Fluticasone and Salmeterol (Lexi-Drugs)

Drug Shortages

One or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information:

ASHP: http://www.ashp.org/menu/DrugShortages

Pronunciation

(floo TIK a sone & sal ME te role)

Brand Names: US

Advair Diskus; Advair HFA; AirDuo RespiClick

Brand Names: Canada

Advair; Advair Diskus

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 (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 upon asthma severity; may increase dose after 2 weeks of therapy in patients who are not adequately controlled.

Advair Diskus: 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 RespiClick: Dry powder inhaler:

No prior treatment with inhaled corticosteroids: 1 inhalation of fluticasone propionate 55 mcg/salmeterol 14 mcg twice daily (maximum dose: 1 inhalation of fluticasone propionate 232 mcg/salmeterol 14 mcg twice daily)

Prior treatment with inhaled corticosteroid: 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]: Dry powder inhaler: Two inhalations twice daily, morning and evening, 12 hours apart

COPD: Oral inhalation: Advair Diskus: 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)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, fluticasone and salmeterol are primarily cleared in the liver and may lead to accumulation in patients with hepatic impairment. Use with caution and monitor closely.

Dosing: Pediatric

Note: Do not use to transfer patients from systemic corticosteroid therapy. 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.

Asthma, maintenance treatment: Note: Initial dose prescribed should be based upon asthma severity. Dose may be increased after 2 weeks if patient does not respond adequately. Patients should be titrated to lowest effective dose once stable.

Advair Diskus:

Children 4 to 11 years: Fluticasone 100 mcg/salmeterol 50 mcg: Oral inhalation: 1 inhalation twice daily. Maximum daily dose: 2 inhalations/day (Fluticasone 200 mcg/salmeterol 100 mcg)

Children ≥12 years and Adolescents: Oral inhalation:

Fluticasone 100 mcg/salmeterol 50 mcg: 1 inhalation twice daily. Maximum daily dose: 2 inhalations/day (Fluticasone 200 mcg/salmeterol 100 mcg)

Fluticasone 250 mcg/salmeterol 50 mcg: 1 inhalation twice daily. Maximum daily dose: 2 inhalations/day (Fluticasone 500 mcg/salmeterol 100 mcg)

Fluticasone 500 mcg/salmeterol 50 mcg: 1 inhalation twice daily. Maximum daily dose: 2 inhalations/day (Fluticasone 1000 mcg/salmeterol 100 mcg)

Advair HFA:

Children ≥12 years and Adolescents: Oral inhalation:

Fluticasone 45 mcg/salmeterol 21 mcg: 2 inhalations twice daily. Maximum daily dose: 4 inhalations/day (Fluticasone 180 mcg/salmeterol 84 mcg)

Fluticasone 115 mcg/salmeterol 21 mcg: 2 inhalations twice daily. Maximum daily dose: 4 inhalations/day (Fluticasone 460 mcg/salmeterol 84 mcg)

Fluticasone 230 mcg/salmeterol 21 mcg: 2 inhalations twice daily. Maximum daily dose: 4 inhalations/day (Fluticasone 920 mcg/salmeterol 84 mcg)

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment required; manufacturer suggests close monitoring of patients with hepatic impairment.

Use: Labeled Indications

Asthma: Treatment of asthma in patients 4 years and older (Advair Diskus) and in patients 12 years and older (Advair HFA, AirDuo RespiClick).

Chronic obstructive pulmonary disease (Advair Diskus 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 Diskus is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.

Fluticasone 250 mcg/salmeterol 50 mcg Diskus 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 Diskus over fluticasone 250 mcg/salmeterol 50 mcg Diskus has not been demonstrated.

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

Clinical Practice Guidelines

Asthma:

Global Strategy for Asthma Management and Prevention (GINA), 2018 Update

NHLBI and NAEPP The Expert Panel Report 3: “Guidelines for the Diagnosis and Management of Asthma,” Full Report 2007

COPD:

ACCP/CTS, “Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease: American College of Chest Physicians and Canadian Thoracic Society Guideline,” 2014

Canadian Thoracic Society Recommendations for Management of Chronic Obstructive Pulmonary Disease, 2007 Update

GOLD 2018 Global Strategy for Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2018

Administration: Inhalation

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

Advair Diskus: 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 Diskus. 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 Diskus 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 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).

