Flumetol® Easycap is a combination of Salmeterol Xinafoate and Fluticasone Propionate.Salmeterol Xinafoate is a selective, long-acting beta-2 agonist. It binds to beta-2 receptors on the smooth muscle cells that surround the airways, causing the muscle cells to relax and opening the airways. Fluticasone Propionate is a synthetic corticosteroid which is a glucocorticoid receptor agonist with mainly potent anti-inflammatory activity.

Asthma:

Flumetol® Easycap is indicated for the regular treatment of asthma (Reversible Obstructive Airways Disease), where use of a combination product (bronchodilator and inhaled corticosteroid) is appropriate.

This may include:
Patients on effective maintenance doses of both long-acting beta agonists and inhaled corticosteroids using separate products.
Patients who are not adequately controlled on current inhaled corticosteroid therapy.
Patients who are not adequately controlled on “as needed” short-acting beta-agonists, as an alternative to initiation of maintenance therapy with moderate or high doses of inhaled corticosteroid alone. Flumetol® Easycap should not typically be used for the initial management of asthma, unless symptoms are severely uncontrolled, nor in patients whose asthma can be managed by occasional use of short-acting beta-2 agonists.
Flumetol® Easycap should not be used in the treatment of acute asthmatic symptoms.

COPD:

Flumetol® Easycap is indicated for the symptomatic treatment of patients with moderate to severe COPD (pre-bronchodilator FEV1<60% predicted normal), who have significant symptoms despite bronchodilator therapy.

Asthma:

Patients should be given the strength of Flumetol® Easycap containing the appropriate fluticasone propionate dosage for the severity of their disease. Patients should be instructed not to take additional doses to treat symptoms but to take a short-acting inhaled beta-2 agonist.

Adults and adolescents 12 years and older: Flumetol® 50/100 Easycap (50 mcg salmeterol and 100 mcg fluticasone propionate): 1 Easycap twice daily. or, Flumetol® 50/250 Easycap (50 mcg salmeterol and 250 mcg fluticasone propionate): 1 Easycap twice daily.or,Flumetol® 50/500 Easycap (50 mcg salmeterol and 500 mcg fluticasone propionate): 1 Easycap twice daily.

Children 4 years and older: Flumetol® 50/100 Easycap (50 mcg salmeterol and 100 mcg fluticasone propionate) twice daily.

Children under 4 years of age: There are insufficient clinical data at present to recommend use of Flumetol® Easycap in children aged under 4 years.

COPD:

Adults: Flumetol® 50/250 Easycap (50 mcg salmeterol and 250 mcg fluticasone propionate) twice daily. For patients who require additional symptomatic control, replace the 50/250 mcg strength with the 50/500mcg strength.

Flumetol® Easycap is contraindicated in patients with a history of hypersensitivity to salmeterol xinafoate , fluticasone propionate or any of the excipients. Flumetol® Easycap is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

Use in asthma patients:

Flumetol® Easycap should not be initiated in patients during an exacerbation, or if they have unstable or acutely deteriorating asthma. Flumetol® Easycap is not for relief of acute symptoms for which a fast and short-acting bronchodilator (e.g. salbutamol) is required. Patients should be advised to have their relief medication available at all times.

Asthma-related adverse events: Serious asthma-related adverse events and exacerbations may occur during treatment with Flumetol® Easycap. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Flumetol® Easycap.

Paradoxical Bronchospasm:

As with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a fast and shortacting inhaled bronchodilator. Flumetol® Easycap should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. The pharmacological sideeffects of beta-2 agonist treatment, such as tremor, subjective palpitations and headache have been reported, but tend to be transient and to reduce with regular therapy.

Use in COPD patients: There was an increased reporting of pneumonia in studies of patients with COPD receiving salmeterol/fluticasone inhaler. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbation frequently overlap.

Corticosteroids: Flumetol® Easycap contains an inhaled corticosteroid (fluticasone propionate). 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. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation and (very rarely) behavioral disturbances in children and adolescents, decrease in bone mineral density, cataract and glaucoma. Therefore, it is important, that the patient is reviewed regularly and the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control is maintained..

As the combination inhaler 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 or Fluticasone

Propionate, are given below: Salmeterol: The pharmacological side effects of beta-2 agonist treatment, such as tremor, subjective palpitations and headache have been reported but tend to be transient and reduce with regular therapy. Cardiac arrhythmia (including atrial fibrillation, supraventricular tachycardia and extra systoles) may occur, usually in susceptible patients. There have been reports of arthralgia and hypersensitivity reactions including rash, edema and angioedema and

oropharyngeal irritation. Fluticasone Propionate: Hoarseness and candidiasis (thrush) of the mouth and throat can occur in some patients. Cutaneous hypersensitivity reactions have been reported. Rare cases of facial and oropharyngeal edema have been reported.

Pregnancy:

Administration of Flumetol® Easycap during pregnancy and lactation should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus or child. There is insufficient experience of the use of salmeterol xinafoate and fluticasone propionate in human pregnancy. Reproductive toxicity studies in animals, either with single agent or in combination, revealed the fetal effects expected at excessive systemic exposure levels of a potent beta-2- adrenoreceptor agonist & glucocorticosteroid.

Lactation:

Administration of Flumetol® Easycap in breast-feeding mothers should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus or child. There is insufficient experience of the use of salmeterol xinafoate and fluticasone propionate in human lactation. Salmeterol and fluticasone propionate concentrations in plasma after inhaled therapeutic doses are very low and therefore concentrations in human breast milk are likely to be correspondingly low. This is supported by studies in lactating animals, in which low concentrations were measured in milk. There are no data available for human breast milk.

Care should be taken when co administering known strong CYP3A4 inhibitors (e.g., Ketoconazole, Ritonavir), as there is potential for increased systemic exposure to Fluticasone Propionate. Both non-selective and selective beta-blockers should be avoided in patients with asthma, unless there are compelling reasons for their use. Due to the very low plasma concentrations achieved after inhaled dosing clinically significant drug interactions are unlikely.

No human over dosage data has been reported for this combination inhaler; however data on overdose with both drugs are given below: Salmeterol: The signs and symptoms of Salmeterol overdose are seizures, angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Other signs of over dosage may include hypokalemia and hyperglycemia. Treatment consists of discontinuation of Salmeterol together with appropriate cardio selective beta-blocking agents, which should be used with caution in patients with a history of bronchospasm.

Fluticasone Propionate: Acute inhalation of Fluticasone Propionate doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not need emergency action as adrenal function is recovered in a few days. Chronic overdose of inhaled Fluticasone Propionate may lead to adrenal suppression. Monitoring of adrenal reserve may be necessary. In cases of Fluticasone Propionate overdose this combination inhaler therapy may still be continued at a suitable dosage for symptom control.

Flumetol® Easycap must not be swallowed. Insert the Easycap in the Easyhaler® for best performance. Remove Flumetol® Easycap capsule from the blister pack just prior to use, as Easycap exposed to moisture may not tear easily. Avoid storage in direct sunlight or heat. Store below 30C. Keep away from children.