Prescribing Information

Trimbow 87/5/9 and 172/5/9 pMDI & Trimbow 88/5/9 NEXThaler (DPI)

Please refer to the Summary of Product Characteristics (SPC) before prescribing. Presentation: Each Trimbow 87/5/9 pMDI delivered dose contains 87micrograms (mcg) of beclometasone dipropionate (BDP), 5mcg of formoterol fumarate dihydrate (formoterol) and 9mcg of glycopyrronium. Each Trimbow 88/5/9 NEXThaler delivered dose contains 88 micrograms of BDP, 5 micrograms of formoterol and 9 micrograms of glycopyrronium. These are both the equivalent to a metered dose of 100mcg BDP, 6mcg formoterol and 10mcg glycopyrronium. Each Trimbow 172/5/9 pMDI delivered dose contains 172mcg of BDP, 5mcg of formoterol and 9mcg of glycopyrronium. This is equivalent to a metered dose of 200mcg BDP, 6mcg formoterol and 10mcg glycopyrronium. Indication: COPD (Trimbow 87/5/9 pMDI and Trimbow 88/5/9 NEXThaler only): Maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist or a combination of a long-acting beta2-agonist and a long-acting muscarinic antagonist (for effects on symptoms control and prevention of exacerbations see section 5.1 of the SPC). Asthma (Trimbow 87/5/9): Maintenance treatment of asthma, in adults not adequately controlled with a maintenance combination of a long-acting beta2-agonist and medium dose of inhaled corticosteroid, and who experienced one or more asthma exacerbations in the previous year. Asthma (Trimbow 172/5/9): Maintenance treatment of asthma, in adults not adequately controlled with a maintenance combination of a long-acting beta2-agonist and high dose of inhaled corticosteroid, and who experienced one or more asthma exacerbations in the previous year. Dosage and administration: For inhalation in adult patients (≥18 years). COPD & Asthma: 2 inhalations twice daily. Maximum dose 2 inhalations twice daily. Trimbow pMDI can be used with the AeroChamber Plus^® spacer device. Patients should be advised to take Trimbow every day even when asymptomatic. If symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be used for immediate relief. When choosing the starting dose strength of Trimbow in asthma patients, the patients’ disease severity, their previous asthma therapy including the inhaled corticosteroid (ICS) dose as well as the patients’ current control of asthma symptoms and risk of future exacerbation should be considered. Patients should be regularly reassessed by a doctor, so that their doses of Trimbow remain optimal and are only changed on medical advice. The doses should be titrated to the lowest doses at which effective control of asthma symptoms is maintained. The aerosol particles of Trimbow are characterised by an extrafine particle size distribution. For BDP this results in a more potent effect than formulations of BDP with a non-extrafine particle size distribution (100mcg of BDP extrafine in Trimbow are equivalent to 250mcg of BDP in a non-extrafine formulation). Contraindications: Hypersensitivity to the active substances or to any of the excipients. Warnings and precautions: Not for acute use in treatment of acute episodes of bronchospasm or to treat an acute disease exacerbation. Discontinue immediately if hypersensitivity or paradoxical bronchospasm occur. Deterioration of disease: Trimbow should not be stopped abruptly. Cardiovascular effects: Due to the presence of a long-acting beta2-agonist and a long-acting muscarinic antagonist, use with caution in patients with cardiac arrhythmias, idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart disease, occlusive vascular diseases, arterial hypertension and aneurysm. Caution should also be used when treating patients with known or suspected prolongation of the QTc interval (QTc > 450 milliseconds for males, or > 470 milliseconds for females) either congenital or induced by medicinal products. Limited data in asthmatic patients with cardiovascular co-morbidities or risk-factors suggest that these patients are also at higher risk of adverse reactions like local fungal infections or dysphonia. Trimbow should not be administered for at least 12 hours before the start of anaesthesia as there is a risk of cardiac arrhythmias. Caution in patients with thyrotoxicosis, diabetes mellitus, pheochromocytoma and untreated hypokalaemia. Increase in pneumonia and pneumonia hospitalisation in COPD patients receiving ICS observed. Clinical features of pneumonia may overlap with symptoms of COPD exacerbations. Systemic effects of ICS may occur, particularly at high doses for long periods, but are less likely than with oral steroids. The daily dose of both Trimbow 87/5/9 & 88/5/9 correspond to a medium dose of ICS and the daily dose of Trimbow 172/5/9 corresponds to a high dose of ICS. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation, decrease in bone mineral density and, more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression and aggression. Patients on Trimbow should be reviewed regularly and the dose of ICS is reduced to the lowest dose at which effective control of asthma is maintained. Use with caution in patients with pulmonary tuberculosis or fungal/viral airway infections. Potentially serious hypokalaemia may result from beta2-agonist therapy (particular caution with severe disease). Formoterol may cause a rise in blood glucose levels. Glycopyrronium should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or urinary retention. 

