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Flovent® HFA - United States Availability

Flovent® HFA (fluticasone propionate), a chlorofluorocarbon-free (CFC) formulation of fluticasone for inhalation, was FDA approved in September, 2004. GlaxoSmithKline has announced that this product will be available in March of 2005. Flovent® Inhaler (CFC formulation) is expected to be phased out of distribution by mid-March of 2005.

Pronunciation:

(floo TIK a sone)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Inhalation: Maintenance treatment of asthma as prophylactic therapy. It is also indicated for patients requiring oral corticosteroid therapy for asthma to assist in total discontinuation or reduction of total oral dose. NOT indicated for the relief of acute bronchospasm.

Intranasal: Management of seasonal and perennial allergic rhinitis and nonallergic rhinitis in patients 4 years of age

Topical: Relief of inflammation and pruritus associated with corticosteroid-responsive dermatoses in patients 3 months of age

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Topical: Do not use if infection is present at treatment site, in the presence of skin atrophy, or for the treatment of rosacea or perioral dermatitis

Warnings/Precautions:

Controlled clinical studies have shown that orally-inhaled and intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients. (In studies of orally-inhaled corticosteroids, the mean reduction in growth velocity was approximately 1 centimeter per year [range 0.3-1.8 cm per year] and appears to be related to dose and duration of exposure.) To minimize the systemic effects of orally-inhaled and intranasal corticosteroids, each patient should be titrated to the lowest effective dose. The risk of growth velocity reduction with intranasal administration of fluticasone may be very low; in a small, placebo-controlled study, no statistically-significant reduction was observed.

May suppress the immune system, patients may be more susceptible to infection. Use with caution, if at all, in patients with systemic infections, active or quiescent tuberculosis infection, or ocular herpes simplex. Avoid exposure to chickenpox and measles.

Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Rare cases of vasculitis (Churg-Strauss syndrome) or other eosinophilic conditions can occur.

Inhalation: Not to be used in status asthmaticus or for the relief of acute bronchospasm. Flovent® Rotadisk® and Flovent® Diskus® [CAN] contain lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Topical: May also cause suppression of HPA axis, especially when used on large areas of the body, denuded areas, for prolonged periods of time or with an occlusive dressing. Pediatric patients may be more susceptible to systemic toxicity. Safety and efficacy in pediatric patients <3 months of age have not been established.

Adverse Reactions:

Oral inhalation:

>10%:

Central nervous system: Headache (5% to 11%)

Respiratory: Upper respiratory tract infection (16% to 18%)

3% to 10%:

Respiratory: Throat irritation (8% to 10%), sinusitis/sinus infection (4% to 7%), cough (4% to 6%; placebo: 5%), bronchitis (2% to 6%; placebo 5%), hoarseness/dysphonia (2% to 6%), upper respiratory tract inflammation (2% to 5%)

Miscellaneous: Candidiasis (2% to 5%)

1% to 3%:

Cardiovascular: Chest symptoms

Central nervous system: Dizziness, fever, migraine, pain

Gastrointestinal: Diarrhea, dyspepsia, gastrointestinal infection (viral), gastrointestinal discomfort/pain, hyposalivation

Genitourinary: Urinary tract infection

Neuromuscular & skeletal: Musculoskeletal pain, muscle pain, muscle stiffness/tightness/rigidity

Respiratory: rhinitis, pharyngitis/throat infection, rhinorrhea/postnasal drip, nasal sinus disorder, laryngitis

Miscellaneous: Viral infection, injuries (including muscle, soft tissue)

Postmarketing and/or case reports: Aggression, agitation, anaphylactic reaction, angioedema, aphonia, asthma exacerbation, bronchospasm (immediate and delayed), cataracts, chest tightness, Churg-Strauss syndrome, contusion, cough, Cushingoid features, cutaneous hypersensitivity, depression, dyspnea, ecchymoses, facial edema, growth velocity reduction in children/adolescents, HPA axis suppression, hyperglycemia, hypersensitivity reactions (immediate and delayed), oropharyngeal edema, osteoporosis, paradoxical bronchospasm, pneumonia, pruritus, rash, restlessness, throat irritation, throat soreness, urticaria, vasculitis, weight gain, wheeze

Nasal inhalation:

>10%:

Central nervous system: Headache (7% to 16%)

Respiratory: Pharyngitis (6% to 8%)

