SALMETEROL-FLUTICASONE 50/100MCG 60 CAPS & DEVICE

Pharmacokinetics: For pharmacokinetic purposes, each component can be considered separately. Salmeterol: Salmeterol acts locally in the lungs, therefore plasma levels are not an indication of therapeutic effects. Furthermore, there are only limited data on the pharmacokinetics of salmeterol due to the technical difficulty of assaying the active substance in plasma due to the low plasma concentrations at therapeutic doses (approximately 200 pg / ml or less) achieved after inhaled dosing.

Fluticasone propionate:

Absorption: The absolute bioavailability of a single dose of inhaled Fluticasone propionate in healthy subjects varies between approximately 5-11% of the nominal dose depending on the inhalation device used. In patients with asthma or COPD, a lower degree of systemic exposure to inhaled fluticasone propionate has been observed.

Systemic absorption occurs primarily through the lungs and is initially rapid and then prolonged. The remainder of the inhaled dose can be swallowed, but contributes minimally to systemic exposure due to low aqueous solubility and presystemic metabolism, resulting in oral availability of less than 1%. There is a linear increase in systemic exposure with increasing inhaled dose.

Distribution: The disposition of Fluticasone propionate is characterized by a high plasma clearance (1,150 ml / min), a large volume of distribution at steady state (approximately 300 L), and a terminal half-life of approximately 8 hours.

The plasma protein binding is 91%.

Biotransformation: Fluticasone propionate is eliminated very quickly from the systemic circulation. The main pathway is metabolism to an inactive carboxylic acid metabolite, by the enzyme cytochrome P450 CYP3A4. Other unidentified metabolites are also found in faeces.

Elimination: The renal clearance of Fluticasone propionate is negligible. Less than 5% of the dose is excreted in the urine, mainly as metabolites. The main part of the dose is excreted in the faeces as metabolites and unchanged active substance.

Pediatric population: In a population pharmacokinetic analysis using data from 9 different device-controlled clinical trials including 350 asthma patients 4 to 77 years of age (174 patients 4 to 11 years of age), Fluticasone propionate systemic exposure after treatment with Fluticasone / salmeterol 50 µg / 100 µg were observed compared to Fluticasone propionate 100 µg.

Special Populations: Hepatic failure can cause an accumulation of fluticasone propionate and salmeterol in plasma, therefore patients in these groups should be closely monitored. In a population pharmacokinetic analysis using data from 9 controlled clinical studies with different devices (IPS, IDM) that included 350 patients with asthma aged 4 to 77 years (174 patients aged 4 to 11 years), a higher systemic exposure of Fluticasone propionate after treatment with salmeterol / Fluticasone propionate IPS 100/50, compared to Fluticasone propionate IPS 100. Geometric mean ratio [90% CI] for salmeterol / Fluticasone propionate vs comparison of Fluticasone propionate in child and adolescent / adult populations.