Spiriva Respimat - instructions for use, doses, side effects, contraindications

Active substanceTiotropium bromideTiotropium bromide

Similar drugsTo uncover

Spiriva®

capsules d / inhal.

Boehringer Ingelheim International GmbH Germany

Spiriva® Respimat®

solution d / inhal.

Boehringer Ingelheim International GmbH Germany

Tiotropium-native

capsules d / inhal.

NATIVA, LLC Russia

Dosage form: & nbspinhalation solution

Composition:

Active substance: tiotropium - 2.5 μg (correspondingly tiotropium bromide monohydrate - 3,1235 μg.

Excipients: benzalkonium, chloride - 1,105 μg, disodium edetate - 1,105 μg, hydrochloric acid 1M to pH 2.8-3.0, water-up to 11.05 mg.

Description:

a clear, colorless or almost colorless solution in a 4.5 ml cartridge placed in an aluminum cylinder /

Pharmacotherapeutic group:M-holinoblokator

ATX: & nbsp

R.03.B.B Holinblockers

R.03.B.B.04 Tiotropium bromide

Pharmacodynamics:

Tand bromide is an antimuscarinic long-acting drug, often called m-holin-blocking agent in clinical practice. The drug has the same affinity for Ml - M5 subtypes of muscarinic receptors. The result of the inhibition of M3 receptors in the airway is the relaxation of smooth muscles. The bronchodilator effect is dose dependent and persists for at least 24 hours. A significant duration of action is probably connected,with a very slow dissociation of the drug from the M3 receptors; the half-dissociation period is much longer than in ipratropium bromide. When Inhalation mode of administration of tiotropium bromide, as an N-quaternary ammonium derivative, exerts a local selective effect (on the bronchi), while in therapeutic doses does not cause systemic m-cholinoblocking side effects. Dissociation from M2-receptors occurs faster than from M3 receptors, which indicates about prevalence

selectivity for the M3 receptor subtype over M2 receptors. The high affinity for the receptors and the slow dissociation of the drug from the receptor binding cause expressed 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 clinical trials, it has been shown that the use of SPIRIVA RESPIMAT once a day results in a significant improvement (compared to placebo) in lung function (forced expiratory volume per second FEV1 and forced vital capacity of the FVC lungs) within 30 minutes after the first dose .The improvement in lung function persists for 24 hours at an equilibrium concentration. Pharmacodynamic equilibrium was achieved within one week. SPIRIVA RESPIMAT significantly improved the morning and evening

inhalation mode of administration of tiotropium bromide, as Nis a quaternary ammonium derivative, has a local selective effect (on the bronchi), while in therapeutic doses does not cause systemic m-cholinoblocking side effects. Dissociation from M2-receptors occurs faster than from M3 receptors, which indicates a predominance

selectivity for the M3 receptor subtype over M2 receptors. The high affinity for the receptors and the slow dissociation of the drug from the bond with the receptors cause a pronounced and

prolonged bronchodilator

In clinical trials, it has been shown that the use of SPIRIVA RESPIMAT once a day results in a significant improvement (compared with placebo) functionlungs (volume of forced expiration in 1 second FEV1 and forced vital capacity of the FVC lungs) within 30 minutes after the first dose. The improvement in lung function persists for 24 hours at an equilibrium concentration. Pharmacodynamic equilibrium was achieved RESPIMAT significantly improved the morning and evening peak volumetric expiratory flow rate (PER), measured by patients.

The use of SPIRIVA RESPIMAT resulted in a decrease (in comparison with placebo) in the use of the bronchodilator as an ambulance.

Bronchodilator effect of the drug

persists for 48 weeks; signs of addiction is not noted.

The analysis of the combined data of two randomized, placebo-

controlled, cross-sectional clinical trials showed that

bronchodilator effect of the drug

SPIRIVA RESPIMAT (5 μg) after 4 weeks of treatment was in

quantitative ratio is higher than the effect preparation of SPIRIVA (18 μg).

In long-term (12-month) studies it was found that SPIRIVA RESPIMAT significantly reduces shortness of breath; improves the quality of life; reduces psychosocial effects of COPD and increased activity.

The drug SPIRIVA RESPIMAT significantly improved the overall health (total score) compared with placebo at the end of two 12-month studies, this difference persisted throughout the treatment period; the drug SPIRIVA RESPIMAT significantly reduced the number of exacerbations of COPD, and increased the period until the moment of the first exacerbation compared with placebo.