Administration: Pediatric

Oral inhalation:

Advair Diskus: After removing from box and foil pouch, write the “Pouch opened” and “Use by” dates on the label on top of the Diskus. 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 Diskus 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). Rinse mouth with water after use and spit to reduce risk of oral candidiasis.

Advair HFA: Shake well for 5 seconds before using. Prime before using the first time by releasing 4 test sprays into the air away from the face, shaking well for 5 seconds before each spray. 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. Rinse mouth with water after use and spit to reduce risk of oral candidiasis. Never immerse canister into water.

Dietary Considerations

Advair Diskus powder for oral inhalation contains lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Storage/Stability

Advair Diskus: Store at 20°C to 25°C (68°F to 77°F). Store in a dry place out of direct heat or sunlight. Diskus 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 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.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, common cold symptoms, or pharyngitis. Have patient report immediately to prescriber signs of infection, signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), angina, tachycardia, 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, insomnia, severe loss of strength and energy, vaginitis, weight gain, mouth sores, mouth irritation, thrush, or difficulty breathing, wheezing, or coughing after use (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Advair Diskus: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm111326.pdf

Advair HFA: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021254s026lbl.pdf#page=46

Contraindications

Hypersensitivity to fluticasone, salmeterol, or any component of the formulation; status asthmaticus; acute episodes of asthma or COPD; severe hypersensitivity to milk proteins (Advair Diskus, AirDuo RespiClick)

Documentation of allergenic cross-reactivity for corticosteroids and sympathomimetics are 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

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 is associated with an increased risk of asthma-related deaths. In a large, randomized, placebo-controlled US trial, salmeterol was associated with an increase in asthma-related deaths (SMART 2006); risk is considered a class effect of LABA monotherapy. Additional data from other clinical trials suggests LABA monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. However, data from large randomized, double-blind active-controlled trials do not show a significant increase in the risk of serious asthma-related events (including hospitalizations, intubations, and death) in adult, adolescent, and pediatric (aged 4 to 11 years) patients when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy. In addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). Current guidelines recommend the use of an inhaled corticosteroid before adding a LABA (GINA 2018; NIH/NHLBI 2007). Assess patients at regular intervals once asthma control is maintained on combination therapy to determine if step-down therapy is appropriate (without loss of asthma control), and the patient can be maintained on an inhaled corticosteroid only. LABAs are not appropriate in patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

• 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 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: Do not use for acute bronchospasm. Short-acting beta-2 agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments. Do not initiate in patients with significantly worsening or acutely deteriorating asthma.

• 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 HF); 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).

• COPD: 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; beta2 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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 RespiClick) 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.

Geriatric Considerations

No differences in safety or effectiveness have been seen in studies of patients ≥65 years of age. However, the decreased number and sensitivity of the β-adrenergic receptors could potentially have an impact on outcomes (Scarpace 1988). Monitoring for efficacy is of utmost importance in older adults. Elderly patients may be more sensitive to the side effects of β-agonists (eg, tremor, tachycardia). Use with caution in patients with concomitant cardiovascular disease. Counsel on proper use of inhaler. Elderly patients may find it beneficial to utilize a spacer device when using a metered-dose inhaler (fluticasone/salmeterol HFA product), and this should be strongly encouraged when the older adult is not self-administering their metered-dose inhaler (eg, long-term care patients).

Pregnancy Considerations

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

Breast-Feeding Considerations

It is not known if fluticasone or salmeterol are present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Refer to individual agents.

Briggs’ Drugs in Pregnancy & Lactation
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

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Refer to individual components.

Drug Interactions 

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

Amphotericin B: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy

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

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

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

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Risk D: Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Risk X: 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. Risk C: Monitor therapy

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

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

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

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

Cobicistat: May increase the serum concentration of Fluticasone (Oral Inhalation). Risk X: Avoid combination

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. Risk D: Consider therapy modification

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Risk C: Monitor therapy

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

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy

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

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy

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

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

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

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Risk D: Consider therapy modification

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

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

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

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

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

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification

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

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

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

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

Loop Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Loop Diuretics. Risk C: 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. Risk X: Avoid combination

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

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

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

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Risk D: Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Risk C: Monitor therapy

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

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

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. Risk C: Monitor therapy

Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Risk C: Monitor therapy

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

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: 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. Risk D: Consider therapy modification

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

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

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

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Risk C: Monitor therapy

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

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

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

Tipranavir: May increase the serum concentration of Fluticasone (Oral Inhalation). Risk X: Avoid combination

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

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Risk D: Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

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

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Risk D: Consider therapy modification

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).

Advanced Practitioners Physical Assessment/Monitoring

See individual agents.

Nursing Physical Assessment/Monitoring

See individual agents.

Dosage Forms Considerations

Advair HFA 8 g canisters contain 60 inhalations, and the 12 g canisters contain 120 inhalations

AirDuo RespiClick contains 60 inhalations

Dosage Forms: US

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

Aerosol, for oral inhalation:

Advair HFA:

45/21: Fluticasone propionate 45 mcg and salmeterol 21 mcg per inhalation (8 g, 12 g) [chlorofluorocarbon free]

115/21: Fluticasone propionate 115 mcg and salmeterol 21 mcg per inhalation (8 g, 12 g) [chlorofluorocarbon free]

230/21: Fluticasone propionate 230 mcg and salmeterol 21 mcg per inhalation (8 g, 12 g) [chlorofluorocarbon free]

Powder, for oral inhalation:

Advair Diskus:

100/50: Fluticasone propionate 100 mcg and salmeterol 50 mcg (14s, 60s) [contains lactose]

250/50: Fluticasone propionate 250 mcg and salmeterol 50 mcg (14s, 60s) [contains lactose]

500/50: Fluticasone propionate 500 mcg and salmeterol 50 mcg (14s, 60s) [contains lactose]

AirDuo RespiClick:

55/14: Fluticasone propionate 55 mcg and salmeterol 14 mcg (0.45 g) [contains lactose]

113/14: Fluticasone propionate 113 mcg and salmeterol 14 mcg (0.45 g) [contains lactose]

232/14: Fluticasone propionate 232 mcg and salmeterol 14 mcg (0.45 g) [contains lactose]

Generic:

55/14: Fluticasone propionate 55 mcg and salmeterol 14 mcg (0.45 g)

100/50: Fluticasone propionate 100 mcg and salmetrol 50 mcg (60s)

113/14: Fluticasone propionate 113 mcg and salmeterol 14 mcg (0.45 g)

232/14: Fluticasone propionate 232 mcg and salmeterol 14 mcg (0.45 g)

250/50: Fluticasone propionate 250 mcg and salmetrol 50 mcg (60s)

500/50: Fluticasone propionate 500 mcg and salmetrol 50 mcg (60s)

Dosage Forms: Canada

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

Aerosol, for oral inhalation:

Advair;

125/25: Fluticasone propionate 125 mcg and salmeterol 25 mcg per inhalation (12 g) [120 metered actuations]

250/25: Fluticasone propionate 250 mcg and salmeterol 25 mcg per inhalation (12 g) [120 metered actuations]

Anatomic Therapeutic Chemical (ATC) Classification
  • R03AK06
Generic Available (US)

May be product dependent

Pricing: US

Aerosol (Advair HFA Inhalation)

45-21 mcg/ACT (per gram): $31.87

115-21 mcg/ACT (per gram): $31.87

230-21 mcg/ACT (per gram): $47.27

Aerosol powder (Advair Diskus Inhalation)

100-50 mcg/dose (per each): $13.01

250-50 mcg/dose (per each): $13.01

500-50 mcg/dose (per each): $21.20

Aerosol powder (AirDuo RespiClick 113/14 Inhalation)