1% to 10%:

Central nervous system: Dizziness (1% to 3%), fever (1% to 3%)

Gastrointestinal: Nausea/vomiting (3% to 5%), abdominal pain (1% to 3%), diarrhea (1% to 3%)

Respiratory: Epistaxis (6% to 7%), asthma symptoms (3% to 7%), cough (4%), blood in nasal mucous (1% to 3%), runny nose (1% to 3%), bronchitis (1% to 3%)

Miscellaneous: Aches and pains (1% to 3%), flu-like symptoms (1% to 3%)

<1% and postmarketing reports: Alteration or loss of sense of taste and/or smell, anaphylaxis/anaphylactoid reactions, angioedema, blurred vision, bronchospasm, cataracts, conjunctivitis, dry/irritated eyes, dry throat, dyspnea, edema (face and tongue), glaucoma, hoarseness, hypersensitivity reactions, increased intraocular pressure, nasal septal perforation (rare), nasal ulcer, pruritus, skin rash, sore throat, throat irritation, urticaria, voice changes, wheezing

Topical: Pruritus (3%), skin irritation (3%), exacerbation of eczema (2%), dryness (1%), numbness of fingers (1%)

Reported with other topical corticosteroids (in decreasing order of occurrence): Irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria, pustular psoriasis from chronic plaque psoriasis

Overdosage/Toxicology:

Drug Interactions:

CYP3A4 inhibitors: Serum level and/or toxicity of fluticasone may be increased; this effect was shown with ketoconazole, but not erythromycin. Other potential inhibitors include amiodarone, cimetidine, clarithromycin, delavirdine, diltiazem, dirithromycin, disulfiram, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nevirapine, propoxyphene, quinupristin-dalfopristin, ritonavir, saquinavir, verapamil, zafirlukast, zileuton.

Ritonavir: May increase serum levels (due to CYP3A4 inhibition) and the potential for steroid-related adverse effects (eg, Cushing syndrome, adrenal suppression). Avoid concurrent use.

Salmeterol: The addition of salmeterol has been demonstrated to improve response to inhaled corticosteroids (as compared to increasing steroid dosage).

Ethanol/Nutrition/Herb Interactions:

Stability:

Aerosol, cream: Store between 2°C to 30°C (36°F to 86°F). Store aerosol with nozzle end down, protect from freezing and direct sunlight. Discard aerosol after labeled number of doses has been used.

Flovent® HFA: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Store with mouthpiece down.

Nasal spray: Store between 4°C to 30°C (39°F to 86°F). Discard after labeled number of doses has been used, even if bottle is not completely empty.

Powder for oral inhalation:

Flovent® Diskus® [CAN]: Store between 2°C to 30°C in a dry place away from direct frost, heat, or sunlight. Do not store in a damp environment (eg, bathroom). Protect from temperatures >30°C (>86°F).

Flovent® Rotadisk®: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Use blisters within 2 months of opening protective pouch.

Mechanism of Action:

Pharmacodynamics/Kinetics:

Absorption:

Topical cream: 5% (increased with inflammation)

Oral inhalation: Absorbed systemically primarily via lungs, minimal GI absorption due to presystemic metabolism

Distribution: 4.2 L/kg

Protein binding: 91%

Metabolism: Hepatic via CYP3A4 to 17-carboxylic acid (negligible activity)

Bioavailability: Oral inhalation: Flovent®: 30%; decreased with Flovent® HFA (30% lower)

Excretion: Feces (as parent drug and metabolites); urine (<5% as metabolites)

Dosage:

Children:

Asthma: Inhalation, oral:

Flovent®, Flovent® HFA:

Children <12 years (unlabeled use): NIH Asthma Guidelines (administer in divided doses twice daily):

"Low" dose: 88-176 mcg/day

"Medium" dose: 176-440 mcg/day

"High" dose: >440 mcg/day

Children 12 years: Refer to Adults dosing.

Flovent® Rotadisk®: Note: Titrate to the lowest effective dose once asthma stability is achieved.

Children 4-11 years: Dosing based on previous therapy

Bronchodilator alone: Recommended starting dose: 50 mcg twice daily; highest recommended dose: 100 mcg twice daily

Inhaled corticosteroids: Recommended starting dose: 50 mcg twice daily; highest recommended dose: 100 mcg twice daily; a higher starting dose may be considered in patients previously requiring higher doses of inhaled corticosteroids

Children 11 years: Refer to Adults dosing.

