Spiolto Respimat - Instructions For Use Of The Inhaler, Price, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Spiolto Respimat

Spiolto Respimat: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Spiolto Respimat

ATX code: R03AL06

Active ingredient: tiotropium bromide (Tiotropium bromide) + olodaterol (Olodaterol)

Producer: Boehringer Ingelheim Pharma (Germany)

Description and photo updated: 2018-29-11

Prices in pharmacies: from 2523 rubles.

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Spiolto Respimat is a combined bronchodilator.

Release form and composition

Dosage form - dosed solution for inhalation: almost colorless or colorless, transparent (in a cardboard box 1 cartridge of 4.5 ml, containing 60 inhalation doses, which corresponds to 30 therapeutic doses, the set contains the Respimat inhaler and instructions for the use of Spiolto Respimat).

Active substances in 1 dose:

• olodaterol - 2.5 mcg (olodaterol hydrochloride - 2.736 mcg);
• tiotropium bromide - 2.5 μg (tiotropium bromide monohydrate - 3.124 μg).

Auxiliary components: disodium edetate, benzalkonium chloride solution, 1M hydrochloric acid (up to pH 2.9), purified water.

Pharmacological properties

Pharmacodynamics

Spiolto Respimat is one of the combined bronchodilator drugs. Olodaterol is a long-acting β ₂ -adrenomimetic, tiotropium bromide is an m-anticholinergic. When used in combination, the active components of Spiolto Respimat provide complementary bronchodilation, which occurs due to the different mechanism of their action and the different localization of target receptors in the lungs.

Olodaterol has a high affinity and selectivity for β ₂ -adrenergic receptors. Due to the activation of β ₂ -adrenergic receptors in the respiratory tract, intracellular adenylate cyclase is stimulated, which is involved in the biosynthesis of cAMP (cyclic 3,5-adenosine monophosphate). With an increase in the level of cAMP, bronchodilation is noted and, as a result, relaxation of the smooth muscle cells of the airways. Olodaterol is a long-acting selective β ₂ -adrenergic receptor agonist, which is characterized by a rapid onset of action and long-term (at least 24 hours) preservation of the effect. β ₂-adrenergic receptors are found not only in smooth muscle cells, but are also present in many other cells, including in endothelial and epithelial cells of the heart and lungs. Until now, the exact function of β ₂ receptors in the heart is not fully understood, but their presence indicates the possibility of even highly selective beta ₂ -adrenergic agonists acting on the heart.

Tiotropium bromide is a long-acting m-anticholinergic blocker, has the same affinity for the M ₁ –M ₅ subtypes of muscarinic receptors. As a result of inhibition in the airways of M ₃ -cholinoreceptors, relaxation of smooth muscles occurs. The bronchodilating effect is dose-dependent and persists for at least 24 hours. It is assumed that the significant duration of exposure to the substance is based on the very slow dissociation of the drug from M ₃-cholinoreceptors: the half-dissociation period of tiotropium bromide significantly exceeds the value of this indicator for ipratropium bromide. As an N-quaternary ammonium derivative, tiotropium bromide, when administered by inhalation, has a local selective effect (on the bronchi), while when used in therapeutic doses, systemic m-cholinergic blocking side reactions do not develop. Dissociation from M ₂ cholinergic receptors occurs more rapidly than from M ₃ cholinergic receptors, which suggests a predominance of selectivity for the M ₃ subtype of cholinergic receptors over M ₂-cholinoreceptors. The prolonged and pronounced bronchodilatory effect in patients with COPD (chronic obstructive pulmonary disease) is due to the slow dissociation of the substance from the connection with the receptors and the high affinity for the receptors. The bronchodilation that develops after inhalation of tiotropium bromide is based primarily on local (in the respiratory tract), and not systemic action.

