Spiolto respimat solution for inhalation 2.5 μg + 2.5 μg/dose 4 ml

Active substance

Olodaterol, Tiotropium bromide

Composition

1 dose contains:

Olodaterol hydrochloride - 2.736 mcg, which corresponds to the content of olodaterol - 2.5 mcg
tiotropium bromide monohydrate - 3.124 mg, which corresponds to the content of tiotropium - 2.5 mg
Excipients: benzalkonium chloride solution - 0.0022 mg (respectively, benzalkonium chloride - 0.0011 mg), disodium edetate - 0.0011 mg, anhydrous citric acid 1M - to pH 2.9, purified water - up to 11.05 mg.

pharmachologic effect

Bronchodilator.
Olodaterol, a long-acting beta2-adrenergic agonist — and tiotropium bromide — an m-anticholinergic agent — provide complementary bronchodilatation as a result of a different mechanism of action of the active substances and different localization of the target receptors in the lungs.
Olodaterol has a high affinity and selectivity for beta2-adrenergic receptors. Activation of beta2-adrenoreceptors in the airways leads to the stimulation of intracellular adenylate cyclase, which is involved in the synthesis of cAMP. Increased cAMP causes bronchodilation, relaxing the smooth muscle cells of the respiratory tract. Olodaterol is a selective long-acting beta2-adrenoreceptor agonist with a rapid onset of action and a prolonged (at least 24 h) persistence of the effect.Beta2-adrenoreceptors are present not only in smooth muscle cells, but also in many other cells, including epithelial and endothelial cells of the lungs and heart. The exact function of beta2-receptors in the heart has not been fully studied, but their presence indicates the possibility of even highly selective beta2-adrenergic agonists to affect the heart.
Tiotropium bromide is a long-acting muscarinic receptor antagonist, often referred to as m-anticholinergic blocking agent in clinical practice. It has the same affinity for the m1-m5-subtypes of muscarinic receptors. The result of inhibition of m3 receptors in the respiratory tract is the relaxation of smooth muscles. The bronchodilating effect is dose dependent and lasts for at least 24 hours. A significant duration of action is probably associated with a very slow dissociation of tiotropium bromide from m3 receptors: the half-dissociation period is significantly longer than that of ipratropium bromide. In the case of inhalation administration of tiotropium, bromide, as an N-quaternary ammonium derivative, has a local selective effect (on the bronchi), while at therapeutic doses without causing systemic m-anticholinergic side effects. Dissociation from m2 receptors occurs faster than from m3 receptors, which indicates a predominance of selectivity for the m3 subtype of receptors over m2 receptors. The high affinity for receptors and the slow dissociation of tiotropium bromide from association with receptors cause a pronounced and prolonged bronchodilatory effect in patients with COPD.
Bronchodilation, which develops after inhalation of tiotropium bromide, is primarily due to local effects (on the respiratory tract), and not systemic.

Indications

The SPIOLTO RESPIMAT preparation, taken once a day, is indicated for long-term maintenance therapy in patients with chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, to reduce airway obstruction and concomitant shortness of breath; reduce the frequency of exacerbations; improve exercise tolerance and quality of life.

Contraindications

The drug SPIOLTO RESPIMAT is contraindicated in patients with hypersensitivity to olodaterol, tiotropium bromide, or to any component of the drug; patients who have previously experienced hypersensitivity to atropine or its derivatives, such as ipratropium and oxitropia; not recommended for use in children under 18 years (due to lack of data on efficacy and safety).

Side effects

On the part of the nervous system: dizziness, insomnia.

Metabolism and nutrition: dehydration.

On the part of the organ of vision: increased intraocular pressure, glaucoma; blurred vision.

Cardiovascular: atrial fibrillation, palpitations, tachycardia, supraventricular tachycardia, increased blood pressure.

From the organ of respiration, organs of the chest and mediastinum: cough, nosebleeds, pharyngitis, dysphonia, bronchospasm, laryngitis, sinusitis.

On the part of the gastrointestinal tract: slight dry mouth, constipation, oral candidiasis, dysphagia, gastroesophageal reflux, gingivitis, glossitis, stomatitis; intestinal obstruction, including paralytic intestinal obstruction.

On the part of the skin: skin infections and ulcers on the skin, dry skin.

Allergic reactions: rash, pruritus, angioedema, urticaria, hypersensitivity, including immediate type reactions.

Musculoskeletal system and connective tissue diseases related to it: arthralgia, swelling in the joints, back pain *.

On the part of the kidneys and urinary system: dysuria, urinary retention (more often in men with the presence of predisposing factors), infection of the urinary tract.

Infections and invasions: nasopharyngitis.

Interaction

Although there were no special studies of drug interactions, tiotropium bromide was used in conjunction with other drugs to treat COPD, including methylxanthines, steroids for oral administration and inhalation use, with no clinical signs of drug interactions.

Long-term combined use of tiotropium bromide with other m-anticholinergic drugs has not been studied. Therefore, long-term joint use of the drug Spiolto Respimat with other m-anticholinergic drugs is not recommended.

The simultaneous use of other adrenergic drugs may enhance the unwanted effects of the drug Spiolto Respimat.

The simultaneous use of xanthine derivatives, steroids or diuretics (not belonging to the group of potassium-sparing) can enhance the hypokalemic effect of adrenomimetics.