Flovent® Diskus® [CAN]:

Children 4-16 years: Usual starting dose: 50-100 mcg twice daily; may increase to 200 mcg twice daily in patients not adequately controlled; titrate to the lowest effective dose once asthma stability is achieved

Children 16 years: Refer to Adults dosing.

Inflammation/pruritus associated with corticosteroid-responsive dermatoses: Topical: Children 3 months: Apply sparingly in a thin film twice daily; therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Safety and efficacy for use in pediatric patients <3 months have not been established.

Rhinitis: Intranasal: Children 4 years and Adolescents: Initial: 1 spray (50 mcg/spray) per nostril once daily; patients not adequately responding or patients with more severe symptoms may use 2 sprays (100 mcg) per nostril. Depending on response, dosage may be reduced to 100 mcg daily. Total daily dosage should not exceed 2 sprays in each nostril (200 mcg)/day. Dosing should be at regular intervals.

Adults:

Asthma: Inhalation, oral: Note: Titrate to the lowest effective dose once asthma stability is achieved

Flovent®, Flovent® HFA: Manufacturers labeling: Dosing based on previous therapy

Bronchodilator alone: Recommended starting dose: 88 mcg twice daily; highest recommended dose: 440 mcg twice daily

Inhaled corticosteroids: Recommended starting dose: 88-220 mcg twice daily; highest recommended dose: 440 mcg twice daily; a higher starting dose may be considered in patients previously requiring higher doses of inhaled corticosteroids

Oral corticosteroids: Recommended starting dose:

Flovent®: 880 mcg twice daily

Flovent® HFA: 440 mcg twice daily

Highest recommended dose: 880 mcg twice daily; starting dose is patient dependent. In patients on chronic oral corticosteroids therapy, reduce prednisone dose no faster than 2.5-5 mg/day on a weekly basis; begin taper after 1 week of fluticasone therapy

NIH Asthma Guidelines (administer in divided doses twice daily).

"Low" dose: 88-264 mcg/day

"Medium" dose: 264-660 mcg/day

"High" dose: >660 mcg/day

Flovent® Rotadisk®: Dosing based on previous therapy

Bronchodilator alone: Recommended starting dose 100 mcg twice daily; highest recommended dose: 500 mcg twice daily

Inhaled corticosteroids: 100-250 mcg twice daily; highest recommended dose: 500 mcg twice daily; a higher starting dose may be considered in patients previously requiring higher doses of inhaled corticosteroids

Oral corticosteroids: 1000 mcg twice daily; highest recommended dose: 1000 mcg twice daily; starting dose is patient dependent. In patients on chronic oral corticosteroids therapy, reduce prednisone dose no faster than 2.5 mg/day on a weekly basis; begin taper after 1 week of fluticasone therapy

Flovent® Diskus® [CAN]:

Mild asthma: 100-250 mcg twice daily

Moderate asthma: 250-500 mcg twice daily

Severe asthma: 500 mcg twice daily; may increase to 1000 mcg twice daily in very severe patients requiring high doses of corticosteroids

Inflammation/pruritus associated with corticosteroid-responsive dermatoses: Topical: Apply sparingly in a thin film twice daily; therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Rhinitis: Intranasal: Initial: 2 sprays (50 mcg/spray) per nostril once daily; may also be divided into 100 mcg twice a day. After the first few days, dosage may be reduced to 1 spray per nostril once daily for maintenance therapy. Dosing should be at regular intervals.

Elderly: No differences in safety have been observed in the elderly when compared to younger patients. Based on current data, no dosage adjustment is needed based on age.

Dosage adjustment in hepatic impairment: Fluticasone is primarily cleared in the liver. Fluticasone plasma levels may be increased in patients with hepatic impairment, use with caution; monitor.

Administration:

Aerosol inhalation: Shake container thoroughly before using. Take 3-5 deep breaths. Use inhaler on inspiration. Allow 1 full minute between inhalations. Rinse mouth with water after use to reduce aftertaste and incidence of candidiasis. Flovent® HFA inhaler must be primed before first use, when not used for 7 days, or if dropped. To prime the first time, release 4 sprays into air; shake well before each spray and spray away from face. If dropped or not used for 7 days, prime by releasing a single test spray.

