Salmeterol + fluticasone

Inhalation
Asthma
Adult: Dosage is individualised based on the severity of the disease and adjusted based on response and tolerance. Titrate to the lowest effective dose once control is achieved. Treatment guidelines must be considered. Aerosol for inhalation: Salmeterol 21 mcg and fluticasone 45 mcg per actuation Salmeterol 21 mcg and fluticasone 115 mcg per actuation Salmeterol 21 mcg and fluticasone 230 mcg per actuation Salmeterol 25 mcg and fluticasone 50 mcg per dose/actuation Salmeterol 25 mcg and fluticasone 125 mcg per dose/actuation Salmeterol 25 mcg and fluticasone 250 mcg per dose/actuation 2 inhalations bid. Powder for inhalation: Salmeterol 14 mcg and fluticasone 55 mcg per dose Salmeterol 14 mcg and fluticasone 113 mcg per dose Salmeterol 14 mcg and fluticasone 232 mcg per dose Salmeterol 50 mcg and fluticasone 100 mcg per dose/blister Salmeterol 50 mcg and fluticasone 250 mcg per dose/blister Salmeterol 50 mcg and fluticasone 500 mcg per dose/blister 1 inhalation bid.
Child: Aerosol for inhalation: Salmeterol 25 mcg and fluticasone 50 mcg 4-11 years 2 inhalations bid. Use of spacer device is recommended in patients who have or most likely to have difficulties in administration. Salmeterol 21 mcg and fluticasone 45 mcg Salmeterol 21 mcg and fluticasone 115 mcg Salmeterol 21 mcg and fluticasone 230 mcg Salmeterol 25 mcg and fluticasone 50 mcg Salmeterol 25 mcg and fluticasone 125 mcg Salmeterol 25 mcg and fluticasone 250 mcg ≥12 years Same as adult dose. Powder for inhalation: Salmeterol 50 mcg and fluticasone 100 mcg 4-11 years 1 inhalation bid. Salmeterol 14 mcg and fluticasone 55 mcg Salmeterol 14 mcg and fluticasone 113 mcg Salmeterol 14 mcg and fluticasone 232 mcg Salmeterol 50 mcg and fluticasone 100 mcg Salmeterol 50 mcg and fluticasone 250 mcg Salmeterol 50 mcg and fluticasone 500 mcg ≥12 years Same as adult dose.

Inhalation
Chronic obstructive pulmonary disease
Adult: Dosage is individualised based on the severity of the disease. Powder for inhalation: Salmeterol 50 mcg and fluticasone 250 mcg per dose or blister Salmeterol 50 mcg and fluticasone 500 mcg per dose or blister 1 inhalation bid.

Acute episodes of asthma or COPD; status asthmaticus.

Patient with active or quiescent pulmonary tuberculosis, systemic fungal, viral, bacterial or parasitic infections; CV disease (e.g. arrhythmia, coronary insufficiency, heart failure, hypertension), diabetes mellitus, hypokalaemia or predisposition to hypokalaemia, thyrotoxicosis, predisposition to decreased bone mineral count (e.g. family history of osteoporosis, prolonged immobilisation, postmenopausal status, tobacco use), history of increased intraocular pressure, cataracts, glaucoma, seizure disorders, low BMI. Patient transferring from systemic corticosteroid to inhaled corticosteroid. Patient undergoing surgery or subjected to stress. Not for initiation in patient with significantly deteriorating asthma or COPD. Avoid abrupt withdrawal and dose reduction. Hepatic impairment. Children and elderly. Pregnancy and lactation. Patient Counselling Do not switch between brands or types of inhalation devices including spacer devices unless instructed by your doctor. Rinse the mouth with water after using inhalation devices. Monitoring Parameters Perform pulmonary function tests (e.g. forced expiratory volume in 1 second [FEV₁], peak flow). Monitor blood pressure, heart rate, CNS stimulation, bone mineral density (at baseline and periodically thereafter); serum K (in hypokalaemic patients); glucose (in diabetic patients). Assess for signs and symptoms of oral candidiasis, adrenal insufficiency, glaucoma or cataracts. Monitor growth in adolescents and children via stadiometry.

