Tiotropium bromide duration of action. Medicinal reference book geotar

13.05.2020

Bronchodilator - m-cholinergic receptor blocker

Active substance

Tiotropium bromide monohydrate (tiotropium bromide)

Release form, composition and packaging

Powder capsules for inhalation hard gelatinous, size No. 3, light greenish-blue, opaque; with company symbol and "TI 01" printed in black ink; the contents of the capsules are white powder.

	1 caps.
tiotropium bromide monohydrate	22.5 mcg,
which corresponds to the content of tiotropium	18 mcg

Excipients: lactose monohydrate, 200 M - 5.2025 mg, micronized lactose monohydrate - 0.2750 mg.

Capsule composition (mg / capsule): macrogol - 2.4000 mg, (E132) - 0.0120 mg, titanium dioxide (E171) - 1.0240 mg, iron oxide yellow (E172) - 0.0120 mg, gelatin - 44.5160 mg.

10 pieces. - blisters (1) complete with or without the HandiHaler® inhaler - cardboard packs.
10 pieces. - blisters (3) complete with or without the HandiHaler® inhaler - cardboard packs.
10 pieces. - blisters (6) complete with or without the HandiHaler® inhaler - cardboard packs.

pharmachologic effect

Long-acting m-cholinergic receptor blocker.

It has the same affinity for various subtypes of muscarinic receptors from M 1 to M 5. As a result of inhibition of M 3 receptors in respiratory tract relaxation of smooth muscles occurs. The bronchodilating effect depends on the dose and lasts for at least 24 hours. The significant duration of action is probably associated with a very slow release from the connection with M 3 receptors, compared with ipratropium bromide. When administered by inhalation, tiotropium bromide, as an anticholinergic agent of the N-quaternary structure, has a local selective effect, while in therapeutic doses does not cause systemic anticholinergic side effects... The release of tiotropium bromide from the bond with the M 2 receptors is faster than from the bond with the M 3 receptors. The high affinity for the receptors and the slow release from the binding to them cause an intense and long-lasting bronchodilating effect in patients with COPD.

Bronchodilation after inhalation of tiotropium bromide is a local, not systemic, effect.

IN clinical research it was shown that 30 minutes after single dose Spiriva significantly improves lung function for 24 hours (increase in FEV 1 and FVC). Pharmacodynamic equilibrium was achieved within the 1st week, and a pronounced bronchodilatory effect was observed on the 3rd day. Spiriva significantly increases the morning and evening peak expiratory flow rate measured by patients. Spiriva's bronchodilating effect, assessed throughout the year, did not reveal any manifestations of tolerance.

Spiriva significantly reduces shortness of breath throughout the treatment period. In two randomized, double-blind, placebo-controlled trials, Spiriva was shown to significantly improve tolerance physical activity compared to placebo.

Significantly improves the quality of life, which is observed during the entire period of treatment. Spiriva significantly reduces the number of hospitalizations associated with exacerbation of COPD, and increases the time until the first hospitalization.

It has also been shown that Spiriva leads to a sustained improvement in FEV 1 after use for 4 years without changing the rate of annual decline in FEV 1.

During treatment, there is a 16% reduction in the risk of death.

Compared with salmeterol, the use of Spiriva increases the time to the first exacerbation (187 days versus 145), with a 17% decrease in the risk of exacerbations (hazard ratio 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Также прием препарата Спирива увеличивает время наступления первого тяжелого (требующего госпитализации) обострения (отношение рисков 0.72; 95% ДИ от 0.61 до 0.85; Р<0.001) снижает ежегодное число средних или тяжелых (требующих госпитализации) обострений (0.64 против 0.72; отношение рисков 0.89; 95% ДИ от 0.83 до 0.96; Р=0.002), снижает ежегодное число тяжелых (требующих госпитализации) обострений (0.09 против 0.13; отношение рисков 0.73; 95% ДИ от 0.66 до 0.82; Р<0.001).

Pharmacokinetics

Tiotropium bromide is a quaternary ammonium compound, moderately soluble in water.

Tiotropium bromide has linear pharmacokinetics within therapeutic limits after iv administration and inhalation of dry powder.

