SEREFLO CIPHALER

Posology Patients should be made aware that Sereflo Ciphaler must be used daily for optimum benefit, even when asymptomatic. Patients should be regularly reassessed by a doctor, so that the strength of Sereflo Ciphaler they are receiving remains optimal and is only changed on medical advice.

Patients should be given the strength of Sereflo Ciphaler containing the appropriate fluticasone propionate dosage for the severity of their disease. If an individual patient should require dosages outside the recommended regimen, appropriate doses of β2 agonist and/or corticosteroid should be prescribed.

When it is appropriate to prescribe a different strength than is available for Sereflo Ciphaler, a change to an alternative fixed-dose combination of salmeterol and fluticasone propionate containing a different dose of the inhaled corticosteroid, respectively, is required.

Recommended doses Asthma Adults and adolescents 12 years and older − One inhalation of 50 micrograms salmeterol and 500 micrograms fluticasone propionate twice daily. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained.

Where the control of symptoms is maintained with the lowest strength of the combination given twice daily then the next step could include a test of inhaled corticosteroid alone. As an alternative, patients requiring a long- acting β2 agonist could be titrated to < Sereflo Ciphaler > given once daily if, in the opinion of the prescriber, it would be adequate to maintain disease control.

In the event of once daily dosing when the patient has a history of nocturnal symptoms the dose should be given at night and when the patient has a history of mainly daytime symptoms the dose should be given in the morning. A short-term trial of salmeterol/fluticasone propionate may be considered as initial maintenance therapy in adults or adolescents with moderate persistent asthma (defined as patients with daily symptoms, daily rescue use and moderate to severe airflow limitation) for whom rapid control of asthma is essential.

In these cases, the recommended initial dose is one inhalation of 50 micrograms salmeterol and 100 micrograms fluticasone propionate twice daily, a strength which is available for other similar fixed-dose combination products containing these two active ingredients.

Once control of asthma is attained treatment should be reviewed and consideration given as to whether patients should be stepped down to an inhaled corticosteroid alone. Regular review of patients as treatment is stepped down is important.

A clear benefit has not been shown as compared to inhaled fluticasone propionate alone used as initial maintenance therapy when one or two of the criteria of severity are missing. In general inhaled corticosteroids remain the first line treatment for most patients.

Sereflo Ciphaler is not intended for the initial management of mild asthma. Salmeterol/fluticasone propionate 50 microgram/100 micrograms strength is not appropriate in adults and adolescents with severe asthma; it is recommended to establish the appropriate dosage of inhaled corticosteroid before any fixed- combination can be used in patients with severe asthma.

Paediatric population Sereflo Ciphaler is not recommended in children below 12 years of age due to lack of data on safety and efficacy. COPD Adults − One inhalation of 50 micrograms salmeterol and 500 micrograms fluticasone propionate twice daily.

Special patient groups There is no need to adjust the dose in elderly patients or in those with renal impairment. There are no data available for use of < Sereflo Ciphaler > in patients with hepatic impairment. Method of administration For inhalation use.

Using the inhaler 1. Patient should hold the inhaler in one hand and place the thumb of other hand in the thumb grip. The patient should then push the thumb grip away as far as it will go until the patient hear a click. This will open a small hole in the mouthpiece.

2. Patient should hold the inhaler with the mouthpiece towards themselves. Patient should slide the lever away from the mouthpiece as far as it will go until it clicks. This places a dose of medicine in the mouthpiece. 3. Every time the lever is pulled back a blister is opened inside and the powder made ready for patient to inhale.

Patient should not play with the lever as this opens the blisters and wastes medicine. 4. Before the patient breathes in the dose from the inhaler, the patient should hold the inhaler away from their mouth and breathe out as far as is comfortable.

The patient should not breathe into the mouthpiece. 5. The patient should then put the mouthpiece to the lips. The patient should steadily and deeply breathe through the inhaler. The patient should not breathe in through the nose. 6. Patient should remove the inhaler from the mouth and hold the breath for about 10 seconds, or for as long as it is comfortable.

7. Patient should breathe out slowly. 8. Patient should rinse the mouth with water after breathing in the medicine and spit out the water. This may help the patients from getting thrush and becoming hoarse. 9. To close the inhaler, patient should slide the thumbgrip back towards him/her as far as it will go.

He/she should make sure that the inhaler clicks. The lever will return to its original position and will reset. 10. The inhaler is now ready for use again. The counter on top of the inhaler shows how many doses are left. It counts down to 0.

The numbers 5 to 0 will appear in red to warn the patient that there will be only few doses left. Once the counter shows 0, the inhaler will be empty. Cleaning your inhaler The mouthpiece of the Sereflo Ciphaler should be wiped with a dry tissue to clean it.

As Sereflo Ciphaler contains salmeterol and fluticasone propionate, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no incidence of additional adverse events following concurrent administration of the two compounds.

Adverse events which have been associated with salmeterol/fluticasone propionate are given below, listed by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and not known (cannot be estimated from the available data).

