Spiolo Respimat - instructions for use, dose, side effects, contraindications

Active substanceOlodaterol + Tiotropium bromideOlodaterol + Tiotropium bromide

Similar drugsTo uncover

solution d / inhal.

Boehringer Ingelheim International GmbH Germany

Dosage form: & nbspinhalable solution

Composition:One inhalation dose contains:

Active substance: olodaterol - 0.0025 mg (respectively, olodaterol hydrochloride 0.002736 mg) and tiotropium 0.0025 mg (respectively tiotropium bromide monohydrate 0.003124 mg);

Excipients: benzalkonium chloride solution 0.002200 mg (respectively benzalkonium chloride 0.001100 mg), disodium edetate 0.001100 mg, hydrochloric acid 1M to pH 2.9, water purified to 11.05 mg.

Description:

A clear, colorless or almost colorless solution.

Pharmacotherapeutic group:Bronchodilator combined (long-acting β2-adrenomimetic + m-holinoblokator)

ATX: & nbsp

R.03.A.L.06 Olodaterol and tiotropium bromide

Pharmacodynamics:

Olodaterol - β₂long-acting adrenomimetic and tiotropium bromide-cholinoblocker provide complementary bronchodilation, as a result of different mechanism of action of active substances and different localization of target receptors in the lungs. Olodaterol has a high affinity and selectivity for β₂-adrenoceptors. Activation β₂adrenoreceptors in the airways leads to stimulation of intracellular adenylate cyclase, which is involved in the synthesis of cyclic 3,5-adenosine monophosphate (cAMP). Increased cAMP levels cause bronchodilation, relaxing the smooth muscle cells of the respiratory tract. Olodaterol is a selective agonist β₂-adrenoceptor long-acting with a rapid onset of action and a prolonged (not less than 24 h) preservation of the effect. β₂-adrenoceptors are present not only in smooth muscle cells, but also in many other cells, including those in the epithelial and endothelial cells of the lungs and heart. The exact function of beta₂-receptors in the heart is not fully understood, but their presence indicates the possibility of heart effects even of highly selective beta₂-adrenergic agonists.

Tiotropium bromide is a long-acting antagonist of muscarinic receptors, often called m-holin-blocking agent in clinical practice. The drug has the same affinity for M1 - M5 subtypes of muscarinic receptors. The result of the inhibition of M3-rheinators in the respiratory tract is the relaxation of smooth muscles.The bronchodilator effect is dose dependent and persists for at least 24 hours. The significant duration of action is probably related to the very slow dissociation of the drug from the M3 receptors: the half-dissociation period is much longer than in ipratropium bromide. With the inhalation route of administration tiotropium bromide, as N- quaternary ammonium derivative, has a local selective effect (on the bronchi), while at therapeutic doses without causing systemic m-cholinoblocking side effects. Dissociation from M2-retenters occurs faster than from M3-receptors. which indicates a predominance of selectivity for M3 receptor subtype over M2 receptors. High affinity for reviewers and slow dissociation of the drug from receptor binding cause a pronounced and prolonged bronchodilator effect in patients with chronic obstructive pulmonary disease (COPD).

Bronchodilation, which develops after inhalation of tiotropium bromide, is caused, first of all, by local (on the respiratory tract), and not by systemic action.

In the course of clinical studies it was found that the preparation of SPIOLTO RESPIMAT.applied once a day, in the morning led to a rapid (within 5 minutes after the first dose) improvement in lung function. The effect of the drug SPIOLTO RESPIMAT superior effect entropy bromide at 5 micrograms and olodaterola at a dose of 5 ug, applied as monotherapy (forced expiratory volume in the first second (FEV1) was increased when taking SPIOLTO RESPIMAT at 0,137 x when receiving tiotropium bromide at 0.058 l, with the intake of olodaterol - 0,125 liters).

In applying the drug SPIOLTO RESPIMAT compared to the use of tiotropium bromide and olodaterola as monotherapy achieved a significant bronchodilator effect, and also increased bulk peak expiratory flow rate in the morning and evening.

The use of the drug SPIOLTO RESPIMAT led to a reduction in the risk of exacerbations of COPD compared with placebo.

The preparation of SPIOLTO RESPIMAT significantly improved the inspiratory capacity in comparison with tiotropium bromide, olodaterol or placebo, used as monotherapy.

SPIOLTO RESPIMAT compared with placebo significantly improved the time of exercise tolerance.

