Drug Information for FlunisolideNasal Solution USP, 0.025% (Bausch & Lomb Incorporated): Clinical Pharmacology

  • Flunisolide has demonstrated potent glucocorticoid and weak mineralocorticoid activity in classical animal test systems. As a glucocorticoid it is several hundred times more potent than the cortisol standard. Clinical studies with flunisolide have shown therapeutic activity on nasal mucous membranes with minimal evidence of systemic activity at the recommended doses.

    A study in approximately 100 patients that compared the recommended dose of flunisolide nasal solution with an oral dose providing equivalent systemic amounts of flunisolide has shown that the clinical effectiveness of flunisolide nasal solution, when used topically as recommended, is due to its direct local effect and not to an indirect effect through systemic absorption.

    Following administration of flunisolide to man, approximately half of the administered dose is recovered in the urine and half in the stool: 65 to 70% of the dose recovered in urine is the primary metabolite, which has undergone loss of the 6a fluorine and addition of a 6ß hydroxy group. Flunisolide is well absorbed but is rapidly converted by the liver to the much less active primary metabolite and to glucuronate and/or sulfate conjugates. Because of first-pass liver metabolism, only 20% of the flunisolide reaches the systemic circulation when it is given orally whereas 50% of the flunisolide administered intranasally reaches the systemic circulation unmetabolized. The plasma half-life of flunisolide is 1 to 2 hours.

    The effects of flunisolide on hypothalamic-pituitary-adrenal (HPA) axis function have been studied in adult volunteers. Flunisolide was administered intranasally as a spray in total doses over 7 times the recommended dose (2200 mcg, equivalent to 88 sprays/day) in 2 subjects for 4 days, about 3 times the recommended dose (800 mcg, equivalent to 32 sprays/day) in 4 subjects for 4 days, and over twice the recommended dose (700 mcg, equivalent to 28 sprays/day) in 6 subjects for 10 days. Early morning plasma cortisol concentrations and 24-hour urinary 17-ketogenic steroids were measured daily. There was evidence of decreased endogenous cortisol production at all three doses.

    In controlled studies, flunisolide nasal solution was found to be effective in reducing symptoms of stuffy nose, runny nose and sneezing in most patients. These controlled clinical studies have been conducted in 488 adult patients at doses ranging from 8 to 16 sprays (200-400 mcg) per day and 127 pediatric patients at doses ranging from 6 to 8 sprays (150 to 200 mcg) per day for periods as long as 3 months. In 170 patients who had cortisol levels evaluated at baseline and after 3 months or more of flunisolide treatment, there was no unequivocal flunisolide-related depression of plasma cortisol levels.

    Clinical studies have shown that improvement is usually apparent within a few days after starting flunisolide nasal solution.

    The mechanisms responsible for the anti-inflammatory action of corticosteroids and for the activity of the aerosolized drug on the nasal mucosa are unknown.

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