohaler are registered trademarks of the GlaxoSmithKline Group of Companies. For the UK, further information is available from Customer Contact Centre, GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex UB11 1BT; customercontactuk@gsk.com; Freephone: