Professional Drug Information > Fluticasone Propionate

Fluticasone (Nasal)

VA CLASSIFICATION
Primary: NT201

Commonly used brand name(s): Flonase.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anti-inflammatory, steroidal, (nasal)—

corticosteroid (nasal)—

Indications

Accepted

Rhinitis, perennial allergic (treatment) ^{01}
Rhinitis, seasonal allergic (treatment) or ^{01}
Rhinitis, nonallergic (treatment) ¹—Fluticasone is indicated in the treatment of perennial allergic rhinitis, seasonal allergic rhinitis, and nonallergic rhinitis¹. ^{03}{05}{04}

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    500.58 ^{04}

Mechanism of action/Effect:

The precise mechanism by which corticosteroids affect allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation. ^{{01} {03}}

Absorption:

Nasal fluticasone propionate has an absolute bioavailability averaging less than 2%. After intranasal application for 3 weeks in patients with allergic rhinitis, fluticasone propionate plasma levels were above the level of detection (50 picograms per mL) only when the recommended dose (200 mcg per day) was exceeded and then only in occasional samples. In addition, absorption is low and bioavailability is negligible following oral administration of fluticasone propionate. ^{{01} {03}}

Protein binding:

Approximately 91%, to human plasma proteins following intravenous administration. Fluticasone propionate is weakly and reversibly bound to erythrocytes and freely equilibrates between erythrocytes and plasma. It is not significantly bound to human transcortin. ^{{01} {03}}

Biotransformation:

Hepatic to a 17-beta-carboxylic acid derivative, which has negligible pharmacological activity in animal studies. ^{{01} {03}}

Half-life:

Following intravenous administration, fluticasone propionate has a terminal elimination half-life of approximately 7.8 hours. ^{03}

Onset of action:

Fluticasone, like other corticosteroids, does not have an immediate effect on allergic symptoms. In some patients, a decrease in nasal symptoms has been noted 12 hours after initial treatment. ^{{01} {03}}

Time to peak effect:

Maximum benefit may not be reached for several days ^{01}. Individual patients will experience a variable time of onset and degree of symptom relief. ^{03}

Duration of action:

When treatment is discontinued, symptoms may not return for several days. ^{{01} {03}}

Elimination:
    Less than 5% of a radiolabeled oral dose is excreted in the urine as metabolites; the remainder is excreted in the feces as the parent drug and metabolites. ^{{01} {03}}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to one corticosteroid may be sensitive to other corticosteroids. ^{03}

Tumorigenicity

There was no evidence of tumorigenicity in mice given fluticasone orally in doses of up to 1 mg per kg of body weight (mg/kg) for 78 weeks or in rats receiving inhalation doses of up to 57 mcg per kg of body weight (mcg/kg) for 104 weeks. ^{{01} {03}}

Mutagenicity

Fluticasone 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 administered at high doses by the oral or subcutaneous routes. In addition, fluticasone did not delay erythroblast division in bone marrow. ^{{01} {03}}

Pregnancy/Reproduction
Fertility—
There was no evidence of impairment of fertility in male and female rats given fluticasone in subcutaneous doses of up to 50 mcg/kg. However, prostate weight was significantly reduced. ^{{01} {03}}

Pregnancy—
Adequate and well-controlled studies have not been done in humans. ^{{01} {03}}

Animals given subcutaneous doses: Studies in mice and rats given doses of 45 and 100 mcg/kg (approximately equivalent to and four times, respectively, the maximum recommended daily [MRD] intranasal dose in adult humans on a mcg-per-square-meter [mcg/m ²] basis) have shown that fluticasone causes fetal toxicity characteristic of potent corticosteroids, including embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification. Studies in rabbits given doses of 4 mcg/kg (approximately one third the MRD intranasal dose in adult humans on a mcg/m ² basis) have shown that fluticasone causes fetal weight reduction and cleft palate. ^{{01} {02} {03}}