Use in patients with severe hepatic impairment (classified as having Child-Pugh class C) or severe renal impairment (glomerular filtration rate [GFR] <30mL/min/1.73m²), should only be considered if benefit outweighs the risk. Consider referral of patients reporting blurred vision or visual disturbances to an ophthalmologist as causes may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy. To reduce risk of oropharyngeal candida infection, patients should be advised to rinse mouth or gargle with water without swallowing or brush teeth after inhaling prescribed dose. Trimbow 88/5/9 NEXThaler contains lactose. Lactose includes small amounts of milk proteins, which may cause allergic reactions. Interactions: Since glycopyrronium is eliminated via renal route, interactions could occur with medicinal products affecting renal excretion mechanisms e.g. with cimetidine (an inhibitor of OCT2 and MATE1 transporters in the kidney) co-administration, glycopyrronium showed a slight decrease in renal clearance (20%) and a limited increase in total systemic exposure (16%). Possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded and therefore caution and appropriate monitoring is advised. Related to formoterol: Non-cardioselective beta-blockers (including eye drops) should be avoided as reduces effect of formoterol. Concomitant administration of other beta-adrenergic drugs may have potentially additive effects. Concomitant treatment with quinidine, disopyramide, procainamide, antihistamines, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants and phenothiazines can prolong the QTc interval and increase the risk of ventricular arrhythmias. L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2-sympathomimetics. Hypertensive reactions may occur following co-administration with MAOIs including drugs with similar properties (e.g. furazolidone, procarbazine). Risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons. Concomitant treatment with xanthine derivatives, steroids or diuretics may potentiate a possible hypokalaemic effect of beta2-agonists. Hypokalaemia may increase the likelihood of arrhythmias in patients receiving digitalis glycosides. Related to glycopyrronium: Co-administration with other anticholinergic-containing medicinal products is not recommended. Excipients: Presence of ethanol in Trimbow 87/5/9 and 172/5/9 pMDI may cause theoretical potential interaction in sensitive patients taking metronidazole or disulfiram. Fertility, pregnancy and lactation: No studies have been performed in regards to safety in human fertility, but animal studies show impaired fertility. Should only be used during pregnancy if the expected benefits outweigh the potential risks. If treatment during pregnancy is necessary, the lowest effective dose should be used. Children born to mothers receiving substantial doses should be observed for adrenal suppression. Glucocorticoids and metabolites are excreted in human milk. It is unknown whether formoterol or glycopyrronium (including their metabolites) pass into human breast-milk but they have been detected in the milk of lactating animals. Anticholinergics like glycopyrronium could suppress lactation. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from therapy. Effects on driving and operating machinery: None or negligible. Side effects: Common: pneumonia (in COPD patients), pharyngitis, oral candidiasis, urinary tract infection, nasopharyngitis, headache, dysphonia. Uncommon: influenza, oral fungal infection, oropharyngeal candidiasis, oesophageal candidiasis, fungal oropharyngitis, sinusitis, rhinitis, gastroenteritis, vulvovaginal candidiasis, granulocytopenia, dermatitis allergic, hypokalaemia, hyperglycaemia, restlessness, tremor, dizziness, dysgeusia, hypoaesthesia, otosalpingitis, atrial fibrillation, electrocardiogram QT prolonged, tachycardia, tachyarrhythmia, palpitations, hyperaemia, flushing, hypertension, asthmatic crisis, cough, productive cough, throat irritation, epistaxis, pharyngeal erythema, diarrhoea, dry mouth, dysphagia, nausea, dyspepsia, burning sensation of the lips, dental caries, aphthous stomatitis, rash, urticaria, pruritus, hyperhidrosis, muscle spasms, myalgia, pain in extremity, musculoskeletal chest pain, fatigue, C-reactive protein increased, platelet count increased, free fatty acids increased, blood insulin increased, blood ketone body increased, cortisol decreased. Rare: Lower respiratory tract infection (fungal), hypersensitivity reactions, including erythema, lips, face, eye and pharyngeal oedema, decreased appetite, insomnia, hypersomnia, angina pectoris (stable and unstable), extrasystoles (ventricular and supraventricular), nodal rhythm, sinus bradycardia, blood extravasation, paradoxical bronchospasm, exacerbation of asthma, oropharyngeal pain, pharyngeal inflammation, dry throat, angioedema, dysuria, urinary retention, nephritis, asthenia, blood pressure increased, blood pressure decreased. Very rare: thrombocytopenia, adrenal suppression, glaucoma, cataract, dyspnoea, growth retardation, peripheral oedema, bone density decreased. Frequency not known: psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioural changes, blurred vision. (Refer to SPC for full list of side effects). Legal category: POM. Price and Pack: £44.50 1×120 actuations. Marketing authorisation (MA) No(s): PLGB 08829/0193 (GB), EU/1/17/1208/002 (UKNI), PLGB 08829/0199 (GB), EU/1/17/1208/007 (UKNI), PLGB 08829/0200 (GB), EU/1/17/1208/010 (UKNI). GB MA holder/UKNI Distributor: Chiesi Limited, 333 Styal Road, Manchester, M22 5LG, United Kingdom. Date of Preparation: Jan 2022.

Fostair 100/6 and 200/6 Prescribing Information
Please refer to the full Summary of Product Characteristics (SPC) before prescribing.
Presentation: Each Fostair pressurised metered dose inhaler (pMDI) 100/6 dose contains 100 micrograms (mcg) of beclometasone dipropionate (BDP) and 6mcg of formoterol fumarate dihydrate (formoterol). Each Fostair pMDI 200/6 dose contains 200mcg of BDP and 6mcg of formoterol. Each Fostair NEXThaler 100/6 dry powder inhaler (DPI) dose contains 100mcg of BDP anhydrous and 6mcg of formoterol. Each Fostair NEXThaler 200/6 DPI dose contains 200mcg of BDP anhydrous and 6mcg of formoterol. Indications: Asthma: Regular treatment of asthma where use of an inhaled corticosteroid/long-acting beta₂-agonist (ICS/LABA) combination is appropriate: patients not adequately controlled on ICS and as needed short-acting beta₂-agonist, or patients already adequately controlled on both ICS and LABA. COPD (Fostair 100/6 only): Symptomatic treatment of patients with severe COPD (FEV₁ <50% predicted normal) and a history of repeated exacerbations, who have significant symptoms despite regular therapy with long-acting bronchodilators. Dosage and administration: For inhalation in adult patients (≥18 years). Asthma: Maintenance And Reliever Therapy (Fostair 100/6 only) can be taken as a regular maintenance treatment and as needed in response to asthma symptoms: 1 inhalation twice daily plus 1 additional inhalation as needed in response to symptoms. If symptoms persist after a few minutes, an additional inhalation is recommended. The maximum daily dose is 8 inhalations. Fostair 100/6 may also be used as maintenance therapy (with a separate short-acting bronchodilator as needed). Fostair 200/6 should be used as maintenance therapy only. Maintenance therapy: Fostair 100/6: 1–2 inhalations twice daily. Fostair 200/6: 2 inhalations twice daily. The maximum daily dose is 4 inhalations. Patients should receive the lowest dose that effectively controls their symptoms. COPD (Fostair 100/6 only): 2 inhalations twice daily. Fostair pMDI can be used with the AeroChamber Plus^® spacer device. BDP in Fostair is characterised by an extrafine particle size distribution which results in a more potent effect than formulations of BDP with a non-extrafine particle size distribution (100mcg of BDP extrafine in Fostair are equivalent to 250mcg of BDP in a non-extrafine formulation). When switching patients from previous treatments, it should be considered that the recommended total daily dose of BDP for Fostair is lower than that for non-extrafine BDP containing products and should be adjusted to the needs of the individual patient. However, patients who are transferred between Fostair NEXThaler and Fostair pMDI do not need dose adjustment. Contraindications: Hypersensitivity to the active substances or to any of the excipients. Warnings and precautions: Use with caution in patients with cardiac arrhythmias, aortic stenosis, hypertrophic obstructive cardiomyopathy, ischaemic heart disease, severe heart failure, congestive heart failure, occlusive vascular diseases, arterial hypertension, severe