Sign Out
The management of asthma should normally follow a stepwise programme and patient response should be monitored clinically and by lung function tests.
Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler 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 medicinal product to be used for relief in an acute asthma attack available at all times.
Patients should not be initiated on Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler 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 Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler.
Increasing use of short-acting bronchodilators to relieve asthma symptoms indicates deterioration of asthma 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. The patient should also be medically reviewed where the current dosage of Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler has failed to give adequate control of asthma. Consideration should be given to additional corticosteroid therapies.
Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler. Regular review of patients as treatment is stopped down is important. The lowest effective dose of Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler should be used.
Treatment with Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler should not be stopped abruptly.
As with all inhaled medication containing corticosteroids, Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler should be administered with caution in patients with pulmonary tuberculosis.
Rarely, Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler may cause cardiac arrhythmias e.g. supraventricular tachycardia, extrasystoles and atrial fibrillation, and a mild transient reduction in serum potassium at high therapeutic doses. Therefore Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler should be used with caution in patients with severe cardiovascular disorders, heart rhythm abnormalities, diabetes mellitus, thyrotoxicosis, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium.
There have been very rare reports of increases in blood glucose levels and this should be considered when prescribing to patients with a history of diabetes mellitus.
As with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.
Care should be taken when transferring patients to Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free Inhaler therapy, particularly if there is any reason to suppose that adrenal function is impaired from previous systemic steroid therapy.
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. Those 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, sloop disorders, anxiety, depression or aggression (particularly in children). 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 loss 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.
Systemic absorption of salmeterol and fluticasone propionate Is largely through the lungs. As the use of a spacer device with a metered dose inhaler may increase drug delivery to the lungs it should be noted that this could potentially lead to an increase in the risk of systemic adverse effects.
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 resolve for a considerable time. 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, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects. There is also an increased risk of systemic side effects when combining fluticasone propionate with other potent CYP3A inhibitors.
Physicians should remain vigilant for the possible development of pneumonia and other lower respiratory tract infections in patients with COPD as the clinical features of such infections and exacerbation frequently overlap. If a patient with severe COPD has experienced pneumonia the treatment with Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free Inhaler should be re-evaluated.
Data from a large clinical trial (the Salmeterol Multi-Center Asthma Research Trial, SMART) suggested African-American patients were at increased risk of serious respiratory-related events or deaths when using salmeterol compared with placebo. It is not known if this was due to pharmacogenetic or other factors. Patients of black African or Afro-Caribbean ancestry should therefore be asked to continue treatment but to seek medical advice if asthma symptoms remained uncontrolled or worsen whilst using Salmeterol and Fluticasone Propionate Pressurized Inhalation CFC Free inhaler.
Concomitant use of systemic ketoconazole significantly increases systemic exposure to salmeterol. This may lead to an increase in the incidence of systemic effects (e.g. prolongation in the OTc interval and palpitations). Concomitant treatment with ketoconazole or other potent CYP3A4 inhibitors should therefore be avoided unless the benefits outweigh the potentially increased risk of systemic side effects of salmeterol treatment.
Interaction with other medicinal products and other forms of interaction: Both non-selective and selective beta-blockers should be avoided in patients with asthma, unless there are compelling reasons for their use.
Concomitant use of other beta-adrenergic containing drugs can have a potentially additive effect.
Fluticasone Propionate: Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after inhaled dosing, due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely.
In an interaction study in healthy subjects with intranasal fluticasone propionate, ritonavir (a highly potent cytochrome P450 3A4 inhibitor) 100 mg b.i.d. increased the fluticasone propionate plasma concentrations several hundred fold, resulting in markedly reduced serum cortisol concentrations. Information about this interaction is lacking for inhaled fluticasone propionate, but a marked increase in fluticasone propionate plasma levels is expected.
Cases of Cushing's syndrome and adrenal suppression have been reported. The combination should be avoided unless the benefit outweighs the increased risk of systemic glucocorticoid side-effects.
In a small study in healthy volunteers, the slightly less potent CYP3A inhibitor ketoconazole increased the exposure of fluticasone propionate after a single inhalation by 150%. This resulted in a greater reduction of plasma cortisol as compared with fluticasone propionate alone. Co-treatment with other potent CYP3A inhibitors, such as itraconazole, is also expected to increase the systemic fluticasone propionate exposure and the risk of systemic side-effects. Caution is recommended and long-term treatment with such drugs should if possible be avoided.
Salmeterol: Potent CYP3A4 Inhibitors: Co-administration of ketoconazole (400 mg orally once daily) and salmeterol (50 micrograms inhaled twice daily) in 15 healthy subjects for 7 days resulted in a significant increase in plasma salmeterol exposure (1.4-fold Cmax and 15-fold AUC). This may lead to an increase in the incidence of other systemic effects of salmeterol treatment (e.g. prolongation of arc interval and palpitations) compared with salmeterol or ketoconazole treatment alone.
Clinically significant effects were not seen on blood pressure, heart rate, blood glucose and blood potassium levels. Co-administration with ketoconazole did not increase the elimination half-life of salmeterol or increase salmeterol accumulation with repeat dosing.
The concomitant administration of ketoconazole should be avoided, unless the benefits outweigh the potentially increased risk of systemic side effects of salmeterol treatment. There is likely to be a similar risk of interaction with other potent CYP3A4 Inhibitors (e.g. itraconazole, telithromycin, ritonavir).
Moderate CYP3A4 inhibitors: Co-administration of erythromycin (500mg orally three times a day) and salmeterol (50 micrograms inhaled twice daily) in 15 healthy subjects for 6 days resulted in a small but non-statistically significant increase in salmeterol exposure (1.4-fold Cmax and 1.2-fold AUC). Co-administration with erythromycin was not associated with any serious adverse effects.
Use in Children: Children and adolescents <16 years taking high doses of fluticasone propionate (typically 1000 micrograms/day) may be at particular risk of systemic effects. Systemic effects may occur, particularly at high doses prescribed for long periods. Possible systemic effects include Cushing's syndrome. Cushingoid features, adrenal suppression, acute adrenal crisis and growth retardation in children and adolescents and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression.
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroid is regularly monitored. The dose of inhaled corticosteroid should be reduced to the lowest dose at which effective control of asthma is maintained.