Animals given oral doses: In rats and rabbits, fluticasone crossed the placenta following oral administration of 100 and 300 mcg/kg (approximately 4 and 25 times, respectively, the MRD intranasal dose in adult humans on a mcg/m ² basis). Studies in rabbits given doses of up to 300 mcg/kg (approximately 25 times the MRD intranasal dose in adult humans on a mcg/m ² basis) have not shown any teratogenic effects. ^{{01} {02} {03}}

FDA Pregnancy Category C. ^{{01} {02} {03}}

Breast-feeding

It is not known whether nasal fluticasone is distributed into human breast milk. However, other corticosteroids are distributed into human breast milk. In addition, studies in lactating rats given subcutaneous doses of 10 mcg/kg of fluticasone showed that fluticasone is distributed into the milk in animals. Caution should be exercised when administering to nursing women. ^{{01} {03}}

Pediatrics

For children up to 4 years of age—Safety and efficacy have not been established. ^{{01} {02} {03}}

For children 4 years of age and older—With extended use, oral, and possibly inhaled and intranasal, corticosteroids have been shown to have the potential to cause growth suppression in children and adolescents. ^{{02} {03}} If significant systemic absorption of nasal corticosteroids occurs in pediatric or adolescent patients, adrenal suppression and growth suppression may result. Prolonged or high-dose therapy with these medications requires careful attention to dosage and close monitoring of growth and development ^{{01} {02}}; the benefits of corticosteroid therapy should be weighed against the possibility of growth suppression, if growth appears slowed. ^{03}


Geriatrics


Appropriate studies on the relationship of age to the effects of nasal fluticasone have not been performed in the geriatric population. However, clinical trials included a limited number of older patients (above 60 years of age) and the adverse reactions reported were similar to those in younger adults; therefore, geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected. ^{{01} {03}}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Cytochrome P450 3A4 Inhibitors, especially ketoconazole and ritonavir     (co-administration could result in increased plasma concentrations of fluticasone )

^{04}{05}
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Intolerance to corticosteroids ^{{01} {03}}
Risk-benefit should be considered when the following medical problems exist
Glaucoma    (rare cases of glaucoma have been reported following use of nasal corticosteroids, including nasal fluticasone ^{{01} {02} {03}})


» Infections, fungal, bacterial, parasitic, or systemic viral    (corticosteroids may mask the infection; in addition, some infections, such as chickenpox or measles, may have a more serious course in patients on immunosuppressant doses of corticosteroids ^{{01} {03}})


Nasal septal ulcers, recent or
Nasal surgery, recent or
Nasal trauma, recent    (corticosteroids inhibit wound healing ^{{01} {03}})


» Ocular herpes simplex    (corticosteroids may mask the infection ^{{01} {03}})


» Tuberculosis, latent or active, of respiratory tract    (corticosteroids may mask or activate the infection ^{{01} {03}})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Adrenal function assessment    (assessment of hypothalamic-pituitary-adrenal (HPA) axis function may be advisable at periodic intervals in patients receiving long-term nasal corticosteroid therapy; this is especially important in children and adolescents ^{{01} {03}})


Otolaryngologic examination    (should be performed in patients on long-term therapy [several months or longer] to monitor nasal mucosa and nasal passages for adverse effects such as, infection, nasal septal perforation, nasal membrane ulceration, or other histologic changes ^{{01} {03}})




Side/Adverse Effects

Note: The risk of systemic effects is minimal with usual doses of nasal fluticasone ^{{01} {03}}. Rare cases of cataracts, glaucoma, and increased intraocular pressure have been reported following use of intranasal corticosteroids, including fluticasone ^{02}.
Systemic effects including hypothalamic-pituitary-adrenal (HPA) axis suppression may occur with greater-than-recommended doses of nasal fluticasone. If a patient is particularly sensitive to or has recently used systemic corticosteroids in conjunction with using nasal corticosteroids, the patient may also be predisposed to hypercorticism (see Overdose section). ^{{01} {03}}
The following side/adverse effects were reported voluntarily, post drug approval and without incidence data: Anaphylactoid (rare) or hypersensitivity reactions (angioedema, bronchospasm, dyspnea, edema of face and tongue, pruritis, skin rash, urticaria, wheezing), hoarseness, loss of sense of taste or smell, nasal septal perforation, nasal ulcers, ocular changes (e.g., cataracts, conjunctivitis, glaucoma, increased intraocular pressure), throat irritation and dryness, and voice changes.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more common (>3%)
    
