Fluticasone Propionate / Salmeterol

Pronunciation

Pronunciation: floo-TIK-a-SONE PROE-pee-oh-nate/sal-ME-ter-ol
Class: Respiratory inhalant combination

Trade Names

Advair Diskus
- Powder for inhalation fluticasone propionate 100 mcg/salmeterol 50 mcg
- Powder for inhalation fluticasone propionate 250 mcg/salmeterol 50 mcg
- Powder for inhalation fluticasone propionate 500 mcg/salmeterol 50 mcg

Advair HFA
- Aerosol for inhalation fluticasone propionate 45 mcg/salmeterol 21 mcg
- Aerosol for inhalation fluticasone propionate 115 mcg/salmeterol 21 mcg
- Aerosol for inhalation fluticasone propionate 230 mcg/salmeterol 21 mcg

Advair Inhalation Aerosol (Canada)

Pharmacology

Fluticasone

Inhibits multiple cell types (eg, mast cells) and mediator production or secretion (eg, histamine) involved in the asthmatic response.

Slideshow: Flashback: FDA Drug Approvals 2013

Salmeterol

Produces bronchodilation by relaxing bronchial smooth muscle through beta-2 receptor stimulation.

Indications and Usage

For the treatment of asthma in patients 4 y of age and older ( Advair Diskus ) and in patients 12 y of age and older ( Advair HFA ); maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema ( Advair Diskus ); to reduce exacerbations of COPD in patients with a history of exacerbations ( Advair Diskus 250/50 only).

Contraindications

Primary treatment of status asthmaticus or other acute episodes of asthma or COPD in which intensive measures are required; hypersensitivity to any component of the product; severe hypersensitivity to milk proteins ( Advair Diskus ).

Dosage and Administration

Advair Diskus
Asthma Adults and Adolescents 12 y of age and older

Inhalation 1 inhalation twice daily (morning and evening, approximately 12 h apart) (max, 500/50 twice daily). The recommended starting dosage is based on the patient's asthma severity.

Children 4 to 11 y of age

Inhalation 1 inhalation of fluticasone/salmeterol 100/50 twice daily (morning and evening, approximately 12 h apart). The recommended starting dosage is based on the patient's asthma severity.

COPD Adults

Inhalation 1 inhalation (250/50) twice daily (morning and evening, approximately 12 h apart).

Advair HFA
Asthma Adults and Adolescents 12 y of age and older

Inhalation 2 inhalations twice daily (morning and evening, approximately 12 h apart) (max, 2 inhalations of 230/21 twice daily). The recommended starting dosage is based on the patient's asthma severity.

General Advice

  • Administer by the orally inhaled route only.
  • Titrate to the lowest effective strength after adequate stability is achieved.
  • Rinse mouth with water without swallowing after inhalation is complete.
  • For patients who do not respond adequately to the starting dosage after 2 wk of therapy, a higher strength may provide additional improvement in asthma control.
  • If a previously effective dosage regimen fails to provide adequate improvement in asthma control, the therapeutic regimen should be reevaluated and additional options (eg, replacing current strength with a higher strength, initiating oral corticosteroids, adding additional inhaled corticosteroids) should be considered.
  • Patients receiving fluticasone/salmeterol twice daily should not use additional salmeterol or other inhaled, long-acting beta-2 agonists (eg, arformoterol, formoterol) for prevention of exercise-induced bronchospasm or for any other reason.
  • If symptoms arise in the period between doses, an inhaled, short-acting beta-2 agonist should be taken for immediate relief.
  • More frequent administration or a higher number of inhalations of the prescribed strength is not recommended because some patients are more likely to experience adverse effects with higher doses of salmeterol.
  • Advair HFA
  • Prime aerosol inhalation before using the first time by releasing 4 test sprays into the air away from face, shaking canister well for 5 sec before each spray.
  • If inhaler has not been used for more than 4 wk or if it is dropped, prime inhaler again by shaking well before each spray and releasing 2 test sprays away from the face.
  • Shake inhaler well for 5 sec before use.