Suction

When administered by inhalation, the absolute bioavailability of tiotropium bromide is 19.5%, which indicates a high bioavailability of the fraction of the drug reaching the lungs. C max in the blood is reached 5-7 minutes after inhalation. Tiotropium bromide is poorly absorbed from the gastrointestinal tract. For the same reason, food intake does not affect the absorption of tiotropium. When tiotropium bromide was taken orally in the form of a solution, the absolute bioavailability was 2-3%.

Distribution

Plasma protein binding - 72%. V d - 32 l / kg.

In the equilibrium state, C max in blood plasma in patients with COPD is 12.9 pg / ml and decreases rapidly. This indicates a multi-compartment distribution of the drug. In the equilibrium state, C min of tiotropium in blood plasma is 1.71 pg / ml.

Does not penetrate the BBB.

Metabolism

The degree of biotransformation is negligible. This is confirmed by the fact that after intravenous administration of the drug to young healthy volunteers, 74% of the unchanged substance is found in the urine.

Tiotropium bromide is cleaved non-enzymatically to alcohol-N-methylscopine and dithienyl glycolic acid, which do not bind to muscarinic receptors.

Studies have shown that the drug (<20% от дозы после в/в введения) метаболизируется при участии изоферментов цитохрома P450, путем окисления и последующей конъюгации с глутатионом с образованием различных метаболитов. Нарушение метаболизма может иметь место при использовании ингибиторов CYP2D6 и CYP3А4 (хинидина, и гестодена). Таким образом, изоферменты CYP2D6 и CYP3А4 включаются в метаболизм препарата.

Withdrawal

T1 / 2 of tiotropium after inhalation varies from 27 to 45 hours. The total clearance for intravenous administration to young healthy volunteers is 880 ml / min. Tiotropium after intravenous administration is mainly excreted by the kidneys unchanged (74%). After inhalation of dry powder in an equilibrium state, renal excretion is 7% per day of the dose, the remaining non-absorbed part is excreted through the intestines. The renal clearance of tiotropium exceeds the clearance of creatinine, which indicates a tubular secretion of the drug. After long-term administration of the drug once a day by patients with COPD, the pharmacokinetic equilibrium is achieved on day 7, while further cumulation is not observed.

Pharmacokinetics in special patient groups

In elderly patients, there is a decrease in renal clearance of tiotropium (365 ml / min in patients with COPD under 65 years of age, up to 271 ml / min in patients with COPD over 65 years of age). These changes did not lead to a corresponding increase in AUC values \u200b\u200b0-6 or C max.

In patients with COPD and mild renal impairment (CC 50-80 ml / min), inhalation of tiotropium 1 time / day in an equilibrium state led to an increase in AUC 0-6 by 1.8-30%. The C max value remained the same as in patients with normal renal function (CC\u003e 80 ml / min). In patients with COPD and moderate or severe renal impairment (CC< 50 мл/мин) в/в введение тиотропия приводило к двукратному увеличению концентрации препарата в плазме (значение AUC 0-4 ч увеличивалось на 82% а значение C max увеличивалось на 52%) по сравнению с пациентами с ХОБЛ и нормальной функцией почек. Аналогичное повышение концентрации тиотропия в плазме отмечалось и после ингаляции сухого порошка.

It is expected that it will not significantly affect the pharmacokinetics of tiotropium bromide, because the drug is mainly excreted in the urine and the formation of pharmacologically active metabolites is not associated with the participation of enzymes.

Indications

- as maintenance therapy in patients with COPD, including chronic bronchitis and emphysema (maintenance therapy for persisting shortness of breath and to prevent exacerbations).

Contraindications

- I trimester of pregnancy;

- children and adolescents up to 18 years old;

- hypersensitivity to or its derivatives (including ipratropium and oxytropium);

- hypersensitivity to drug components.

Carefully the drug should be used for angle-closure glaucoma, prostatic hyperplasia, obstruction of the bladder neck.

Dosage

Assign 1 caps / day at the same time in the form of inhalations using the HandiHaler inhaler.

