Indacaterol + Glycopyrronium + Mometasone Furoate

This is indicated as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta 2-agonist and a medium or high dose of an inhaled corticosteroid who experienced one or more asthma exacerbations in the previous 12 months. This is not indicated for the relief of acute bronchospasm.

Indacaterol: Indacaterol is a long-acting beta 2-adrenergic agonist for once-daily administration. The pharmacological effects of beta 2 -adrenoceptor agonists, including indacaterol, 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. In vitro studies have shown that indacaterol is a weak partial agonist at beta 1 -receptors with a potency more than 24-fold greater at beta 2 -receptors compared to beta 1-receptors and is a full agonist at beta 3 -receptors with a potency 20-fold greater at beta 2-receptors compared to beta 3-receptors. When inhaled, indacaterol acts locally in the lung as a bronchodilator. Indacaterol is a nearly full agonist at the human beta 2-adrenergic receptor with nanomolar potency. In isolated human bronchus, indacaterol has a rapid onset of action and a long duration of action. Although beta 2-adrenergic receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1-receptors are the predominant receptors in the human heart, there are also beta 2-adrenergic receptors in the human heart comprising 10% to 50% of the total adrenergic receptors. The precise function of beta 2-adrenergic receptors in the heart is not known, but their presence raises the possibility that even highly selective beta 2-adrenergic agonists may have cardiac effects.

Glycopyrronium: Glycopyrronium is an inhaled long-acting muscarinic receptor antagonist (anti-cholinergic). Glycopyrronium works by blocking the broncho-constrictor action of acetylcholine on airway smooth muscle cells thereby dilating the airways. Of the five known muscarinic receptor subtypes (M1-5), only subtypes M1-3 have a defined physiological function in the human lung. Glycopyrronium is a high affinity muscarinic receptor antagonist of these three receptor subtypes. It demonstrated 4- to 5-fold selectivity for the human M3 and M1 receptors over the human M2 receptor in competition binding studies. It has a rapid onset of action, as evidenced by observed receptor association/dissociation kinetic parameters and by the onset of action after inhalation in clinical studies. The long duration of action can be partly attributed to sustained drug concentrations in the lungs as reflected by the prolonged terminal elimination half-life of glycopyrronium after inhalation via the inhaler in contrast to the half-life after intravenous administration.

Mometasone furoate: Mometasone furoate is a synthetic corticosteroid with high affinity for glucocorticoid receptors and local anti-inflammatory properties. Studies in asthmatic patients have demonstrated that inhaled mometasone furoate provides a favorable ratio of pulmonary to systemic activity. It is likely that much of the mechanism for the effects of mometasone furoate lies in its ability to inhibit the release of mediators of the inflammatory cascade. In vitro, mometasone furoate inhibits the release of leukotrienes (LT) from leukocytes of allergic patients. In cell culture, mometasone furoate demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6 and TNF-alpha. It is also a potent inhibitor of LT production and an extremely potent inhibitor of the production of the Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.

Patients should be made aware that inhalation capsules should be used regularly, even when asymptomatic.

When treating patients with asthma, physicians should only prescribe inhalation capsules for patients not adequately controlled on a long-term asthma control medication containing a LABA and a medium or high dose inhaled corticosteroid and who experienced one or more asthma exacerbations in the previous year.

As with other inhaled drugs containing beta 2-adrenergic agents, inhalation capsules should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result. When beginning treatment with inhalation capsules patients who have been taking rapid onset, short duration, inhaled beta 2-agonists on a regular basis (e.g., q.i.d) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief if they develop acute respiratory symptoms while taking inhalation capsules.

It is crucial to inform patients that inhalation capsules should not be used to treat acute symptoms of asthma. Patients should be prescribed a rapid onset, short duration inhaled bronchodilator (e.g., salbutamol) to relieve acute symptoms such as shortness of breath and advised to have this available for use at all times.

The recommended dose for patients 18 years of age and older: Inhalation of the content of 150/50/160 micrograms one capsule once daily in patients not adequately controlled with a combination of a long-acting beta 2-agonist and a medium or high dose of an inhaled corticosteroid. The maximum recommended dose is 150/50/160 micrograms once daily.

This is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

Pregnant Women: There are insufficient data on the use of indacaterol, glycopyrronium and mometasone furoate in pregnant women to inform a drug-associated risk. Indacaterol and glycopyrronium were not teratogenic in rats and rabbits following subcutaneous or inhalation administration respectively. In animal reproduction studies with pregnant mice, rats and rabbits, mometasone furoate caused increased fetal malformations and decreased fetal survival and growth. This should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the fetus.

Breast-feeding: There is no information available on the presence of indacaterol, glycopyrronium or mometasone in human milk, on the effects on a breastfed child, or on the effects on milk production. Other inhaled corticosteroids, similar to mometasone furoate, are transferred into human milk. Indacaterol, glycopyrronium and mometasone furoate have been detected in the milk of lactating rats. Glycopyrronium reached up to 10-fold higher concentrations in the milk of lactating rats than in the blood of the dam after intravenous administration.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.