Storage/Stability

Advair Diskus

Store at 68° to 77°F in a dry place away from direct heat or sunlight. Discard delivery device 30 days after removing from foil pouch or after every blister has been used and dose indicator reads “0,” whichever comes first.

Advair HFA

Store at 59° to 86°F. Store with mouthpiece down. Use at room temperature. Do not puncture. Do not store near heat or open flame. Exposures to temperature above 120°F may cause bursting. Never throw the container into a fire or incinerator.

Drug Interactions

Beta-adrenergic blocking agents (eg, propranolol)

May block the pulmonary effect of salmeterol. Use cardioselective beta-blockers when coadministration cannot be avoided; use with caution.

CYP3A4 strong inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)

Fluticasone plasma levels may be elevated and increased CV effects may occur; coadministration with fluticasone is not recommended.

Delavirdine

Fluticasone plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. If alternative therapy is not available, use with caution.

Erythromycin

Salmeterol plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Use with caution.

Linezolid, MAOIs (eg, phenelzine), tricyclic antidepressants (eg, amitriptyline)

Use with extreme caution in patients receiving these agents or within 2 wk of discontinuation.

Long-acting beta-2 agonists (eg, formoterol)

Because this product already contains salmeterol, do not use other long-acting inhaled beta-2 agonists for prevention of exercise-induced bronchospasm or maintenance treatment of asthma.

Nonpotassium-sparing diuretics (eg, loop [eg, furosemide], thiazide [eg, chlorothiazide])

ECG changes and/or hypokalemia associated with nonpotassium-sparing diuretics may worsen with coadministration of salmeterol. Use with caution.

Adverse Reactions

Cardiovascular

Arrhythmias, MI, tachycardia (1% to 3%); atrial fibrillation, extrasystoles, hypertension, pallor, supraventricular tachycardia, ventricular tachycardia (postmarketing).

CNS

Headache (21%); dizziness (more than 5%); intoxication and hangover, malaise and fatigue (3%); migraines, sleep disorders (1% to 3%); aggression, agitation, anxiety, behavioral changes including hyperactivity and irritability (primarily in children), depression, paresthesia, restlessness (postmarketing).

Dermatologic

Dermatitis, dermatosis, eczema (1% to 3%); contact dermatitis, contusions, ecchymosis, photodermatitis, pruritus (postmarketing).

EENT

Pharyngitis (13%); throat irritation (9%); nasal congestion, nasopharyngitis (more than 5%); ear, nose, and throat infections (3% or more); allergic eye disorder, ear signs and symptoms, epistaxis, eye edema, eye swelling, laryngitis, nasal blockage, nose dryness, postnasal drip/rhinorrhea, unspecified oropharyngeal plaques (1% to 3%); aphonia, cataracts, earache, facial and oropharyngeal edema, glaucoma, paranasal sinus pain, rhinitis, throat soreness and irritation, tonsillitis (postmarketing).

GI

Oral and throat candidiasis (10%); nausea/vomiting (6%); nausea (more than 5%); diarrhea, GI discomfort and pain, viral GI infection (4%); GI signs and symptoms (3%); abdominal discomfort and pain, constipation, dental discomfort and pain, disorder of hard tissue of teeth, GI gaseous symptoms, GI infection, hemorrhoids, hyposalivation, oral abnormalities (1% to 3%); abdominal pain, dyspepsia, xerostomia (postmarketing).

Genitourinary

Menstruation symptoms (5%); bacterial reproductive infections, urinary infection (1% to 3%); dysmenorrhea, irregular menstrual cycle, pelvic inflammatory disease, vaginal candidiasis, vaginitis, vulvovaginitis (postmarketing).

Hematologic-Lymphatic

Eosinophilic conditions (postmarketing).

Hepatic

Elevated liver enzymes (at least 1%); abnormal LFTs (postmarketing).

Hypersensitivity

Allergies and allergic reactions (1% to 3%); immediate and delayed hypersensitivity reactions, including angioedema, bronchospasm, and rash (rare); anaphylactic reaction (postmarketing).

Metabolic-Nutritional

Weight gain (1% to 3%); Cushing syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism, hyperglycemia, osteoporosis (postmarketing).

