DrugindexOnline^{2nd edition}

Pronouncation: (floo-TIK-a-sone)
Class: Corticosteroid

Trade Names:
Cutivate
- Cream 0.05%
- Lotion 0.05%
- Ointment 0.005%

Trade Names:
Flonase
- Nasal spray 50 mcg/actuation

Trade Names:
Flovent HFA
- Aerosol 44 mcg/actuation
- Aerosol 110 mcg/actuation
- Aerosol 220 mcg/actuation

Trade Names:
Veramyst
- Nasal spray 27.5 mcg/actuation

Florinef (Canada)
Floven HFA (Canada)

Mechanism of Action

Pharmacology

Exerts potent anti-inflammatory effect on nasal passages.

Pharmacokinetics

Absorption

C _max is 0.1 to 1 ng/mL. Systemic bioavailability is 30% for the aerosol. Absolute bioavailability is 0.5% (fluticasone furoate).

Distribution

The average Vd is 4.2 L/kg, and the drug is about 91% protein bound. Following IV administration, Vd is 608 L. Plasma protein binding is greater than 99% (fluticasone furoate).

Metabolism

The major metabolite is a 17β-carboxylic acid derivative metabolized in the liver via the CYP-450 3A4 pathway.

Elimination

The t _½ is about 7.8 h. It is primarily excreted in the feces as parent drug and metabolites, with less than 5% excreted in the urine as metabolites. The t _½ is 15.1 h following IV administration. Excretion is primarily in the feces (fluticasone furoate).

Peak

At least 1 to 2 wk.

Indications and Usage

Relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses ( Cutivate cream and ointment); relief of inflammatory and pruritic manifestations of atopic dermatitis ( Cutivate lotion); management of the nasal symptoms of seasonal and perennial allergic and nonallergic rhinitis in adults and children 4 yr of age and older ( Flonase ); maintenance treatment of asthma as prophylactic therapy in patients 4 yr of age and older ( Flovent HFA ); treatment of symptoms of seasonal and perennial allergic rhinitis in patients 2 yr of age and older ( Veramyst ).

Contraindications

Primary treatment of status asthmaticus or other acute episodes of asthma in which intensive measures are required ( Flovent HFA ); hypersensitivity to any component of the product.

Dosage and Administration

Cutivate
Atopic dermatitis Adults and Children 3 mo of age and older

Topical Cutivate cream: Apply thin film of cream to affected areas 1 to 2 times daily. Rub in gently.

Adults and Children 1 yr of age and older

Topical Cutivate lotion: Apply thin film of lotion to affected areas once daily. Rub in gently.

Adults

Topical Cutivate ointment: Apply thin film of ointment to affected areas 2 times daily. Rub in gently.

Corticosteroid-Responsive Dermatoses Adults and Children 3 mo of age and older

Topical Cutivate cream: Apply thin film of cream to affected areas 2 times daily. Rub in gently.

Flonase
Adults

Nasal inhalation Starting dose is 2 sprays in each nostril every day (total daily dose, 200 mcg). Same dose divided into 100 mcg twice daily also is effective. After the first few days, dose may be reduced to 100 mcg (1 spray each nostril daily) for maintenance therapy. Max daily dose, 200 mcg.

Children 4 yr of age and older

Starting dose is 1 spray in each nostril every day (total daily dose, 100 mcg). May be increased to 200 mcg/day (2 sprays in each nostril) if not adequately responding. Depending on response, dose may be decreased to 100 mcg/day. Max daily dose, 200 mcg.

Flovent HFA

Individuals will experience variable time to onset and degree of symptom relief. Maximum benefit may take 1 to 2 wk or longer. After achieving stability, titrate to lowest effective dose to reduce adverse reactions.

Adults and Children 12 yr of age and older

Inhalation aerosol For patients not responding adequately to the starting dose after 2 wk, higher doses may provide additional asthma control. The recommended starting doses, based on prior asthma therapy are: 1) bronchodilators alone – start with 88 mcg twice daily (max, 440 mcg twice daily); 2) inhaled corticosteroids – start with 88 to 220 mcg twice daily (max, 440 mcg twice daily); and 3) oral corticosteroids – start with 440 mcg twice daily (max, 880 mcg twice daily ).

Inhaled corticosteroid therapy Starting doses above 88 mcg twice daily may be considered for patients with poorer asthma control or who have previously required doses of inhaled corticosteroids in the higher range for that specific agent.

Chronic oral corticosteroid therapy Prednisone should be reduced no faster than 2.5 mg/day on a weekly basis, beginning after at least 1 wk of therapy with Flovent inhalation aerosol or powder.