arterial hypertension, aneurysm, thyrotoxicosis, diabetes mellitus, phaeochromocytoma and untreated hypokalaemia. Caution should also be used when treating patients with known or suspected prolongation of the QTc interval (QTc > 0.44 seconds). Formoterol itself may induce QTc prolongation. Potentially serious hypokalaemia may result from beta₂-agonist therapy and may also be potentiated by concomitant treatments (e.g. xanthine derivatives, steroids and diuretics). Formoterol may cause a rise in blood glucose levels. Fostair should not be administered for at least 12 hours before the start of anaesthesia, if halogenated anaesthetics are planned as there is risk of arrhythmias. Use with caution in patients with pulmonary tuberculosis or fungal/viral airway infections. Increase in pneumonia and pneumonia hospitalisation in COPD patients receiving ICS. Clinical features of pneumonia may overlap with symptoms of COPD exacerbations. Fostair treatment should not be stopped abruptly. Medical attention should be sought if treatment ineffective. Treatment should not be initiated during exacerbations or acutely deteriorating asthma. Fostair treatment should be discontinued immediately if the patient experiences a paradoxical bronchospasm. Fostair is not intended for initial

management of asthma. Systemic effects of ICS may occur, particularly at high doses for long periods, but are less likely than with oral steroids. These include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression and aggression. Consider referral of patients reporting blurred vision or visual disturbances to an ophthalmologist as causes may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy. Prolonged treatment with high doses of ICS may result in adrenal suppression and acute adrenal crisis. Lactose in Fostair NEXThaler contains small amounts of milk proteins, which may cause allergic reactions. Interactions: Possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded and therefore caution and appropriate monitoring is advised. Beta-blockers should be avoided in asthma patients. Concomitant administration of other beta-adrenergic drugs may have potentially additive effects. Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines, monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants can prolong the QTc interval and increase the risk of ventricular arrhythmias. L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta₂-sympathomimetics. Hypertensive reactions may occur following co-administration with MAOIs including agents with similar properties (e.g. furazolidone, procarbazine). Concomitant treatment with xanthine derivatives, steroids or diuretics may potentiate a possible hypokalaemic effect of beta₂-agonists. Hypokalaemia may increase the likelihood of arrhythmias in patients receiving digitalis glycosides. Presence of ethanol in Fostair pMDI may cause potential interaction in sensitive patients taking metronidazole or disulfram. Fertility, pregnancy and lactation: Fostair should only be used during pregnancy or lactation if the expected benefits outweigh the potential risks. A risk/benefit decision should be taken to discontinue/abstain from therapy in the mother or discontinue breastfeeding. Effects on driving and operating machinery: Fostair is unlikely to have any effect on the ability to drive and use machines. Side effects: Common: pneumonia (in COPD patients), pharyngitis, oral candidiasis, headache, dysphonia, tremor. Uncommon: influenza, oral fungal infection, oropharyngeal candidiasis, nasopharyngitis, oesophageal candidiasis, vulvovaginal candidiasis, gastroenteritis, sinusitis, rhinitis, granulocytopenia, allergic dermatitis, hypokalaemia, hyperglycaemia, hypertriglyceridaemia, restlessness, dizziness, otosalpingitis, palpitations, prolongation of QTc interval, ECG change, tachycardia, tachyarrhythmia, atrial fibrillation, sinus bradycardia, angina pectoris, myocardial ischaemia, blood pressure increased, hyperaemia, flushing, cough, productive cough, throat irritation, asthmatic crisis, exacerbation of asthma, dyspnoea, pharyngeal erythema, diarrhoea, dry mouth, dyspepsia, dysphagia, burning sensation of the lips, nausea, dysgeusia, pruritus, rash, hyperhidrosis, urticaria, muscle spasms, myalgia, C-reactive protein increased, platelet count increased, free fatty acids increased, blood insulin increased, blood