The drug should not be swallowed. Spiriv should not be used more than 1 time / day. Spiriva capsules should only be used with the HandiHaler inhaler.

Elderly patients the drug should be taken in the recommended doses.

When impaired renal function patients can use the drug Spiriva in the recommended doses. However, careful monitoring is necessary. patients with moderate or severe receiving the drug Spiriva (as is the case with other drugs excreted mainly by the kidneys).

Patients with hepatic impairment can take the drug in the recommended doses.

How to use the inhaler HandiHaler

The HandiHaler inhaler is designed specifically for use with Spiriva and is not intended to be used with other medications. The patient can use their HandiHaler for one year.

The inhaler includes: dust cap, mouthpiece, base, piercing button, central chamber.

Using the HandiHaler inhaler:

1. Open the dust cap by pressing the piercing button fully and then releasing it.

2. Fully open the dust cap by lifting it up; then open the mouthpiece by lifting it up.

3. Immediately before use, remove the Spiriva capsule from the blister and place it in the central chamber (it does not matter which side of the capsule is placed in the chamber).

4. Close the mouthpiece tightly until it clicks, leave the dust-proof cap open.

5. While holding the HandiHaler with the mouthpiece up, press the piercing button fully once and then release; thus, an opening is formed through which the drug is released from the capsule during inhalation.

6. Exhale completely; never exhale into the mouthpiece.

7. Take HandiHaler into your mouth and close your lips tightly around the mouthpiece; keeping your head straight, inhale slowly and deeply, but at the same time with sufficient force to hear or feel the vibration of the capsule; inhale until the lungs are full; then hold your breath for as long as possible and remove the HandiHaler from your mouth; continue to breathe calmly; repeat procedures 6 and 7 to completely empty the capsule.

Cleaning the HandiHaler inhaler

The HandiHaler should be cleaned once a month. To do this, open the mouthpiece and dust cap, then open the base of the device by lifting the piercing button. Rinse the inhaler thoroughly in warm water until the powder is completely removed. The HandiHaler should be wiped clean with a paper towel and with the mouthpiece, base and dust cap open, air dry for 24 hours. After cleaning in this manner, the instrument is ready for subsequent use. If necessary, the outside of the mouthpiece can be cleaned with a damp but not wet cloth.

Opening the blister

Separate the blister strip along the perforated line. Open a strip of the blister just before use so that one capsule is completely visible. The capsule contains a small amount of powder and is therefore not completely filled.

If the capsule was accidentally opened and exposed to air, it should not be used. Neither in the device nor in the blister capsules should be exposed to high temperatures or sunlight.

Side effects

From the side of metabolism:dehydration*.

From the digestive system:often (≥1% and<10%) – сухость во рту обычно легкой степени выраженности; нечасто (≥0.1% и <1%) , запор, гастроэзофагеальный рефлюкс; редко (≥0.01% и <0.1%) – кандидоз ротоглотки, гингивит, глоссит; кишечная непроходимость, включая паралитический илеус, дисфагия.

From the respiratory system:infrequently (≥0.1% and<1%) - дисфония, кашель, фарингиты; редко (≥0.01% и <0.1%) – пародоксальный бронхоспазм, ларингиты, синуситы, носовое кровотечение.

On the part of the cardiovascular system:infrequently (≥0.1% and<1%) - мерцательная аритмия; редко (≥0.01% и <0.1%) – тахикардия (включая суправентрикулярную тахикардию), ощущение сердцебиения.

From the urinary system:infrequently (≥0.1% and<1%) - затрудненное мочеиспускание и задержка мочеиспускания (у мужчин с предрасполагающими факторами), дизурия; редко (≥0.01% и <0.1%) - инфекции мочевыводящих путей.

Allergic reactions:infrequently (≥0.1% and<1%) - сыпь; редко (≥0.01% и <0.1%) - крапивница, зуд, реакции повышенной чувствительности, включая реакции немедленного типа, ангионевротический отек*.

From the side of the skin:skin infections and skin ulcers, dry skin *.

From the musculoskeletal system:swelling of the joints *.