It is proved that SPIRIVA RESPIMAT reduces the risk of exacerbation of COPD and significantly reduces the incidence of hospitalization.

In the retrospective analysis of individual clinical studies, there was a statistically inaccurate increase in the number of deaths in patients with cardiac rhythm disturbances, compared with placebo. However, these data are not statistically confirmed and may be associated with heart disease.

In clinical studies in patients, suffering from bronchial asthma and continuing to experience the symptoms of the disease, despite supporting therapy with an inhaled corticosteroid, including in combination with long- active beta agonist 2- adrenoreceptors, it was found that the addition of SPIRIVA RESPIMAT to maintenance therapy led to a significant improvement in lung function compared to placebo, significantly reduced the number of serious exacerbations and periods of worsening of symptoms of bronchial asthma, and increased the period before their first onset, led to a significant improvement in the quality of life and an increase in the number of patients with a positive response to maintenance therapy.

Bronchodilator effect of the drug persisted for 1 year, no signs of addiction were noted.

Pharmacokinetics:

Tiotropium bromide is a quaternary derivative ammonium, moderately soluble in water. Tiotropium bromide Issued in the form of a solution for inhalation, which is used with the aid of the inhaler RESPMIT.

Approximately 40% of the value Inhalation dose is deposited in the lungs, the rest is transferred to the gastrointestinal tract. Some of the pharmacokinetic data described below were obtained using doses exceeding those recommended for treatment.

Suction

After inhalation of the solution with young healthy volunteers found that about 33% of the inhalation dose comes into the systemic circulation. The intake of pitti does not affect the absorption of tiotropium bromide, due to the fact. that it is poorly absorbed from the gastrointestinal tract.

Absolute bioavailability in admission inside is 2 - 3%. The maximum concentration in plasma is observed in 5-7 minutes after inhalation. At the stage of dynamic equilibrium, the peak concentration of tiotropium in the blood plasma in patients with COPD is 10.5 pg / ml and rapidly decreases. This indicates a multi-compartmental type of drug distribution. At the stage of dynamic equilibrium, the basal concentration of tiotropium in blood plasma is 1.6 pg / ml. At the stage of dynamic equilibrium, the peak concentration of tiotropium in blood plasma in patients with bronchial asthma was 5.15 pg / ml and was achieved after 5 min. Distribution

The binding of the drug to plasma proteins is 72%; volume of distribution 32 l / kg. Studies have shown that tiotropium bromide does not penetrate

blood-brain barrier. Biotransformation

The degree of biotransformation is insignificant.This is confirmed by the fact that after intravenous administration of the drug to young healthy volunteers in urine 74% of the substance tiotropium bromide is found in unchanged form. Tiotropium bromide is an ether that is split into ethanol-M-methylskopine. and dithienylglycolic acid; these compounds do not bind to muscarinic receptors.

In studies in vitro It was shown that some part of the drug (<20% of the dose after intravenous administration) metabolized by oxidation with cytochrome P450, followed by conjugation with glutathione and the formation of various metabolites. This mechanism can be inhibited by inhibitors isozymes CYP450 2D6 and 3A4, quinidine, ketoconazole and Gestodene. In this way, CYP450 2D6 and 4A participate in metabolism Tiotropium bromide does not inhibit cytochrome P450 1A1, 1A2, 2B6, 2C9, 2C19 even in super therapeutic concentrations, 2D6, 2E1 or FOR in microsomes of human liver.

Excretion

The terminal half-life of tiotropium bromide after inhalation is from 27 to 45 hours in patients with COPD. In patients with asthma, the effective half-life after inhalation is 34 hours.

The total clearance after intravenous injection of the drug to young healthy volunteers was 880 ml / min. Tiotropium bromide after intravenous administration is mainly excreted by the kidneys in unchanged form (74%). After inhalation solution in patients with COPD, renal excretion is 18.6% (0.93 μg), the remaining unabsorbed part is excreted through the intestine. In the stage of pharmacokinetic equilibrium in patients with asthma, 11.9% (0.595 μg) of the dose is excreted unchanged in the urine 24 hours after taking the drug. The renal clearance of tiotropium bromide exceeds the creatinine clearance, which indicates its tubular secretion. After a long inhalation intake of the drug once a day, patients with COPD pharmacokinetic equilibrium is achieved on day 7; while in the future there is no accumulation.