Pharmacokinetics:

The pharmacokinetics of the combined preparation of SPIOLTO RESPIMAT is equivalent to the pharmacokinetics of separately used olodaterol and tiotropium bromide.

Olodaterol and tiotropium bromide are characterized by linear pharmacokinetics.

Steady state of pharmacokinetics of olodaterol was achieved after 8 days with application once a day, and the degree of exposure increased in comparison with the use of a single dose of 1.8 times. The steady state of pharmacokinetics of tiotropium bromide was applied once a day after 7 days.

Suction

Olodaterol is rapidly absorbed, after inhalation of the drug, the maximum concentration in the plasma is usually achieved within 10-20 minutes. In healthy volunteers after inhalation of the drug, the absolute bioavailability of olodaterol was about 30%. while the absolute bioavailability of olodaterol after oral administration of the solution was less than 1%.

Thus, the systemic effect of olodaterol after inhalation is mainly realized by absorption in the lungs, and the contribution of the swallowed portion of the dose to the systemic impact is negligible.

After inhalation of a solution of tiotropium bromide, about 33% of the inhalation dose arrives in the systemic circulation. Absolute bioavailability with oral administration is 2 - 3%.The maximum concentration in plasma is observed in 5-7 minutes after inhalation.

Distribution

The binding of olodaterol to plasma proteins is approximately 60%, and the volume of distribution -1110 liters.

The binding of tiotropium bromide to plasma proteins is 72%: the volume of distribution is 32 l / kg. Pre-clinical studies have shown that tiotropium bromide does not penetrate the blood-brain barrier.

Biotransformation

Olodaterol is largely metabolized by direct glucuronization and O-demethylation followed by conjugation. Of the six identified metabolites with β₂-receptors bind only one unconjugated demethylation derivative (SOM 1522); however, this metabolite is not detected in plasma after prolonged inhalation of the drug at the recommended therapeutic dose or at doses exceeding the therapeutic dose by 4 times. In the O-demethylation of olodaterol, cytochrome P450 (isozyme CYP2C9, CYP2C8 and to an insignificant degree CYP3A4). In the formation of glucuronides of olodaterol involved isoforms of uridine diphosphate glycosyltransferase, UGT2B7, UGT1A1, 1A7 and 1A9.

The degree of biotransformation of tiotropium bromide is negligible. This is confirmed by the fact that after intravenous administration of tiotropium bromide to young healthy volunteers, 74% of tiotropium bromide is excreted by the kidneys unchanged. Tiotropium bromide is an ether that is split into ethanol-N-methylskopine, and dithienylglycolic acid; these compounds do not bind to muscarinic receptors.

In studies in vitro It is shown that some part of the drug (<20% of the dose after intravenous administration) is metabolized by oxidation with cytochrome P450 (CYP2D6 and 3A4) followed by conjugation with glutathione and the formation of various metabolites.

Excretion

The total clearance of olodaterol in healthy volunteers is 872 ml / min. and a renal clearance of 173 ml / min. The final half-life after intravenous administration of olodaterol is 22 hours, while the final half-life after inhalation is approximately 45 hours. It follows that in the latter case the excretion is more dependent on absorption.

The total isotope-labeled dose of olodaterol, excreted through the kidneys (including the parent compound and all metabolites) was 38% after intravenous administration, after oral administration of 9%.The total isotope-labeled dose, secreted through the kidneys of unchanged olodaterol, was 19% after intravenous administration. The total isotope-labeled dose, excreted through the intestine, was 53% and 84% after intravenous administration after ingestion.

More than 90% of the dose was withdrawn after intravenous administration for 5 days and after ingestion for 6 days. After inhalation, the excretion of unaltered olodaterol by the kidney during the dosing interval was 5-7% of the dose in healthy volunteers during the steady state of pharmacokinetics.

Tiotropium bromide after intravenous administration is mainly excreted by the kidneys unchanged (74%). The total clearance after intravenous administration of tiotropium bromide to young healthy volunteers is 880 ml / min. After inhalation solution in patients with COPD, renal excretion is 18.6% (0.93 mkt), the remaining unabsorbed part is excreted through the intestine. The renal clearance of tiotropium bromide exceeds the creatinine clearance, which indicates its tubular secretion. The terminal half-life of tiotropium bromide after inhalation is 27 to 45 hours.

Pharmacokinetics in elderly patients

Clinical studies have shown: despite the influence of age, sex and body weight on the systemic effects of olodaterol, dose adjustment is not required.

