Advair Diskus
Buy Advair DiskusAdvair Diskus Information
Brand Names: Advair Diskus, Seretide
Generic Names: Salmeterol, Fluticasone Propionate
Other Common Names: Advair Discus, Advair
Advair Diskus is indicated for the long-term, twice-daily, maintenance treatment of asthma in patients 12 years of age and older.
Fluticasone and salmeterol used in Advair Diskus are a combination of two medicines that are used to help control the symptoms of asthma and improve lung function. However, this medicine will not relieve an asthma attack that has already started.
Inhaled fluticasone belongs to the family of medicines known as corticosteroids (cortisone-like medicines). It works by preventing certain cells in the lungs and breathing passages from releasing substances that cause asthma symptoms. Thus, Advair Diskus will not relieve an asthma attack that has already started.
How Does Advair Diskus Work?
Advair Diskus:
Advair Diskus is designed to produce a greater improvement in pulmonary function and symptom control than either fluticasone propionate or salmeterol used alone at their recommended dosages. Since Advair Diskus contains both fluticasone propionate and salmeterol, the mechanisms of action described below for the individual components apply to Advair Diskus. These drugs represent 2 classes of medications (a synthetic corticosteroid and a long-acting beta-adrenergic receptor agonist) that have different effects on clinical, physiological, and inflammatory indices of asthma.
Fluticasone Propionate:
Fluticasone propionate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. In vitro assays using human lung cytosol preparations have established fluticasone propionate as a human glucocorticoid receptor agonist with an affinity 18 times greater than dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results.
The precise mechanisms of fluticasone propionate action in asthma are unknown. Inflammation is recognized as an important component in the pathogenesis of asthma. Corticosteroids have been shown to inhibit multiple cell types (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and mediator production or secretion (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in the asthmatic response. These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma.
Salmeterol Xinafoate:
Salmeterol is a long-acting beta2-adrenergic agonist. In vitro studies and in vivo pharmacologic studies demonstrate that salmeterol is selective for beta2-adrenoceptors compared with isoproterenol, which has approximately equal agonist activity on beta1- and beta2-adrenoceptors. In vitro studies show salmeterol to be at least 50 times more selective for beta2-adrenoceptors than albuterol. Although beta2-adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-adrenoceptors are the predominant receptors in the heart, there are also beta2-adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects.
The pharmacologic effects of beta2-adrenoceptor agonist drugs, including salmeterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.
In vitro tests show that salmeterol is a potent and long-lasting inhibitor of the release of mast cell mediators, such as histamine, leukotrienes, and prostaglandin D2, from human lung. Salmeterol inhibits histamine-induced plasma protein extravasation and inhibits platelet-activating factor-induced eosinophil accumulation in the lungs of guinea pigs when administered by the inhaled route. In humans, single doses of salmeterol administered via inhalation aerosol attenuate allergen-induced bronchial hyper-responsiveness.
Advair Diskus Ingredients and Composition
How To Take Advair Diskus and Advair Diskus Dosage and Administration
Advair Diskus is available in 3 strengths, Advair Diskus 100/50, Advair Diskus 250/50, and Advair Diskus 500/50, containing 100, 250, and 500 mcg of fluticasone propionate, respectively, and 50 mcg of salmeterol per inhalation. Advair Diskus should be administered by the orally inhaled route only.
For patients 12 years of age and older, the dosage is 1 Advair Diskus inhalation twice daily (morning and evening, approximately 12 hours apart).
The recommended starting dosages for Advair Diskus are based upon patients' current asthma therapy.
- For patients who are not currently on an inhaled corticosteroid, whose disease severity warrants treatment with 2 maintenance therapies, including patients on non-corticosteroid maintenance therapy, the recommended starting dosage is Advair Diskus 100/50 twice daily.
- For patients on an inhaled corticosteroid, the maximum recommended dosage is Advair Diskus 500/50 twice daily.
Advair Diskus should be administered twice daily every day. More frequent administration (more than twice daily) or a higher number of inhalations (more than 1 inhalation twice daily) of the prescribed strength of Advair Diskus is not recommended as some patients are more likely to experience adverse effects with higher doses of salmeterol. The safety and efficacy of Advair Diskus when administered in excess of recommended doses have not been established.
If symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be taken for immediate relief.
Patients who are receiving Advair Diskus twice daily should not use salmeterol for prevention of EIB, or for any other reason.
Improvement in asthma control following inhaled administration of Advair Diskus can occur within 30 minutes of beginning treatment, although maximum benefit may not be achieved for 1 week or longer after starting treatment. Individual patients will experience a variable time to onset and degree of symptom relief.
For patients who do not respond adequately to the starting dosage after 2 weeks of therapy, replacing the current strength of Advair Diskus with a higher strength may provide additional asthma control.
If a previously effective dosage regimen of Advair Diskus fails to provide adequate control of asthma, the therapeutic regimen should be reevaluated and additional therapeutic options, e.g., replacing the current strength of Advair Diskus with a higher strength, adding additional inhaled corticosteroid, or initiating oral corticosteroids, should be considered.
If you suspect a Advair Diskus Overdose
No deaths occurred in rats given combinations of salmeterol and fluticasone propionate at acute inhalation doses of 3.6 and 1.9 mg/kg, respectively (approximately 320 and 15 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis).