Beta-blockers may weaken the effect of olodaterol or counteract this effect. In this case, it is preferable to use running1-blockers, although they should be used with caution.

MAO inhibitors, tricyclic antidepressants or other drugs that can lengthen the QTc interval, can enhance the effect of Spiolto Respimat on the cardiovascular system.

The combined use of olodaterol with Ketoconazole led to an increase in systemic exposure to olodaterol by 1.7 times. However, this did not affect safety. Dose change is not required.

How to take, the course of administration and dosage

The recommended therapeutic dose is 2 inhalations of a spray from the Respimat inhaler (5 mcg / therapeutic dose of tiotropium bromide and 5 mcg / therapeutic dose of olodaterol) 1 time / day, at the same time of day (see instructions for use).

In elderly patients, the drug Spiolto Respimat can be used at the recommended dose.

In patients with mild to moderate hepatic insufficiency, Spiolto Respimat can be used at the recommended dose.

Data on the use of olodaterol in patients with severe hepatic insufficiency is not available.

In patients with impaired renal function, Spiolto Respimat can be used at the recommended dose.

Patients with moderate to severe renal failure who use Spiolto Respimat must be under the close supervision of a physician.

Overdose

An overdose of olodaterol can lead to pronounced effects typical of beta2-adrenergic mimics, for example, myocardial ischemia, an increase or decrease in blood pressure, tachycardia, arrhythmias, palpitations, dizziness, nervousness, insomnia, anxiety, headache, tremor, dry mouth, spasm muscle, nausea, fatigue, malaise, hypokalemia, hyperglycemia, and metabolic acidosis.

With the use of high doses of tiotropium bromide, manifestations of m-anticholinergic action are possible. After a 14-day inhalation use of tiotropium bromide in doses up to 40 μg, no significant adverse events were observed in healthy individuals, except for a feeling of dryness of the mucous membranes of the nose and oropharynx, the frequency of which depended on the dose (10-40 μg / day). The exception was a clear decrease in salivation, starting from day 7 of the drug.

Treatment

The drug Spiolto Respimat should be discontinued. Showing supportive and symptomatic treatment. In severe cases, hospitalization is necessary. The use of beta1-adrenergic blockers may be recommended, but only with special caution, since the use of these drugs can cause bronchospasm.

Special instructions

Spiolto Respimat should not be used for bronchial asthma. The efficacy and safety of Spiolto Respimat in bronchial asthma has not been studied.

Hypersensitivity

After the use of the drug Spiolto Respimat, the development of immediate-type hypersensitivity reactions is possible.

Acute bronchospasm

Spiolto Respimat is not indicated for the treatment of acute episodes of bronchospasm, i.e. as a means of first aid.

Paradoxical bronchospasm

The use of the drug Spiolto Respimat, as well as other inhalation drugs, can lead to paradoxical bronchospasm, sometimes life-threatening. In the case of the development of paradoxical bronchospasm, the use of the drug Spiolto Respimat should be immediately discontinued and alternative therapy should be prescribed.

Patients with impaired renal function

Since tiotropium bromide is excreted mainly by the kidneys; patients with moderate to severe renal insufficiency (CC <50 ml / min) using the drug Spiolto Respimat must be under the close supervision of a physician.

Violations by the organ of vision

Patients should be informed about the correct use of the drug Spiolto Respimat. Do not allow the solution or aerosol in the eyes. Pain or discomfort in the eyes, blurred vision, visual halos around light sources, combined with red eyes caused by conjunctival edema and corneas can be symptoms of acute angle-closure glaucoma. With the development of any combination of these symptoms should immediately consult a specialist.Eye drops with a miotic effect are not considered an effective treatment.

Cardiovascular effects

Olodaterol, like other beta-adrenomimetics, may have a clinically significant effect on the cardiovascular system in some patients (increased heart rate, increased blood pressure and / or the appearance of relevant symptoms). In the event of such symptoms, it may be necessary to discontinue treatment. In addition, it was reported that beta2-adrenomimetics led to such ECG changes as flattening of the T wave and depression of the ST segment, although the clinical significance of these changes is unknown.

Hypokalemia

Beta2-adrenomimetics in some patients can lead to the development of hypokalemia, which creates prerequisites for the occurrence of undesirable effects on the cardiovascular system. The decrease in the concentration of potassium in the blood serum is usually short-lived and does not require its completion. In patients with severe COPD, hypokalemia may increase due to hypoxia and concomitant treatment and increase the risk of arrhythmias.

Hyperglycemia

Inhalation use of large doses of beta2-adrenomimetik can lead to an increase in plasma glucose concentration.

Spiolto Respimat should not be used in combination with any other drug that contains long-acting beta2-adrenomimetics.

Patients who frequently use inhaled short-acting beta2-adrenergic mimics (for example, 4 times a day) need to be instructed that these drugs are used only to alleviate the acute symptoms of bronchospasm.

The drug Spiolto Respimat is intended for the maintenance treatment of patients with COPD. Due to the fact that in the general population of COPD, patients over the age of 40 years predominate significantly. When prescribing the drug to patients younger than 40 years old, a spirometric confirmation of the diagnosis of COPD is required.

The effect of the drug on the ability to drive vehicles and mechanisms

Studies on the effect on the ability to drive vehicles and mechanisms have not been conducted. Care should be taken when performing these activities, because may develop dizziness or blurred vision.

Release form

Dosing solution for inhalation