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Fluticasone and Salmeterol

Medically reviewed by Drugs.com. Last updated on Jul 7, 2020.

Pronunciation

(floo TIK a sone & sal ME te role)

Index Terms

  • Fluticasone Propionate and Salmeterol Xinafoate
  • Fluticasone/Salmeterol
  • Salmeterol and Fluticasone
  • Wixela Inhub

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol, Inhalation:

Advair HFA: Fluticasone propionate 45 mcg and salmeterol 21 mcg per dose (8 g, 12 g); Fluticasone propionate 115 mcg and salmeterol 21 mcg per dose (8 g, 12 g); Fluticasone propionate 230 mcg and salmeterol 21 mcg per dose (8 g, 12 g)

Aerosol Powder Breath Activated, Inhalation:

Advair Diskus: Fluticasone propionate 100 mcg and salmeterol 50 mcg per dose (14 ea, 60 ea); Fluticasone propionate 500 mcg and salmeterol 50 mcg per dose (14 ea, 60 ea); Fluticasone propionate 250 mcg and salmeterol 50 mcg per dose (14 ea, 60 ea) [contains milk protein]

AirDuo Digihaler: Fluticasone propionate 55 mcg and salmeterol 14 mcg per dose (1 ea); Fluticasone propionate 232 mcg and salmeterol 14 mcg per dose (1 ea); Fluticasone propionate 113 mcg and salmeterol 14 mcg per dose (1 ea) [contains lactose monohydrate]

AirDuo RespiClick 55/14: Fluticasone propionate 55 mcg and salmeterol 14 mcg per dose (1 ea) [contains lactose monohydrate]

AirDuo RespiClick 232/14: Fluticasone propionate 232 mcg and salmeterol 14 mcg per dose (1 ea) [contains lactose monohydrate]

AirDuo RespiClick 113/14: Fluticasone propionate 113 mcg and salmeterol 14 mcg per dose (1 ea) [contains lactose monohydrate]

Wixela Inhub: Fluticasone propionate 100 mcg and salmeterol 50 mcg per dose (60 ea); Fluticasone propionate 250 mcg and salmeterol 50 mcg per dose (60 ea); Fluticasone propionate 500 mcg and salmeterol 50 mcg per dose (60 ea) [contains milk protein]

Generic: Fluticasone propionate 100 mcg and salmeterol 50 mcg per dose (60 ea); Fluticasone propionate 113 mcg and salmeterol 14 mcg per dose (1 ea); Fluticasone propionate 232 mcg and salmeterol 14 mcg per dose (1 ea); Fluticasone propionate 250 mcg and salmeterol 50 mcg per dose (60 ea); Fluticasone propionate 500 mcg and salmeterol 50 mcg per dose (60 ea); Fluticasone propionate 55 mcg and salmeterol 14 mcg per dose (1 ea)

Brand Names: U.S.

  • Advair Diskus
  • Advair HFA
  • AirDuo Digihaler
  • AirDuo RespiClick 113/14
  • AirDuo RespiClick 232/14
  • AirDuo RespiClick 55/14
  • Wixela Inhub

Pharmacologic Category

  • Beta2 Agonist
  • Beta2-Adrenergic Agonist, Long-Acting
  • Corticosteroid, Inhalant (Oral)

Pharmacology

Combination of fluticasone (corticosteroid) and salmeterol (long-acting beta2-agonist) designed to improve pulmonary function and control over what is produced by either agent when used alone. Because fluticasone and salmeterol act locally in the lung, plasma levels do not predict therapeutic effect.

Fluticasone: The mechanism of action for all topical corticosteroids is believed to be a combination of three important properties: Anti-inflammatory activity, immunosuppressive properties, and antiproliferative actions. Fluticasone has extremely potent vasoconstrictive and anti-inflammatory activity.

Salmeterol: Relaxes bronchial smooth muscle by selective action on beta2-receptors with little effect on heart rate

Use: Labeled Indications

Asthma: Treatment of asthma in patients ≥4 years of age (Advair Diskus, Wixela Inhub) and in patients ≥12 years of age (Advair HFA, AirDuo Digihaler, AirDuo RespiClick).

Chronic obstructive pulmonary disease (Advair Diskus and Wixela Inhub only): Maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Fluticasone 250 mcg/salmeterol 50 mcg is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.