During clinical studies, it was found that the use of Spiolto Respimat 1 time per day in the morning leads to a rapid (within 5 minutes after the first dose) improvement in lung function. The effect of therapy exceeded the effect of the use of 5 mcg of tiotropium bromide and 5 mcg of olodaterol, used as monotherapy, the value of FEV ₁ (forced expiratory volume in the first second of the forced expiratory maneuver): Spiolto Respimat - by 0.137 L; tiotropium bromide - by 0.058 l; olodaterol - 0.125 liters.

Against the background of therapy with Spiolto Respimat, in comparison with the use of tiotropium bromide and olodaterol in the form of monotherapy, a more significant bronchodilating effect is achieved, and the peak volumetric expiratory flow rate increases both in the morning and in the evening.

Compared with placebo, the use of Spiolto Respimat leads to a decrease in the risk of exacerbations of COPD.

Spiolto Respimat significantly improves inspiratory capacity in comparison with tiotropium bromide, olodaterol, or placebo used as monotherapy. The drug also significantly improves exercise tolerance time compared to placebo.

Pharmacokinetics

The pharmacokinetic parameters of Spiolto Respimat are equivalent to those of olodaterol and tiotropium bromide used separately.

The active components of the drug are characterized by linear pharmacokinetics.

The steady state of olodaterol pharmacokinetics is achieved in 8 days when applied once a day, and the degree of effect increases in comparison with a single dose by 1.8 times. When applied once a day, a steady state of tiotropium bromide pharmacokinetics is achieved within 7 days.

Olodaterol

The substance is rapidly absorbed, C _max (maximum concentration of the substance) in plasma after inhalation is usually reached within 10-20 minutes. The absolute bioavailability in healthy volunteers after inhalation is approximately 30%, while when the substance is taken orally in the form of a solution, it is less than 1%. Thus, after inhalation use, the systemic effect of olodaterol is mainly realized by absorption in the lungs, and the swallowed part of the dose does not significantly affect the systemic effect.

Olodaterola binding level with plasma proteins - about 60%, V _d (volume of distribution) - 1110 liters.

The substance is metabolized to a large extent by direct glucuronidation and O-demethylation followed by conjugation. 6 metabolites have been identified, of which only one unconjugated demethylated derivative binds to β ₂ -adrenergic receptors (SOM 1522). This metabolite is not detected in plasma after prolonged inhalation of olodaterol at the recommended therapeutic dose or at doses 4 times higher than the therapeutic dose. Cytochrome P450 (isoenzymes CYP2C9, CYP2C8, and also to a small extent CYP3A4) takes part in the O-demethylation of the substance, in the process of formation of glucuronides of olodaterol - isoforms of uridine diphosphate glycosyl transferase, UGT1A1, UGT2B7, 1A7.

In healthy volunteers, the renal clearance of olodaterol is 173 ml / min, and the total clearance is 872 ml / min. The final T _1/2 (half-life) after intravenous administration of the substance is 22 hours, while the value of this indicator after inhalation is about 45 hours. Thus, excretion in the latter case depends on absorption to a greater extent.

The total isotope-labeled dose of olodaterol, which is excreted by the kidneys (including all metabolites of the parent compound), is: intravenous administration - 38%, oral administration - 9%. The total renal excreted isotope-labeled dose of unchanged substance after intravenous administration is 19%. The total isotope-labeled dose excreted through the intestine is: intravenous administration - 53%, oral administration - 84%.

More than 90% of the dose of olodaterol after intravenous administration is excreted in 5 days, after oral administration - in 6 days. After inhalation, the renal excretion of the unchanged substance during the dosing interval in healthy volunteers during the steady state of pharmacokinetics is 5-7% of the dose.

Tiotropium bromide

After inhalation, approximately 33% of the inhalation dose enters the systemic circulation. The absolute oral bioavailability is 2-3%. The time to reach C _max in plasma after inhalation is 5–7 minutes.

The level of binding of the substance to plasma proteins is 72%, _Vd is 32 l / kg. During preclinical studies, it was found that tiotropium bromide does not penetrate the blood-brain barrier.