Children 4 to 11 yr of age

Start with 88 mcg twice daily (max, 88 mcg twice daily).

Veramyst
Adults and Children 12 yr of age and older

Nasal spray Start with 110 mcg once daily administered as 2 sprays (27.5 mcg/spray) in each nostril. Titrate to the minimum effective dosage. When the max benefit has been achieved and symptoms have been controlled, reducing the dosage to 55 mcg (1 spray in each nostril) once daily may be effective in maintaining control of allergic rhinitis symptoms.

Children 2 to 11 yr of age

Nasal spray Start with 55 mcg once daily administered as 1 spray (27.5 mcg/spray) in each nostril. Children not adequately responding to 55 mcg may use 110 mcg (2 sprays in each nostril) once daily. Once symptoms have been controlled, the dosage may be decreased to 55 mcg once daily.

General Advice

• Oral inhalation of aerosol
• For oral inhalation only. Avoid spraying into the nose or eyes.
• Shake well before each use.
• If patient is also receiving bronchodilators by inhalation, administer bronchodilator 5 min before fluticasone to enhance penetration of latter drug into bronchial tree.
• Before oral inhalation, give patient drink of water to moisten throat. Place inhaler mouthpiece 2 fingerbreadths away from patient's mouth. Tilt patient's head back slightly. Instruct patient to take slow, deep breaths while inhaler is being activated and to hold breath for 5 to 10 sec and then breathe out slowly. A spacing device (eg, Aerochamber ) may be used to enhance delivery of medication. Have patient rinse mouth after inhalations are complete.
• If more than 1 spray/dose is ordered, administer each spray individually, waiting a few seconds between sprays.

• Nasal inhalation
• Shake well before each use.
• Actuate the pump 6 times to prime before first use or after a period of nonuse of more than 1 wk.
• Before nasal inhalation, instruct patient to blow nose gently to clear nasal passages. If needed, a topical decongestant may be used 5 to 10 min before administration to ensure adequate tissue penetration. Nasal lavage with saline also may help remove secretions. Clean outer portion of nose with a damp tissue. Wash and dry hands.
• Insert nozzle into patient's nostril. Use finger to keep other nostril closed. Instruct patient to inhale through nostril while you activate the spray pump. Repeat with other nostril.
• If 2 sprays/dose are ordered, administer 1 spray in each nostril, wait a few seconds, and administer second spray into each nostril.

• Cutivate cream or lotion
• Do not use with occlusive dressings or apply in diaper areas or plastic pants; diapers and plastic pants may constitute as an occlusive dressing.

• Flovent HFA
• Prime inhaler before using for first time by releasing 4 test sprays into air away from face, shaking well for 5 seconds before each spray. In the event that inhaler is not used for more than 7 days or when it is dropped, prime inhaler again by shaking well for 5 seconds before each spray and releasing 1 test spray into air.

• Veramyst
• Prime inhaler before using for first time by shaking contents well and releasing 6 test sprays into air away from face. In the event that nasal spray is not used for more than 30 days or if cap has been left off bottle for 5 days or longer, prime pump again until a fine mist appears.
• Shake the container well before each use.

Storage/Stability

Cutivate cream and ointment

Store at 36° to 86°F.

Cutivate lotion

Store at 59° to 86°F. Do not refrigerate. Keep container tightly sealed.

Flonase

Store at 39° to 86°F. Protect from freezing.

Flovent HFA

Store at 59° to 86°F. Store inhaler with mouthpiece down. For best results, use inhaler at room temperature. Shake well before using.

Veramyst

Store at 59° to 86°F. Store in the upright position with the cap in place. Do not freeze or refrigerate.

Drug Interactions

Ketoconazole

Concomitant use may increase fluticasone concentrations and reduce plasma cortisol AUC.

Ritonavir

Can significantly increase plasma fluticasone exposure, resulting in significantly reduced serum cortisol concentrations. Systemic effects, including Cushing syndrome and adrenal suppression, have been reported.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Cutivate ointment

Lightheadedness (1%).

Flonase

Headache (16%).

Flovent HFA

Headache (11%); dizziness (1% to 3%); aggression, agitation, anxiety, behavioral changes including hyperactivity and irritability, depression, restlessness (postmarketing).

Veramyst

Headache (9%); pyrexia (5%).

Dermatologic

Cutivate cream

Facial telangiectasias (5%); burning sensation, dusky erythema, erythematous rash, exacerbation of eczema and pruritus, non-facial telangiectasias, urticaria (2%); dry skin, erythema, infected eczema (1%).

Cutivate cream and ointment

Acute urticarial reaction including edema, pruritus, throat swelling, and urticaria (postmarketing).