113-14 mcg/ACT (per each): $384.28

Aerosol powder (AirDuo RespiClick 232/14 Inhalation)

232-14 mcg/ACT (per each): $384.28

Aerosol powder (AirDuo RespiClick 55/14 Inhalation)

55-14 mcg/ACT (per each): $384.28

Aerosol powder (Fluticasone-Salmeterol Inhalation)

55-14 mcg/ACT (per each): $119.25

100-50 mcg/dose (per each): $5.96

113-14 mcg/ACT (per each): $119.25

232-14 mcg/ACT (per each): $119.25

250-50 mcg/dose (per each): $7.41

500-50 mcg/dose (per each): $9.74

Aerosol powder (Wixela Inhub Inhalation)

100-50 mcg/dose (per each): $6.02

250-50 mcg/dose (per each): $7.48

500-50 mcg/dose (per each): $9.84

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

See individual agents.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Localized infections with Candida albicans or Aspergillus niger have occurred frequently in the mouth and pharynx with repetitive use of oral inhaler of corticosteroids. These infections may require treatment with appropriate antifungal therapy or discontinuance of treatment with corticosteroid inhaler.

Effects on Bleeding

No information available to require special precautions

Index Terms

AirDuo RespiClick; Fluticasone Propionate and Salmeterol Xinafoate; Fluticasone/Salmeterol; Salmeterol and Fluticasone

References

Advair (fluticasone/salmeterol) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; October 2018.

Advair Diskus (fluticasone/salmeterol) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; January 2019.

Advair Diskus (fluticasone/salmeterol) [product monograph]. Mississauga, Ontario: GlaxoSmithKline Inc; January 2017.

Advair HFA (fluticasone/salmeterol) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; February 2019.

AirDuo RespiClick (fluticasone/salmeterol) [prescribing information]. Frazer, PA: Teva Respiratory, LLC; March 2018.

Anderson JL, Adams CD, Antman EM, et al, “ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration With the American College of Emergency Physicians, The Society of Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons,” J Am Coll Cardiol, 2007, 50(7):e1-157.[PubMed 17692738]

Bateman ED, Boushey HA, Bousquet J, et al, “Can Guideline-Defined Asthma Control Be Achieved? The Gaining Optimal Asthma Control Study,” Am J Respir Crit Care Med, 2004, 170(8):836-44.[PubMed 15256389]

Castle W, Fuller R, Hall J, et al, “Serevent Nationwide Surveillance Study: Comparison of Salmeterol With Salbutamol in Asthmatic Patients Who Require Regular Bronchodilator Treatment,” BMJ, 1993, 306(6884):1034-7.[PubMed 8098238]

Global Initiative for Asthma (GINA). GINA report, Global Strategy for Asthma Management and Prevention. https://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/. Updated 2018. Accessed September 30, 2018.

National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel on the Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.

Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM; SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129(1):15-26.[PubMed 16424409]

Peters SP, Bleecker ER, Canonica GW, et al. Serious asthma events with budesonide plus formoterol vs. budesonide alone. N Engl J Med. 2016;375(9):850-860. doi: 10.1056/NEJMoa1511190.[PubMed 27579635]

Scarpace PJ. Decreased receptor activation with age. Can it be explained by desensitization? J Am Geriatr Soc. 1988;36(11):1067-1071.[PubMed 2844878]

Stempel DA, Raphiou IH, Kral KM, et al; AUSTRI Investigators. Serious asthma events with fluticasone plus salmeterol versus fluticasone alone. N Engl J Med. 2016a;374(19):1822-1830. doi: 10.1056/NEJMoa1511049.[PubMed 26949137]

Stempel DA, Szefler SJ, Pedersen S, et al; VESTRI Investigators. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med. 2016b;375(9):840-849. doi: 10.1056/NEJMoa1606356.[PubMed 27579634]

US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. http://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf. Published August 28, 2007.