ketone body increased, blood cortisol decrease, oropharyngeal pain, fatigue, irritability, cortisol free urine decreased, blood potassium increased, blood glucose increased, ECG poor r-wave progression. Rare: ventricular extrasystoles, paradoxical bronchospasm, angioedema, nephritis, blood pressure decreased. Very rare: thrombocytopenia, hypersensitivity reactions, including erythema, lips, face, eyes and pharyngeal oedema, adrenal suppression, glaucoma, cataract, peripheral oedema, bone density decreased. Unknown frequency: psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioural changes, blurred vision. (Refer to SPC for full list of side effects). Legal category POM Price and Pack: £29.32 1×120 actuations Marketing authorisation (MA) No(s): PL 08829/0156, PL 08829/0175, PL 08829/0173, PL 08829/0174 MA holder: Chiesi Ltd, 333 Styal Road, Manchester, M22 5LG. Date of Preparation: Aug 2018. AeroChamber Plus^® is a registered trademark of Trudell Medical International.

CLENIL MODULITE 50, 100, 200, 250 Prescribing Information
Please refer to Summary of Product Characteristics (SPC) before prescribing.
Presentation: Each Clenil Modulite pressurised metered dose inhaler (pMDI) 50 dose contains 50 micrograms (mcg) of beclometasone dipropionate (BDP). Each Clenil Modulite pMDI 100 dose contains 100 mcg of BDP. Each Clenil Modulite pMDI 200 dose contains 200 mcg of BDP. Each Clenil Modulite 250 dose contains 250 mcg of BDP. Indications: Prophylactic management of mild, moderate, or severe asthma in adults or children. Dosage and administration: For inhalation use only. A Volumatic™ spacer device may be used by patients who have difficulty synchronising actuation with inspiration and must always be used when Clenil Modulite administered to adults and adolescents 16 years of age and older taking total daily doses of 1000 mcg or greater and when administered to children and adolescents 15 years of age and under, whatever dose prescribed. Starting dose of inhaled BDP should be adjusted to severity of disease. Dose may then be adjusted until control achieved and then should be titrated to lowest dose at which effective control of asthma maintained. Total daily dosage should be administered as two to four divided doses. Adults: Clenil Modulite 50, 100 & 200: Usual starting dose is 200 mcg twice daily. In severe cases this may be increased to 600 to 800 mcg daily. Clenil Modulite 250: Usually 1000 mcg daily, which may be increased to 2000 mcg daily. Clenil Modulite 200 & 250 presentations not recommended for children. Children: Clenil Modulite 50 & 100: Usual starting dose 100 mcg twice daily. Depending on severity of asthma, daily dose may be increased up to 400 mcg. Contraindications: Hypersensitivity to active substances or to any excipients (HFA-134a, ethanol, glycerol). Warnings and Precautions: Active or quiescent pulmonary tuberculosis. Patients should have relief medication available for acute asthma symptoms. Severe asthma requires regular medical assessment as risk of severe attacks and even death. Patients must seek medical attention and have their condition assessed, should they find that they are using their relief medication more often than normal or if it appears less effective. Do not stop Clenil Modulite treatment abruptly. Systemic effects may occur particularly with high doses for prolonged periods. These include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density and more rarely psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Monitor growth of children on prolonged 

treatment and if necessary reduce dose. Consider referral of patients reporting blurred vision or visual disturbances to an ophthalmologist as causes may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy. Prolonged treatment with high doses of inhaled corticosteroids may result in clinically significant adrenal suppression. Additional systemic steroid cover may be necessary during periods of stress or elective surgery. Care needed in transferring patients to Clenil Modulite from long-term/high-dose systemic steroids. Monitor adrenocortical function regularly as dose of systemic steroid is gradually reduced. Some patients may experience symptoms during withdrawal from systemic steroids, these patients should be encouraged to continue with the gradual withdrawal and change to inhaled BDP unless there are objective signs of adrenal insufficiency. Patients withdrawn from systemic steroids whose adrenocortical function is impaired should carry steroid warning card. Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies. Interactions: Due to small amount of ethanol there is theoretical potential for interaction in sensitive patients taking disulfiram or metronidazole. Possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded and therefore caution and appropriate monitoring is advised. Fertility, pregnancy and lactation: Should not be used in pregnancy or lactation unless expected benefits to the mother are thought to outweigh any potential risks to the fetus or neonate. Side effects Very common: oral candidiasis. Common: hoarseness and throat irritation. Uncommon: rash, urticaria, pruritus, erythema. Very Rare: oedema of eyes, face, lips and throat, adrenal suppression, growth retardation (children and adolescents), bone density decreased, cataract, glaucoma, paradoxical bronchospasm, wheezing, dyspnoea, cough. Unknown: psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioural disorders (predominantly in children), headache, nausea, blurred vision. (Refer to SPC for full list of side effects). Legal category: POM. Packs and prices: Each presentation provides 200 actuations. Clenil Modulite 50 £3.70, Clenil Modulite 100 £7.42, Clenil Modulite 200 £16.17 and Clenil Modulite 250 £16.29. Marketing authorisation (MA) no(s): PL 08829/0133, PL 08829/0134, PL 08829/0135, PL08829/0136. MA Holder: Chiesi Limited, 333 Styal Road, Manchester, M22 5LG, United Kingdom. Date of preparation: Apr 2018. Volumatic™ is a registered trademark of the GlaxoSmithKline Group of Companies.

Atimos Modulite 12 micrograms Pressurised Metered Dose Inhaler (pMDI) Prescribing Information.
Please refer to the full Summary of Product Characteristics (SPC) before prescribing.
Presentation: Each Atimos Modulite dose contains 12 micrograms of formoterol fumarate dihydrate. Indications: Asthma: Long-term symptomatic treatment of persistent, moderate to severe asthma in patients requiring regular bronchodilator therapy in combination with long-term anti-inflammatory therapy (inhaled and/or oral glucocorticoids). Glucocorticoid therapy should be continued on a regular basis. COPD: Relief of broncho-obstructive symptoms in patients with chronic obstructive pulmonary disease. Dosage and administration: Asthma: Adults, including the elderly, and adolescents aged 12 years and above: usually, one actuation twice daily (morning and evening). In severe cases, a maximum of two actuations twice daily can be used. Atimos is not intended to relieve acute asthma attacks. In the event of an acute attack, a short-acting beta₂-agonist should be used. Atimos should not be used in children under 12 years. COPD: Adults aged 18 years and over: the usual dose is one actuation twice daily (morning and evening). If required, up to two additional inhalations may be used for relief of symptoms, up to a maximum total daily dose of 4 inhalations (48 micrograms/day). No more than 2 inhalations should be taken on any single occasion. Contraindications: Hypersensitivity to any of the components. Warnings and Precautions: Atimos should not be used (and is not sufficient) as the first treatment for asthma. Asthmatic patients, who require therapy with long-acting beta₂-agonists, should also receive optimal maintenance anti-inflammatory therapy with corticosteroids. Patients must be advised to continue taking their anti-inflammatory therapy after the introduction of formoterol even when symptoms decrease. Should symptoms persist, or treatment with beta₂-agonists needs to be increased, this indicates a worsening of the underlying condition and warrants a reassessment of the maintenance therapy. Patients should not be initiated on Atimos during an acute severe asthma exacerbation or if they have significantly worsening or acutely deteriorating asthma. Serious asthma-related adverse events and exacerbations may occur during treatment with Atimos. Patients should continue treatment but should seek medical advice if asthma remains uncontrolled or worsens after initiation of Atimos. The lowest effective dose of Atimos should be used. The maximum daily dose should not be exceeded. Caution in third degree atrioventricular block, refractory diabetes