ADVAIR HFA has been used concomitantly with other drugs, including short-acting beta2-agonists, methylxanthines, and intranasal corticosteroids, commonly used in patients with asthma, without adverse drug reactions. No formal drug interaction studies have been performed with ADVAIR HFA.
Short-Acting Beta 2-Agonists
In three 12-week US clinical trials, the mean daily need for additional beta2-agonist use in 277 patients receiving ADVAIR HFA was approximately 1.2 inhalations/day and ranged from 0 to 9 inhalations/day. Two percent (2%) of patients receiving ADVAIR HFA in these trials averaged 6 or more inhalations per day over the course of the 12-week trials. No increase in frequency of cardiovascular events was observed among patients who averaged 6 or more inhalations per day.
ADVAIR HFA Inhalation Aerosol
No deaths occurred in rats given a single-dose combination of salmeterol 3.6 mg/kg and fluticasone propionate 1.9 mg/kg given as the inhalation powder (approximately 290 and 15 times, respectively, the maximum recommended human daily inhalation dose on a mg/m2 basis).
Chronic overdosage with fluticasone propionate may result in signs/symptoms of hypercorticism (see PRECAUTIONS: General: Metabolic and Other Effects). 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 CFC inhalation aerosol were well tolerated. Fluticasone propionate given by inhalation aerosol at dosages 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. In mice the oral median lethal dose was >1,000 mg/kg (>4,400 times the maximum recommended human daily inhalation dose on a mg/m2 basis). In rats the subcutaneous median lethal dose was >1,000 mg/kg (>8,800 times the maximum recommended human daily inhalation dose on a mg/m2 basis).
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 ADVERSE REACTIONS, 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.
As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of salmeterol.
Treatment consists of discontinuation of salmeterol together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of salmeterol. Cardiac monitoring is recommended in cases of overdosage.
No deaths were seen in rats given salmeterol at an inhalation dose of 2.9 mg/kg (approximately 280 times the maximum recommended human daily inhalation dose on a mg/m2 basis) and in dogs at an inhalation dose of 0.7 mg/kg (approximately 230 times the maximum recommended human daily inhalation dose on a mg/m2 basis). By the oral route, no deaths occurred in mice at 150 mg/kg (approximately 7,200 times the maximum recommended human daily inhalation dose on a mg/m2 basis) and in rats at 1,000 mg/kg (approximately 97,000 times the maximum recommended human daily inhalation dose on a mg/m2 basis).