(Generic versions may still be available.)
General Pharmacology: Flunisolide nasal spray has demonstrated potent glucocorticoid and weak mineralocorticoid activity in classical animal test systems. As a glucocorticoid it was 180 times more potent than the cortisol standard in a rat anti-granuloma assay.
Pharmacokinetics: Flunisolide is well absorbed and is rapidly converted by the liver to the much less active primary metabolite and to glucuronide and sulfate conjugates. The primary metabolite results from the loss of the 6(alpha) fluorine and addition of a 6(beta) hydroxy group. Following administration of radiolabeled flunisolide to man, approximately half of the label is recovered in the urine and half in the stool. The primary metabolite accounts for 65% to 70% of the amount recovered in the urine. Due to first-pass liver metabolism, only 20% of an oral flunisolide dose reaches the systemic circulation unmetabolized as compared to 50% of an intranasal dose. The plasma half-life of flunisolide is 1 to 2 hours.
In a pharmacokinetic study comparing NASAREL with NASALIDE (flunisolide (nasal spray)) ®, the original formulation, the two formulations were not bioequivalent. The total absorption of NASAREL was 25% less than that of NASALIDE (flunisolide (nasal spray)) , and the peak plasma concentration was 30% lower. The clinical significance of these differences is likely to be small, particularly since clinical efficacy is attributable to a local effect on nasal mucosa (see Pharmacodynamics).
Pharmacodynamics: A study in approximately 100 patients compared control of hay fever symptoms by the recommended dose of flunisolide as NASALIDE (flunisolide (nasal spray)) (200 mcg/day), with control by an oral dose of flunisolide providing equivalent plasma levels. The results demonstrated that the clinical effectiveness was due to the direct topical effect of flunisolide and not to an indirect effect through systemic absorption.
The effects of flunisolide on hypothalamic-pituitary-adrenal (HPA) axis function have been studied in adult volunteers. Flunisolide as NASALIDE (flunisolide (nasal spray)) , the original nasal formulation, was administered to 20 subjects intranasally in average total daily doses ranging from approximately 350 mcg to 2200 mcg (equivalent to about 14 to 88 sprays per day) for 4 to 10 days. Early morning plasma cortisol concentrations and 24-hour urinary 17-ketogenic steroids were measured daily. There was no consistent effect on endogenous cortisol production, although evidence of mild adrenal suppression was seen in some subjects.
Controlled studies evaluated adult patients receiving average total daily doses ranging from approximately 50 to 400 mcg (equivalent to about 2 to 16 sprays per day) of NASALIDE (flunisolide (nasal spray)) , the original flunisolide nasal spray, for periods as long as 3 months. Three hundred and thirty-nine patients from these studies were entered into a long-term open label study. Morning plasma cortisol levels were available for 182 patients at baseline, 129 after 6 months, and 36 after 12 months of continuous treatment with flunisolide. No effect of flunisolide on cortisol production was detected.
The mechanisms responsible for anti-inflammatory action of corticosteroids and for their effect on the nasal mucosa are not completely understood.
The effectiveness of NASAREL was tested in 289 patients for up to 6 weeks at doses up to 300 mcg per day. NASAREL was shown to be effective in treating the symptoms of allergic rhinitis, including rhinorrhea, nasal congestion and sneezing.
A pivotal, 3-center trial involved 196 patients with seasonal allergic rhinitis randomized to NASALIDE (flunisolide (nasal spray)) , the vehicle of NASALIDE (flunisolide (nasal spray)) , NASAREL and the vehicle of NASAREL. Both active treatments were statistically significantly more effective than the vehicles. There was not statistically significant difference in efficacy between NASALIDE (flunisolide (nasal spray)) and NASAREL.
The two formulations do differ in the nature and incidence of adverse complaints. There were more reports of nasal burning and stinging with NASALIDE (flunisolide (nasal spray)) and more problems related to taste, such as aftertaste, with NASAREL, owing to the differences in their respective vehicles. Some patients may prefer one formulation to the other.
INDIVIDUALIZATION OF DOSAGE: The therapeutic effects of corticosteroid nasal sprays, unlike those of decongestants, are not immediate. This should be explained to the patient in advance in order to ensure cooperation and continuation of treatment with the prescribed dosage regimen. Full therapeutic benefit requires regular use and is usually evident within a few days. A longer period of therapy may be required for some patients. However, NASAREL should not be continued beyond 3 weeks in the absence of significant symptomatic improvement (see PRECAUTIONS, WARNINGS, Information for Patients and ADVERSE REACTIONS sections).
A starting dose of 2 sprays in each nostril twice daily is recommended. If greater control of symptoms is needed, the dose may be increased to 2 sprays in each nostril 3 times a day. For adults, maximum total daily doses should not exceed 8 sprays in each nostril per day (464 mcg/day).
After the desired clinical effect is obtained, the maintenance dose should be reduced to the smallest amount necessary to control the symptoms. Some patients with perennial rhinitis may be maintained on as little as 1 spray in each nostril per day. It is always desirable to titrate an individual patient to the minimum effective dose to reduce the possibility of side effects.
NASAREL and NASALIDE (flunisolide (nasal spray)) should not be considered to be identical. Physicians should consider the observed differences in the mean responses in terms of side effects (see ADVERSE REACTIONS) and flunisolide absorption (see Pharmacokinetics) in treating individual patients.
For pediatric patients 6 to 14 years of age, the recommended starting dose of NASAREL is one spray (29 mcg) in each nostril 3 times a day (total dose 174 mcg/day) or 2 sprays (58 mcg) in each nostril 2 times a day (total dose 232 mcg/day). Maximum daily doses should not exceed 4 sprays in each nostril per day (total dose 232 mcg/day) as the safety and efficacy of higher doses have not been established. NASAREL is not recommended for use in pediatric patients less than 6 years of age as the safety and efficacy have not been assessed in this age group.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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