Musculoskeletal

Musculoskeletal pain (9%); back pain (more than 5%); muscle pain (4%); muscle cramps and spasms, muscle injuries (3%); arthralgia, articular rheumatism, bone and skeletal pain, musculoskeletal inflammation (1% to 3%); cramps, myositis, osteoporosis (postmarketing).

Respiratory

Upper respiratory tract infection (27%); pneumonia (16%); bronchitis (8%); upper respiratory tract inflammation (7%); cough, lower respiratory viral infection (6%); hoarseness/dysphonia, sinusitis (more than 5%); lower respiratory hemorrhage, lower respiratory tract infection, lower respiratory tract signs and symptoms (1% to 3%); asthma; asthma exacerbation; chest congestion; chest tightness; dyspnea; immediate bronchospasm; paradoxical bronchospasm; tracheitis; upper respiratory symptoms of laryngeal spasm, irritation, or swelling, including choking and stridor; wheezing (postmarketing).

Miscellaneous

Candidiasis (more than 5%); fever (4%); pain (3%); bacterial infections, congestion, inflammation, poisoning and toxicity, postoperative complications, pressure-induced disorder, soft tissue injuries, viral infections, wounds and lacerations (1% to 3%).

Precautions

Warnings

Long-acting beta-2 adrenergic agonists, such as salmeterol, may increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of salmeterol or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from long-acting beta-2 adrenergic agonists. Available data from controlled clinical trials suggest that long-acting beta-2 adrenergic agonists increase the risk of hospitalization in children and adolescents.

Therefore, when treating patients with asthma, only prescribe fluticasone/salmeterol for patients not adequately controlled on a long-term asthma-control medication (eg, inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and long-acting beta-2 adrenergic agonist. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (eg, discontinue fluticasone/salmeterol) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use fluticasone/salmeterol for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.


Monitor

Carefully monitor lung function (mean forced expiratory volume in 1 second or morning peak expiratory flow), beta-agonist use, and asthma symptoms during withdrawal of corticosteroids. Frequently assess patient for response to treatment. Periodically review therapy in patient with COPD associated with chronic bronchitis for periods longer than 6 mo to assess the continuing benefits and potential risks of treatment. Observe patients for evidence of systemic corticosteroid effects. Monitor growth of children routinely (eg, via stadiometry). Ensure BMD is assessed prior to starting therapy and periodically thereafter in patients with risk factors for decreased BMD who are being treated for COPD. Consider regular eye exams. Monitor patients during periods of stress for evidence of inadequate adrenal response. Closely monitor patients with hepatic disease.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children with asthma younger than 4 y of age ( Advair Diskus ). Safety and efficacy not established in children younger than 12 y of age ( Advair HFA ).

Elderly

Use with caution in elderly patients who have concurrent CV disease.

Hypersensitivity

Immediate hypersensitivity reactions may occur.

Hepatic Function

Impairment of hepatic function may lead to plasma accumulation of the drugs.

Special Risk Patients

Use with caution, if at all, in patients with active or quiescent tuberculosis of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; ocular herpes simplex; convulsive disorders; preexisting diabetes mellitus; ketoacidosis; or thyrotoxicosis.

Adrenal suppression

Hypothalamic-pituitary-adrenal suppression may occur.

BMD

Be prepared to introduce therapy to treat or prevent osteoporosis if indicated.

Candida infections

Infections of the mouth and pharynx with Candida albicans has occurred.

CNS effects

Excessive beta-adrenergic stimulation has been associated with dizziness, fatigue, headache, insomnia, malaise, nervousness, and tremor.

CV disorders

Use with caution in patients with CV disease, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Excessive beta-adrenergic stimulation has been associated with angina, arrhythmias, hypertension or hypotension, palpitation, and tachycardia.

Eosinophilic conditions

Rarely, systemic eosinophilic conditions (eg, vasculitis) may occur.

Growth velocity

A reduction of growth velocity in children and adolescents may occur as a result of poorly controlled asthma or from the therapeutic use of corticosteroids, including inhaled corticosteroids.