From the nervous system:infrequently (≥0.1% and<1%) - головокружение; редко - (≥0.01% и <0.1%) - бессонница.

On the part of the organ of vision:infrequently (≥0.1% and<1%) - нечеткое зрение; редко - (≥0.01% и <0.1%) - повышение внутриглазного давления, глаукома.

* in the combined database of clinical trials, these adverse reactions were not identified; only a few reports of these side reactions were noted with the widespread use of the drug, however, the connection with the m-anticholinergic effect of the drug Spiriva has not been proven; the frequency of these rare events is difficult to assess.

Overdose

Symptoms: when high doses are used, manifestations of anticholinergic action are possible - dry mouth, accommodation disturbances, increased heart rate.

After inhalation of a single dose of up to 282 μg, no systemic anticholinergic effects were observed in healthy volunteers. After repeated administration of a single daily dose of 141 μg in healthy volunteers, bilateral conjunctivitis was observed in combination with dry mouth, which disappeared with continued treatment. In a study examining the effects of tiotropium with repeated use in patients with COPD who received a maximum of 36 mcg of the drug for more than 4 weeks, dry mouth was the only side effect.

Acute intoxication associated with accidental ingestion of capsules is unlikely due to the low bioavailability of the drug.

Drug interactions

It is possible to prescribe the drug Spiriva in combination with other drugs usually used to treat COPD: sympathomimetics, methylxanthine derivatives, oral and inhaled GCS. Combined use with long-acting beta 2 -agonists, inhaled corticosteroids and their combinations does not affect the effect of tiotropium.

Limited information on the joint use with anticholinergic drugs was obtained from two clinical studies: a single administration of 1 dose of ipratropium bromide against the background of continuous administration of Spiriva in patients with COPD (64 people) and in healthy volunteers (20 people) did not lead to a decrease in adverse reactions, a change in vital parameters and ECG. However, the continuous combined use of anticholinergics and Spiriva has not been studied and is therefore not recommended.

special instructions

The drug Spiriva is not intended to relieve acute attacks of bronchospasm.

After inhalation of Spiriva powder, immediate hypersensitivity reactions may develop.

The inhalation process of Spiriva (like other inhaled drugs) can cause bronchospasm.

Patients with renal insufficiency (CC ≤50 ml / min) should be carefully observed when Spiriva is prescribed.

Patients should be familiarized with the rules for using the inhaler. Do not let the powder get into your eyes. Eye pain or discomfort, blurred vision, visual halos combined with eye redness, conjunctival congestion, and corneal edema may indicate an acute attack of angle-closure glaucoma. If any combination of these symptoms develops, the patient should immediately see a doctor. The use of only drugs that cause miosis is not an effective treatment in this case.

One capsule contains 5.5 mg of lactose monohydrate.

Influence on the ability to drive vehicles and use mechanisms

Studies to study the effect of the drug on the ability to drive vehicles and control mechanisms have not been conducted. Cases of dizziness and blurred vision when using the drug can have a negative effect on the above-mentioned ability.

Pregnancy and lactation

Data on the use of tiotropium in human pregnancy are limited. In animal studies, no indication has been obtained of direct or indirect adverse effects on pregnancy, embryo / fetal development, labor, or postnatal development.

As a precautionary measure, it is preferable to refrain from using Spiriva during pregnancy.

Clinical data on the use of tiotropium in women who are breastfeeding are not available. In preclinical studies, data have been obtained that, a small amount of tiotropium is excreted in breast milk.

Spiriva should not be used in pregnant or breastfeeding women, unless the expected benefit outweighs the potential risk to the fetus or baby.

Use in the elderly

Terms of dispensing from pharmacies

The drug is available by prescription.

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature not exceeding 25 ° C; do not freeze. Shelf life is 2 years.

Once opened, the blister should be used within 9 days.

