Anoro Ellipta, 22 mcg + 55 mcg/dose 30 doses

The drug Anoro Ellipt® is a combination of a long-acting inhaled muscarinic cholinoreceptor antagonist and a long-acting inhaled beta2-adrenomimetic.

After oral inhalation, both compounds have a local effect on the airways, causing bronchodilation through different mechanisms of action.

Vilanterol belongs to the class of selective long-acting beta2-adrenergic receptor agonists (beta2-agonists).

The pharmacological effects of beta2-adrenergic receptor agonists, including vilanterol, are at least in part due to stimulation of intracellular adenylate cyclase, the enzyme that catalyzes the conversion of ATP to cAMP.

The increase in the level of cAMP leads to relaxation of the bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity reactions from cells (primarily from mast cells).

Umeclidinium is a long-acting muscarinic receptor antagonist (also called an anticholinergic). It is a quinuclidine derivative that is a muscarinic receptor antagonist that acts on muscarinic cholinergic receptors of various subtypes.

Umeclidinium has a bronchodilator effect by competitive inhibition of acetylcholine binding to muscarinic acetylcholine receptors of airway smooth muscle. In preclinical studies in in vitro models, the compound demonstrated slow reversibility of action on human M3 subtype muscarinic receptors, and in vivo models showed prolonged action of the drug after injection directly into the lungs.

Pharmacodynamic effects.

Two placebo-controlled clinical efficacy studies observed an increase in first-second forced expiratory volume (FEF1) after the first dose of vilanterol and umeclidinium combination on day 1.

This index increased by 0.11 and 0.13 L 15 min after using the drug at doses of 22+55 mcg/dose and 22+113 mcg/dose, respectively, compared with the same index when using placebo (in both cases pThe effect of vilanterol and umeclidinium combination on QT interval duration was evaluated in a placebo and moxifloxacin-controlled study. 103 healthy volunteers used the combination of vilanterol and umeclidinium for 10 days once daily at doses of 22+113 or 88+452 mcg/dose.

There was no clinically significant effect on QT interval duration (corrected by the Frederick method) after multiple uses of this drug.

. In addition, there was no clinically significant effect of vilanterol and umeclidinium combination on heart rate on 24-hour Holter ECG monitoring in 108 patients with COPD who received this drug for 6 months (of which 53 patients received 22+55 mcg/dose and 55 received 22+113 mcg/dose once daily) and in 226 patients who received 22+113 mcg/dose once daily for 12 months.

Indications

Maintenance bronchodilator therapy aimed at relieving symptoms of chronic obstructive pulmonary disease.

Pharmacological effect

Anoro Ellipta® is a combination of a long-acting inhaled muscarinic cholinergic receptor antagonist and a long-acting inhaled beta2-adrenergic agonist.

Following oral inhalation, both compounds exert local effects on the respiratory tract, causing bronchodilation through different mechanisms of action.

Vilanterol belongs to the class of selective long-acting beta2-adrenergic receptor agonists (beta2-agonists).

The pharmacological effects of beta2-adrenergic agonists, including vilanterol, are at least in part due to stimulation of intracellular adenylate cyclase, an enzyme that catalyzes the conversion of ATP to cAMP.

An increase in cAMP levels leads to relaxation of bronchial smooth muscles and inhibition of the release of mediators of immediate hypersensitivity reactions from cells (primarily mast cells).

Umeclidinium is a long-acting muscarinic receptor antagonist (also called an anticholinergic). It is a quinuclidine derivative that is a muscarinic receptor antagonist that acts on various muscarinic cholinergic receptor subtypes.

Umeclidinium exerts its bronchodilator effect by competitively inhibiting the binding of acetylcholine to muscarinic acetylcholine receptors on airway smooth muscle. In preclinical studies using in vitro models, this compound demonstrated a slow reversibility of action on human muscarinic receptors of the M3 subtype, and in vivo models demonstrated the duration of action of the drug after administration directly to the lungs.

Pharmacodynamic effects.

In two placebo-controlled clinical efficacy studies, an increase in forced expiratory volume in the first second (FEV1) was observed after the first dose of the combination of vilanterol and umeclidinium on day 1.

This indicator increased by 0.11 and 0.13 l 15 minutes after administration of the drug at a dosage of 22 + 55 mcg / dose and 22 + 113 mcg / dose, respectively, compared with the same indicator when using placebo (in both cases). a combination of vilanterol and umeclidinium for 10 days, 1 time per day at a dosage of 22+113 or 88+452 mcg/dose.

After repeated use of this drug, no clinically significant effect on the duration of the QT interval (corrected using the Frederick method) was observed.