Fluticasone 250 mcg/salmeterol 50 mcg (Advair Diskus, Wixela Inhub) twice daily is the only approved dosage for the treatment of COPD because an efficacy advantage of the higher strength fluticasone 500 mcg/salmeterol 50 mcg over fluticasone 250 mcg/salmeterol 50 mcg has not been demonstrated.

Limitations of use: Fluticasone/salmeterol is not indicated for the relief of acute bronchospasm.

Contraindications

Hypersensitivity to fluticasone, salmeterol, or any component of the formulation; status asthmaticus; acute episodes of asthma or chronic obstructive pulmonary disease; severe hypersensitivity to milk proteins (Advair Diskus, AirDuo Digihaler, AirDuo RespiClick, Wixela Inhub)

Documentation of allergenic cross-reactivity for corticosteroids and sympathomimetics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): IgE mediated allergic reactions to lactose; cardiac tachyarrhythmias; untreated fungal, bacterial, or tuberculosis infections of the respiratory tract

Dosing: Adult

Note: Do not use to transfer patients from systemic corticosteroid therapy. Patients receiving fluticasone/salmeterol should not use additional salmeterol or other inhaled, long-acting beta-2 agonists (LABAs) (eg, formoterol, arformoterol) for any other reason. The maximum dose is based on the salmeterol component; to increase the dose of the inhaled glucocorticoid component, a separate inhaler with a higher fluticasone dose per inhalation must be prescribed.

Asthma: Oral inhalation: Note: The recommended starting dose is based on asthma severity and previous asthma therapy (including inhaled corticosteroid [ICS] dosage). Titrate to the lowest effective dose (step down) once asthma is well controlled after 2 to 3 months (GINA 2020).

Advair Diskus, Wixela Inhub: Dry powder inhaler: Initial: 1 inhalation of fluticasone propionate 100 mcg/salmeterol 50 mcg, or fluticasone propionate 250 mcg/salmeterol 50 mcg, or fluticasone propionate 500 mcg/salmeterol 50 mcg twice daily (maximum dose: 1 inhalation of fluticasone propionate 500 mcg/salmeterol 50 mcg twice daily).

Advair HFA: Metered dose inhaler: Initial: 2 inhalations of fluticasone propionate 45 mcg/salmeterol 21 mcg, or fluticasone propionate 115 mcg/salmeterol 21 mcg, or fluticasone propionate 230 mcg/salmeterol 21 mcg twice daily (maximum dose: 2 inhalations of fluticasone propionate 230 mcg/salmeterol 21 mcg twice daily).

AirDuo Digihaler, AirDuo RespiClick: Dry powder inhaler: Initial: 1 inhalation of fluticasone propionate 55 mcg/salmeterol 14 mcg, or fluticasone propionate 113 mcg/salmeterol 14 mcg, or fluticasone propionate 232 mcg/salmeterol 14 mcg twice daily (maximum dose: 1 inhalation of fluticasone propionate 232 mcg/salmeterol 14 mcg twice daily).

Advair 125 or Advair 250 [Canadian products]: Metered dose inhaler: 2 inhalations twice daily, morning and evening, 12 hours apart.

Chronic obstructive pulmonary disease: Oral inhalation: Advair Diskus, Wixela Inhub: Dry powder inhaler: 1 inhalation of fluticasone propionate 250 mcg/salmeterol 50 mcg twice daily (maximum dose: 1 inhalation of fluticasone propionate 250 mcg/salmeterol 50 mcg twice daily). Note: For more moderate to severe symptoms, may increase dose to 1 inhalation of fluticasone propionate 500 mcg/salmeterol 50 mcg twice daily or switch to triple-combination therapy (eg, ICS/LABA/long-acting muscarinic antagonists) rather than dose escalation of glucocorticoid component and increased risk of adverse effects (eg, pneumonia) (Calverley 2007; GOLD 2018; GOLD 2020; Hanania 2012; Jenkins 2009).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Patients receiving fluticasone/salmeterol twice daily should not use additional salmeterol or other inhaled, long-acting beta-2 agonists (eg, formoterol, arformoterol) for any other reason. The maximum dose is based on the salmeterol component; to increase the dose of the inhaled glucocorticoid component, a separate inhaler with a higher fluticasone dose per inhalation must be prescribed.

