fluticasone furoate inhaled (Rx)

>10%

Nasopharyngitis (8-13%)

Headache (6-13%)

1-10%

Bronchitis (4-7%)

Sinusitis (4-7%)

Influenza (4-7%)

Pharyngitis (3-6%)

URT infection (2-6%)

Oropharyngeal pain (3-4%)

Toothache (3%)

Back pain (3%)

Viral gastroenteritis (3%)

Abdominal pain (3%)

Cough (3%)

Oropharyngeal candidiasis (3%)

Dysphonia (2-3%)

Oral candidiasis (<1-3%)

Procedural pain (<1-3%)

Rhinitis (<1-3%)

Throat irritation (<1-3%)

Contraindications

Status asthmaticus or other acute episodes of asthma

Hypersensitivity, including severe allergy to milk protein

Cautions

Localized infections of the mouth and pharynx with Candida albicans reported with inhaled corticosteroids

Not indicated for use as rescue therapy for acute bronchospasm (see Contraindications)

Potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex; more serious or even fatal course of chickenpox or measles in susceptible patients; use caution because of potential for worsening of these infections; if exposed to chickenpox, prophylaxis with varicella-zoster immune globulin or pooled IV immunoglobulin may be indicated; if a patient is exposed to measles, prophylaxis with pooled IM immunoglobulin (IG) may be indicated

Caution when withdrawing from systemic corticosteroids and transferring to inhaled corticosteroids; taper systemic corticosteroids gradually and monitor for symptoms of HPA axis suppression and adrenal insufficiency; prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy

Systemic absorption from inhaled corticosteroids is low, but hypercorticism and adrenal suppression may occur with very high dosages or at regular dosage in susceptible individuals; if changes occur, discontinue therapy slowly

CYP3A4 substrate; strong CYP3A4 inhibitors may increase fluticasone systemic exposure

Paradoxical bronchospasm with immediate increase in wheezing after dosing reported; treat immediately with inhaled short-acting bronchodilator and discontinue fluticasone inhaled

Hypersensitivity reactions (eg, urticaria, flushing, allergic dermatitis, bronchospasm) reported; anaphylaxis in patients with severe milk protein allergy observed with other inhaled powder products that contain lactose

Long-term use decreases bone mineral density; patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care

May cause reduction in growth velocity when administered to children and adolescents

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids

Epistaxis, nasal ulceration, Candida albicans infection, nasal septal perforation, impaired wound healing; monitor patients periodically for signs of adverse effects on nasal mucosa; avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma

Pregnancy

Insufficient data on use in pregnant women

Animal studies

• No fetal structural abnormalities were observed in animal (ie, rats, rabbits) reproduction studies during organogenesis at doses 4 times (rat) and 1 times (rabbit) the maximum recommended human daily inhalation dose

Clinical considerations

• In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate
• Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control

Lactation

No information is available on the presence of fluticasone furoate in human milk, the effects on the breastfed child, or the effects on milk production

Low concentrations of other inhaled corticosteroids have been detected in human milk

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child from fluticasone furoate or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Synthetic trifluorinated corticosteroid that elicits anti-inflammatory activity

Exact mechanism of action is unknown, but corticosteroids have shown to exhibit anti-inflammatory effect on neutrophils, eosinophils, macrophages, mast cells, lymphocytes, and mediators (histamine, leukotrienes, cytokines, eicosanoids)

Exhibits binding affinity for the human glucocorticoid receptor that is approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate

Absorption

Bioavailability, inhaled: 13.9% (inhaled portion of the dose delivered to the lung)

Bioavailability, oral: 1.3% (low from swallowed portion due to extensive first-pass metabolism)

Peak plasma time: 0.5-1 hr

AUC: 26% lower in patients with asthma compared with healthy volunteers

Distribution

Protein bound: 99.6%

Vd: 661 L

Metabolism

Cleared from systemic circulation principally by hepatic metabolism via CYP3A4

Metabolites have significantly reduced activity

Elimination

Half-life: 24 hr (with repeat dosing)

Excretion: >99% feces; ~1% urine

Inhaled Administration

For oral inhalation only

Rinse mouth with water and expectorate after each dose to prevent oral/esophageal candidiasis

Storage

Store at room temperature between 68-77°F (20-25°C); excursions permitted from 59-86°F (15-30°C)

Store in a dry place away from direct heat or sunlight