Tiotropium bromide is biotransformed to an insignificant extent. This is confirmed by the fact that the substance is excreted unchanged by the kidneys after intravenous administration. Tiotropium bromide is an ester that cleaves into dithienyl glycolic acid and ethanol-N-methylscopine; these compounds do not bind to muscarinic receptors.

Studies have shown that some part of the dose (after intravenous administration - less than 20% of the dose) is metabolized by oxidation by cytochrome P ₄₅₀ (CYP3A4 and CYP2D6), after which conjugation with glutathione and the formation of various metabolites occurs.

After intravenous administration, the substance is excreted mainly by the kidneys unchanged (74%), the total clearance in young healthy volunteers is 880 ml / min. In patients with COPD after inhalation of the solution, renal excretion is 0.93 μg (18.6%), the remaining unabsorbed part is excreted through the intestine. The renal clearance of tiotropium bromide is higher than CC (creatinine clearance), which is evidence of its tubular secretion. The terminal T _{1/2 of the} substance after inhalation is in the range from 27 to 45 hours.

Pharmacokinetics in special clinical situations

During clinical studies, it was found that, despite the effect of weight, age and gender on the systemic exposure of olodaterol, its dose adjustment is not required.

In elderly patients with COPD, there is a decrease in the renal clearance of tiotropium: up to 65 years - 347 ml / min, from 65 years - 275 ml / min. At the same time, this does not lead to an increase in the values of the concentration indicators of the substance (C _max, _ss) and the area under the concentration-time curve (AUC _0-6, _ss).

In severe renal failure (in patients with CC <30 ml / min), the systemic exposure of olodaterol increases by an average of 1.4 times. Given the experience gained with olodaterol in clinical trials, this increased exposure does not raise safety concerns.

During the period of equilibrium after inhalation of tiotropium once a day in patients with COPD and mild renal failure (with CC 50-80 ml / min), there is an increase in AUC _0-6, _ss by 1.8-30% and C _max, _ss in comparison with patients with no impaired renal function (with CC> 80 ml / min). In patients with COPD and moderate and severe renal failure (with CC <50 ml / min) with intravenous administration of tiotropium bromide, there is a twofold increase in the total exposure to the substance (AUC value _0-4 increases by 82%, and C _max- by 52%) in comparison with patients with no renal dysfunction. A similar increase in plasma concentration is observed after inhalation of dry powder.

In mild and moderate hepatic insufficiency, the systemic effect of olodaterol does not change, in severe hepatic impairment it has not been studied. Hepatic failure, presumably, does not have a significant effect on the pharmacokinetics of tiotropium bromide, since tiotropium bromide is excreted mainly by the kidneys and by non-enzymatic cleavage of the ester bond with the formation of derivatives that do not possess pharmacological activity.

Indications for use

Spiolto Respimat is prescribed for long-term maintenance treatment in patients with COPD, emphysema, chronic bronchitis to achieve the following goals:

• reduction of airway obstruction and associated shortness of breath;
• a decrease in the incidence of exacerbations;
• improving the quality of life and exercise tolerance.

Contraindications

Absolute:

• age up to 18 years;
• lactation period;
• individual intolerance to the components of the drug, as well as the presence of hypersensitivity to atropine / its derivatives, including ipratropium and oxitropium.

Relative (Spiolto Respimat is prescribed under medical supervision):

• cardiovascular diseases, including coronary insufficiency, heart rhythm disturbances, prolongation of the QT interval, hypertrophic obstructive cardiomyopathy, thyrotoxicosis, arterial hypertension, convulsions;
• aggravated history of myocardial infarction or hospitalization for heart failure (during the previous 12 months), life-threatening arrhythmia, paroxysmal tachycardia with a heart rate> 100 beats / min;
• angle-closure glaucoma;
• unusual reactions to sympathomimetic amines;
• hyperplasia of the prostate and bladder neck obstruction;
• pregnancy.

Spiolto Respimat, instructions for use: method and dosage

Spiolto Respimat is intended for inhalation use, preferably at the same time of day.