Asthma, maintenance treatment: Note: Initial dose is based on previous asthma therapy, current control, and risk of exacerbation. If adequate response is not seen after 2 weeks of initial dose, increase dosage; once adequate control achieved, doses should be titrated to lowest effective dose.

Advair Diskus, Wixela Inhub: Dry powder inhaler: Note: Do not administer more than 1 inhalation twice daily.

Children 4 to 11 years: Fluticasone propionate 100 mcg/salmeterol 50 mcg: Oral inhalation: 1 inhalation twice daily.

Children ≥12 years and Adolescents: Oral inhalation:

Fluticasone propionate 100 mcg/salmeterol 50 mcg: 1 inhalation twice daily.

Fluticasone propionate 250 mcg/salmeterol 50 mcg: 1 inhalation twice daily.

Fluticasone propionate 500 mcg/salmeterol 50 mcg: 1 inhalation twice daily.

AirDuo Digihaler, AirDuo RespiClick: Dry powder inhaler:

Children ≥12 years and Adolescents: Oral inhalation: Dosing based on disease severity and/or previous asthma therapy; may increase dose after 2 weeks of therapy in patients who are not adequately controlled; do not administer more than 1 inhalation twice daily:

No prior treatment with inhaled corticosteroid: Fluticasone propionate 55 mcg/salmeterol 14 mcg: 1 inhalation twice daily.

Prior treatment with inhaled corticosteroid: Note: Base starting dosage on strength of previous inhaled corticosteroid and disease severity.

Fluticasone propionate 55 mcg/salmeterol 14 mcg: 1 inhalation twice daily.

Fluticasone propionate 113 mcg/salmeterol 14 mcg: 1 inhalation twice daily.

Fluticasone propionate 232 mcg/salmeterol 14 mcg: 1 inhalation twice daily.

Advair HFA: Metered-dose inhaler:

Children ≥12 years and Adolescents: Oral inhalation: Note: Do not administer more than 2 inhalations twice daily:

Fluticasone propionate 45 mcg/salmeterol 21 mcg: 2 inhalations twice daily.

Fluticasone propionate 115 mcg/salmeterol 21 mcg: 2 inhalations twice daily.

Fluticasone propionate 230 mcg/salmeterol 21 mcg: 2 inhalations twice daily.

Advair 125 or Advair 250 [Canadian products]: Metered-dose inhaler:

Children ≥12 years and Adolescents: Oral inhalation:

Fluticasone propionate 125 mcg/salmeterol 25 mcg: 2 inhalations twice daily, morning and evening, 12 hours apart.

Fluticasone propionate 250 mcg/salmeterol 25 mcg: 2 inhalations twice daily, morning and evening, 12 hours apart.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Following administration, rinse mouth with water after use (do not swallow) to reduce risk of oral candidiasis.

Advair Diskus, Wixela Inhub: Dry powder inhaler: After removing from box and foil pouch, write the “Pouch opened” and “Use by” dates on the label on top of the device. The “Use by” date is 1 month from date of opening the pouch. Every time the lever is pushed back, a dose is ready to be inhaled. Do not close or tilt the device after the lever is pushed back. Do not play with the lever or move the lever more than once. The dose indicator tells you how many doses are left. When the numbers 5 to 0 appear in red, only a few doses remain. Discard device 1 month after you remove it from the foil pouch or when the dose counter reads “0” (whichever comes first).

Advair HFA: Metered dose inhaler: Shake well for 5 seconds before each spray. Prime with 4 test sprays (into air and away from face) before using for the first time. If canister is dropped or not used for >4 weeks, prime with 2 sprays. Patient should contact pharmacy for refill when the dose counter reads “020”. Discard device when the dose counter reads “000”. Do not spray in eyes.

AirDuo Digihaler, AirDuo RespiClick: Dry powder inhaler: Inhaler does not require priming and do not use with a spacer or volume holding chamber. Do not wash or place any part of inhaler in water; if mouthpiece needs cleaning, gently wipe with a dry cloth or tissue. When the number 20 appears in red, only a few doses remain. Discard inhaler 30 days after opening the foil pouch or when the counter reads "0", whichever comes first (device is not reusable).

