Fluticasone 125 inhaler

(i) ROUTE OF ADMINISTRATION

Inhalation

DOSAGE AND ADMINISTRATION

Adults and children over 16 years of age :
100 to 1,000 µg twice daily. Patients should be given a starting dose of inhaled fluticasone propionate which is appropriate for the severity of their disease

Mild asthma: 100 to 250 µg twice daily.
Moderate asthma: 250 to 500 µg twice daily.
Severe asthma: 500 to 1,000 µg twice daily.

Children over 4 years :
50 to 100 µg twice daily.

Children under 4 years
Not recommended.

(ii) THERAPEUTIC / DIAGNOSTIC CLAIMS

Health 2000 Fluticasone 125 mcg inhaler is indicated for the maintenance treatment of asthma in adults and children above 4 years as prophylactic therapy. It is also indicated for patients requiring oral corticosteroid therapy for asthma. Many of these patients may be able to reduce or eliminate their requirement for oral corticosteroid over time.

Health 2000 Fluticasone 125 mcg inhaler are not indicated for the relief of acute bronchospasm.
Health 2000 Fluticasone 125 mcg inhaler may be used with a Health 2000 Spacer device in patients who find it difficult to synchronise aerosol actuation with inspiration of breath.

(iii) DESCRIPTION OF DOSAGE FORM

Fluticasone propionate is a synthetic, trifluorinated glucocorticoid with potent anti- inflammatory activity. In vitro assays have established fluticasone propionate as a human glucocorticoid receptor agonist with an affinity 18 times greater than dexamethasone, almost twice that of beclomethasone-17-mono-propionate, the active metabolite of beclomethasone dipropionate, and over three times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results.
Inflammation is recognized as an important component in the pathogenesis of asthma. Glucocorticoids have been shown to inhibit multiple cell types (eg mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and mediator production or secretion (e.g. histamine, eicosanoids, leukotrienes, and cytokines) involved in the asthmatic response. These anti-inflammatory actions of glucocorticoids may contribute to their efficacy in asthma.

Though highly effective for the treatment of asthma, glucocorticoids do not affect asthma symptoms immediately. However, improvement following inhaled administration of fluticasone propionate can occur within 24 hours of beginning treatment, although maximum benefit may not be achieved for 1 to 2 weeks or longer after starting treatment. When glucocorticoids are discontinued, asthma stability may persist for several days or longer.

(iv) CONTRAINDICATIONS

HEALTH 2000 FLUTICASONE 125MCG INHALER is contraindicated in the following situations: in patients with a history of hypersensitivity to any of its components, in children under 4 years of age, and in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

WARNINGS AND PRECAUTIONS

Patient's inhaler technique should be checked regularly to make sure that inhaler actuation is synchronised with inspiration to ensure optimum delivery of the drug to the lungs.
Health 2000 Fluticasone 125 mcg inhaler is not designed to relieve acute symptoms, for which an inhaled short-acting bronchodilator is required. Patients should be advised to have such rescue medication available.

Severe asthma requires regular medical assessment, including lung-function testing, as patients are at risk of severe attacks and even death.
Increasing use of short-acting inhaled beta2-agonists to relieve symptoms indicates deterioration of asthma control. If patients find that short-acting relief bronchodilator treatment becomes less effective, or they need more inhalations than usual, medical attention must be sought.

In this situation patients should be reassessed and consideration given to the need for increased anti-inflammatory therapy (e.g. higher doses of inhaled corticosteroids or a course of oral corticosteroids). Severe exacerbations of asthma must be treated in the normal way.

Adrenal function and adrenal reserve usually remain within the normal range on inhaled fluticasone propionate. However, some systemic effects may occur in a small proportion of adult patients after prolonged treatment at high doses. Patients transferred from other inhaled steroids or oral steroids remain at risk of impaired adrenal reserve for a considerable time after transferring to inhaled fluticasone propionate.
Patients in a medical or surgical emergency, who in the past have required high doses of other inhaled steroids and/or intermittent treatment with oral steroids, remain at risk of impaired adrenal reserve for a considerable time after transferring to inhaled fluticasone propionate. The extent of the adrenal impairment may require specialist advice before elective procedures. The possibility of residual impaired adrenal response should always be borne in mind in emergency and elective situations likely to produce stress, and appropriate corticosteroid treatment must be considered.

In children taking recommended doses of inhaled fluticasone propionate, adrenal function and adrenal reserve usually remain within the normal range. Very rarely biochemical changes suggestive of systemic effects have been reported. The clinical relevance of these changes has not been substantiated, and, in particular, no stunting of growth in children has been observed. The possible effects of previous or intermittent treatment with oral steroids should not be discounted. The benefits of Health 2000 Fluticasone 125 mcg inhaler should minimise the need for oral steroids.

Lack of response or severe exacerbations of asthma should be treated by increasing the dose of inhaled fluticasone propionate and, if necessary, by giving a systemic steroid and/or an antibiotic if there is an infection.

For the transfer of patients being treated with oral corticosteroids:
The transfer of oral steroid-dependent patients to Health 2000 Fluticasone 125 mcg inhaler and their subsequent management, needs special care as recovery from impaired adrenocortical function, caused by prolonged systemic steroid therapy, may take a considerable time.
Patients who have been treated with systemic steroids for long periods of time, or at a high dose, may have adrenocortical suppression. With these patients, adrenocortical function should be monitored regularly and their dose of systemic steroid reduced cautiously.

After approximately a week, gradual withdrawal of the systemic steroid is started by reducing the daily dose by 1 mg prednisolone, or its equivalent, at not less than weekly intervals. For maintenance doses of prednisolone in excess of 10 mg daily, it may be appropriate to cautiously use larger reductions in dose at weekly intervals.

Some patients feel unwell in a non-specific way during the withdrawal phase despite maintenance or even improvement of respiratory function. They should be encouraged to persevere with Health 2000 Fluticasone 125 mcg inhaler and to continue withdrawal of systemic steroid, unless there are objective signs of adrenal insufficiency.

Patients transferred from oral steroids whose adrenocortical function is still impaired should carry a steroid warning card indicating that they need supplementary systemic steroid during periods of stress, e.g. worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.
Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies such as allergic rhinitis or eczema previously controlled by the systemic drug. These allergies should be symptomatically treated with antihistamine and/or topical preparations, including topical steroids.

Treatment with Health 2000 Fluticasone 125 mcg inhaler should not be stopped abruptly. Special care is necessary in patients with active or quiescent pulmonary tuberculosis.

PREGNANCY AND LACTATION
There is inadequate evidence of safety of fluticasone propionate in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development, including cleft palate and intrauterine growth retardation. There may therefore be a very small risk of such effects in the human foetus. It should be noted, however, that the foetal changes in animals occur after relatively high systemic exposure. Because fluticasone propionate is delivered directly to the lungs by the inhaled route it avoids the high level of exposure that occurs when corticosteroids are given by systemic routes. Administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

The secretion of fluticasone propionate in human breast milk has not been investigated. Subcutaneous administration of fluticasone propionate to lactating laboratory rats produced measurable plasma levels and evidence of fluticasone propionate in the milk. However plasma levels in humans after inhalation at recommended doses are likely to be low. When fluticasone propionate is used in breast-feeding mothers the therapeutic benefits must be weighed against the potential hazards to mother and baby.

(v) SIDE EFFECTS

Candidiasis of the mouth and throat (thrush) occurs in some patients. Such patients may find it helpful to rinse out their mouth with water after use. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with inhaled fluticasone propionate.
In some patients inhaled fluticasone propionate may cause hoarseness. It may be helpful to rinse out the mouth with water immediately after inhalation.
There have been rare reports of cutaneous hypersensitivity to fluticasone propionate inhaled preparations.
As with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This responds to a fast-acting inhaled bronchodilator. The preparation should be discontinued immediately, the patient assessed, and, if necessary, alternative therapy instituted.

(vi) TOXIC EFFECTS

MUTAGENICITY

No evidence of mutagenicity has been found in microbial tests.Mice have been dosed daily for 18 months with 1 mg.kg-1 orally and rats have had snout applications daily for 2 years without evidence of carcinogenicity.

No evidence of a tumorigenic effect was observed in either a 2 year study in rats receiving doses of fluticasone propionate up to 57 µg/kg/day by inhalation or in an 18 month study in mice receiving oral doses of fluticasone propionate up to 1 mg/kg/day. There was no evidence of a mutagenic potential in a standard battery of mutagenicity assays.
A fertility study in rats showed decreased mean fetal weight, retardation of ossification, and decreased postnatal viability at the dose of 50 µg/kg/day SC of fluticasone propionate.

CARCINOGENICITY

Two 18-month studies were performed in mice to evaluate the carcinogenic potential of fluticasone propionate when given topically (as an 0.05% ointment) and orally. No evidence of carcinogenicity was found in either study.

TERATOGENECITY

Teratogenicity studies in mice, rats and rabbits have shown effects which are similar to those of other corticosteroids with growth retardation, cleft palate, and decreased cranial ossification. In pregnant rats, subcutaneous doses of 10, 30 or 100 mg.kg-1 daily were administered on days 6 to 15 of pregnancy.No important effects were seen. In pregnant mice treated with 15 to 150 mg.kg-1 from day 6 to day 15 of pregnancy a single cleft palate occurred at 45 mg.kg-1 and 150 mg.kg-1 daily cleft palate was observed in more than half of litters with an increased in impaired cranial ossification.