Pharmacological properties

Pharmacodynamics. Tiotropium bromide is a long-acting specific anticholinergic agent that has an affinity for the M1-M5 subtypes of muscarinic receptors. By competitively and reversibly blocking M3 receptors in the airways, it leads to relaxation of the smooth muscles of the bronchi. In in vitro and in vivo studies, the bronchodilating effect was dose-dependent and lasted more than 24 hours. This duration of effect is probably due to the very slow release of the drug from the connection with the M3 receptors, which determines the long half-life and significantly exceeds that of ipratropium bromide. As a quaternary ammonium compound, tiotropium bromide has a predominantly local effect when used by inhalation; its systemic anticholinergic effects are weak. Dissociation from binding to M2 receptors is faster than from binding to M3 receptors in vitro. M3 is a more acceptable (kinetically controlled) receptor subtype. The high efficacy of the drug and slow dissociation from the binding to the receptors clinically correlated with significantly pronounced and prolonged bronchodilation in patients with COPD. Bronchodilation after inhalation of tiotropium is primarily a local effect on the airways, not a systemic one. The use of the drug Spiriva 1 time per day was accompanied by a significant increase in lung function (an increase in forced expiratory volume in the first second and forced vital capacity of the lungs) within 30 minutes after inhalation, the duration of the effect was 24 hours. A stable pharmacotherapeutic effect is achieved within 1 week from the start of treatment ... With daily use, Spiriva significantly increases the morning and evening maximum expiratory flow rate. Improvement of lung function during treatment persists for a long period, signs of development of tolerance to the drug were not observed. Bronchodilation lasts over the 24-hour dosing interval compared to placebo. This did not take into account the regimen of taking the drug (morning or evening). In long-term studies (throughout the year) it has been established: the drug Spiriva significantly reduces shortness of breath; improvement in the condition was maintained throughout the entire period of treatment; significantly reduces the number of exacerbations of COPD and stops the first exacerbation; significantly improves the quality of life; improvement was noted throughout the treatment period; significantly reduces the number of hospitalized patients with exacerbated COPD, with the first hospitalization required later. In 2 studies, it was found that after taking the drug Spiriva significantly increased exercise tolerance, limited by the symptoms of the disease - by 19.7 and 28.3%, respectively. In a study of the use of 18 and 54 mcg (3 times a day, 18 mcg) Spiriva for 12 days, there was no prolongation of the Q – T interval according to ECG indicators. Pharmacokinetics. Tiotropium bromide is a quaternary ammonium compound that is poorly soluble in water; therefore, it is used for inhalation in powder form. As a rule, most of the dose inhaled during inhalation settles on the walls of the pharynx and then is swallowed, a smaller part settles on the walls of the bronchi. After inhalation of dry powder in healthy young volunteers, the absolute bioavailability was 19.5%, which is a sign of a high bioavailability of the fraction reaching the lungs. Taking into account the chemical structure of the active substance (quaternary ammonium compound), tiotropium bromide is assumed to be absorbed only to a small extent in the digestive tract. For the same reason, concurrent food intake does not affect its absorption. The absolute bioavailability of tiotropium bromide in the form of a solution for oral administration is 2-3%. The maximum concentration of tiotropium bromide in the blood plasma is observed 5 minutes after inhalation. 72% of the drug binds to blood plasma proteins. The volume of distribution is 32 l / kg. At equilibrium, the maximum level of tiotropium bromide in the blood plasma in patients with COPD was 17–19 pg / ml when determined 5 minutes after inhalation at a dose of 18 μg and then rapidly gradually decreased. The local concentration in the lungs is not known, but based on the route of administration, a high concentration in the lungs is allowed. Tiotropium bromide does not penetrate the BBB to a significant extent. The degree of biotransformation is insignificant. Tiotropium as an ester disintegrates non-enzymatically to form alcoholic N-methylscopine and dithienyl glycolic acid, which have no affinity for muscarinic receptors. Tiotropium, even at a concentration higher than the therapeutic one, does not inhibit cytochrome P450 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A. The final elimination half-life occurs 5-6 days after inhalation. After inhalation in the form of a powder, 14% of the dose is excreted in the urine, the rest is not absorbed in the intestine and is excreted in the feces. The renal clearance of tiotropium bromide exceeds the clearance of creatinine, which indicates excretion in the urine. After constant daily inhalation in patients with COPD, the equilibrium state is achieved after 2-3 weeks without subsequent cumulation. Tiotropium exhibited linear pharmacokinetic properties over the therapeutic range after dry powder inhalation. Pharmacokinetics in elderly patients As for all other drugs that are mainly excreted in the urine, the use of tiotropium in elderly patients is associated with a decrease in renal clearance due to a decrease in renal function (326 ml / min in patients with COPD over 58 years old compared with 163 ml / min in patients with COPD over the age of 70). The excretion of tiotropium in the urine after inhalation decreases from 14% (in healthy young volunteers) to 7% (in elderly patients with COPD), however, the concentration in blood plasma does not significantly change in elderly patients with COPD and does not exceed the interindividual and individual variability (43% increase in AUC after inhalation of dry powder). Pharmacokinetics in patients with impaired renal function In patients with renal impairment, the concentration of the drug in the blood plasma increases, and renal clearance decreases. With mild renal failure (creatinine clearance 50–80 ml / min), the concentration of tiotropium bromide in the blood plasma increases slightly (an increase in the AUC value after intravenous infusion by 39%). Pharmacokinetics in patients with impaired liver function Hepatic failure does not significantly affect the pharmacokinetics of the drug. Tiotropium is mostly excreted by renal elimination (up to 74% in healthy young volunteers) and by simple non-enzymatic degradation of the ester to products that do not bind to muscarinic receptors.