mellitus, thyrotoxicosis, phaeochromocytoma, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, tachyarrhythmias or severe heart failure and occlusive vascular diseases, especially arteriosclerosis. Formoterol may induce prolongation of the QTc-interval. Caution should be observed when treating patients with prolongation of the QTc-interval e.g. congenital or drug-induced (QTc > 0.44 seconds) and in patients treated with drugs affecting the QTc-interval. Additional blood glucose monitoring is recommended initially in diabetic patients. Atimos should not be administered for at least 12 hours before the start of anaesthesia, if anaesthesia with halogenated anaesthetics is planned. Discontinue treatment immediately and start alternative therapy if patient experiences paradoxical bronchospasm. Potentially serious hypokalaemia may result from beta₂-agonist therapy. The hypokalaemic effect may be potentiated by concomitant treatment with xanthine-derivatives, steroids and diuretics, therefore, 

serum potassium levels should be monitored. Potassium levels have to be regularly monitored particularly in patients with low basic potassium values or peculiar risks for decreased blood potassium levels. Where applicable, potassium has to be substituted. The effects of digitalis therapy may be enhanced if hypokalaemia occurs. Atimos Modulite contains a small amount of ethanol: each actuation contains 8.9 mg of ethanol. Interactions: There is a theoretical interaction with drugs known to prolong the QTc interval causing an increased risk of ventricular arrhythmias (e.g. terfenadine, astemizole, mizolastine, quinidine, disopyramide, procainamide, erythromycin and tricyclic antidepressants). Concomitant administration with other sympathomimetic substances (e.g. other beta₂-agonists and ephedrine) may potentiate the undesirable effects of formoterol and may require titration of the dose. Simultaneous use of formoterol and theophylline may result in mutual potentiation of effects, and the likelihood of increased undesirable effects e.g. cardiac dysrhythmias. Co-administration of L-dopa, L-thyroxine, oxytocin and alcohol can also affect cardiovascular regulation. Co-administration of monoamine oxidase inhibitors or tricyclic antidepressants may potentiate the action of Atimos on the cardiovascular system and care should be taken. Concomitant treatment with xanthine-derivatives, steroids and diuretics (e.g. thiazides or loop diuretics) may potentiate a rare hypokalaemic adverse effect. Hypokalaemia may increase risk of arrhythmias in patients treated with digitalis glycosides. There is an increased risk of arrhythmias with co-administration of anaesthesia with halogenated hydrocarbons. The bronchodilating effects of Atimos can be enhanced by anticholinergic drugs. Beta-blockers may weaken or inhibit the effect of Atimos, they should not be co-administered unless there are compelling reasons for their use. Fertility, Pregnancy and Lactation: Treatment with formoterol may be considered at all stages of pregnancy if needed to obtain asthma control, and if the expected benefit to the mother is greater than any possible risk to the fetus. It is unknown whether formoterol is excreted in human milk. Administration of formoterol to women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child. Effects on driving and operating machinery: Atimos has no influence on the ability to drive and use machines. Side effects: Common: tremor; headache; palpitations; and cough. Uncommon: hypokalaemia; hyperglycaemia; agitation; restlessness; sleep disorder; dizziness; taste disturbances; tachycardia; throat irritation; nausea; hyperhidrosis; muscle cramps; myalgia. Rare: hypersensitivity reactions e.g. angioedema; bronchospasm; exanthema; urticaria; pruritus; cardiac arrhythmias e.g. atrial fibrillation; supraventricular tachycardia; extrasystoles; angina pectoris; variations in blood pressure; bronchospasm paradoxical; nephritis. Very rare: thrombopenia; abnormal behaviour; hallucination; central nervous system stimulation; prolongation of QTc interval; dyspnoea; exacerbation of asthma; oedema peripheral. (Refer to SPC for full list of side effects). Legal Category: POM. Price and Pack: £30.06 1×100 actuation inhaler. Marketing Authorisation (MA) no: PL 08829/0154. MA Holder: Chiesi Limited, 333 Styal Road, Manchester, M22 5LG, United Kingdom. Date of Preparation: August 2022