Cutivate lotion

Dry skin (7%); stinging at application site (5%); burning/stinging skin, excoriation (2%).

Cutivate ointment

Burning sensation, hives, hypertrichosis, increased erythema, irritation (1%).

Flonase

Dizziness (1% to 3%).

Flovent HFA

Viral skin infections (1% to 3%); contusions, cutaneous hypersensitivity reactions, ecchymosis, pruritus (postmarketing).

EENT

Cutivate cream and ointment

Blurred vision (postmarketing).

Flonase

Pharyngitis (8%); nosebleed (7%); nasal burning and itching (3%); blood in nasal mucus, runny nose (1% to 3%); alteration or loss of sense of taste and/or smell, blurred vision, cataract, conjunctivitis, cough, eye dryness and irritation, glaucoma, hoarseness, increased IOP, nasal septal perforation, nasal ulcer, sore throat, throat irritation and dryness, voice change (postmarketing).

Flovent HFA

Throat irritation (10%); sinusitis/sinus infection (7%); hoarseness/dysphonia (6%); laryngitis, nasal sinus disorder, pharyngitis/throat infection, rhinitis, rhinorrhea/postnasal drip (1% to 3%); aphonia, cataracts, facial and oropharyngeal edema including angioedema and throat soreness and irritation (postmarketing).

Veramyst

Epistaxis (6%); nasopharyngitis (5%); pharyngolaryngeal pain (4%); nasal ulceration (1%).

GI

Cutivate lotion

Diarrhea, vomiting (1%).

Flonase

Nausea/vomiting (5%); abdominal pain, diarrhea (1% to 3%).

Flovent HFA

Candidiasis mouth/throat and non–site specific (5%); diarrhea, dyspeptic symptoms, GI discomfort and pain, GI signs and symptoms, hyposalivation, viral GI infections (1% to 3%).

Genitourinary

Flovent HFA

Urinary infections (1% to 3%).

Hematologic-Lymphatic

Cutivate cream and ointment

Leukopenia, thrombocytopenia (postmarketing).

Flovent HFA

Eosinophilic conditions (postmarketing).

Metabolic-Nutritional

Cutivate cream and ointment

Glycosuria, hyperglycemia (postmarketing).

Flovent HFA

Cushingoid features, growth velocity reduction in children and adolescents, hyperglycemia, osteoporosis, weight gain (postmarketing).

Musculoskeletal

Flovent HFA

Injuries, muscle injuries, muscle pain, muscle stiffness/tightness/rigidity, musculoskeletal pain, soft tissue injuries (1% to 3%).

Veramyst

Back pain (1%).

Respiratory

Cutivate lotion

Influenza (2%).

Cutivate cream and ointment

Pneumocystis carinii pneumonia (postmarketing).

Flonase

Asthma symptoms (7%); cough (4%); bronchitis (1% to 3%).

Flovent HFA

Upper respiratory tract infection (18%); bronchitis, cough (6%); upper respiratory inflammation (5%); asthma exacerbation, chest tightness, cough, dyspnea, immediate and delayed bronchospasm, paradoxical bronchospasm, pneumonia, wheezing (postmarketing).

Veramyst

Cough (4%).

Miscellaneous

Cutivate lotion

Common cold (4%).

Cutivate cream and ointment

Cushing syndrome, generalized body edema, immunosuppression (postmarketing).

Cutivate ointment

Secondary infection.

Flonase

Aches and pains, fever, flu-like symptoms (1% to 3%); growth suppression, hypersensitivity reactions including anaphylaxis, angioedema, bronchospasm, dyspnea, edema of the face and tongue, pruritus, skin rash, urticaria, and wheezing (postmarketing).

Flovent HFA

Chest symptoms, fever, pain, viral infections (1% to 3%); anaphylactic reaction (postmarketing).

Precautions

Monitor Assess patient's symptoms before initiating therapy and periodically during treatment. Monitor patients for any evidence of systemic corticosteroid effect. Since glaucoma and/or cataracts can occur with use of nasal and inhaled fluticasone, closely monitor patients with vision changes or with history of increased IOP, glaucoma, and/or cataracts.

Pregnancy

Category C .

Lactation

Undetermined; however, other corticosteroids have been detected in human milk.

Children

Cutivate cream

Safety and efficacy not established in children younger than 3 mo of age.

Cutivate lotion

Safety and efficacy not established in children younger than 1 yr of age.

Cutivate ointment

Safety and efficacy not established.

Flonase

Safety and efficacy not established for children younger than 4 yr of age.

Flovent HFA inhalation aerosol

Safety and efficacy not established for children younger than 12 yr of age.