Tiotropium bromide has a linear pharmacokinetics within the therapeutic limits after intravenous administration, inhalation of dry powder and inhalation solution. Pharmacokinetics in elderly patients

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 and asthma over 65 years of age)that in patients with bronchial asthma, the effect of tiotropium bromide does not depend on the age of the patients.

Patients with impaired renal function After inhalation, tiotropium once a day during a steady state of pharmacokinetics in patients with COPD and minor renal impairment (creatinine clearance 50-80 ml / min) there was a slight increase in the values AUC₀-6, ss on 1,8-30% and C_max,_Ss compared with patients with normal renal function (creatinine clearance >80 ml / min). In patients with COPD and moderate or significant impairment of renal function (creatinine clearance <50 ml / min), the intravenous application of tiotropium bromide resulted in a twofold increase in the total exposure (area under the "concentration / time" curve AUC₀-4₄ increased by 82% and the quantity Cmax increased by 52 %) compared with patients with COPD and normal function of the kidneys. A similar increase in plasma concentration was noted after inhalation of dry powder.

In patients with bronchial asthma and minor impairment of renal function (creatinine clearance 50-80 ml / min) inhalation of tiotropium bromide did not lead to a significant increase in the effect compared with patients with normal renal function.

Patients with hepatic impairment

It is assumed that the hepatic insufficiency 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:

2. Remove the cartridge (H) from the package. Paste it narrow end in the inhaler until fixation (Figure 2a).

To ensure that the cartridge is fully inserted, strong press the cartridge onto a hard surface (Fig. 2b). In this case, the bottom of the cartridge should not be flush with the lower edge of the inhaler, the lower part of the silver cartridge should be visible.

After the cartridge is inserted into the inhaler, do not remove it.

The drug SPIRIVA RESPIMAT is shown:

- for maintenance treatment of patients with COPD, chronic bronchitis, emphysema; maintenance therapy with persistent dyspnea; improve the quality of life impaired due to COPD, andreducing the frequency of exacerbations.

- as an additional maintenance therapy in patients with bronchial asthma, with persisting symptoms of the disease on the background of taking, at least,inhaled glucocorticosteroids; to reduce the symptoms of bronchial asthma, improve quality of life and reduce the frequency of exacerbations

Contraindications:

The drug SPIRIVA RESPIMAT is contraindicated in patients who previously had a hypersensitivity to atropine; or a derivative thereof, for example, ipratropium bromide, oxytropium bromide, or any component of these preparations. The drug SPIRIVA RESPMIT is not recommended for use in children under 18 years of age (due to lack of data on efficacy and safety).

Carefully:

closed-angle glaucoma, prostatic hyperplasia, obstruction of the neck of the bladder.

Pregnancy and lactation:

Data on the effect of the drug SPIRIVVA RESPIMAT on pregnancy are limited. In the study of reproductive toxicity in animals no indication of direct or indirect adverse effects of the drug has been obtained. As a precaution, it is preferable to refrain from

use of SPIRIVA RESPIMAT during pregnancy Clinical data on the effects of tiotropium bromide in breast-feeding women do not.The drug should not be used in pregnant or breast-feeding women, unless the potential benefit to the mother exceeds the potential risk to the fetus and the baby. For the period of application of the drug, it is necessary to stop breastfeeding the baby.

Dosing and Administration:

Recommended therapeutic dose is two inhalation doses of the spray from the inhaler RESPIMAT (5 μg / dose) once a day, at the same time of the day (see Instructions for Use).

When treating bronchial asthma, a complete The therapeutic effect comes in a few days.

In elderly patients, patients with impaired liver function and patients with minor renal impairment (creatinine clearance 50 - 80 ml / min), SPIRIVA RESPIMAT can be used at the recommended dose.

However, the use of the drug in patients with moderate or significant impairment of renal function (creatinine clearance less than 50 mL / min) should be carefully monitored.

COPD usually does not occur in children. Safety and efficacy of spiriva in children have not been studied.

Instructions for use Please read this manual and carefully follow it.

(see figures)

After the first use, the SPIRIVA respirator should be disposed of no later than three months, even if not all of the medication has been applied.

Care of the inhaler

The mouthpiece and the metal part of the spray gun must be cleaned with a damp soft cloth at least once a week.

A slight discoloration of the mouthpiece does not affect the functioning of the SPIRIVVA RESPmit inhaler.

If necessary, wipe the SPIRIVVA RESPIMAT inhaler also from the outside with a damp cloth.

