FLUTICASONE: Package Insert and Label Information

FLUTICASONE- fluticasone propionate spray, metered
Lake Erie Medical DBA Quality Care Products LLC

1 INDICATIONS AND USAGE

Fluticasone Propionate Nasal Spray, USP 50 mcg per spray is indicated for the management of the nasal symptoms of perennial nonallergic rhinitis in adult and pediatric patients aged 4 years and older.

2 DOSAGE AND ADMINISTRATION

Administer Fluticasone Propionate Nasal Spray by the intranasal route only. Prime Fluticasone Propionate Nasal Spray before using for the first time or after a period of non-use (1 week or more) by shaking the contents well and releasing 6 sprays into the air away from the face. Shake Fluticasone Propionate Nasal Spray gently before each use.

Patients should use Fluticasone Propionate Nasal Spray at regular intervals since its effectiveness depends on its regular use. Maximum effect may take several days and individual patients will experience a variable time to onset and different degree of symptom relief.

2.1 Adults

The recommended starting dosage in adults is 2 sprays (50 mcg of fluticasone propionate each) in each nostril once daily (total daily dose, 200 mcg). The same total daily dose, 1 spray in each nostril administered twice daily (e.g., 8 a.m. and 8 p.m.) is also effective. After the first few days, patients may be able to reduce their dose to 1 spray in each nostril once daily for maintenance therapy.

Maximum total daily doses should not exceed 2 sprays in each nostril (total dose, 200 mcg/day). There is no evidence that exceeding the recommended dose is more effective.

2.2 Adolescents and Children (Aged 4 Years and Older)

The recommended starting dosage in adolescents and children, aged 4 years and older is 1 spray in each nostril once daily (total daily dose, 100 mcg). Patients not adequately responding to 1 spray in each nostril may use 2 sprays in each nostril once daily (total daily dose, 200 mcg). Once adequate control is achieved, the dosage should be decreased to 1 spray in each nostril once daily.

The maximum total daily dosage should not exceed 2 sprays in each nostril (200 mcg/day). There is no evidence that exceeding the recommended dose is more effective.

3 DOSAGE FORMS AND STRENGTHS

Fluticasone Propionate Nasal Spray is a nasal spray suspension. Each 100-mg spray delivers 50 mcg of fluticasone propionate.

4 CONTRAINDICATIONS

Fluticasone Propionate Nasal Spray is contraindicated in patients with hypersensitivity to any of its ingredients [see Warnings and Precautions (5.3), Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Local Nasal Effects

Epistaxis

In clinical trials of 2 to 26 weeks’ duration, epistaxis was observed more frequently in subjects treated with Fluticasone Propionate Nasal Spray than those who received placebo [see Adverse Reactions (6.1)].

Nasal Ulceration

Postmarketing cases of nasal ulceration have been reported in patients treated with Fluticasone Propionate Nasal Spray [see Adverse Reactions (6.2)].

Candida Infection

In clinical trials with fluticasone propionate administered intranasally, the development of localized infections of the nose and pharynx with Candida albicans has occurred. When such an infection develops, it may require treatment with appropriate local therapy and discontinuation of 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.

Nasal Septal Perforation

Postmarketing cases of nasal septal perforation have been reported in patients treated with Fluticasone Propionate Nasal Spray [see Adverse Reactions (6.2)].

Impaired Wound Healing

Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should avoid using Fluticasone Propionate Nasal Spray until healing has occurred.

5.2 Glaucoma and Cataracts

Use of intranasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.

5.3 Hypersensitivity Reactions including Anaphylaxis

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, and rash) have been reported after administration of Fluticasone Propionate Nasal Spray. Discontinue Fluticasone Propionate Nasal Spray if such reactions occur [see Contraindications (4)]. Rarely, immediate hypersensitivity reactions may occur after the administration of Fluticasone Propionate Nasal Spray.

5.4 Immunosuppression

Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect 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 a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the complete prescribing information for VZIG and IG.) If chickenpox develops, treatment with antiviral agents may be considered.

Intranasal corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

5.5 Hypercorticism and Adrenal Suppression

When intranasal corticosteroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, 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.

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. In addition, some patients may experience symptoms of corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, 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 patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause a severe exacerbation of their symptoms.

5.6 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors

The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, nefazodone, voriconazole) with Fluticasone Propionate Nasal Spray is not recommended because increased systemic corticosteroid adverse effects may occur [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

5.7 Effect on Growth

Intranasal corticosteroids may cause a reduction in growth velocity when administered to pediatric patients [see Use in Specific Populations (8.4)]. Monitor the growth routinely of pediatric patients receiving Fluticasone Propionate Nasal Spray. To minimize the systemic effects of intranasal corticosteroids, including Fluticasone Propionate Nasal Spray, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration (2), Use in Specific Populations (8.4)].