Indications

maintenance therapy in patients with COPD (chronic bronchitis and pulmonary emphysema); maintenance therapy of shortness of breath due to COPD, and prevention of exacerbations of the disease.

Application

The recommended dose of Spiriva is 1 inhalation (contents of 1 capsule) per day using the Heyler's inhalation device, carried out at the same time of the day. Spiriva's capsules are not intended for oral administration. Correction of the dose of the drug in the elderly, patients with renal insufficiency is not required, however, patients with moderate or severe renal insufficiency during the period of treatment with the drug should be under medical supervision. There is no experience of using Spiriva in children. The HandyHeiler device is designed specifically for inhalation of Spiriva, it should not be used with other drugs. HandyHeiler can be used for 1 year. To prepare the device for operation, open the dust cap by lifting it up, then open the mouthpiece. Remove the Spiriva capsule from the blister pack immediately before use and place it in the center of the device membrane (it does not matter which side to place the capsule in the chamber). Then close the mouthpiece tightly (until it clicks), leaving the dust cap open. During inhalation, HandyHeiler is held with the mouthpiece up, press the button until it stops 1 time and release, after which they tightly clasp the mouthpiece with their lips and inhale. Do not breathe air into the device. Then you should repeat the inhalation from the device to completely empty the capsule, then open the mouthpiece again and remove the used capsule. Close mouthpiece and dust cap. The HandyHeiler device should be rinsed once a month with warm water to remove powder residues, then dry thoroughly by blotting out the remaining water with a paper towel, and air-dried for 24 hours, leaving the dust cap, mouthpiece and base open. If necessary, the mouthpiece can be cleaned with a damp but not wet cloth.

Contraindications

hypersensitivity to the drug, atropine or its derivatives (for example, ipratropium or oxitropium bromide) or other components of the drug.

Side effects

many of the listed side effects can be attributed to the anticholinergic properties of the drug Spiriva. The frequency of manifestations below is based on the data on the frequency of adverse reactions that were observed in 5437 patients who used tiotropium in 19 clinical placebo-controlled studies with treatment periods ranging from 4 weeks to 1 year. From the side of the central nervous system (≥0.1%, but ≤1%): dizziness. On the part of the organ of vision (≥0.01%, but ≤0.1%): blurred vision, increased intraocular pressure; glaucoma*. From the side of the cardiovascular system (≥0.01%, but ≤0.1%): tachycardia, palpitations; supraventricular tachycardia, atrial fibrillation *. Respiratory, thoracic and mediastinal disorders (≥0.1%, but ≤1%): dysphonia, and, as with any other inhalation agents, bronchospasm, cough, laryngeal irritation; (≥0.01% and ≤0.1%): nosebleeds. From the gastrointestinal tract (≥1%, but ≤10%): dry mouth, usually mild, often disappears with continued treatment; (0.1%, but ≤1%): oral candidiasis; (≥0.01% but ≤0.1%): constipation, gastroesophageal reflux disease; intestinal obstruction, including paralytic obstruction, dysphagia. From the immune system, skin and subcutaneous tissues (≥0.01%, but ≤0.1%): skin rash, urticaria, itching and other allergic reactions (including allergic reactions of an immediate type). From the genitourinary system (≥0.01%, but ≤0.1%): impaired urination and urinary retention (usually in men who are predisposed to this), urinary tract infection.