Side effects:

Many of the undesirable reactions listed below may be due to the m-cholinoblocking properties of the drug.

Adverse reactions were identified on the basis of data obtained during clinical trials and individual reports during the post-marketing use of the drug.

From the side of metabolism: dehydration*.

From the nervous system: infrequently (≥0.1% and <1%) - dizziness; insomnia*.

From the side of the organ of vision: rarely (≥0.01% and <0.1%) - increased intraocular pressure, glaucoma, fuzzy vision.

From the cardiovascular system: infrequent (> 0.1% and <1%) - atrial fibrillation, tachycardia (including supraventricular tachycardia), palpitation.

On the part of the respiratory system: infrequently (≥0.1% and <1%) - cough, nosebleeds, pharyngitis, dysphonia; rarely (≥0.01% and <0.1%) - paradoxical bronchospasm, laryngitis; sinusitis*.

From the digestive system: often (≥1% and <10%) - a slight transient dryness of the pharyngeal mucosa; infrequently (> 0.1% and <1%) - constipation, candidiasis of the oral cavity, dysphagia; rarely (≥0.01% and <0.1%) - gastroesophageal reflux, gingivitis, glossitis, stomatitis; intestinal obstruction, including paralytic intestinal obstruction *.

From the skin: rarely (≥0.01% and <0.1%) - skin infections and skin ulcers, dry skin.

Allergic reactions: infrequently (> 0.1% and <1%) - rash, itching; rarely (≥0.01% and <0.1%) - angioedema, hives; hypersensitivity, including reactions of immediate type *.

From the osteomuscular system and connective tissue: swelling of the joints.

From the urinary system: infrequent (> 0.1% and <1%) - dysuria, urinary retention (more often in men with predisposing factors); rarely (≥0.01% and <0.1%) is a urinary tract infection.

* in the combined database of clinical studies, these adverse reactions were not identified; there were only isolated reports of these adverse reactions with a wide application of the drug, but the association with the m-cholinoblocking action of the drug has not been proven; the frequency of these rare phenomena is difficult to assess.

Overdose:

When using high doses of the drug manifestations of m-cholinoblocking action are possible.

After a 14-day inhalation The use of tiotropium bromide in doses as high as 40 mcg showed no significant adverse effects 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 μg per day).

The exception was a clear decrease salivation, starting from the 7th day of application of the drug. In six long-term studies in patients with COPD with inhalation of a solution of tiotropium bromide in a daily dose of 10 μg in flow 4-48 weeks there were no significant adverse events.

Interaction:

Although special studies drug interactions were not conducted, tiotropium bromide was used in conjunction with other drugs for the treatment of COPD, including sympathomimetic bronchodilators, methylxanthines, steroids for ingestion and inhalation, antihistamines, mucolytics, leukotriene modifiers, cromones, anti- IgE drugs in this clinical signs of drug interactions were not noted.

Joint application with long-acting beta2-agonists, inhaled glucocorticosteroids and their combinations does not affect the action of tiotropium.

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 SPIRIVA RESPIMAT with other m-cholin-blocking drugs is not pRecommended.

Special instructions:

The drug SPIRIVA RESPIMAT, as a bronchodilator used once a day for maintenance treatment, should not be used as an initial therapy for acute attacks of bronchospasm or for the elimination of acute symptoms. In the case of development of an acute attack, fast-acting (32-agonists.

The drug SPIRIVA RESPMIT should not be used to treat bronchial asthma as first-line therapy. Patients should be recommended to continue anti-inflammatory therapy (eg, inhaled glucocorticosteroids), even if the symptoms decrease, when SPIRIVA RESPIMAT is taken.

After application of the drug, immediate reactions of increased sensitivity can develop.

Inhalation of the drug can cause bronchospasm.

With moderate or severe renal failure (creatinine clearance <50 ml / min), the drug should be administered under close supervision, as with all medications,excreted mainly by the kidneys. Patients should be familiar with the instructions for use. Do not allow solution or aerosol to enter the eyes. Pain or discomfort in the eyes, blurred vision, visual halos combined with red eyes, conjunctival edema and cornea may 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.

The drug SPIRIVA RESPMIT should not be used more than once a day. Cartridges SPIRIVES should be used only with inhaled respirator.

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; may develop dizziness or blurred vision.

Form release / dosage:

Solution for inhalation 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 cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Use within 3 months after the first inhalation

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000890

Date of registration:18.10.2011

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

Manufacturer: & nbsp