Asthma symptoms ^{03} (shortness of breath)
    
cough ^{03}
    
epistaxis ^{{01} {03}} (bloody mucus; unexplained nosebleeds )
    
headache ^{{01} {03}}
    
nausea ^{03}
    
vomiting ^{03}

Incidence less frequent (1 to 3%)
    
Abdominal pain ^{03} (stomach pain)
    
bronchitis (cough; excessive mucus)^{01}{03}
    
diarrhea ^{03}
    
dizziness ^{01}{03}
    
fever ^{03}
    
influenza-like symptoms ^{03} (fever; headache; general aches and pains; loss of appetite; weakness)

Incidence rare
    
Nasal or pharyngeal candidiasis ^{{01} {02} {03}} (white patches inside nose or throat)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Burning, dryness, or other irritation inside the nose ^{{01} {03}}
    
pharyngitis ^{{01} {03}} (sore throat)

Incidence less frequent
    
Rhinorrhea ^{{01} {03}} (runny nose)






Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
For acute overdose—Adverse effects due to acute overdose are unlikely with the small quantities of corticosteroid contained in the nasal preparation. ^{{01} {03}}

For chronic overdose—If symptoms of chronic overdose occur, nasal corticosteroids should be discontinued slowly ^{01}. Chronic overdose may manifest as signs and symptoms of hypercorticism or Cushing's syndrome (bone fractures, diabetes mellitus [blindness, blurred vision, increased thirst or urination], excess facial hair growth in females, fullness of face, neck, and trunk, hypertension, impotence in males, lack of menstrual periods, muscle wasting, and weakness) ^{{03} {04}}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Fluticasone (Nasal).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Intolerance to corticosteroids

Pregnancy—No studies have been done in pregnant women. Subcutaneous doses of fluticasone in mice, rats, and rabbits have caused fetal toxicity; studies in rats and rabbits have shown that fluticasone crosses the placenta





Breast-feeding—It is not known whether fluticasone propionate is distributed into human breast milk. Studies in rats showed that subcutaneous fluticasone is distributed into the milk of lactating animals





Use in children—Importance of monitoring growth and development with prolonged or high-dose therapy; safety and efficacy in children younger than 4 years of age have not been established.

Other medical problems, especially fungal, bacterial, parasitic, or systemic viral infections; latent or active tuberculosis of respiratory tract; or ocular herpes simplex

Proper use of this medication
» Proper administration technique; reading patient directions carefully before use

Priming the bottle pump and clearing nasal passages before use; tilting the head forward slightly, inserting the nasal applicator into the nostril, and spraying while breathing in through the nostril

» Avoid spraying into the eyes

» Compliance with therapy

» Importance of not using more medication than the amount prescribed because of potential enhanced absorption and increased severity of side effects

» Proper dosing
Missed dose: Using as soon as possible; skipping missed dose if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress during prolonged therapy

» Checking with physician if signs of infection of the nose, throat, or sinuses occur


Side/adverse effects
Signs of potential side effects, especially abdominal pain, anaphylactoid or immediate hypersensitivity reactions, asthma symptoms, bronchitis, cough, diarrhea, dizziness, epistaxis, fever, flu-like symptoms, headache, nasal or pharyngeal candidiasis, nasal septal perforation, nasal ulcers, nausea, ocular changes, pruritus, rhinorrhea, urticaria, voice changes, or wheezing


General Dosing Information
Regular use of nasal fluticasone is required to obtain full therapeutic benefit. ^{{01} {03}}

Fluticasone propionate nasal suspension dosage form contains no fluorocarbon propellants. ^{{01} {03}}

The dosage of other corticosteroids being administered concurrently by other routes of administration, including oral inhalation, should be taken into account when determining the prescribing limits of nasal corticosteroids ^{{01} {03}} and may increase the risk of hypercorticism and hypothalamic-pituitary-adrenal (HPA) axis suppression. ^{03}