Brand Names: International

Adeflo (PH); Adeflo MDI (PH); Adomir (JP); Advair (BM); Aerivio Spiromax (NO); Aeronid (PE); Airflusal (ZW); Airflusal Forspiro (KR, PH); Aroflo (BD); Combiwave SF (MY, PH, VN, ZW); Fluamar (CO); Fludalt Duo (MY); Flutias (ID); Flutizal (PH); Forair (PH); Forspiro (ZW); Kovent SF (PH); Salflu (BD); Salflu MDI (BD); Salmed (PH); Salmeflo (PH); Salmex (NO); Seretaide (PT); Seretide (AR, AT, BB, BE, BG, BM, BR, BS, BZ, CH, CL, CN, CO, CR, CZ, DK, DO, EC, EE, EG, ES, FI, FR, GB, GT, GY, HK, HN, HR, ID, IE, IL, IN, IS, IT, JM, KR, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PY, RO, SE, SG, SI, SK, SR, SV, TH, TT, TW, UA, VE, VN, ZW); Seretide Accuhaler (AU); Seretide Diskus (AE, CY, JO, KW, LB, SA); Seretide Evohaler (BH, JO, LK); SeretideDiskus (BH); Serflu (UY); Serkep (NO); Serocort Inhaler (ZW); Seroflo (HK, MY); Seroxyn (BD); Sirdupla (GB); Viani (DE)

Fluticasone and Salmeterol (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(floo TIK a sone & sal ME te role)