The recommended therapeutic dose is 2 inhalations of spray from the Respimat inhaler once a day.

Rules for using the inhaler

The inhaler is intended for use once a day. Each time you use it, you should do 2 inhalations.

In preparation for the first use, the following steps must be followed:

1. Remove the transparent sleeve by pressing the locking button while pulling firmly on the transparent sleeve with the other hand.
2. Insert the cartridge into the inhaler with the narrow end, for this you need to place the inhaler with the bottom of the cartridge on a hard surface and press firmly on it, the cartridge is put into place with a click.
3. Reinstall the transparent sleeve (until it clicks).
4. Rotate the transparent sleeve in the direction indicated by the arrows on the label until you hear a click (requires half a turn).
5. Open the cap as far as it will go.
6. Press the dose button while pointing the inhaler down.
7. Close the cap and repeat steps 4-6 until a cloud of aerosol appears. After that, repeat steps 4-6 three more times.

For daily use, steps 4-5 should be followed. Then a full slow exhalation is performed, the mouthpiece is wrapped around the lips, while it is necessary to ensure that the air intakes do not overlap. Simultaneously with a slow, deep breath through the mouth, press the dose delivery button without interrupting the inhalation. After that, hold the breath for about 10 seconds or as long as possible. The second inhalation is similar.

Daily check of the inhaler after its preparation for use is not required.

The inhaler should be kept out of the reach of children, do not freeze.

If the inhaler has not been used for more than 7 days, before use, you must point it down and press the dose delivery button once. If the break is longer than 21 days, repeat steps 4-6 until the aerosol cloud appears, and then repeat them three more times.

Do not touch the piercing element located inside the transparent sleeve.

The mouthpiece, including the metal part inside it, is cleaned with a damp cloth or cloth at least once every 7 days.

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

The inhaler contains 60 inhalation doses (i.e., if used in accordance with the dosage regimen, 30 therapeutic doses).

The dose indicator reflects the approximate number of doses remaining in the inhaler. If the indicator points to the red area of the scale, this means that the drug remains for about 7 days of use. After reaching the end of the red area of the scale, the inhaler is automatically locked (it will be impossible to turn the transparent sleeve), therefore, no inhalation dose can be received anymore.

The inhaler can be used no longer than three months, even if the drug remains in it. At the end of this period, it should be discarded.

If you accidentally turn the transparent sleeve, before installing the cartridge, you must open the cap and press the dose delivery button, and then install the cartridge with the narrow end.

If it is impossible to press the dose delivery button, check whether the transparent sleeve has been turned or whether the drug has run out in the inhaler.

It should be taken into account that the dose indicator counts every turn of the transparent sleeve, regardless of whether a cartridge has been installed.

Do not remove the transparent sleeve and take out the cartridge after preparing the inhaler for use.

Side effects

Adverse reactions identified during clinical studies of Spiolto Respimat (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare; c unspecified frequency - it is not possible to set the frequency of occurrence of unwanted effects):

• nervous system: infrequently - insomnia, dizziness;
• respiratory system: infrequently - dysphonia, cough; rarely - pharyngitis, laryngitis, nosebleeds; with an unknown frequency - sinusitis, bronchospasm;
• cardiovascular system: infrequently - palpitations, atrial fibrillation, tachycardia, increased blood pressure; rarely - supraventricular tachycardia;
• digestive system: often - xerostomia (usually minor); infrequently - constipation; rarely - gingivitis, oral candidiasis; with an unknown frequency - intestinal obstruction, including paralytic intestinal obstruction, gastroesophageal reflux, stomatitis, glossitis, dysphagia;
• musculoskeletal system: rarely - back pain, arthralgia; with an unspecified frequency - swelling in the joints;
• kidneys and urinary system: rarely - urinary retention (more common in men in the presence of predisposing factors), urinary tract infection, dysuria;
• skin and subcutaneous tissue: with unknown frequency - dry skin, skin infections and skin ulcers;
• organ of vision: rarely - blurry vision; with an unknown frequency - glaucoma, increased intraocular pressure;
• infectious and parasitic diseases: rarely - nasopharyngitis;
• allergic reactions: rarely - hypersensitivity (including immediate reactions), urticaria, angioedema, itching; with an unspecified frequency - rash;
• metabolism: with an unknown frequency - dehydration.

