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

Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required

Severe hypersensitivity to milk proteins or demonstrated hypersensitivity to drug

Cautions

Localized infections of the mouth and pharynx with Candida albicans reported with inhaled corticosteroids; treat with appropriate local or systemic (eg, oral) antifungal therapy while treatment continues; at times therapy may need to be interrupted

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

Therapy not to be regarded as bronchodilator and not indicated for rapid relief of bronchospasm; instruct patient to contact physicians immediately when episodes of asthma that are not responsive to bronchodilators occur during course of treatment; during such episodes, patients may require therapy with oral corticosteroids

If patient is exposed to chickenpox, may administer prophylaxis with varicella-zoster immune globulin (VZIG); if a patient is exposed to measles, may administer prophylaxis with pooled intramuscular immunoglobulin (IG) (See respective package inserts for complete VZIG and IG prescribing information); if chickenpox develops, treatment with antiviral agents may be considered; use with caution, if at all, in patients with active or quiescent tuberculosis infections of respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex

Anaphylactic reactions in patients with severe milk protein allergy after inhalation of powder products containing lactose reported; patients with severe milk protein allergy should not use product

Decreases in bone mineral density (BMD) reported with long-term administration of products containing ICS; clinical significance of small changes in BMD with regard to longterm consequences such as fracture is unknown; monitor and treat patients with established standards of care 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 (eg, anticonvulsants, oral corticosteroids)

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients; monitor growth of pediatric patients receiving ICS routinely (eg. via stadiometry); to minimize systemic effects of orally inhaled corticosteroids, titrate each patient’s dosage to lowest dosage that effectively controls his/her symptoms

Paradoxical bronchospasm may occur with immediate increase in wheezing after dosing; if bronchospasm occurs following dosing treat immediately with an inhaled, short-acting bronchodilator; discontinued therapy immediately; and institute alternative therapy

CYP3A4 substrate; strong CYP3A4 inhibitors may increase fluticasone systemic exposure

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

Epistaxis, nasal ulceration, 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

Eosinophilic conditions

• In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions; some patients have clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy; these events, have been associated (not always) with reduction and/or withdrawal of oral corticosteroid therapy following introduction of fluticasone propionate
• Cases of serious eosinophilic conditions have also been reported with other ICS in this clinical setting; physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients; a causal relationship between fluticasone propionate and these underlying conditions not established

Transferring patients from systemic corticosteroid therapy

• Particular care needed for patients transferred from systemically active corticosteroids to ICS; deaths due to adrenal insufficiency during and after transfer from systemic corticosteroids to less systemically available ICS
• After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function
• During periods of stress or a severe asthma attack, instruct patients who have been withdrawn from systemic corticosteroids to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction; patients should carry warning card indicating possible need for supplementary systemic steroids in such emergencies
• Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to ICS; prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with ICS
• Lung function (mean forced expiratory volume in 1 second [FEV1] or morning peak expiratory flow [AM PEF]), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids
• Patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension
• Transfer of patients from systemic corticosteroid therapy to ICS may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions)
• Systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects; if effects occur, ICS dose should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of asthma symptoms should be considered

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