Brand Names: US

Advair Diskus; Advair HFA; AirDuo RespiClick

Brand Names: Canada

Advair; Advair Diskus

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.
What do I need to tell my doctor BEFORE I take this drug?
  • All products:
  • If you have an allergy to fluticasone, salmeterol, or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are using another drug like this one.
  • If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this drug, like certain drugs that are used for HIV, infections, or depression. There are many drugs that must not be taken with this drug. Your doctor or pharmacist can tell you if you are taking a drug that must not be taken with this drug.
  • Inhaler (powder):
  • If you have a milk allergy.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • For all uses of this drug:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • It may take 1 week to see the full effect.
  • If you have high blood sugar (diabetes), talk with your doctor. This drug may raise blood sugar.
  • Call your doctor right away if your breathing problems get worse, if your rescue inhaler does not work as well, or if you need to use your rescue inhaler more often.
  • Do not take more of this drug or use it more often than you have been told. Deaths have happened when too much of this type of drug has been taken. Talk with your doctor.
  • When changing from an oral steroid to another form of a steroid, there may be very bad and sometimes deadly side effects. Signs like weakness, feeling tired, dizziness, upset stomach, throwing up, not thinking clearly, or low blood sugar may happen. Call your doctor right away if you have any of these signs. If you have a bad injury, have surgery, or any type of infection, you may need extra doses of oral steroids. These extra steroids will help your body deal with these stresses. Carry a warning card saying that there may be times when you may need extra steroids.
  • Long-term use may raise the chance of cataracts or glaucoma. Talk with the doctor.
  • Have an eye exam as you have been told by your doctor.
  • This drug may cause weak bones (osteoporosis) with long-term use. Talk with your doctor to see if you have a higher chance of weak bones or if you have any questions.
  • Have a bone density test as you have been told by your doctor. Talk with your doctor.
  • You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
  • Chickenpox and measles can be very bad or even deadly in some people taking steroid drugs like this drug. Avoid being near anyone with chickenpox or measles if you have not had these health problems before. If you have been exposed to chickenpox or measles, talk with your doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • COPD:
  • The chance of getting pneumonia is higher in people with COPD. This drug may raise the chance of getting pneumonia. Talk with the doctor.
What are some side effects that I need to call my doctor about right away?
  • 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:
  • 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.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
  • Signs of a weak adrenal gland like a very bad upset stomach or throwing up, very bad dizziness or passing out, muscle weakness, feeling very tired, mood changes, not hungry, or weight loss.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Chest pain or pressure or a fast heartbeat.
  • Shakiness.
  • Feeling nervous and excitable.
  • Change in how you act.
  • Change in eyesight, eye pain, or very bad eye irritation.
  • A burning, numbness, or tingling feeling that is not normal.
  • Choking.
  • Change in voice.
  • Seizures.
  • Bone pain.
  • Not able to sleep.
  • Feeling very tired or weak.
  • Vaginal itching or discharge.
  • Weight gain.
  • Mouth irritation or mouth sores.
  • Redness or white patches in mouth or throat.
  • This drug can cause very bad breathing problems right after you take a dose. Sometimes, this may be life-threatening. If you have trouble breathing, breathing that is worse, wheezing, or coughing after using this drug, use a rescue inhaler and get medical help right away.
What are some other side effects of this drug?
  • 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:
  • Headache.
  • Upset stomach or throwing up.
  • Throat irritation.
  • Signs of a common cold.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Follow how to use as you have been told by the doctor or read the package insert.
  • To gain the most benefit, do not miss doses.
  • Keep using this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Use this drug at the same time of day.
  • For breathing in only.
  • Rinse out mouth after each use. Do not swallow the rinse water. Spit it out.
  • Have your inhaler use checked with your doctor at each visit. Read and follow facts on how to use the inhaler. Make sure you use the inhaler the right way.
  • If you are using more than 1 inhaled drug, ask the doctor which drug to use first.
  • Inhaler (aerosol):
  • Shake well before use.
  • Prepare the inhaler before first use, by spraying 4 test sprays into the air away from the face. If the inhaler has not been used for more than 4 weeks or if it is dropped, spray 2 sprays into the air away from the face. Shake well before each test spray.
  • Put the cap back on after you are done using your dose.
  • This drug may catch on fire. Do not use near an open flame or while smoking.
  • This inhaler has a dose counter to keep track of how many doses are left. Throw the inhaler away when the dose counter has a 0 in it.
  • Inhaler (powder):
  • Do not prepare a dose until you need to take it. If you prepare a dose and close the inhaler without taking a dose, it will waste the drug and may damage the inhaler.
  • Do not breathe out into the inhaler. Close the inhaler after you use your dose.
  • Do not take the device apart or wash it. Do not use it with a spacer. Do not breathe out into the device.
  • Clean mouthpiece by wiping with a dry tissue or cloth. Do not wash or put in water.
  • This inhaler has a dose counter to keep track of how many doses are left. Throw away the inhaler when the dose counter has a 0 in it, 1 month after opening the foil pouch, or after the expiration date, whichever comes first.
What do I do if I miss a dose?
  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Inhaler (aerosol):
  • Store with the mouthpiece down.
  • Protect from heat or open flame. Do not puncture or burn even if it seems empty.
  • Inhaler (powder):
  • Store in foil pouch until ready for use.
  • Protect from heat, cold, and light.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Fluticasone and Salmeterol (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(floo TIK a sone & sal ME te role)