Dietary Considerations

Some products may contain lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Storage

Advair Diskus, Wixela Inhub: Store at 20°C to 25°C (68°F to 77°F). Store in a dry place out of direct heat or sunlight. Device should be discarded 1 month after removal from foil pouch, or when dosing indicator reads “0” (whichever comes first); device is not reusable.

Advair HFA: Store at 20°C to 25°C (68°F to 77°F), excursions permitted from 15°C to 30°C (59°F to 86°F). Store with mouthpiece down. Discard after 120 inhalations. Discard device when the dose counter reads “000”. Device is not reusable.

AirDuo Digihaler, AirDuo RespiClick: Store at 15°C to 25°C (59°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F). Avoid extreme heat, cold, or humidity. Discard 30 days after removal from foil pouch, or when dose counter reads “0” (whichever comes first); device is not reusable.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Cosyntropin: Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Salmeterol. Exceptions: Grapefruit Juice. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Fluticasone (Oral Inhalation). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Salmeterol. Avoid combination

Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. Avoid combination

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Methacholine: Beta2-Agonists (Long-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting beta2 agonists for 36 hours before methacholine use. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Procarbazine: May enhance the adverse/toxic effect of Sympathomimetics. Management: Consider alternatives to this combination when possible. Procarbazine prescribing information states that this combination should be avoided. Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tipranavir: May increase the serum concentration of Salmeterol. Avoid combination

Tobacco (Smoked): May diminish the therapeutic effect of Corticosteroids (Orally Inhaled). Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Adverse Reactions

Adverse reactions occur in adults and adolescents unless otherwise specified.

>10%:

Central nervous system: Headache (5% to 21%)

Respiratory: Upper respiratory tract infection (16% to 27%), pneumonia (4% to 18%; higher incidence is associated with older adults), pharyngitis (≤13%)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (1% to 3%), myocardial infarction (1% to 3%), tachycardia (1% to 3%), palpitations (<3%)

Central nervous system: Voice disorder (≤5%), dizziness (≤4%), migraine (1% to 3%), sleep disorder (1% to 3%)

Dermatologic: Dermatitis (1% to 3%), dermatologic disease (1% to 3%; includes dermatosis and disorder of sweat and sebum), eczema (1% to 3%), contact dermatitis (<3%), pruritus (1%)

Endocrine & metabolic: Weight gain (1% to 3%)

Gastrointestinal: Oral candidiasis (1% to 10%; including mouth and throat infections), nausea and vomiting (4% to 6%), nausea (>5%), gastrointestinal distress (≤4%), viral gastrointestinal infection (3% to 4%), diarrhea (2% to 4%), abdominal distress (1% to 3%), abdominal pain (1% to 3%), dental discomfort (1% to 3%), dental disease (disorder of hard tissue of teeth: 1% to 3%), gastrointestinal infection (1% to 3%), infection of mouth (unspecified oropharyngeal plaque: 1% to 3%), toothache (1% to 3%), xerostomia (1% to 3%), dyspepsia (<3%), upper abdominal pain (<3%)

Genitourinary: Genitourinary infection (1% to 3%), urinary tract infection (1% to 3%)

Hypersensitivity: Hypersensitivity reaction (1% to 3%; can be immediate or delayed), local ocular hypersensitivity (1% to 3%)

Infection: Candidiasis (3%), bacterial infection (1% to 3%), viral infection (1% to 3%), influenza (<3%)

Neuromuscular & skeletal: Musculoskeletal pain (4% to 7%), myalgia (≤4%), back pain (3%), arthralgia (1% to 3%), arthritis (1% to 3%), muscle injury (1% to 3%), muscle spasm (1% to 3%), ostealgia (1% to 3%), skeletal muscle disease (inflammation: 1% to 3%), skeletal pain (1% to 3%), limb pain (<3%), muscle cramps (≤3%)

Ophthalmic: Ocular edema (1% to 3%)

Otic: Ear sign or symptom (1% to 3%)