In the elderly, there is a decrease in renal clearance of tiotropium (347 ml / min in patients with COPD before the age of 65 and 275 ml / min in patients with COPD over 65 years old). However, this did not lead to an increase in the value AUC_0-6,_ss and C_max,_ss.

Race

Comparison of pharmacokinetic data obtained in clinical studies of olodaterol. revealed a trend towards a higher systemic exposure to olodaterol in patients from Japan and other patients of the Asian race compared with patients of the European race. In clinical studies of olodaterol. used in doses that exceeded twice the recommended therapeutic dose, in Europoid and Asian race patients, no safety concerns were established.

Patients with disturbed function of packets

In patients with severe renal insufficiency (creatinine clearance (CC) <30 ml / min) systemic exposure to olodaterol increased by an average of 1.4 times. This The increase in exposure does not raise concerns about safety, given the experience gained with the use of olodaterol in clinical trials.

After inhalation, tiotropium once a day during a steady state of pharmacokinetics in patients with COPD and renal insufficiency of a lethal severity (creatinine clearance 50-80 ml / min) there was a slight increase in the values AUC_{0- 6.}_ssby 1.8-30% and C_max_._sscompared with patients with normal renal function (creatinine clearance> 80 ml / min). In patients with COPD and moderate to severe renal insufficiency (creatinine clearance <50 mL / min) intravenous tiotropium bromide resulted in a twofold increase in the total exposure to tiotropium bromide (value AUC_0-4increased by 82%, and the value of C_max increased by 52%) compared with patients with normal renal function. A similar increase in plasma concentration was noted after inhalation of dry powder.

Patients with hepatic impairment

In patients with hepatic insufficiency of a lethal and moderate severity, the systemic effect of olodaterol did not change. The systemic effect of olodaterol in patients with hepatic insufficiency of severe severity was not studied.

It is suggested that liver failure does not have a significant effect on the pharmacokinetics of tiotropium bromide, since tiotropium bromide is mainly excreted by the kidneys and by the non-enzymatic cleavage of the ester bond to form derivatives that do not possess pharmacological activity.

Indications:

The drug SPIOLTO RESPIMAT, 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 dyspnea; reducing the frequency of exacerbations; improve the tolerance of physical activity 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.

The drug SPIOLTO RESPIMAT is contraindicated in patients who have previously been noted hypersensitivity to atropine or its derivatives, eg ipratropium and oxytropium.

Preparation SPIOLTO RESPIMAT is not recommended for use in children under 18 years of age (due to lack of data on efficacy and safety).

Carefully:

In patients with acute angular glaucoma, prostatic hyperplasia and obstruction of the neck of the bladder.

Patients with cardiovascular diseases, incl. Coronary insufficiency, heart rhythm disturbances, lengthening of the interval QT, hypertrophic obstructive cardiomyopathy, arterial hypertension, thyrotoxicosis, seizures. Patients with a history of such diseases as: myocardial infarction or hospitalization for heart failure (during the previous year), life-threatening arrhythmia, paroxysmal tachycardia with heart rate> 100.

In patients with unusual reactions to sympathomimetic amines.

Pregnancy and lactation:

There are no clinical data on the effect of maloduterol / tiotropium bromide on pregnancy. In preclinical studies using high doses of olodaterol, several times higher than therapeutic doses, the effects typical of β₂-adrenomimetics. It is necessary to take into account the inhibitory effect of olodaterol on the contractile capacity of the uterus. The drug SPIOLTO RESPIMAT should not be used in pregnant women, unless the potential benefit to the mother does not exceed the potential risk to the fetus.

Clinical data on the use of olodaterol / tiotropium bromide in women breastfeeding, no. The drug SPIOLTO RESPIMAT should not be used in breast-feeding women, unless the potential benefit to the mother does not exceed the potential risk to the child.

For the period of application of the drug, it is necessary to stop breastfeeding the baby.

Dosing and Administration:

The recommended therapeutic dose is two inhalations of the spray from the inhaler RESPIMAT (5 μg / therapeutic dose of tiotropium bromide and 5 μg / therapeutic dose of olodaterol) once a day at the same time of the day (see "Instructions for use").

In elderly patients, you can use the drug SPIOLTO RESPIMAT in 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 hepatic insufficiency of severe severity is not available.

In patients with impaired renal function, you can use the drug SPIOLTO RESPIMAT in the recommended dose.

Patients with renal insufficiency of moderate and severe severity,using the preparation of SPIOLTO RESPIMAT, should be under close supervision of the doctor.