Brand Names: US

Advair Diskus; Advair HFA; AirDuo RespiClick

Brand Names: Canada

Advair; Advair Diskus

What is this drug used for?
  • It is used to treat asthma.
  • This drug is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.
  • If your child has been given this drug for some other reason, talk with the doctor about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.
What do I need to tell the doctor BEFORE my child takes this drug?
  • All products:
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is using another drug like this one.
  • If your child is taking any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this drug, like certain drugs that are used for HIV, infections, or depression. There are many drugs that must not be taken with this drug.
  • Inhaler (powder):
  • If your child is allergic to milk, talk with the doctor.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • It may take 1 week to see the full effect.
  • If your child has high blood sugar (diabetes), talk with the doctor. This drug can raise blood sugar.
  • Call the doctor right away if your child has breathing problems that get worse, if the rescue inhaler does not work as well, or if your child needs to use the rescue inhaler more often.
  • Do not give more of this drug or have your child use it more often than you were told. Deaths have happened when too much of this type of drug has been taken. Talk with your child’s doctor.
  • When changing from an oral steroid to another form of steroid, there may be very bad and sometimes deadly side effects. Signs like weakness, feeling tired, dizziness, upset stomach, throwing up, not thinking clearly, or low blood sugar may happen. Call the doctor right away if your child has any of these signs. If your child has a bad injury, has surgery, or any type of infection, he/she may need extra doses of oral steroids. These extra steroids will help your child’s body deal with these stresses. Have your child wear medical alert ID (identification).
  • Long-term use may raise the chance of cataracts, glaucoma, or weak bones (osteoporosis). Talk with your child’s doctor.
  • Your child may need to have a bone density test. Talk with the doctor.
  • Have your child get an eye exam as you have been told by the doctor.
  • Your child may have more chance of getting infections. Have your child wash hands often. Avoid crowds and people with infections, colds, or flu.
  • Chickenpox and measles can be very bad or even deadly in some people taking steroid drugs like this drug. Avoid having your child near anyone with chickenpox or measles if your child has not had these health problems before. If your child has been exposed to chickenpox or measles, talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
What are some side effects that I need to call my child’s doctor about right away?
  • 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 child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • 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.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
  • Signs of a weak adrenal gland like a very bad upset stomach or throwing up, very bad dizziness or passing out, muscle weakness, feeling very tired, mood changes, not hungry, or weight loss.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Chest pain or pressure or a fast heartbeat.
  • Feeling nervous and excitable.
  • Shakiness.
  • Change in the way your child acts.
  • Change in eyesight, eye pain, or very bad eye irritation.
  • A burning, numbness, or tingling feeling that is not normal.
  • Choking.
  • Change in voice.
  • Seizures.
  • Bone pain.
  • Not able to sleep.
  • Feeling very tired or weak.
  • Vaginal itching or discharge.
  • Weight gain.
  • Mouth irritation or mouth sores.
  • Redness or white patches in mouth or throat.
  • This drug can cause very bad breathing problems right after your child takes a dose. Sometimes, this may be life-threatening. If your child has trouble breathing, breathing that is worse, wheezing, or coughing after using this drug, have your child use a rescue inhaler and get medical help right away.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Headache.
  • Upset stomach or throwing up.
  • Throat irritation.
  • Signs of a common cold.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Follow how to give this drug as you have been told by your child’s doctor or read the package insert.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Give this drug at the same time of day.
  • For breathing in only.
  • Have your child rinse out the mouth after each use. Do not let your child swallow the rinse water. Have your child spit it out.
  • Check your child’s inhaler use with the doctor at each visit. Read and follow facts on how to use the inhaler. Make sure your child uses the inhaler the right way.
  • If your child is using more than 1 inhaled drug, ask your child’s doctor which inhaled drug to give first.
  • Inhaler (aerosol):
  • Shake well before use.
  • Prepare the inhaler before first use, by spraying 4 test sprays into the air away from the face. If the inhaler has not been used for more than 4 weeks or if it is dropped, spray 2 sprays into the air away from the face. Shake well before each test spray.
  • Put the cap back on after your child is done using a dose.
  • This drug may catch on fire. Do not use near an open flame or while smoking.
  • This inhaler has a dose counter to keep track of how many doses are left. Throw the inhaler away when the dose counter has a 0 in it.
  • Inhaler (powder):
  • Do not prepare a dose until your child needs to take it. If you prepare a dose and close the inhaler before your child takes a dose, it will waste the drug and may damage the inhaler.
  • Do not let your child breathe out into the inhaler. Close the inhaler after giving a dose.
  • Do not take the device apart or wash it. Do not use it with a spacer. Be sure your child does not breathe out into the device.
  • Clean mouthpiece by wiping with a dry tissue or cloth. Do not wash or put in water.
  • This inhaler has a dose counter to keep track of how many doses are left. Throw away the inhaler when the dose counter has a 0 in it, 1 month after opening the foil pouch, or after the expiration date, whichever comes first.
What do I do if my child misses a dose?
  • Skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Inhaler (aerosol):
  • Store with the mouthpiece down.
  • Protect from heat or open flame. Do not puncture or burn even if it seems empty.
  • Inhaler (powder):
  • Store in foil pouch until ready for use.
  • Protect from heat, cold, and light.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.