Caution is recommended if a systemic corticosteroid is replaced with a nasal corticosteroid, such as fluticasone propionate, since adrenal insufficiency may occur. In addition, some patients may experience symptoms of withdrawal, such as joint or muscular pain, lassitude, or depression. It is recommended that patients previously treated for prolonged periods with systemic corticosteroids and transferred to nasal corticosteroids be carefully monitored for acute adrenal insufficiency in response to stress. ^{{01} {03}}


Nasal Dosage Forms

FLUTICASONE PROPIONATE NASAL SUSPENSION

Usual adult dose
Rhinitis, perennial allergic (treatment) or
Rhinitis, seasonal allergic (treatment) or
Rhinitis, nonallergic (treatment)
Initial: Nasal, 200 mcg (0.2 mg) a day, administered as 2 metered sprays in each nostril once a day or 1 metered spray in each nostril two times a day. ^{{01} {02} {03}{05}}

Maintenance: Nasal, 100 mcg (0.1 mg) a day, administered as 1 metered spray in each nostril once a day. Maintenance dosage may be initiated as soon as four to seven days after initial treatment is started. ^{{01} {02} {03}}


Usual adult prescribing limits
Nasal, 200 mcg (0.2 mg) per day. ^{{01} {02} {03}}

Note: Canadian manufacturer: some patients may benefit from up to 400 mcg (0.4 mg) per day, given as 2 metered sprays in each nostril every twelve hours.^{05}


Usual pediatric dose
Rhinitis, perennial allergic (treatment) or
Rhinitis, seasonal allergic (treatment) or
Rhinitis, nonallergic (treatment)¹
Infants and children up to 4 years of age: Safety and efficacy have not been established. ^{{01} {02} {03}}

Children 4 years of age and older (including adolescents): Nasal, 100 mcg (0.1 mg) a day, administered as 1 metered spray in each nostril once a day. ^{{01} {02} {03}}

Note: Children and adolescents not adequately responding to 100 mcg (0.1 mg) a day may use 200 mcg (0.2 mg) a day, administered as an initial dose of 2 metered sprays in each nostril once a day^{05} or 1 metered spray in each nostril two times a day. Once adequate control is achieved, the dosage should be decreased to 100 mcg (0.1 mg) once a day. ^{{01} {02} {03}{04}}



Usual pediatric prescribing limits
Nasal, 200 mcg (0.2 mg) per day. ^{{01} {02} {03}}

Strength(s) usually available
U.S.—


50 mcg (0.05 mg) per metered spray (0.05%) (Rx) [Flonase^{01}{03} (benzalkonium chloride) (carboxymethylcellulose sodium) (dextrose ) (microcrystalline cellulose) ( phenylethyl alcohol) (polysorbate 80)]

Canada—


50 mcg (0.05 mg) per metered spray (0.05%) (Rx) [Flonase ( benzalkonium chloride) (carboxymethylcellulose sodium ) (dextrose) (microcrystalline cellulose) (phenylethyl alcohol) ( polysorbate 80)]^{05}

Packaging and storage:
Store between 4 and 30 °C (39 and 86 °F), ^{{01} {03}} unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • For the nose. ^{{01} {03}}
   • Shake gently before use. ^{{01} {03}}

Note: Explain administration technique. ^{{01} {03}}

Revised: 03/06/2001

References

1. Flonase package insert (Allen & Hanburys—US), Rev 10/94, Rec 12/94.
   

2. Flonase package insert (Glaxo Wellcome—US), Rev 10/97, Rec 11/11/97.
   

3. Flonase package insert (Glaxo Wellcome—US), Rev 12/98, Rec 3/99.
   

4. Product Information: Flonase®, fluticasone propionate. Glaxo Wellcome Inc., Research Triangle Park, NC. (PI revised 10/2000) PI reviewed 2/2001.
   

5. Product Information: Flonase®, fluticasone propionate. Glaxo Wellcome Inc., Mississauga, Ontario, Canada. (PI revised 6/2000) PI reviewed 2/2001.
   

Link to this Page

Printable Version

Email Page