Formal pharmacokinetic studies using AirDuo Digihaler have not been conducted in patientswith renal impairment.
10 OVERDOSAGE
AirDuo Digihaler contains both fluticasone propionate and salmeterol; therefore, the risksassociated with overdosage for the individual components described below apply to AirDuoDigihaler. Treatment of overdosage consists of discontinuation of AirDuo Digihaler togetherwith institution of appropriate symptomatic and/or supportive therapy. The judicious use of acardioselective beta-receptor blocker may be considered, bearing in mind that such medicationcan produce bronchospasm. Cardiac monitoring is recommended in cases of overdosage.
Fluticasone propionate
Chronic overdosage of fluticasone propionate may result in signs/symptoms of hypercorticism[see Warnings and Precautions (5.7)]. Inhalation by healthy volunteers of a single dose of4,000 mcg of fluticasone propionate inhalation powder or single doses of 1,760 or 3,520 mcg offluticasone propionate CFC inhalation aerosol was well tolerated. Fluticasone propionate givenby inhalation aerosol at dosages of 1,320 mcg twice daily for 7 to 15 days to healthy humanvolunteers was also well tolerated. Repeat oral doses up to 80 mg daily for 10 days in healthyvolunteers and repeat oral doses up to 20 mg daily for 42 days in subjects were well tolerated.
Adverse reactions were of mild or moderate severity, and incidences were similar in active andplacebo treatment groups.
Salmeterol
The expected signs and symptoms with overdosage of salmeterol are those of excessivebeta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptomsof beta-adrenergic stimulation (e.g., seizures, angina, hypertension or hypotension, tachycardiawith rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, muscle cramps, drymouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia,metabolic acidosis). Overdosage with salmeterol can lead to clinically significant prolongation ofthe QTc interval, which can produce ventricular arrhythmias.
As with all inhaled sympathomimetic medicines, cardiac arrest and even death may be associated
with an overdose of salmeterol.
11 DESCRIPTION
AirDuo Digihaler 55/14 mcg, AirDuo Digihaler 113/14 mcg and AirDuo Digihaler 232/14 mcgare combinations of fluticasone propionate and salmeterol.
Fluticasone PropionateOne active component of AirDuo Digihaler is fluticasone propionate, a corticosteroid having thechemical name S-(fluoromethyl) 6α,9-difluoro-11ß,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17ß-carbothioate, 17-propionate, and the following chemical structure:
Fluticasone propionate is a white powder with a molecular weight of 500.6, and the empiricalformula is C25H31F3O5S. It is practically insoluble in water, freely soluble in dimethyl sulfoxideand dimethylformamide, and slightly soluble in methanol and 95% ethanol.
Salmeterol Xinafoate
The other active component of AirDuo Digihaler is salmeterol xinafoate, a beta2–adrenergicbronchodilator. Salmeterol xinafoate is the racemic form of the 1-hydroxy-2-naphthoic acid saltof salmeterol. It has the chemical name 4-hydroxy-α -[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol, 1-hydroxy-2-
naphthalenecarboxylate and the following chemical structure:
S |