Significant: Adrenal suppression, acute adrenal crisis (prolonged use); laryngeal spasm, irritation and swelling; lower respiratory tract infections (e.g. pneumonia, bronchitis), oral candidiasis; decreased bone mineral density; elevated blood pressure and heart rate, QTc prolongation, hypokalaemia (high doses); increased intraocular pressure, glaucoma, cataracts, central serous chorioretinopathy; Cushing's syndrome, Cushingoid features; growth retardation in children; hypersensitivity reactions (e.g. urticaria, angioedema, rash, hypotension, anaphylaxis). Rarely, cardiac arrhythmias (e.g. supraventricular tachycardia, extrasystoles, atrial fibrillation), increased serum glucose levels, systemic eosinophilic conditions (e.g. eosinophilic granulomatosis with polyangiitis); psychological or behavioural effects (e.g. psychomotor hyperactivity, depression, aggression) in children. Cardiac disorders: Palpitation, angina pectoris. Musculoskeletal and connective tissue disorders: Muscle cramps and spasms, arthralgia, myalgia, traumatic fractures. Nervous system disorders: Headache, tremor. Psychiatric disorders: Anxiety, sleep disorders. Respiratory, thoracic and mediastinal disorders: Throat irritation, hoarseness or dysphonia, sinusitis, nasopharyngitis. Skin and subcutaneous tissue disorders: Contusions.
Potentially Fatal: Paradoxical bronchospasm.

Symptoms: Dizziness, increased systolic blood pressure, tremor, headache, tachycardia, hypokalaemia, seizures, angina, hypotension, arrhythmias, nervousness, muscle cramps, dry mouth, palpitation, nausea, fatigue, dizziness, malaise, insomnia, metabolic acidosis, hyperglycaemia; temporary adrenal suppression (acute inhalation); prolongation of QTc interval. Rarely, adrenal crisis (particularly in children). Management: Supportive and symptomatic treatment. Monitor and correct K levels. In chronic cases, monitor adrenal reserve and give systemic corticosteroids as needed, continue with inhaled steroids at the recommended dose once stabilised.

Increased plasma concentration with strong CYP3A4 inhibitors (e.g. ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin). Salmeterol: May have diminished or antagonised therapeutic effect with β-blockers. May increase the risk of hypokalaemia and ECG changes with loop or thiazide diuretics. May have enhanced adverse effect when used concomitantly with other β-adrenergic drugs. Effects on the vascular system may be potentiated with concomitant use or within 2 weeks of discontinuation of MAOIs or TCAs.

Salmeterol is a selective long-acting β₂ receptor agonist that acts locally in the lungs. Its action is suspected to be mediated, at least in part, by the activation of intracellular adenyl cyclase resulting in increased cyclic adenosine monophosphate (cAMP) levels, thus causing relaxation of bronchial smooth muscle and prevention of release of mediators of immediate hypersensitivity from cells, particularly from mast cells. Fluticasone is a corticosteroid that provides significantly potent vasoconstrictive and anti-inflammatory effects.
Onset: Salmeterol: 30-48 minutes (asthma); 2 hours (COPD).
Duration: Bronchodilation: Salmeterol: 12 hours.
Absorption: Salmeterol: Minimal systemic absorption. Time to peak plasma concentration: Approx 20 minutes. Fluticasone: Systemically absorbed via the lungs. Bioavailability: Approx 5-11%, depending on the inhalation device used. Time to peak plasma concentration: 0.5-1 hour.
Distribution: Salmeterol: Plasma protein binding: Approx 94-98%. Fluticasone: Plasma protein binding: 91%.
Metabolism: Salmeterol: Extensively metabolised in the liver via hydroxylation and via aliphatic oxidation by CYP3A4 isoenzyme to α-hydroxysalmeterol. Fluticasone: Metabolised in the liver by CYP3A4 isoenzyme to 17β-carboxylic acid (inactive metabolite).
Excretion: Salmeterol: Via faeces (60%); urine (25%). Elimination half-life: 5.5 hours. Fluticasone: Via faeces (as unchanged drug and metabolites); urine (<5% primarily as metabolites). Elimination half-life: Approx 11.2 hours.

Inhalation: Store below 30°C. Aerosol for inhalation: Protect from direct sunlight. Storage recommendations may vary among individual products. Refer to specific product guideline.

Antiasthmatic & COPD Preparations

D07AC17 - fluticasone ; Belongs to the class of potent (group III) corticosteroids. Used in the treatment of dermatological diseases.
R03AC12 - salmeterol ; Belongs to the class of adrenergic inhalants, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.
R03BA05 - fluticasone ; Belongs to the class of other inhalants used in the treatment of obstructive airway diseases, glucocorticoids.
R01AD08 - fluticasone ; Belongs to the class of topical corticosteroids used for prophylaxis and treatment of allergic rhinitis.