6 ADVERSE REACTIONS

Systemic and local corticosteroid use may result in the following:

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In controlled US clinical trials, more than 3,300 subjects with allergic and nonallergic rhinitis received treatment with intranasal fluticasone propionate. In general, adverse reactions in clinical trials have been primarily associated with irritation of the nasal mucous membranes, and the adverse reactions were reported with approximately the same frequency by subjects treated with placebo. Less than 2% of subjects in clinical trials discontinued because of adverse reactions; this rate was similar for vehicle placebo and active comparators.

The safety data described below are based on 7 placebo-controlled clinical trials in subjects with allergic rhinitis. The 7 trials included 536 subjects (57 girls and 108 boys aged 4 to 11 years, 137 female and 234 male adolescents and adults) treated with Fluticasone Propionate 200 mcg once daily over 2 to 4 weeks and 2 placebo-controlled clinical trials which included 246 subjects (119 female and 127 male adolescents and adults) treated with Fluticasone Propionate 200 mcg once daily over 6 months (Table 1). Also included in Table 1 are adverse reactions from 2 trials in which 167 children (45 girls and 122 boys aged 4 to 11 years) were treated with Fluticasone Propionate 100 mcg once daily for 2 to 4 weeks.

Table 1. Adverse Reactions with Fluticasone Propionate Nasal Spray with >3% Incidence and More Common than Placebo in Subjects ≥4 Years with Allergic Rhinitis
Adverse Reaction Fluticasone Propionate 100 mcg Once Daily (n = 167) % Fluticasone Propionate 200 mcg Once Daily (n = 782) % Placebo (n = 758) %
Headache 6.6 16.1 14.6
Pharyngitis 6.0 7.8 7.2
Epistaxis 6.0 6.9 5.4
Nasal burning/nasal irritation 2.4 3.2 2.6
Nausea/vomiting 4.8 2.6 2.0
Asthma symptoms 7.2 3.3 2.9
Cough 3.6 3.8 2.8

Other adverse reactions with Fluticasone Propionate Nasal Spray observed with an incidence less than or equal to 3% but greater than or equal to 1% and more common than with placebo included: blood in nasal mucus, runny nose, abdominal pain, diarrhea, fever, flu-like symptoms, aches and pains, dizziness, and bronchitis.

6.2 Postmarketing Experience

In addition to adverse events reported from clinical trials, the following adverse events have been identified during postapproval use of intranasal fluticasone propionate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate or a combination of these factors.

General Disorders and Administration Site Conditions

Hypersensitivity reactions, including angioedema, skin rash, edema of the face and tongue, pruritus, urticaria, bronchospasm, wheezing, dyspnea, and anaphylaxis/anaphylactoid reactions, which in rare instances were severe.

Ear and Labyrinth Disorders

Alteration or loss of sense of taste and/or smell and, rarely, nasal septal perforation, nasal ulcer, sore throat, throat irritation and dryness, cough, hoarseness, and voice changes.

Eye Disorders

Dryness and irritation, conjunctivitis, blurred vision, glaucoma, increased intraocular pressure, and cataracts.

Cases of growth suppression have been reported for intranasal corticosteroids, including Fluticasone Propionate [see Warnings and Precautions (5.7)].

7 DRUG INTERACTIONS

7.1 Inhibitors of Cytochrome P450 3A4

Fluticasone propionate is a substrate of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, nefazodone, voriconazole) with Fluticasone Propionate Nasal Spray is not recommended because increased systemic corticosteroid adverse effects may occur.

Ritonavir

A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology (12.3)]. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate products, including Fluticasone Propionate Nasal Spray, USP 50 mcg per spray, with ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression.

Ketoconazole

Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under the curve (AUC), but had no effect on urinary excretion of cortisol.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects

Pregnancy Category C. There are no adequate and well-controlled trials with Fluticasone Propionate Nasal Spray in pregnant women. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Because animal reproduction studies are not always predictive of human response, Fluticasone Propionate Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking Fluticasone Propionate Nasal Spray.

Mice and rats at fluticasone propionate doses approximately 1 and 4 times, respectively, the maximum recommended human daily intranasal dose (MRHDID) for adults (on a mg/m2 basis at maternal subcutaneous doses of 45 and 100 mcg/kg/day, respectively) showed fetal toxicity characteristic of potent corticosteroid compounds, including embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification. No teratogenicity was seen in rats at doses up to 3 times the MRHDID (on a mg/m2 basis at maternal inhalation doses up to 68.7 mcg/kg/day).

In rabbits, fetal weight reduction and cleft palate were observed at a fluticasone propionate dose approximately 0.3 times the MRHDID for adults (on a mg/m2 basis at a maternal subcutaneous dose of 4 mcg/kg/day). However, no teratogenic effects were reported at fluticasone propionate doses up to approximately 20 times the MRHDID for adults (on a mg/m2 basis at a maternal oral dose up to 300 mcg/kg/day). No fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration [see Clinical Pharmacology (12.3)].

Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.

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.

Nonteratogenic Effects

Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.

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