Not indicated for treatment of acute symptoms of asthma. Not for use in patients with rapidly deteriorating or life-threatening episodes of asthma. Fatalities have been reported. Do not use in conjunction with other long-acting beta2 agonist inhalers. Do not exceed recommended dosage; short-acting beta2 agonist should be used for acute symptoms and symptoms occurring between treatments. Do not use to transfer patients from oral corticosteroid therapy. Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) have been reported. Rare cases of vasculitis (Churg-Strauss syndrome) have been reported with fluticasone use. May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving 20 mg per day of prednisone (or equivalent) may be most susceptible. Concurrent use of ritonavir (and potentially other strong inhibitors of CYP3A4) may increase fluticasone levels and effects on HPA suppression. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections. May suppress the immune system; use with caution in patients with systemic infections or ocular herpes simplex. Avoid exposure to chickenpox and measles.
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 ~1 cm per year [range 0.3-1.8 cm per year] and appears to be related to dose and duration of exposure.) Long-term use may affect bone mineral density in adults. To minimize the systemic effects of orally-inhaled and intranasal corticosteroids, each patient should be titrated to the lowest effective dose.
Beta agonists may cause elevation in blood pressure, heart rate, and result in CNS excitement. Use caution in patients with cardiovascular disease (arrhythmia or hypertension or CHF), convulsive disorders, diabetes, glaucoma, hyperthyroidism, or hypokalemia. May increase risk of arrhythmia and may increase serum glucose or decrease serum potassium concentrations. In a large, randomized clinical trial (SMART), salmeterol was associated with a small, but statistically significant increase in asthma-related deaths (when added to usual asthma therapy); risk may be greater in African-American patients versus Caucasians. The elderly may be at greater risk of cardiovascular side effects. Safety and efficacy have not been established in children <4 years of age.
Powder for oral inhalation contains lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.
Percentages reported in patients with asthma >10%:
Central nervous system: Headache (12% to 13%)
Endocrine & metabolic: Serum glucose increased, serum potassium decreased
Respiratory: Upper respiratory tract infection (21% to 27%), pharyngitis (10% to 13%)
>3% to 10%:
Gastrointestinal: Nausea/vomiting (4% to 6%), diarrhea (2% to 4%), GI pain/discomfort (1% to 4%), oral candidiasis (1% to 4%)
Neuromuscular & skeletal: Musculoskeletal pain (2% to 4%)
Respiratory: Bronchitis (2% to 8%), upper respiratory tract inflammation (6% to 7%), cough (3% to 6%), sinusitis (4% to 5%), hoarseness/dysphonia (2% to 5%), viral respiratory tract infection (4%)
1% to 3%:
Cardiovascular: Chest symptoms, fluid retention, palpitation
Central nervous system: Compressed nerve syndromes, hypnagogic effects, pain, sleep disorders, tremor
Dermatologic: Hives, skin flakiness/ichthyosis, urticaria, viral skin infection
Gastrointestinal: Appendicitis, constipation, dental discomfort/pain, gastrointestinal disorder, gastrointestinal infection, gastrointestinal signs and symptoms (nonspecified), oral discomfort/pain, oral erythema/rash, oral ulcerations, unusual taste, viral GI infection (0% to 3%)
Hematologic: Contusions/hematomas, lymphatic signs and symptoms (nonspecified)
Hepatic: Abnormal liver function tests
Neuromuscular & skeletal: Arthralgia, articular rheumatism, bone/cartilage disorders, fractures, muscle injuries, muscle stiffness, tightness/rigidity
Ocular: Conjunctivitis, eye redness, keratitis
Otic: Ear signs and symptoms (nonspecified)
Respiratory: Blood in nasal mucosa, congestion, ear/nose/throat infection, lower respiratory tract infection, lower respiratory signs and symptoms (nonspecified), nasal irritation, nasal signs and symptoms (nonspecified), nasal sinus disorders, pneumonia, rhinitis, rhinorrhea/post nasal drip, sneezing, wheezing
Miscellaneous: Allergies/allergic reactions, bacterial infection, burns, candidiasis (0% to 3%), sweat/sebum disorders, diaphoresis, viral infection, wounds and lacerations
Postmarketing and/or case reports: Serious exacerbations of asthma (some fatal), abdominal pain, agitation, aggression, aphonia, arrhythmia, back pain, bronchospasm and immediate bronchospasm, cataracts, chest congestion, chest tightness, choking, contact dermatitis, contusions, cramps, Cushing syndrome, Cushingoid features, depression, dysmenorrhea, dyspnea, dyspepsia, earache, ecchymoses, eosinophilic conditions, glaucoma, growth velocity reduction in children/adolescents, hypercorticism, hyperglycemia, hypersensitivity reaction (immediate and delayed), hypokalemia, hypothyroidism, influenza, laryngeal spasm/irritation, irregular menstruation, muscle spasm, myositis, osteoporosis, pallor, paresthesia, paradoxical tracheitis, paranasal sinus pain, photodermatitis, PID, restlessness, stridor, syncope, throat soreness/irritation, vaginal candidiasis, vaginitis, vulvovaginitis, rare cases of vasculitis (Churg-Strauss syndrome), ventricular tachycardia, weight gain, xerostomia
Fluticasone: Substrate of CYP3A4 (major) Beta-adrenergic blockers (eg, propranolol): Decreased effect of salmeterol component and may cause bronchospasm in asthmatics; use with caution.