Fluticasone Propionate:
Chronic overdosage with fluticasone propionate may result in signs/symptoms of hypercorticism. Inhalation by healthy volunteers of a single dose of 4,000 mcg of fluticasone propionate inhalation powder or single doses of 1,760 or 3,520 mcg of fluticasone propionate inhalation aerosol was well tolerated. Fluticasone propionate given by inhalation aerosol at doses of 1,320 mcg twice daily for 7 to 15 days to healthy human volunteers was also well tolerated. Repeat oral doses up to 80 mg daily for 10 days in healthy volunteers and repeat oral doses up to 20 mg daily for 42 days in patients were well tolerated. Adverse reactions were of mild or moderate severity, and incidences were similar in active and placebo treatment groups. The oral and subcutaneous median lethal doses in mice and rats were >1,000 mg/kg (>4,300 and >8,700 times, respectively, the maximum recommended daily inhalation dose in adults on a mg/m2 basis).
Salmeterol:
The expected signs and symptoms with overdosage of salmeterol are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms listed under SIDE EFFECTS, e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Overdosage with salmeterol may be expected to result in exaggeration of the pharmacologic adverse effects associated with beta-adrenoceptor agonists, including tachycardia and/or arrhythmia, tremor, headache, and muscle cramps. Overdosage with salmeterol can lead to clinically significant prolongation of the QTc interval, which can produce ventricular arrhythmias. Other signs of overdosage may include hypokalemia and hyperglycemia.
Contraindications to Advair Diskus
Advair Diskus is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.
Advair Diskus Side Effects
SMART Study
DATA FROM A LARGE PLACEBO-CONTROLLED SAFETY STUDY THAT WAS STOPPED EARLY SUGGEST THAT SALMETEROL, A COMPONENT OF ADVAIR DISKUS, MAY BE ASSOCIATED WITH RARE SERIOUS ASTHMA EPISODES OR ASTHMA-RELATED DEATHS. The Salmeterol Multi-center Asthma Research Trial (SMART) enrolled long-acting beta2-agonist-naive patients with asthma to assess the safety ofsalmeterol (Serevent Inhalation Aerosol) 42 mcg twice daily over 28 weeks compared to placebo, when added to usual asthma therapy. The primary endpoint was the combined number of respiratory-related deaths or respiratory-related life-threatening experiences (intubation and mechanical ventilation). Other endpoints included combined asthma-related deaths or life-threatening experiences and asthma-related deaths.
A planned interim analysis was conducted when approximately half of the intended number of patients had been enrolled (N = 26,353). The analysis showed no significant difference for the primary endpoint for the total population. However, a higher number of asthma-related deaths or life-threatening experiences (36 vs. 23) and a higher number of asthma-related deaths (13 vs. 4) occurred in the patients treated with Serevent Inhalation Aerosol. Post hoc subgroup analyses revealed no significant increase in respiratory- or asthma-related episodes, including deaths, in Caucasian patients. In African-Americans, the study showed a small, though statistically significantly greater, number of primary events (20 vs. 7), asthma-related deaths or life-threatening experiences (19 vs. 4), and asthma-related deaths (8 vs. 1) in patients taking Serevent Inhalation Aerosol compared to those taking placebo. Even though SMART did not reach predetermined stopping criteria for the total population, the study was stopped due to the findings in African-American patients and difficulties in enrollment. The data from the SMART study are not adequate to determine whether concurrent use of inhaled corticosteroids, such as fluticasone propionate, a component of Advair Diskus, provides protection from this risk. Therefore, it is not known whether the findings seen with Serevent Inhalation Aerosol would apply to Advair Diskus.
Findings similar to the SMART study findings were reported in a prior 16-week clinical study performed in the United Kingdom, the Salmeterol Nationwide Surveillance (SNS) study. In the SNS study, the incidence of asthma-related death was numerically, though not statistically, greater in patients with asthma treated with salmeterol (42 mcg twice daily) versus albuterol (180 mcg 4 times daily) added to usual asthma therapy.
Given the similar basic mechanisms of action of beta2-agonists, it is possible that the findings seen in the SMART study may be consistent with a class effect.
Advair Diskus Clinical Trials and Studies
Taking Advair Diskus during Pregnancy or Breast-feeding
Plasma levels of salmeterol, a component of Advair Diskus, after inhaled therapeutic doses are very low. In rats, salmeterol xinafoate is excreted in the milk. There are no data from controlled trials on the use of salmeterol by nursing mothers. It is not known whether fluticasone propionate, a component of Advair Diskus, is excreted in human breast milk; however, other corticosteroids have been detected in human milk. Subcutaneous administration to lactating rats of 10 mcg/kg tritiated fluticasone propionate (less than the maximum recommended daily inhalation dose in adults on a mcg/m2 basis) resulted in measurable radioactivity in milk.
Since there are no data from controlled trials on the use of Advair Diskus by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue Advair Diskus, taking into account the importance of Advair Diskus to the mother.
Caution should be exercised when Advair Diskus is administered to a nursing woman.
Advair and Race
Data from a large placebo-controlled US study that compared the safety of salmeterol (Serevent Inhalation Aerosol) or placebo added to usual asthma therapy showed a small but significant increase in asthma-related deaths in patients receiving salmeterol (13 deaths out of 13,174 patients treated for 28 weeks) versus those on placebo (4 of 13,179). Subgroup analyses suggest the risk may be greater in African-American patients compared to Caucasians.
Additional Notes
Advair Diskus is not indicated for the relief of acute bronchospasm.
Information about the Manufacturer of Advair Diskus
Advair Diskus is manufactured by: GlaxoSmithKline.
Articles and information related to Advair Diskus
Buy Advair Diskus