In addition, there was no clinically significant effect of the combination of vilanterol and umeclidinium on heart rate during 24-hour Holter ECG monitoring in 108 patients with COPD who received this drug for 6 months (of which 53 patients received the drug at a dosage of 22 + 55 mcg / dose and 55 at a dosage of 22 + 113 mcg / dose once a day), as well as in 226 patients receiving the drug at a dosage of 22+113 mcg/dose once a day for 12 months.

Special instructions

Anoro Ellipta® is intended for use as maintenance therapy for COPD. This drug should not be used to relieve acute symptoms, i.e. as emergency treatment for an acute episode of bronchospasm. To relieve acute symptoms, a short-acting bronchodilator should be used. An increase in the frequency of use of short-acting bronchodilators to relieve symptoms indicates a deterioration in control of the disease, in which case the patient needs to consult a doctor.

There have been no studies on the use of Anoro Ellipta® in patients with bronchial asthma, therefore the use of this drug for therapy in this group of patients is not recommended.

As with other types of inhalation therapy, the use of Anoro Ellipta® may cause paradoxical bronchospasm, which can be life-threatening. If paradoxical bronchospasm develops, treatment with the drug should be discontinued and, if necessary, alternative therapy may be prescribed.

Anoro Ellipta® is intended for the maintenance treatment of patients with COPD. Due to the fact that in the general COPD population there is a significant predominance of patients over the age of 40 years, when prescribing the drug to patients under 40 years of age, spirometric confirmation of the diagnosis of COPD is required.

Impact on the ability to drive vehicles and operate machinery. Studies have not been conducted to study the effect of Anoro Ellipta® on the ability to drive vehicles and operate machinery.

Active ingredient

Vilanterol, Umeclidinium bromide

Composition

1 dose/cell:

Strip with vilanterol:

– vilanterol triphenatate micronized 40 mcg (equivalent to 25 mcg vilanterol)

excipients:

magnesium stearate 125 mcg;

lactose monohydrate up to 12.5 mg

Strip with umeclidinium:

– umeclidinium bromide micronized 74.2 mcg (equivalent to 62.5 mcg umeclidinium)

excipients:

magnesium stearate 75 mcg;

lactose monohydrate up to 12.5 mg

Contraindications

– children under 18 years of age and a history of severe allergic reactions to milk protein or hypersensitivity to the active substances or any other component included in the drug;

With caution: after using sympathomimetics and muscarinic receptor antagonists, incl. and the drug Anoro Ellipta®, from the cardiovascular system, undesirable reactions such as arrhythmia (for example, atrial fibrillation and tachycardia) may be observed. 4

In this regard, patients with severe forms of cardiovascular disease should prescribe Anoro Ellipta® with caution.

Given the antimuscarinic activity of this drug, it should be used with caution in patients with angle-closure glaucoma or urinary retention.

Side Effects

From the heart: infrequently – atrial fibrillation, tachycardia.
From the respiratory system, chest and mediastinal organs: often – cough.
From the gastrointestinal tract: often – constipation, dry mouth.

The safety profile of the combination of vilanterol and umeclidinium is based on data from clinical studies that included 2454 patients with COPD who received at least one dose of the combination of vilanterol and umeclidinium during the study.

All patients used the drug once a day; of these, 1124 received the drug at a dosage of 22 + 55 mcg/dose and 1330 – 22 + 113 mcg/dose.

The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is determined as follows: very often (≥1/10); often (≥1/100 and Infectious and parasitic diseases: often – pharyngitis.

Interaction

Beta-blockers can weaken the effects of beta2-agonists or act as antagonists of drugs in this group, incl. and vilanterol.

The simultaneous use of non-selective and selective beta-blockers should be avoided unless there are compelling reasons for their combined use.

Vilanterol, a component of Anoro Ellipta®, is rapidly metabolized mainly in the gastrointestinal tract and liver via the CYP3A4 isoenzyme of the cytochrome P450 system.

When prescribing the drug simultaneously with strong inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole), caution should be exercised, because there is a possibility of increasing the systemic exposure of vilanterol, which in turn may lead to an increased risk of adverse reactions (see “Pharmacokinetics”).

Overdose

Treatment: in case of overdose, symptomatic therapy is required and, if necessary, the patient is provided with appropriate monitoring. Further management of patients in case of overdose should be carried out in accordance with clinical indications.

During clinical studies, there was no evidence of an overdose of the combination of vilanterol and umeclidinium.

Symptoms: Symptoms and signs may develop due to the action of individual components of the drug, including known adverse reactions that develop with exposure to muscarinic receptor antagonists (for example, dry mouth, accommodation disturbances and tachycardia) and signs observed with overdose of other beta2-agonists (for example, tremor, headache and tachycardia).

Manufacturer

Glaxo Operations UK Ltd, UK