Hyperglycemia

Clinically important changes in blood glucose may occur.

Hypokalemia

May occur as a result of intracellular shunting from administration of salmeterol.

Immunosuppression

Patients receiving immunosuppressive therapy may be more susceptible to infection than healthy persons.

Increased use

If therapy becomes less effective, this may be a marker of destabilization of asthma, which requires reevaluation.

Ophthalmic effects

Cataracts, glaucoma, and increased IOP have been reported with long-term administration of fluticasone.

Paradoxical bronchospasm

May occur and be life-threatening.

Respiratory tract infections

Consider the possible development of pneumonia in patients with COPD because the clinical features of pneumonia and exacerbations frequently overlap.

Special warnings

Do not use for transferring patients from systemic corticosteroid therapy; not to be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma; not for use in treating acute asthma symptoms. Do not exceed recommended dose. Do not use in conjunction with an inhaled, long-acting beta-agonist.

Systemic corticosteroids

Withdrawal symptoms (eg, depression, joint and/or muscular pain, lassitude) may occur after transferring patients from oral to inhaled corticosteroids. Transfer patients from systemically active corticosteroids to the less systemically available inhaled corticosteroids with particular care because death caused by adrenal insufficiency has occurred in asthmatic patients during and after transfer; transfer may unmask conditions previously suppressed by systemic corticosteroid therapy (eg, arthritis, conjunctivitis, eczema, eosinophilic conditions, rhinitis).

Upper airway symptoms

Irritation, laryngeal spasm, or swelling (eg, choking, stridor) may occur.

Overdosage

Symptoms

Angina, arrhythmias, cardiac arrest, death, dizziness, dry mouth, fatigue, headache, hypercorticism, hyperglycemia, hypertension, hypokalemia, hypotension, insomnia, malaise, muscle cramps, nausea, nervousness, palpitation, prolongation of the QTc interval, seizures, tachycardia, tremor.

Patient Information

  • Instruct patient to continue using other medications for asthma or COPD as prescribed by health care provider.
  • Advise patient to read the Medication Guide that comes with the product before starting use and each time a refill is obtained.
  • Inform patient that the salmeterol ingredient may increase the risk of asthma-related death.
  • Caution patient not to stop therapy without health care provider guidance because symptoms may recur.
  • Inform patient that long-term use of product may increase risk of some eye problems (eg, cataracts, glaucoma).
  • Inform patients at increased risk for decreased BMD that use of this product may pose an additional risk and BMD may need to be monitored.
  • Advise patient never to administer Advair Diskus with a spacer device.
  • Caution patient not to exceed prescribed dose of 1 inhalation ( Advair Diskus ) or 2 inhalations ( Advair HFA ) twice daily, morning and evening, and to rinse mouth with water, without swallowing, after each dose.
  • Caution patient not to use salmeterol or other long-acting bronchodilators (eg, formoterol) for prevention of exercise-induced asthma or for maintenance treatment of asthma.
  • Warn patient that this drug is an asthma controller and is not to be used to treat an acute asthma attack. Rescue medication (bronchodilator) must be used to obtain rapid relief of asthma symptoms.
  • Explain that effects of drug are not immediate. Benefit requires daily use as instructed and may occur after 30 min, but may take 1 wk or longer.
  • Advise patient not to increase dose and to inform health care provider if symptoms do not improve or if they worsen, if more short-acting bronchodilator than usual is needed, or if the short-acting bronchodilator appears to become less effective.
  • If patient is being converted from oral corticosteroids, review signs and symptoms of adrenal insufficiency, which may occur days or weeks after conversion is complete. Advise patient to carry medical identification (eg, card, bracelet) indicating that supplemental systemic corticosteroids may be needed during periods of stress or a severe asthma attack.
  • Advise patient to report the following symptoms to health care provider: chest pain, nervousness, palpitations, persistent cough, rapid heart rate, sore throat or mouth, tremor.
  • Advise patient to avoid exposure to chickenpox and measles, and to seek medical advice immediately if exposed.

Copyright © 2009 Wolters Kluwer Health.

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