special instructions

During pregnancy and breastfeeding. There are no clinical data regarding the safety of Spiriva's use during pregnancy, however, experimental studies have not revealed a direct or indirect effect on the course of pregnancy and the development of the embryo / fetus, childbirth and postnatal development. There are no clinical data regarding the safety of Spiriva's use during lactation, but it has been experimentally established that a small amount of tiotropium bromide passes into breast milk. The drug should not be used during pregnancy and lactation without careful assessment of the expected benefit to the mother and the potential risk to the fetus or baby. Based on the fact that there is no experience of using Spiriva in the treatment of children, the drug is recommended to be used only in adults. Spiriva is a bronchodilator, which is prescribed once a day for maintenance therapy and is not used to relieve acute attacks of bronchospasm. As with other anticholinergics, Spiriva should be used with caution in patients with angle-closure glaucoma, prostatic hyperplasia, or bladder neck obstruction. Inhaled drugs can cause the development of paradoxical (inhalation-induced) bronchospasm. Patients should be instructed in the correct use of Spiriva capsules. Do not allow the powder to get into the eyes, which can provoke an attack of angle-closure glaucoma. Signs of angle-closure glaucoma can be pain or discomfort in the eyes, blurred vision, the appearance of a halo around objects or colored spots before the eyes, combined with conjunctival or corneal hyperemia. Consultation with an ophthalmologist is required, as the use of miotic eye drops may be ineffective. Spirivu should not be used more than 1 time per day. Spiriva capsules should only be used with the HandyHeiler device. The drug contains 5.5 mg of lactose monohydrate in one capsule. Impact on the ability to drive vehicles and work with mechanical devices. No research was carried out. Dizziness or blurred vision can affect the ability to drive vehicles and mechanical devices.

Interaction

Despite the fact that formal studies of interaction with other drugs were not carried out, tiotropium bromide was used simultaneously with other drugs (sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids, which are used in the treatment of COPD) without the development of side effects. Insufficient information on the use of other anticholinergic drugs in combination with Spiriva's drug: a single dose of ipratropium bromide with prolonged use of Spiriva's drug in patients with COPD and healthy volunteers was not associated with an increase in the number of adverse reactions, changes in the main indicators of the state of the body or ECG results. The appointment of Spiriva in combination with other drugs containing anticholinergics has not been studied and therefore is not recommended.

Overdose

taking the drug Spiriva in high doses can cause anticholinergic effects, although in the study, systemic anticholinergic side effects were absent when the drug was prescribed to healthy volunteers in a single dose up to 282 mcg. Bilateral conjunctivitis and dry mouth were noted after inhalation of 141 μg of tiotropium per day; with continued treatment, the signs of conjunctivitis disappear. With repeated administration of the drug to patients with COPD in a daily dose of 36 μg for 4 weeks, only a feeling of dry mouth was noted.

Storage conditions

at temperatures up to 25 ° C. Do not allow capsules to heat, freeze or be exposed to direct sunlight. After opening, the contents of the blister should be used within 9 days. Registration number:P No. 014410/01 dated 19.11.2007

Trade (proprietary) name: Spiriva ®

International non-proprietary name:tiotropium bromide

Dosage form:

Powder capsules for inhalation
Composition

1 capsule contains active substance: tiotropium bromide monohydrate 0.0225 mg tiotropium equivalent 0.0180 mg

excipients: lactose monohydrate, 200 M 5.2025 mg; lactose monohydrate micronized 0.2750 mg.

