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|Fluticasone Propionate/Salmeterol

Fluticasone Propionate/Salmeterol

Trade Names:
Advair Diskus
- Powder for inhalation 100 mcg fluticasone propionate, 50 mcg salmeterol
- Powder for inhalation 250 mcg fluticasone propionate, 50 mcg salmeterol
- Powder for inhalation 500 mcg fluticasone propionate, 50 mcg salmeterol

Mechanism of Action

Pharmacology

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

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

Pharmacokinetics

Absorption

Peak plasma levels of fluticasone are achieved in 1 to 2 hr, and those of salmeterol are achieved in about 5 min.

Elimination

The terminal t _½ of fluticasone averaged 5.33 to 7.65 hr when administered as Advair Diskus .

Indications and Usage

Long-term maintenance treatment of asthma in patients 4 yr of age and older; COPD associated with chronic bronchitis.

Contraindications

Primary treatment of status asthmaticus or other acute episodes of asthma in which intensive measures are required; hypersensitivity to any component of the product.

Dosage and Administration

Advair Diskus is available in 3 strengths, containing 100, 250, and 500 mcg of fluticasone propionate each in combination with 50 mcg of salmeterol.

Inhalation 1 inhalation bid (morning and evening, approximately 12 hr apart). For patients not currently on an inhaled corticosteroid, the recommended starting dose is fluticasone/salmeterol 100/50 or 250/50 bid. For patients on an inhaled corticosteroid, the recommended starting dose of fluticasone/salmeterol varies from 100/50 to 500/50 bid, depending on the concomitant inhaled corticosteroid and the dose.

Inhalation 100/50 mcg bid (morning and evening, approximately 12 hr apart).

Inhalation 1 inhalation (250/50 mcg) bid (morning and evening, approximately 12 hr apart).

General Advice

• If patient also is receiving short-acting bronchodilator by inhalation, administer bronchodilator 5 min before fluticasone/salmeterol to enhance penetration of latter drugs into bronchial tree.
• Have patient rinse mouth with water without swallowing after inhalation is complete.

Storage/Stability

Store delivery device at controlled room temperature (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.”

Drug Interactions

May block the pulmonary effect of salmeterol.

Plasma levels of fluticasone may be increased and plasma cortisol AUC may be reduced. Avoid coadministration of ritonavir, if possible.

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.

ECG changes and hypokalemia may be worsened.

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

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations, syncope (1% to 3%).

CNS

Dizziness, headache (at least 3%); compressed nerve syndrome, hypnagogic effects, situational disorder, sleep disorder, tremor (1% to 3%).

Dermatologic

Acquired ichthyosis, burns, contusion, disorders of sweat/sebum, hematoma, laceration, skin flakiness, sweating, urticaria, viral skin infection, wound (1% to 3%).

GI

Appendicitis, candidiasis mouth/throat, constipation, diarrhea, GI discomfort/pain, nausea, viral GI infection, vomiting (at least 3%); dental discomfort/pain, gastroenteritis, GI disorders, GI infection, GI signs/symptoms, oral discomfort/pian, oral erythema/rash, oral ulcerations (1% to 3%).

Hepatic

Abnormal LFT (1% to 3%).

Hematologic-Lymphatic

Lymphatic signs and symptoms (1% to 3%).

Metabolic

Hypothyroidism (1% to 3%).

Musculoskeletal

Muscle cramps/spasms, musculoskeletal pain (at least 3%); arthralgia, articular rheumatism, bone and cartilage disorders, muscle injuries, muscle stiffness (1% to 3%).

Ophthalmic

Conjunctivitis, eye redness, keratitis, viral eye infection (1% to 3%).

Respiratory

Bronchitis, cough, epistaxis, ear/nose/throat infection, hoarseness/dysphonia, oral candidiasis, pharyngitis, sinusitis, throat irritation, upper respiratory inflammation, upper respiratory tract infection, viral respiratory infection (at least 3%); blood in nasal mucosa, breathing disorder, ear signs and symptoms, laryngitis, lower respiratory infection, nasal symptoms, pneumonia, rhinitis, rhinorrhea, sneezing (1% to 3%); serious, sometimes fatal, exacerbations of asthma (postmarketing).

Miscellaneous

Candidiasis, chest symptoms, fatigue, fever, malaise (at least 3%); allergic reaction, bacterial infection, chest symptoms, congestion, edema, fluid retention, fracture, hives, pain, unusual taste, viral infection, wheezing (1% 3%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined; however, other corticosteroids are excreted in breast milk.

Undetermined.

Children

Safety and efficacy not established in children with asthma younger than 4 yr of age.

Elderly

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

Hypersensitivity

Immediate hypersensitivity reactions may occur.

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; or ocular herpes simplex.

Adrenal suppression

Hypothalamic-pituitary-adrenal suppression may occur.

Bone mineral density

Ensure bone mineral density (BMD) is assessed prior to starting therapy and periodically thereafter in patient with risk factors for decreased BMD being treated for COPD. Be prepared to introduce therapy to treat or prevent osteoporosis if indicated.

CV disorders

Use with caution in patients with CV disease, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Immunosuppression

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

Increased use

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

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.

Paradoxical bronchospasm

May occur and be life-threatening.

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.

Upper airway symptoms

Laryngeal spasm, irritation, or swelling (eg, choking, stridor) may occur.

Overdosage

Symptoms

Hypercorticism.

Excessive beta-adrenergic stimulation or occurrence or exaggeration of adverse effects (eg, seizures, angina, hypertension, hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia), prolongation of the QTc interval, hypokalemia, hyperglycemia, cardiac arrest, death.

Patient Information

• Explain name, dose, action, and potential side effects of drug.
• 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 patient at increased risk for decreased BMD that use of product may pose an additional risk and to monitor and, where appropriate, seek treatment for this condition.
• Advise patient that medication should never be administered with a spacer device.
• Caution patient not to exceed prescribed dose of 1 inhalation bid, 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 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 more.
• Advise patient that he or she may or may not feel or taste a dose of medicine during inhalation. Caution patient not to exceed the prescribed dose of 1 inhalation bid if delivered dose.
• Advise patient not to increase dose and to inform health care provider if symptoms do not improve or 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 Medi-Alert card indicating that supplemental systemic corticosteroids may be needed during periods of stress or a severe asthma attack.
• Advise patient to carry Medi-Alert card if experiencing acute severe asthma attacks requiring rapid systemic treatment.
• Advise patient to report the following symptoms to health care provider: sore throat or mouth, persistent cough, palpitations, chest pain, rapid heart rate, tremor, nervousness.
• Advise patient to avoid exposure to chickenpox and measles and to seek medical advice immediately if exposed.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Caution patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise patient that follow-up visits may be required to monitor therapy and to keep appointments.