Seroflo Rotacap -250 General Medicines

SEROFLO 100 Rotacaps

Each rotacap contains:

Salmeterol (As Salmeterol Xinafoate IP)a a a 50 mcg

Fluticasone Propionate IP ..................................100 mcg

Excipienta a a a a a a a .................................q.s.

SEROFLO 250 Rotacaps

Each rotacap contains:

Salmeterol (As Salmeterol Xinafoate IP)a a a 50 mcg

Fluticasone Propionate IP................................. 250 mcg

Excipienta a a a a a a a .................................q.s.

SEROFLO 500 Rotacaps

Each rotacap contains:

Salmeterol (As Salmeterol Xinafoate IP)...a a 50 mcg

Fluticasone Propionate IP..................................500 mcg

Excipienta a a a a a a a ................................q.s.

Since SEROFLO Rotacaps contain both fluticasone propionate and salmeterol, the mechanism of action described below for the individual components apply to SEROFLO Rotacaps. These drugs represent two classes of medications (a synthetic corticosteroid and a selective, long-acting beta2-adrenergic receptor agonist) that have different effects on the clinical, physiologic, and inflammatory indices of asthma.

Fluticasone Propionate

Fluticasone propionate is a synthetic, trifluorinated corticosteroid with potent anti-inflammatory activity. In vitro assays using cytosol preparations from human lungs have established fluticasone propionate as a human glucocorticoid receptor agonist with an affinity eighteen times greater than dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over three times that of budesonide. Data from the McKenzie vasoconstrictor assay in humans are consistent with these results.

Inflammation is 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.

Studies in patients with asthma have shown a favorable ratio between topical anti-inflammatory activity and systemic corticosteroid effects with recommended doses of orally inhaled fluticasone propionate. This is explained by a combination of a relatively high local anti-inflammatory effect, negligible oral systemic bioavailability (<1%), and the minimal pharmacological activity of the only metabolite detected in man.

Salmeterol

Salmeterol is a long-acting beta2-adrenergic agonist. which has approximately equal agonist activity on beta1- and beta2-adrenoceptors. In vitro studies show salmeterol to be at least fifty times more selective for beta2-adrenoceptors than salbutamol. 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 10a 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but their presence raises the possibility that even 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 catalyses 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.