Many of these disorders are related to the anticholinergic properties of tiotropium bromide or to the β-adrenomimetic properties of olodaterol. Therefore, it is necessary to take into account the likelihood of developing undesirable effects that are characteristic of the entire class of β-adrenergic agonists, including arrhythmia, angina pectoris, myocardial ischemia, arterial hypotension, tremor, nervousness, headache, nausea, muscle spasms, malaise, fatigue, metabolic acidosis, hypokalemia and hyperglycemia …

Overdose

The main symptoms are:

• olodaterol: severe effects typical of β ₂ -adrenomimetics, including myocardial ischemia, increase / decrease in blood pressure, tachycardia, arrhythmias, palpitations, dizziness, nervousness, nausea, malaise, fatigue, insomnia, anxiety, headache, tremor, xerostomia muscle spasms, metabolic acidosis, hypokalemia, and hyperglycemia;
• tiotropium bromide: manifestations of m-anticholinergic effects. After inhalation for 14 days at doses up to 40 mcg, no significant adverse events were observed in healthy individuals, excluding the feeling of dryness of the mucous membranes of the oropharynx and nose, the incidence of these disorders varied depending on the daily dose (10-40 mcg). An exception is a clear decrease in salivation starting from the seventh day of tiotropium bromide administration.

Therapy: cancellation of Spiolto Respimat, maintenance and symptomatic treatment. In severe cases, hospitalization is indicated. Perhaps the appointment of β ₁ -adrenergic blockers, however, their use requires special care, as this can lead to bronchospasm.

special instructions

With bronchial asthma, Spiolto Respimat should not be used, the safety profile of the drug in this group of patients has not been studied.

For the treatment of acute episodes of bronchospasm, i.e., as an ambulance, the drug is not intended.

It must be borne in mind that during the use of Spiolto Respimat, immediate hypersensitivity reactions may develop.

As with therapy with other inhaled drugs, during the use of Spiolto Respimat, paradoxical bronchospasm may develop, which in some cases is life-threatening, which requires immediate discontinuation of the drug and transfer of the patient to alternative therapy.

For the condition of patients with moderate and severe renal failure (with CC <50 ml / min), medical supervision should be established, since the excretion of tiotropium bromide is carried out mainly by the kidneys.

Eye contact should be avoided. Blurred vision, discomfort and / or pain in the eyes, visual halos around light sources, accompanied by eye redness associated with corneal and conjunctival edema, can be symptoms of acute angle-closure glaucoma. If these symptoms appear in any combination, you should immediately consult a doctor. Eye drops with myotic effects are not considered effective treatments.

Like other β ₂ -adrenomimetics, olodaterol in some patients can have a clinically significant effect on the cardiovascular system (manifested as an increase in heart rate, increased blood pressure and / or the occurrence of corresponding symptoms). Patients who develop these signs should refuse further use of Spiolto Respimat. In addition, there is evidence that therapy with β ₂ -adrenomimetics can lead to ECG changes, including depression of the ST segment and flattening of the T wave (the clinical significance of these changes is unknown).

In some patients, β ₂ -adrenomimetics can cause hypokalemia, which creates prerequisites for the development of undesirable effects on the cardiovascular system. The decrease in serum potassium concentration in the blood is usually short-term, and its replenishment is not required. Hypoxia and concomitant therapy may increase hypokalemia in patients with severe COPD, which increases the risk of arrhythmias.

With inhalation use of β ₂ -adrenomimetics in large doses, an increase in the plasma concentration of glucose in the blood is possible.

Spiolto Respimat should not be used in combination with any other drug that contains a long-acting β ₂ -adrenomimetic.