Veramyst

Safety and efficacy not established in children younger than 2 yr of age.

Elderly

Flovent , Veramyst

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Hypersensitivity

Reactions, including anaphylaxis, may occur.

Hepatic Function

Since fluticasone is predominately cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone in plasma. Closely monitor patients with hepatic function impairment.

Veramyst

Use with caution.

Adrenal suppression

Prolonged therapy may lead to hypothalamic-pituitary-adrenal (HPA) suppression.

Fungal infections

Local fungal infections have rarely developed. Antifungal treatment or discontinuance of drug may be necessary.

General

Rare instances of wheezing, nasal septum perforation, cataracts, glaucoma, and increased IOP may occur.

Growth velocity

A reduction in growth velocity may occur as a result of inadequate control of chronic diseases such as asthma or from use of corticosteroids for treatment.

Immunosuppression

Immunosuppressed individuals are more susceptible to infections than healthy persons. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using fluticasone.

Impaired wound healing

Patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should not use Veramyst until healing has occurred.

Infections

Drug may mask signs of infection and may decrease host-defense mechanisms.

Route change

Particular caution is needed when transferring patient from systemically active corticosteroids to fluticasone inhaler because deaths caused by adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic to aerosol corticosteroids.

Withdrawal

Because deaths caused by adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids, particular care is needed for patients who are transferred from systemically active corticosteroids to fluticasone. After withdrawal from systemic corticosteroids, a number of months are needed for recovery of HPA function. Patients maintained on prednisone 20 mg/day or more (or its equivalent) may be most susceptible, especially when the systemic corticosteroid is almost completely withdrawn.

Patient Information

• Advise patient to continue taking other medications for same condition as prescribed by health care provider.
• Review proper administration technique. Have patient demonstrate technique.
• Advise patient that dose may be changed periodically depending on how well symptoms are controlled.
• Instruct patient not to exceed prescribed dose.
• Explain that effects of drug are not immediate. Benefit requires daily use as instructed and usually occurs after 1 to 2 days, but full relief may take 1 to 2 wk.
• Instruct patient not to stop the medication once symptoms have been controlled. Continued daily use is necessary to continue to control symptoms.
• Advise patient not to increase dose and to inform health care provider if symptoms do not improve or if they worsen.
• If patient is being converted from oral corticosteroids to inhaled or intranasal corticosteroids, review signs and symptoms of adrenal insufficiency, which may occur days or weeks after conversion is complete. Advise patient to carry medical identification (eg, card, bracelet) indicating they may need supplemental systemic corticosteroids during periods of stress or a severe asthma attack.
• Advise patient to discard the aerosol canister or nasal spray bottle when the labeled number of doses has been used. Advise patient using dry powder inhalation device on storage and expiration dates once device or blisters are removed from moisture-protective foil overwrap.
• Advise patient to avoid exposure to chickenpox and measles, and to seek medical advice immediately if exposed.

• Oral inhalation (aerosol)
• Warn patient that drug is an “asthma controller” and is not to be used to treat an acute asthma attack. They must use their “rescue medication” (bronchodilator) to obtain rapid relief of asthma symptoms.
• Instruct patient to carry medical identification (eg, card, bracelet) if experiencing acute severe asthma attacks requiring rapid systemic treatment.
• Advise patient to rinse mouth with water after inhalations are complete. Instruct patient to spit rinse water out and not to swallow rinse water.
• Advise patient to report the following symptoms to health care provider: sore throat or mouth, cough, dry mouth, rash, facial swelling, or worsening asthma symptoms (eg, increasing need for bronchodilator).

• Nasal inhalation
• Instruct patient to use with caution if sores develop or injuries occur in nasal passages. Drug may prevent or slow proper healing.
• Advise patient to report the following symptoms to health care provider: sneezing, nasal irritation, nosebleed.

• Cutivate cream, lotion, and ointment
• Explain that product is for external use only and to avoid contact with the eyes.
• Advise patients not to bandage or otherwise cover or wrap area so as to be occlusive unless directed by health care provider.
• Advise patients to report any sign of local adverse reactions to health care provider.
• Inform patients that this product should not be used on the face, underarms, or groin areas unless directed by health care provider.
• Instruct patients to contact health care provider if no improvement is seen within 2 wk.
• Advise parents not to use this product to treat diaper dermatitis or to apply product to diaper areas because diaper or plastic pants may constitute occlusive dressing ( Cutivate cream, lotion).

• Flovent HFA
• Advise patient to clean inhaler at least once a weekk after the evening dose to prevent medicine buildup.
• Caution patient to never immerse the canister into water to determine the amount remaining in the canister.