Frequencies were derived from clinical trial data. The incidence in placebo was not taken into account. System Organ Class Adverse Event Frequency Infections and Infestations Candidiasis of the mouth and throat Pneumonia (in COPD patients) Bronchitis Oesophageal candidiasis Common Common1, 3, 5 Common1, 3 Rare Immune System Disorders Hypersensitivity reactions with the following manifestations: Cutaneous hypersensitivity reactions Angioedema (mainly facial and oropharyngeal oedema) Respiratory symptoms (dyspnoea) Respiratory symptoms (bronchospasm) Anaphylactic reactions including anaphylactic shock Uncommon Rare Uncommon Rare Rare Endocrine Disorders Cushing's syndrome, Cushingoid features, Adrenal suppression, Growth retardation in children and adolescents, Decreased bone mineral density Rare4 Metabolism and Nutrition Disorders Hypokalaemia Hyperglycaemia Common3 Uncommon4 Psychiatric Disorders Anxiety Sleep disorders Behavioural changes, including psychomotor hyperactivity and irritability (predominantly in children) Depression, aggression (predominantly in children) Uncommon Uncommon Rare Not Known Nervous System Disorders Headache Tremor Very Common1 Uncommon Eye Disorders Cataract Glaucoma Vision, blurred Uncommon Rare4 Not Known4 Cardiac Disorders Palpitations Tachycardia Cardiac arrhythmias (including supraventricular tachycardia and extrasystoles).

Atrial fibrillation Angina pectoris Uncommon Uncommon Rare Uncommon Uncommon Respiratory, Thoracic and Mediastinal Disorders Nasopharyngitis Throat irritation Hoarseness/dysphonia Sinusitis Paradoxical bronchospasm Very Common2, 3 Common Common Common1, 3 Rare4 Skin and Subcutaneous Tissue Disorders Contusions Common1, 3 Musculoskeletal and Connective Tissue Disorders Muscle cramps Traumatic fractures Arthralgia Myalgia Common Common1, 3 Common Common 1.

Reported commonly in placebo 2. Reported very commonly in placebo 3. Reported over 3 years in a COPD study 4. 4

Deterioration of disease Sereflo Ciphaler should not be used to treat acute asthma symptoms for which a fast- and short- acting bronchodilator is required. Patients should be advised to have their inhaler to be used for relief in an acute asthma attack available at all times.

Patients should not be initiated on Sereflo Ciphaler during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Serious asthma-related adverse events and exacerbations may occur during treatment with Sereflo Ciphaler.

Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Sereflo Ciphaler . Increased requirements for use of reliever medication (short-acting bronchodilators), or decreased response to reliever medication indicate deterioration of control and patients should be reviewed by a physician.

Sudden and progressive deterioration in control of asthma is potentially life- threatening and the patient should undergo urgent medical assessment. Consideration should be given to increasing corticosteroid therapy. Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Sereflo Ciphaler .

Regular review of patients as treatment is stepped down is important. 2). For patients with COPD experiencing exacerbations, treatment with systemic corticosteroids is typically indicated, therefore patients should be instructed to seek medical attention if symptoms deteriorate with Sereflo Ciphaler .

Treatment with Sereflo Ciphaler should not be stopped abruptly in patients with asthma due to risk of exacerbation. Therapy should be down-titrated under physician supervision. For patients with COPD cessation of therapy may also be associated with symptomatic decompensation and should be supervised by a physician.

As with all inhaled medication containing corticosteroids, Sereflo Ciphaler should be administered with caution in patients with active or quiescent pulmonary tuberculosis and fungal, viral or other infections of the airway. Appropriate treatment should be promptly instituted, if indicated.

g. supraventricular tachycardia, extrasystoles and atrial fibrillation, and a mild transient reduction in serum potassium at high therapeutic doses. Sereflo Ciphaler should be used with caution in patients with severe cardiovascular disorders or heart rhythm abnormalities and in patients with diabetes mellitus, thyrotoxicosis, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium.

8) and this should be considered when prescribing to patients with a history of diabetes mellitus. Paradoxical bronchospasm As with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing.

Paradoxical bronchospasm responds to a rapid-acting bronchodilator and should be treated straightaway. < Sereflo Ciphaler > should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. The pharmacological side effects of β2 agonist treatment, such as tremor, palpitations and headache, have been reported, but tend to be transient and reduce with regular therapy.

Systemic corticosteroid effects Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects 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 or aggression (particularly in children) (see Paediatric population sub-heading below for information on the systemic effects of inhaled corticosteroids in children and adolescents).

It is important, therefore, that the patient is reviewed regularly and the dose of inhaled corticosteroid is reduced to the lowest dose at which effective control of asthma is maintained. Prolonged treatment of patients with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis.

Very rare cases of adrenal suppression and acute adrenal crisis have also been described with doses of fluticasone propionate between 500 and less than 1000 micrograms. Situations, which could potentially trigger acute adrenal crisis include trauma, surgery, infection or any rapid reduction in dosage.

Presenting symptoms are typically vague and may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, hypotension, decreased level of consciousness, hypoglycaemia, and seizures. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

The benefits of inhaled fluticasone propionate therapy should minimise the need for oral steroids, but patients transferring from oral steroids may remain at risk of impaired adrenal reserve for a considerable time. Therefore these patients should be treated with special care and adrenocortical function regularly monitored.

Patients who have required high dose emergency corticosteroid therapy in the past may also be at risk. This possibility of residual impairment should always be borne in mind in emergency and elective situations likely to produce stress, and appropriate corticosteroid treatment must be considered.

The extent of the adrenal impairment may require specialist advice before elective procedures. Ritonavir can greatly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant use should be avoided, […]

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