Patients who frequently use short-acting inhaled β ₂ -adrenomimetics (for example, 4 times a day) should take into account that these drugs are used only to relieve acute symptoms of bronchospasm.

Before the appointment of Spiolto Respimat, patients under 40 years of age need a spirometric confirmation of the diagnosis of COPD.

Influence on the ability to drive vehicles and complex mechanisms

During the period of therapy with Spiolto Respimat, care must be taken when driving vehicles, which is associated with the likelihood of developing blurred vision and dizziness.

Application during pregnancy and lactation

• pregnancy: Spiolto Respimat can only be used in cases where the expected benefit to the mother is higher than the existing harm to the fetus. Clinical studies of the use of the active components of the drug in this group of patients have not been conducted. When conducting preclinical studies using high doses of olodaterol (several times higher than therapeutic), an effect typical for β ₂ -adrenomimetics was established. It is necessary to take into account the inhibitory effect of olodaterol on the contractility of the uterus;
• lactation period: breastfeeding should be discontinued during the use of the drug. Clinical studies of the use of the active components of the drug in this group of patients have not been conducted. Spiolto Respimat can be prescribed only in cases where the expected benefit to the mother is higher than the existing harm to the child.

Pediatric use

Spiolto Respimat is not prescribed to patients under 18 years of age, the safety profile has not been studied.

With impaired renal function

Careful medical supervision should be established for the condition of patients with moderate to severe renal failure.

For violations of liver function

There are no data on the use of olodaterol in severe hepatic impairment.

Drug interactions

Special studies of drug interactions with Spiolto Respimat have not been conducted, however, there is experience of using tiotropium bromide simultaneously with other drugs for the treatment of COPD, including methylxanthines, steroids for oral administration and inhalation, with signs of drug interactions that are of clinical significance, was not noted.

Long-term concomitant use of tiotropium bromide with other m-anticholinergic drugs has not been studied. In this regard, long-term combined use of Spiolto Respimat with other m-anticholinergics is not recommended.

With simultaneous use with other adrenergic drugs, the undesirable effects of Spiolto Respimat may increase.

The hypokalemic effect of adrenomimetics is enhanced by combination therapy with xanthine derivatives, steroids or diuretics (not belonging to the potassium-sparing group).

Weakening of the effect of olodaterol or counteracting the development of this effect is possible with simultaneous use with β-blockers. In such cases, it is preferable to use β ₁ -adrenergic blockers (with caution).

Combined therapy with monoamine oxidase inhibitors, tricyclic antidepressants or other drugs that can prolong the QT interval _c may increase the effect of Spiolto Respimat on the cardiovascular system.

With the combined use of ketoconazole and olodaterol, the systemic effect of the latter increases by 1.7 times, which does not affect the safety of therapy and does not require dose changes.

Analogs

The analogues of Spiolto Respimat are: Astmasol-SOLOpharm, Berodual, Berodual N, Ditek, Inspirax, Ipraterol-Aeronativ, Ipraterol-native, Fenipra, etc.

Terms and conditions of storage

Store at temperatures up to 25 ° C. Do not freeze. Keep out of the reach of children.

The shelf life is 3 years.

After the first inhalation, the drug can be used for three months.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Spiolto Respimate

Reviews of Spiolto Respimat are few, since the drug was recently registered. In most cases, it is described as an effective but expensive tool. Side effects are infrequent.

Price for Spiolto Respimat in pharmacies

The approximate price for Spiolto Respimat (1 cartridge of 4.5 ml with an inhaler) is 2986–3079 rubles.

Spiolto Respimat: prices in online pharmacies

Drug name Price Pharmacy

Spiolto Respimat 2.5 μg + 2.5 μg / dose Dosed solution for inhalation complete with Respimat inhaler 4 ml 1 pc. 2523 RUB Buy

Spiolto Respimat solution for inhalation. doses. 2.5mcg + 2.5mkg / dose 4ml RUB 2985 Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!