Instructions for use

Introduction

Read these Instructions for Use before using SPIOLTO RESPIMAT.

You will need to use this inhaler only ONCE DAY. Each time you apply it, DO TWO INHALATIONS.

How to store the inhaler SPIOLTO RESPIMAT

- Keep SPIOLTO RESPIMAT out of the reach of children

- Do not freeze SPIOLTO RESPIMAT

- If the SPIOLTO RESPIMAT inhaler has not been used for more than 7 days, direct it before use down and press once on the dose button.

- If the SPIOLTO RESPIMAT inhaler has not been used for more than 21 days, repeat steps 4-6 from "Preparing for first use" until the aerosol cloud appears. Then repeat steps 4-6 three more times.

Do not use the SPIOLTO RESPIMAT inhaler after the expiration date. Do not touch the piercing element inside the transparent sleeve.

How to take care of your inhaler SPIOLTO RESHIMAT

Clean the mouthpiece, including the metal part inside the mouthpiece, with a damp cloth or cloth, at least once a week.

Any slight change in the color of the mouthpiece does not affect the operation of your SPIOLTO RESPmit inhaler.

- Your inhaler SPIOLTO RESPIMAT contains 60 inhalation doses (ie 30 therapeutic doses) provided that it is administered as directed (two inhalation doses once a day).

- The dose indicator shows how many doses are left.

- When the dose indicator shows on the red area of the scale, it means that the medication remains for about 7 days (14 inhalation doses).

- When the dose indicator of the inhaler reaches the end of the red scale, the SPIOLTO RESPIMAT inhaler will automatically be blocked - no inhalation dose can be received any more (no turning of the transparent sleeve).

- Three months after the first use, SPIOLTO RESPmit should be discarded, even if it is not completely used.

Answers to frequently asked questions

1. It is difficult to install the cartridge to the required depth.

You accidentally turned the transparent sleeve before installing the cartridge? Open the cap, press the dose button, then insert the cartridge.

Do you insert the cartridge with a wide end? Insert the cartridge with its narrow end into the inhaler.

2. I can not press the dose button.

Have you turned the transparent sleeve? If not, rotate the transparent sleeve one continuous motion until it clicks (half a turn).

Indicator doses of the inhaler SPIOLTO RESPIMAT indicates zero? The SPIOLTO RESPIMAT inhaler is blocked after the release of 60 inhalation doses (30 therapeutic doses). Prepare and use the new inhaler SPIOLTO RESPIMAT.

3. I can not turn the transparent sleeve.

Have you already turned the transparent sleeve? If the transparent sleeve is already turned, follow the "Open" and "Click" steps in the "Daily use" section to get the inhalation dose.

4. The indicator of doses of the inhaler SPIOLTO RESPIMAT reaches zero too quickly.

Have you used SPIOLTO RESPIMAT according to the directions (two inhalation doses once a day)? The drug SPIOLTO RESPIMAT lasts for 30 days with the use of two inhalations once a day.

Did you rotate the transparent sleeve before installing the cartridge? The dose indicator counts each turn of the transparent cartridge case, regardless of whether the cartridge is installed or not.

Did you use inhalation doses in the air to test the performance of SPIOLTO RESPMIT? After preparation of the inhaler for use, a daily inhalation check is not required.

Did you install the cartridge in the used inhaler SPIOLTO RESPIMAT?

Always install a new cartridge in a new inhaler SPIOLTO RESPIMAT.

5. My inhaler SPIOLTO RESPIMAT releases inhalation doses automatically.

Was the cap opened when you turned the transparent sleeve? Close the cap, then turn the transparent sleeve.

Did you press the dose button while turning the transparent case?

Close the cap so that the dose button is closed, then turn the transparent sleeve.

Did you stop during the rotation of the transparent sleeve, until the click sound?

Turn the transparent sleeve one continuous movement until it clicks (half a turn).

6. My inhaler SPIOLTO RESPIMAT does not release an inhalation dose. Have you installed the cartridge? If not, install the cartridge.

Have you repeated the steps Turn, Open, Press less than three times after installing the cartridge? Repeat the steps. Turn, Open. Press three times after installing the cartridge as described in "Preparing for first use", steps 4-6. Indicator doses of the inhaler SPIOLTO RESPIMAT indicates zero? If the dose indicator indicates zero, then the inhaler is empty and blocked.

Do not remove the transparent sleeve and do not remove the cartridge after preparing the inhaler for use. Always install a new cartridge in the new inhaler SPIOLTO RESPIMAT.