Beta2-agonists (long-acting): Should not be coadministered with fluticasone/salmeterol combination.
Diuretics (loop, thiazide): Hypokalemia from diuretics may be worsened by beta-agonists (dose related); use with caution.
CYP3A4 inhibitors: May increase levels and/or effects of fluticasone. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.
MAO inhibitors, tricyclic antidepressants: Increased toxicity (cardiovascular); wait at least 2 weeks after discontinuing these agents to start fluticasone/salmeterol.
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.
Oral inhalation: Note: Do not use to transfer patients from systemic corticosteroid therapy. COPD: Adults: Fluticasone 250 mcg/salmeterol 50 mcg twice daily, 12 hours apart
Asthma:
Children 4-11 years: Fluticasone 100 mg/salmeterol 50 mg twice daily, 12 hours apart
Children 
12 and Adults: One inhalation twice daily, morning and evening, 12 hours apart
Note: Advair Diskus® is available in 3 strengths, initial dose prescribed should be based upon previous asthma therapy. Dose should be increased after 2 weeks if adequate response is not achieved. Patients should be titrated to lowest effective dose once stable. (Because each strength contains salmeterol 50 mcg/inhalation, dose adjustments should be made by changing inhaler strength. No more than 1 inhalation of any strength should be taken more than twice a day). Maximum dose: Fluticasone 500 mcg/salmeterol 50 mcg, one inhalation twice daily.
Patients not currently on inhaled corticosteroids: Fluticasone 100 mcg/salmeterol 50 mcg
Patients currently using inhaled beclomethasone dipropionate:
420 mcg/day: Fluticasone 100 mcg/salmeterol 50 mcg
462-840 mcg/day: Fluticasone 250 mcg/salmeterol 50 mcg
Patients currently using inhaled budesonide:
400 mcg/day: Fluticasone 100 mcg/salmeterol 50 mcg
800-1200 mcg/day: Fluticasone 250 mcg/salmeterol 50 mcg
1600 mcg/day: Fluticasone 500 mcg/salmeterol 50 mcg
Patients currently using inhaled flunisolide:
1000 mcg/day: Fluticasone 100 mcg/salmeterol 50 mcg
1250-2000 mcg/day: Fluticasone 250 mcg/salmeterol 50 mcg
Patients currently using inhaled fluticasone propionate aerosol:
176 mcg/day: Fluticasone 100 mcg/salmeterol 50 mcg
440 mcg/day: Fluticasone 250 mcg/salmeterol 50 mcg
660-880 mcg/day: Fluticasone 500 mcg/salmeterol 50 mcg
Patients currently using inhaled fluticasone propionate powder:
200 mcg/day: Fluticasone 100 mcg/salmeterol 50 mcg
500 mcg/day: Fluticasone 250 mcg/salmeterol 50 mcg
1000 mcg/day: Fluticasone 500 mcg/salmeterol 50 mcg
Patients currently using inhaled triamcinolone acetonide:
1000 mcg/day: Fluticasone 100 mcg/salmeterol 50 mcg
1100-1600 mcg/day: Fluticasone 250 mcg/salmeterol 50 mcg
Elderly: No differences in safety or effectiveness have been seen in studies of patients 65 years of age. However, increased sensitivity may be seen in the elderly. Use with caution in patients with concomitant cardiovascular disease.
Dosage adjustment in renal impairment: Specific guidelines are not available
Dosage adjustment in hepatic impairment: Fluticasone is cleared by hepatic metabolism. No dosing adjustment suggested. Use with caution in patients with impaired liver function.
National Asthma Education and Prevention Program, "Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma," Bethesda, MD, National Institutes of Health, 1997. NIH publication 97-4051.
National Asthma Education and Prevention Program, "Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics - 2002,"J Allergy Clin Immunol, 2002, 110(5 Suppl):141-219.
