WARNINGS

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency, and in addition some patients may experience symptoms of withdrawal, e.g., joint and/or muscular pain, lassitude, and depression. Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In those patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms.

The concomitant use of intranasal corticosteroids with other inhaled corticosteroids could increase the risk of signs or symptoms of hypercorticism and/or suppression of the HPA axis.

Patients who are on immunosuppressant drugs are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in patients on immunosuppressant doses of corticosteroids. In such patients who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective prescribing informatio for complete VZIG and IG information.) If chickenpox develops, treatment with antiviral agents may be considered.

PRECAUTIONS

General: Rarely, immediate hypersensitivity reactions or contact dermatitis may occur after the administration of fluticasone propionate nasal spray. Rare instances of wheezing, nasal septum perforation, cataracts, glaucoma and increased intraocular pressure have been reported following the intranasal application of corticosteroids, including fluticasone propionate.

Use of excessive doses of corticosteroids may lead to signs or symptoms of hypercorticism, suppression of HPA function, and/or reduction of growth velocity in children or teenagers. Physicians should closely follow the growth of children and adolescents taking corticosteroids, by any route, and weigh the benefits of corticosteroid therapy against the possibility of growth suppression if growth appears slowed.

Although systemic effects have been minimal with recommended doses of fluticasone propionate nasal spray, potential risk increases with larger doses. Therefore, larger than recommended doses of fluticasone propionate nasal spray should be avoided.

When used at higher than recommended doses, or in rare individuals at recommended doses, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of fluticasone propionate nasal spray should be discontinued slowly consistent with accepted procedures for discontinuing oral corticosteroid therapy.

In clinical studies with fluticasone propionate administered intranasally, the development of localized infections of the nose and pharynx with Candida albicans has occurred only rarely. When such an infection develops, it may require treatment with appropriate local therapy and discontinuation of treatment with fluticasone propionate nasal spray. Patients using fluticasone propionate nasal spray over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.

Fluticasone propionate nasal spray should be used with caution, if at all, in patients with active or quiescent tuberculous infection; untreated local or systemic fungal or bacterial, or systemic viral infections or parasitic infection; or ocular herpes simplex.

Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred.

Information for the Patient: Patients being treated with fluticasone propionate nasal spray should receive the following information and instructions. This information is intended to aid them in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Patients should be warned to avoid exposure to chickenpox or measles and, if exposed, to consult their physician without delay.

Patients should use fluticasone propionate nasal spray at regular intervals as directed since its effectiveness depends on its regular use. A decrease in nasal symptoms may occur as soon as 12 hours after starting therapy with fluticasone propionate nasal spray. Results in several clinical trials indicate statistically significant improvement within the first day or two of treatment; however, the full benefit of fluticasone propionate nasal spray may not be achieved until treatment has been administered for several days. The patient should not increase the prescribed dosage but should contact the physician if symptoms do not improve or if the condition worsens. For the proper use of the nasal spray and to attain maximum improvement, the patient should read and follow carefully the accompanying patient's instructions.

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1000 mcg/kg (approximately 20 times the maximum recommended daily intranasal dose in adults and approximately 10 times the maximum recommended daily intranasal dose in children on a mcg/m2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 2 times the maximum recommended daily intranasal dose in adults and approximately equivalent to the maximum recommended daily intranasal dose in children on a mcg/m2 basis) for 104 weeks.

Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the mouse micronucleus test when administered at high doses by the oral or subcutaneous routes. Furthermore, the compound did not delay erythroblast division in bone marrow.

No evidence of impairment of fertility was observed in reproductive studies conducted in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 2 times the maximum recommended daily intranasal dose in adults on a mcg/m2 basis). Prostate weight was significantly reduced at a subcutaneous dose of 50 mcg/kg.

Pregnancy, Teratogenic Effects, Pregnancy Category C: Subcutaneous studies in the mouse and rat at 45 and 100 mcg/kg, respectively (approximately equivalent to and 4 times the maximum recommended daily intranasal dose in adults on a mcg/m2 basis, respectively) revealed fetal toxicity characteristic of potent corticosteroid compounds, including embryonic growth retardation, omphalocele cleft palate, and retarded cranial ossification.

In the rabbit, fetal weight reduction and cleft palate were observed at a subcutaneous dose of 4 mcg/kg (less than the maximum recommended daily intranasal dose in adults on a mcg/m2 basis).

However, no teratogenic effects were reported at oral doses up to 300 mcg/kg (approximately 25 times the maximum recommended daily intranasal dose in adults on a mcg/m2 basis) of fluticasone propionate to the rabbit. No fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration (see CLINICAL PHARMACOLOGY).

Fluticasone propionate crossesd the placenta following oral administration of 100 mcg/kg to rats or 300 mcg/kg to rabbits (approximately 4 and 25 times, respectively, the maximum recommended daily intranasal dose in adults on a mcg/m2 basis).

There are no adequate and well-controlled studies in pregnant women. Fluticasone propionate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to physiologic, doses suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. In addition, because there is a natural increase in corticosteroid production during pregnancy, most women will require a lower exogenous corticosteroid dose and many will not need corticosteroid treatment during pregnancy.

Nursing Mothers: It is not known whether fluticasone propionate is excreted in human breast milk. When tritiated fluticasone propionate was administered to rats at a subcutaneous dose of 10 mcg/kg (less than the maximum recommended daily intranasal dose in adults on a mcg/m2 basis), radioactivity was excreted in the milk. Because other corticosteroids are excreted in human milk, caution should be exercised when fluticasone propionate nasal spray is administered to a nursing woman.

Pediatric Use: Five hundred (500) patients aged 4 to 11 years of age and 440 patients aged 12 to 17 years were studied in U.S. clinical trials with fluticasone propionate nasal spray. The safety and effectiveness of fluticasone propionate nasal spray in children below 4 years of age have not been established.

Oral and, to a less clear extent, inhaled and intranasal corticosteroids have been shown to have the potential to cause a reduction in growth velocity in children and adolescents with extended use. If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that they are particularly sensitive to this effect of corticosteroids should be considered.

Geriatric Use: A limited number of patients above 60 years of age (n = 275) have been treated with fluticasone propionate nasal spray in U.S. and non-U.S. clinical trials. While the number of patients is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger patients.