Side effects:

Adverse reactions were identified on the basis of data obtained during clinical trials of the drug SPIOLTO RESPIMAT.

The frequency of adverse reactions that may occur during therapy is given in the following gradation: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1,000, <1/100); rarely (≥1 / 10,000, <1/1000); very rarely (<1/10 000); frequency, unspecified * (frequency can not be estimated from available data).

Infectious and parasitic diseases

Rarely: nasopharyngitis;

Disorders from the metabolism and nutrition

Unspecified frequency: dehydration;

Disturbances from the nervous system

Infrequent: dizziness, insomnia;

Disturbances on the part of the organ of sight

Rarely: blurred vision;

Unspecified frequency: increased intraocular pressure, glaucoma;

Disorders from the cardiovascular system

Infrequent: atrial fibrillation, palpitations, tachycardia, increased blood pressure;

Rarely: supraventricular tachycardia;

Disturbances from the respiratory, thoracic and mediastinal organs

Infrequently: cough, dysphonia;

Rarely: laryngitis, pharyngitis, nosebleeds;

Unspecified frequency: bronchospasm, sinusitis;

Disorders from the gastrointestinal tract

Often: dry mouth (usually minor);

Infrequently: constipation;

Rarely: candidiasis of the mouth, gingivitis;

Unspecified frequency: intestinal obstruction, including paralytic intestinal obstruction, gastroesophageal reflux, dysphagia, glossitis, stomatitis;

Disturbances from the skin and subcutaneous tissues

Unspecified frequency: skin infections and skin ulcers, dry skin;

Allergic reactions

Rarely: hypersensitivity (including immediate reactions), angioedema, hives, itching;

Unspecified frequency: rash;

Disturbances from musculoskeletal and connective tissue

Rarely: arthralgia, back pain **;

Unspecified frequency: swelling in the joints;

Disorders from the kidneys and urinary tract

Rarely: dysuria, urinary retention (more often in men with predisposing factors), infection of the urinary tract.

* These adverse reactions were not detected during clinical trials of the drug. With a probability of 95%, the frequency of these adverse reactions does not exceed the category - "infrequently."

** undesirable effects related to the drug SPIOLTO RESPIMAT and not to its components.

Many of these undesirable effects relate to the anticholinergic properties of tiotropium bromide or β-adrenomimeticheskim olodaterola properties.

Therefore it is necessary to take into account the possibility of adverse effects characteristic of the entire class of β-agonists, such as arrhythmia, myocardial ischemia, angina pectoris, hypotension, tremor, headache, nervousness, nausea, muscle cramps, fatigue, malaise, hypokalemia, hyperglycemia, and metabolic acidosis.

Overdose:

Symptoms

Olodaterola Overdosing can lead to marked effects typical of β₂for example, myocardial ischemia, increased or decreased blood pressure, tachycardia, arrhythmias, palpitations, dizziness, nervousness, insomnia, anxiety, headache, tremor, dry mouth, muscle spasm, nausea, fatigue, malaise, hypokalemia, Hyperglycemia and metabolic acidosis.

When high doses of tiotropium bromide are used, manifestations of m-cholinoblocking action are possible. After a 14-day inhalation application of tiotropium bromide in doses as high as 40 μg, no significant adverse events were observed in healthy individuals, except for a feeling of dryness in the mucous membranes of the nose and oropharynx, whose frequency depended on the dose (10-40 mcg per day). The exception was a clear reduction in salivation, starting from day 7 of the drug.

Treatment

Reception of the drug SPIOLTO RESPIMAT should be discontinued. Supportive and symptomatic treatment is indicated. In severe cases, hospitalization is necessary. It may be recommended to use beta₁- adrenoblokatorov, but only with special care, as the use of these drugs can cause bronchospasm.

Interaction:

Although no special studies of drug interactions have been conducted, tiotropium bromide was used in conjunction with other drugs to treat COPD, including methylxanthines, steroids for ingestion and inhalation, with no clinical signs of drug interactions.

Long-term combined use of tiotropium bromide with other m-cholin-blocking drugs has not been studied. Therefore, long-term joint use of the drug SPIOLTO RESPIMAT with other m-holinoblokiruyuschimi drugs is not recommended.

Simultaneous use of other adrenergic drugs may enhance the undesirable effects of the drug SPIOLTO RESPIMAT.

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

β-adrenoblockers can weaken the effect of olodaterol or counteract this effect. In this case, it is preferable to use beta₁adrenoblockers. Although they should be used with caution.

Monoamine oxidase inhibitors, tricyclic antidepressants or other drugs capable of lengthening the interval QTc. 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 a factor of 1.7. However, this did not affect safety.

Dose changes are not required.

Special instructions:

The drug SPIOLTO RESPIMAT should not be used for bronchial asthma. The effectiveness and safety of the drug SPIOLTO RESPIMAT in bronchial asthma have not been studied.

Acute bronchospasm

Preparation SPIOLTO REPIMATE is not indicated for the treatment of acute episodes of bronchospasm, that is, as an ambulance.

Hypersensitivity

After the application of the preparation of SPIOLTO RESPIMAT, the development of immediate-type hypersensitivity reactions is possible.

Paradoxical bronchospasm

The use of the drug SPIOLTO RESPIMAT, as well as other inhaled medications, can lead to a paradoxical bronchospasm, sometimes life-threatening. In case of development of paradoxical bronchospasm, the use of the drug SPIOLTO RESPIMAT should be immediately discontinued andalternative therapy is prescribed.

Patients with impaired renal function

As tiotropium bromide is excreted mainly by the kidneys, patients with renal insufficiency of moderate and severe severity (creatinine clearance <50 ml / min) using the drug SPIOLTO RESPIMAT, should be under close medical supervision.

Disturbances on the part of the organ of sight

Patients should be made aware of the correct use of the drug SPIOLTO RESPIMAT. Do not allow solution or aerosol to enter the eyes. Pain or discomfort in the eyes, fuzzy vision, visual halos around the light sources combined with reddening of the eyes caused by swelling of the conjunctiva and the cornea can be symptoms of acute closed-angle glaucoma. When developing any combination of these symptoms, you should immediately contact a specialist. Eye drops that have a miotic effect are not considered effective treatment.

Cardiovascular Effects

Olodaterol, like other β₂-adrenomimetiki, can have a clinically significant effect on the cardiovascular system in some patients (increased heart rate,increased blood pressure and / or the appearance of the corresponding symptoms). If these symptoms occur, treatment may need to be discontinued. In addition, it was reported that β₂-adrenomimetiki led to such changes in the electrocardiogram (ECG) as a flattening of the T wave and segment depression ST, although the clinical significance of these changes is unknown.

Hypokalemia

β₂-adrenomimetics in some patients may lead to the development of hypokalemia, which creates the prerequisites for the occurrence of undesirable effects on the cardiovascular system. Reducing the concentration of potassium in the blood serum is usually short-term and does not require its replenishment. In patients with severe COPD, hypokalemia may increase due to hypoxia and concomitant treatment and increase the risk of arrhythmias.

Hyperglycaemia

Inhalation use of large doses of β₂-adrenomimetikov can lead to an increase in the concentration of glucose in the blood plasma.

The preparation of SPIOLTO RESPMIT should not be used in combination with any other a drug containing β₂long-acting adenomimetics.

Patients who frequently use inhaled β₂(for example, four times a day), it is necessary to instruct that these drugs are used only to relieve the acute symptoms of bronchospasm.

The preparation of SPIOLTO RESPIMAT is intended for supporting treatment of patients with COPD. Due to the fact that patients in the general population of COPD are significantly older than 40 years of age, spirometric confirmation of the diagnosis of COPD is required when prescribing the drug to patients younger than 40 years of age.

Effect on the ability to drive transp. cf. and fur:

Studies to study the effect on the ability to drive vehicles and mechanisms were not conducted. Care should be taken when performing these types of activities, as dizziness or blurred vision is possible.

Form release / dosage:

Solution for inhalation dosage 2.5 μg + 2.5 μg / dose.

Packaging:

Inhaler Respimat® complete with a cartridge capacity of 4.5 ml, placed in an aluminum cylinder. Inhaler and cylinder with a cartridge with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Use within 3 months after the first inhalation.

Not Use after the expiry date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003164

Date of registration:31.08.2015

Expiration Date:31.08.2020

The owner of the registration certificate:Boehringer Ingelheim International GmbHBoehringer Ingelheim International GmbH Germany

Manufacturer: & nbsp

BOEHRINGER INGELHEIM INTERNATIONAL, GmbH Germany

Representation: & nbspBehringer Ingelheim, LLCBehringer Ingelheim, LLC

Information update date: & nbsp22.09.2017

Illustrated instructions

Instructions

Spiolto® Respimat® (Spiolto® Respimat®)