Nasal spray: Shake bottle gently before using. Prime pump prior to first use (press 6 times until fine spray appears). Blow nose to clear nostrils. Insert applicator into nostril, keeping bottle upright, and close off the other nostril. Breathe in through nose. While inhaling, press pump to release spray. Nasal applicator may be removed and rinsed with warm water to clean.

Powder for oral inhalation:

Flovent® Rotadisk®: Prior to use, one foil disk containing 4 blisters of medication must be inserted into Diskhaler®. After 4 inhalations have been taken from the Diskhaler®, a new foil disk should be inserted. Do not use with a spacer device. Do not exhale into Diskhaler®. Use in horizontal position. At least weekly, Diskhaler® should be cleaned.

Flovent® Diskus® [CAN]: Do not use with a spacer device. Do not exhale into Diskus®. Do not wash or take apart. Use in horizontal position.

Topical: Apply sparingly in a thin film of cream or ointment. Rub in lightly. Do not use for diaper dermatitis.

Monitoring Parameters:

Dietary Considerations:

Patient Education:

Metered-dose inhalation: Sit when using. Take deep breaths for 3-5 minutes, and clear nasal passages before administration (use decongestant as needed). Hold breath for 5-10 seconds after use, and wait 1-3 minutes between inhalations. Follow package insert instructions for use. Do not exceed maximum dosage. If also using inhaled bronchodilator, use before fluticasone. Rinse mouth and throat after use to reduce aftertaste and prevent candidiasis.

Nasal spray: Shake gently before use. Use at regular intervals, no more frequently than directed. Report unusual cough or spasm; persistent nasal bleeding, burning, or irritation; or worsening of condition.

Powder for oral inhalation: Flovent® Diskus®: Do not attempt to take device apart. Do not use with a spacer device. Do not exhale into the Diskus®, use in a level horizontal position. Do not wash the mouthpiece.

Topical: For external use only. Apply thin film of cream to affected area only; rub in lightly. Do not apply occlusive covering unless advised by prescriber. Wash hand thoroughly after use; avoid contact with eyes. Notify prescriber if skin condition persists or worsens. Do not use for treatment of diaper dermatitis or under diapers or plastic pants.

Additional Information:

In the United States, dosage for the metered dose inhaler (Flovent®, Flovent® HFA) is expressed as the amount of drug which leaves the actuater and is delivered to the patient. This differs from other countries, which express the dosage as the amount of drug which leaves the valve.

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Aerosol for oral inhalation, as propionate [contains CFCs] (Flovent®):

44 mcg/inhalation (7.9 g) [60 metered doses], (13 g) [120 metered doses] [DSC]

110 mcg/inhalation (7.9 g) [60 metered doses], (13 g) [120 metered doses] [DSC]

220 mcg/inhalation (7.9 g) [60 metered doses], (13 g) [120 metered doses] [DSC]

Aerosol for oral inhalation, as propionate [CFC free] (Flovent® HFA)

44 mcg/inhalation (10.6 g) [120 metered doses]

110 mcg/inhalation (12 g) [120 metered doses]

220 mcg/inhalation (12 g) [120 metered doses]

Cream, as propionate (Cutivate®): 0.05% (15 g, 30 g, 60 g)

Ointment, as propionate (Cutivate®): 0.005% (15 g, 30 g, 60 g)

Powder for oral inhalation, as propionate [prefilled blister pack] (Flovent® Diskus®) [CAN; not available in the United States]:

50 mcg (28s, 60s) [contains lactose]

100 mcg (28s, 60s) [contains lactose]

250 mcg (28s, 60s) [contains lactose]

500 mcg (28s, 60s) [contains lactose]

Powder for oral inhalation, as propionate [4 blisters of the drug per Rotadisk®, 15 Rotadisks® per pack] (Flovent® Rotadisk®):

50 mcg (60s) [delivers 44 mcg/inhalation, contains lactose/milk protein] [DSC]

100 mcg (60s) [delivers 88 mcg/inhalation, contains lactose/milk protein] [DSC]

250 mcg (60s) [delivers 220 mcg/inhalation, contains lactose/milk protein] [DSC]

Suspension, intranasal spray, as propionate (Flonase®): 50 mcg/inhalation (16 g) [120 metered doses]

International Brand Names: