FLONASE®
Glaxo Wellcome
Fluticasone Propionate
Corticosteroid for Nasal Use
Action And Clinical Pharmacology: Fluticasone is a potent anti-inflammatory steroid with strong topical and weak systemic activity. When administered intranasally in therapeutic doses, it has a direct anti-inflammatory action on the nasal mucosa, the mechanism of which is not yet completely defined.
The onset of action is not immediate, and 2 to 3 days treatment may be required before maximum relief is obtained. This is because the anti-inflammatory activities of glucocorticoids are related to specific steroid effects, which involve several biochemical events, including protein synthesis.
A portion of an intranasally administered dose will be swallowed. However, oral bioavailability of fluticasone approaches zero due to poor absorption and extensive first-pass metabolism. In clinical trials, no hypothalamic-pituitary-adrenal (HPA) axis effects have been observed.
Indications And Clinical Uses: For the treatment of seasonal allergic rhinitis including hay fever, and perennial rhinitis poorly responsive to conventional treatment.
Regular usage is essential for full therapeutic benefit since maximum relief may not be obtained until after 2 to 3 days of treatment.
Contra-Indications: In patients with a history of hypersensitivity to any of its ingredients, and in patients with active or quiescent tuberculosis, or untreated fungal, bacterial and viral infection.
Manufacturers’ Warnings In Clinical States: In patients previously on systemic steroids, either over prolonged periods or in high doses, the replacement with a topical corticosteroid can be accompanied by symptoms of withdrawal e.g. joint and/or muscular pain, lassitude, and depression and, in severe cases, adrenal insufficiency may occur, necessitating the temporary resumption of systemic steroid therapy.
Careful attention must be given to patients with asthma or other clinical conditions in whom a rapid decrease in systemic steroids may cause a severe exacerbation of their symptoms.
Precautions: Patients should be informed that the full effect of fluticasone therapy is not achieved until 2 to 3 days of treatment have been completed. Treatment of seasonal rhinitis should, if possible, start before the exposure to allergens. Although fluticasone will control seasonal allergic rhinitis in most cases, an abnormally heavy challenge of summer allergens may in certain instances necessitate appropriate additional therapy, particularly to control eye symptoms. Under most circumstances, treatment with corticosteroids should not be stopped abruptly but tapered off gradually.
The replacement of a systemic steroid with fluticasone must be gradual and carefully supervised by the physician. The guidelines under Dosage should be followed in all such cases.
Corticosteroids may mask some signs of infection and new infections may appear. A decreased resistance to localized infections has been observed during corticosteroid therapy; this may require treatment with appropriate therapy or stopping the administration of fluticasone.
During long-term therapy, HPA axis function and hematological status should be assessed.
The long-term effects of fluticasone in humans are still unknown, in particular, its local effects; the possibility of atrophic rhinitis and/or pharyngeal candidiasis should be kept in mind.
There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis. ASA should be used cautiously in conjunction with corticosteroids in hypothrombinemia.
In patients who have had recent nasal surgery or trauma, a nasal corticosteroid should be used with caution until healing has occurred, because of the inhibitory effect of corticosteroids on wound healing.
Patients should be advised to inform subsequent physicians of prior use of corticosteroids.
To ensure proper dosage and administration of the drug, the patient should be instructed by a physician or other health professional in the use of fluticasone (see Information for the Patient).
Pregnancy: The safety of fluticasone in pregnancy has not been established. If used, the expected benefits should be weighed against the potential hazard to the fetus, particularly during the first trimester of pregnancy.
Like other glucocorticosteroids, fluticasone is teratogenic to rodent species. Adverse effects typical of potent corticosteroids are only seen at high systemic exposure levels; direct intranasal application ensures minimal systemic exposure. The relevance of these findings to humans has not yet been established. Infants born of mothers who have received substantial doses of glucocorticosteroids during pregnancy should be carefully observed for hypoadrenalism.
Lactation: Glucocorticosteroids are excreted in human milk. It is not known whether fluticasone is excreted in human milk.
When measurable plasma levels were obtained in lactating laboratory rats following s.c. administration there was evidence of fluticasone in the breast milk. However, following intranasal administration to primates, no drug was detected in the plasma, and it is therefore unlikely that the drug would be detectable in milk. The use of fluticasone in nursing mothers, requires that the possible benefits of the drug be weighed against the potential hazards to the infant.
Children: Fluticasone is not presently recommended for children younger than 4 years of age due to limited clinical data in this age group.
Until greater clinical experience has been gained, the continuous, long-term treatment of children under age 12 is not recommended.
Adverse Reactions: Adverse reactions in controlled clinical studies with fluticasone have been primarily associated with irritation of the nasal mucous membranes, and are consistent with those expected from application of a topical medication to an already inflammed membrane. The adverse reactions reported by patients treated with fluticasone were similar to those reported by patients receiving placebo.
These studies conducted in 948 adults and in 499 children evaluated 14 to 28 days of treatment with recommended doses of fluticasone compared with placebo.
In two 6 month trials involving 831 patients aged 12 to 75 years with perennial allergic rhinitis, the adverse reactions reported by patients treated with fluticasone were similar in type and incidence to those reported in seasonal trials, with the exception of epistaxis (13.3%) and blood in nasal mucous (8.3%). In addition to the events reported most frequently in the seasonal trials, patients receiving fluticasone in the 6 month trials reported nasal soreness (2.5%), nasal excoriation (2.0%), sinusitis (1.6%), and nasal dryness (1.3%).
Infrequent adverse reactions (incidence of 0.1% to 1% and greater than placebo) reported by patients receiving fluticasone at the recommended daily dose of 200 g (or 100 g/day for children 4 to 11 years of age) in the aforementioned clinical trials included pharyngeal irritation, nasal stinging, nausea and vomiting, unpleasant smell and taste, and sinus headache (0.3%); lacrimation, eye irritation, xerostomia, cough, urticaria, and rash (0.2%); and nasal septum perforation (0.1%).
Hypersensitivity reactions including skin rash, edema of the face or tongue and, rarely, bronchospasm and anaphylaxis/anaphylactic reactions have been reported.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Like any other nasally administered corticosteroid, acute overdosing is unlikely in view of the total amount of active ingredient present. However, when used chronically in excessive doses or in conjunction with other corticosteroid formulations, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of fluticasone should be discontinued slowly, consistent with accepted procedures for discontinuation of chronic steroid therapy (see Dosage).
The restoration of HPA axis function may be slow. During periods of pronounced physical stress (i.e. severe infections, trauma, surgery) a supplement with systemic steroids may be advisable.
Dosage And Administration: See Warnings.
The therapeutic effects of corticosteroids, unlike those of decongestants, are not immediate. Since the effect of fluticasone depends on its regular use, patients must be instructed to take the nasal inhalation at regular intervals and not, as with other nasal sprays, as they feel necessary.
Adults and Children 12 years of age and older: The usual dosage is 2 sprays (50 g each) in each nostril once a day (total daily dosage, 200 µg). Some patients with severe rhinitis may benefit from 2 sprays in each nostril every 12 hours. The recommended maximum daily dose is 400 g (4 sprays in each nostril).
Children 4 to 11 years of age: The usual dosage is 1 or 2 (50 g/actuation) sprays in each nostril in the morning (100 or 200 g/day). The recommended maximum daily dose is 200 g (2 sprays in each nostril).
The safety and efficacy of fluticasone in children below 4 years of age have not been established and therefore, fluticasone is not recommended in this patient population.
Until greater clinical experience has been gained, the continuous, long-term treatment of children under age 12 is not recommended.
An improvement of symptoms usually becomes apparent within a few days after the start of therapy. However, symptomatic relief may not occur in some patients for as long as 2 weeks. Fluticasone should not be continued beyond three weeks in the absence of significant symptomatic improvement.
In the presence of excessive nasal mucous secretion or edema of the nasal mucosa, the drug may fail to reach the site of action. In such cases it is advisable to use a nasal vasoconstrictor for 2 to 3 days prior to starting treatment with fluticasone. Patients should be instructed on the correct method of use, which is to blow the nose, then insert the nozzle carefully into the nostril, compress the opposite nostril and actuate the spray while inspiring through the nose, with the mouth closed (see Information for the Patient).
Careful attention must be given to patients previously treated for prolonged periods with systemic corticosteroids when transferred to fluticasone. Initially, fluticasone and the systemic corticosteroid must be given concomitantly, while the dose of the latter is gradually decreased. The usual rate of withdrawal of the systemic steroid is the equivalent of 1 mg of prednisone every 4 days if the patient is under close supervision. If continuous supervision is not feasible, the withdrawal of the systemic steroid should be slower, approximately 1 mg of prednisone (or equivalent) every 10 days. If withdrawal symptoms appear, the previous dose of the systemic steroid should be resumed for a week before further decrease is attempted.
Availability And Storage: Each 100 mg of spray delivered by the nasal adaptor (1 actuation), contains: fluticasone propionate 50 g. Nonmedicinal ingredients: benzalkonium chloride, dextrose, microcrystalline cellulose and carboxymethylcellulose sodium, phenylethyl alcohol, Polysorbate 80 and purified water. Amber glass bottles containing sufficient formulation for either 120 metered sprays (16 g net weight) or 60 metered sprays (9 g net weight). Store between 4 and 30°C. Shake gently before use.
FLONASE® Glaxo Wellcome Fluticasone Propionate Corticosteroid for Nasal Use
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