Respiratory: Throat irritation (8% to 9%; children: ≥3%), nasopharyngitis (5% to 9%), bronchitis (8%), upper respiratory tract inflammation (4% to 7%; includes upper respiratory tract irritation), cough (4% to 6%), viral respiratory tract infection (4% to 6%), hoarseness (≤5%), sinusitis (≤5%), ENT infection (children: ≥3%), dry nose (1% to 3%), epistaxis (1% to 3%), laryngitis (1% to 3%), lower respiratory signs and symptoms (1% to 3%), lower respiratory tract infection (1% to 3%), postnasal drip (1% to 3%), respiratory tract hemorrhage (lower respiratory tract: 1% to 3%), nasal congestion (≤3%), allergic rhinitis (<3%), oropharyngeal pain (<3%), respiratory tract infection (<3%), rhinitis (<3%), rhinorrhea (1% to 3%)

Miscellaneous: Fever (4%), inflammation (1% to 3%), laceration (1% to 3%), postoperative complication (1% to 3%), soft tissue injury (1% to 3%), wound (1% to 3%)

Frequency not defined:

Cardiovascular: Edema

Central nervous system: Hypertonia, mouth pain, pain

Dermatologic: Acquired ichthyosis, exfoliation of skin, viral skin infection

Endocrine & metabolic: Fluid retention, hyperglycemia, hypothyroidism

Gastrointestinal: Dysgeusia, oral discomfort, oral lesion, oral mucosa ulcer

Hematologic & oncologic: Hematoma, lymphadenopathy

Hepatic: Increased liver enzymes (incidence may be higher in children but were transient)

Neuromuscular & skeletal: Bone fracture, connective tissue disease (cartilage disorder), muscle rigidity

Ophthalmic: Conjunctivitis, eye infection, keratitis, xerophthalmia

Respiratory: Nasal signs and symptoms, paranasal sinus disease

<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, aggressive behavior, agitation, anaphylaxis, angioedema, anxiety, aphonia, asthma, atrial fibrillation, behavioral changes, blurred vision, bronchospasm (may be immediate), bruise, cataract, chest congestion, chest tightness, choking sensation, cushingoid appearance, Cushing syndrome, decreased linear skeletal growth rate, depression, dysmenorrhea, dyspnea, ecchymoses, esophageal candidiasis, exacerbation of asthma (can be serious), extrasystoles, facial edema, glaucoma, hyperactivity, hypercorticoidism, hypertension, irregular menses, irritability, laryngeal edema, laryngospasm, myositis, oropharyngeal edema, osteoporosis, otalgia, pallor, paradoxical bronchospasm, paresthesia, pelvic inflammatory disease, photodermatitis, restlessness, retinopathy (central serous), sinus pain, skin rash, sore throat, stridor, supraventricular tachycardia, syncope, tonsillitis, tracheitis, upper airway swelling, vaginitis, ventricular tachycardia, vulvovaginal candidiasis, vulvovaginitis, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: Fluticasone may cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis in sensitive patients. 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. Adult patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. 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. Select surgical patients on long-term, high-dose, inhaled corticosteroid should be given stress doses of hydrocortisone IV during the surgical period and the dose reduced rapidly within 24 hours after surgery (NAEPP 2007).

• Asthma-related deaths: The use of long-acting beta-2 agonists (LABAs) as monotherapy has been associated with an increased risk of severe exacerbations and asthma-related deaths (SMART 2006; Walters 2007); additional data from other clinical trials suggest risk of asthma-related hospitalization may also be increased with LABA monotherapy in pediatric and adolescent patients. However, data from large, randomized, double-blind, controlled trials do not show a significant increase in risk of serious asthma-related events (including hospitalizations, intubations, and death) in adults, adolescents, and pediatric patients (aged 4 to 11 years) when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy (FDA 2017). Current guidelines recommend the use of an as-needed low-dose inhaled corticosteroid with formoterol for patients with infrequent symptoms (GINA 2020).

• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; reaction should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue fluticasone/salmeterol and institute alternative therapy.

• Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, have been reported.

• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use if possible in patients with ocular herpes; active or quiescent tuberculosis infections of the respiratory tract; or untreated viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox or measles should be avoided; if the patient is exposed, prophylaxis with varicella zoster immune globulin or pooled intramuscular immunoglobulin, respectively, may be indicated; if chickenpox develops, treatment with antiviral agents may be considered.

• Lower respiratory infections: Pneumonia and other lower respiratory tract infections have been reported in patients with chronic obstructive pulmonary disease (COPD) following the use of inhaled corticosteroids; monitor COPD patients closely since pneumonia symptoms may overlap symptoms of exacerbations.

• Oral candidiasis: Local oropharyngeal Candida infections have been reported; if this occurs, treat appropriately while continuing fluticasone therapy. Patients should be instructed to rinse mouth with water without swallowing after each use.

• Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

• Upper airway symptoms: There have been reports of laryngeal spasm, irritation, and swelling (stridor, choking) with use.

• Vasculitis: Rare cases of vasculitis (eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]) or other systemic eosinophilic conditions can occur; often associated with decrease and/or withdrawal of oral corticosteroid therapy following initiation of inhaled corticosteroid.

Disease-related concerns:

• Asthma: Appropriate use: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Not to be used in status asthmaticus. In patients presenting to primary care or acute care facility, short-acting beta agonists are recommended for the acute management of exacerbations (GINA 2020).

• Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral count 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 or oral corticosteroids); high doses and/or long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension, or heart failure); beta-agonists may cause elevation in blood pressure, heart rate, increase risk of arrhythmia; may also cause ECG changes (eg, flattening of the T wave, QTc prolongation, ST segment depression).

• Chronic obstructive pulmonary disease: Appropriate use: Do not use for acute episodes of COPD. Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Data are not available to determine if LABA use increases the risk of death in patients with COPD.

• Diabetes: Use with caution in patients with diabetes mellitus; beta-2 agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.

• Hepatic impairment: Use with caution in patients with hepatic impairment; may lead to accumulation of fluticasone in plasma; monitor closely.

• Hypokalemia: Use with caution in patients with hypokalemia; beta-2 agonists may decrease serum potassium (effect is usually transient).

• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged fluticasone use. Consider routine eye exams in chronic users.

• Seizure disorders: Use with caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation.

• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in patients with hyperthyroidism and decreases in hypothyroidism.

Special populations:

• Pediatric: LABAs, when used as monotherapy, increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Orally inhaled and intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients (~1 centimeter per year [range 0.3 to 1.8 cm per year] and related to dose and duration of exposure). To minimize the systemic effects of orally inhaled and intranasal corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.

Dosage form specific issues:

• Lactose: Powder for oral inhalation (Advair Diskus, AirDuo Digihaler, AirDuo RespiClick, Wixela Inhub) may contain lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Other warnings/precautions:

• Discontinuation of systemic corticosteroids: Withdraw systemic corticosteroid therapy with gradual tapering of dose; consider reducing the daily prednisone dose by 2.5 to 5 mg on a weekly basis beginning after at least 1 week of inhalation therapy. Monitor lung function, beta-agonist use, asthma symptoms, and for signs and symptoms of adrenal insufficiency (fatigue, lassitude, weakness, nausea and vomiting, hypotension) during withdrawal.

• Patient information: Patients must be instructed to use short-acting beta-2 agonist (eg, albuterol) for acute asthmatic or COPD symptoms and to seek medical attention in cases where acute symptoms are not relieved, or a previous level of response is diminished. The need to increase frequency of use of inhaled short-acting beta-2 agonist may indicate deterioration of asthma, and medical evaluation must not be delayed. Therapy should not be used more than twice daily; do not use with other long-acting beta-2 agonists.

Monitoring Parameters

FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; glaucoma and cataracts; bone mineral density (baseline and periodically thereafter); serum potassium (hypokalemic patients); glucose (diabetic patients); glaucoma/cataracts; signs/symptoms of oral candidiasis; signs/symptoms of HPA axis suppression/adrenal insufficiency; growth (adolescents and children via stadiometry).

Pregnancy Considerations

Adverse events were observed in animal reproduction studies using this combination. Refer to individual agents.

Patient Education

What is this drug used for?

• It is used to treat asthma, some brands are used to treat COPD (chronic obstructive pulmonary disease). This drug is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Common cold symptoms

• Sore throat

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat

• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Tremors

• Anxiety

• Behavioral changes

• Vision changes

• Eye pain

• Severe eye irritation

• Burning or numbness feeling

• Choking

• Change in voice

• Seizures

• Bone pain

• Severe dizziness

• Passing out

• Severe headache

• Trouble sleeping

• Severe loss of strength and energy

• Vaginal pain, itching, and discharge

• Weight gain

• Mouth sores

• Mouth irritation

• Thrush

• Trouble breathing

• Wheezing

• Cough

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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