The composition of the capsule (mg / capsule): macrogol 2.4000 mg, indigo carmine (E132) 0.0120 mg, titanium dioxide (E171) 1.0240 mg, iron oxide yellow (E172) 0.0120 mg, gelatin 44.5160 mg

Description
Hard gelatin capsules, size 3, light greenish blue, opaque, imprinted with the company symbol and TI01 in black ink Capsule contents - white powder.

Pharmacotherapeutic group:M-holinoblokator.

ATC code:RO3BB04

Pharmacological properties

Tiotropium bromide is a long-acting antimuscarinic drug m-anticholinergic, in clinical practice often referred to as an anticholinergic agent. It has the same affinity for the various subtypes of muscarinic receptors from M 1 to M 5. Inhibition of M 3 receptors in the airways results in relaxation of smooth muscles. The bronchodilating effect is dose-dependent and persists for at least 24 hours. The significant duration of action is probably associated with a very slow dissociation from M 3 receptors, compared with ipratropium bromide. When administered by inhalation, tiotropium bromide as an N-quaternary anticholinergic agent has a local selective effect, while at therapeutic doses it does not cause systemic m-anticholinergic side effects. Dissociation from M 2 receptors occurs faster than from M 3. High affinity for receptors and slow dissociation cause a pronounced and prolonged bronchodilatory effect in patients with chronic obstructive pulmonary disease.

Bronchodilation after inhalation of tiotropium bromide is a local, not systemic, effect.

It has been shown that SPIRIVA significantly increases lung function (forced expiratory volume in 1 second FEV1, forced vital capacity of the lungs FVC) 30 minutes after a single dose for 24 hours. Pharmacodynamic equilibrium was achieved within the first week, and a pronounced bronchodilatory effect was observed on day 3. SPIRIVA significantly increases the morning and evening peak expiratory flow rate measured by patients. The bronchodilating effect of SPIRIVA, assessed throughout the year, did not reveal any manifestations of tolerance.

SPIRIVA significantly reduces shortness of breath throughout the treatment period. SPIRIVA was shown to significantly improve exercise tolerance compared to placebo in two randomized, double-blind, placebo-controlled studies.

SPIRIVA significantly reduces the number of exacerbations of COPD, and increases the period to the moment of the first exacerbation compared with placebo.

SPIRIVA significantly improves the quality of life. This improvement is observed throughout the treatment period.

SPIRIVA has been shown to significantly reduce the number of hospitalizations associated with exacerbation of COPD and increase the time to the first hospitalization. It has also been shown that SPIRIVA leads to a persistent improvement in FEV1 after application for 4 years without changing the rate of annual decline in FEV1. During treatment, there is a 16% reduction in the risk of death.

Compared with salmeterol, the use of SPIRIVA increases the time to the first exacerbation (187 days versus 145), with a decrease in the risk of exacerbations by 17% (hazard ratio 0.83; 95% confidence interval [CI], FRT 0.77 to 0, 90; P< 0,001). Также прием Спиривы® увеличивает время наступления первого тяжелого (требующего госпитализации) обострения (отношение рисков 0,72; 95 % ДИ от 0,61 до 0,85; Р< 0,001) снижает ежегодное число средних или тяжелых (требующих госпитализации) обострений (0,64 против 0,72; отношение рисков 0,89; 95 % ДИ от 0,83 до 0,96; Р= 0,002), снижает ежегодное число тяжелых (требующих госпитализации) обострений (0,09 против 0,13; отношение рисков 0,73; 95 % ДИ от 0,66 до 0,82; Р< 0,001)

Pharmacokinetics

Tiotropium is a quaternary ammonium compound, moderately soluble in water. Absorption: When administered by inhalation, the absolute bioavailability of tiotropium is 19.5%, indicating that the fraction of the drug reaching the lungs is highly bioavailable. Tiotropium in solution when taken orally has an absolute bioavailability equal to 2-3%. Food intake does not affect the absorption of tiotropium. The maximum concentration of tiotropium in plasma (C max) after inhalation is reached after 5-7 minutes. At the stage of dynamic equilibrium, the peak plasma concentration of tiotropium in patients with COPD is 12.9 pg / ml and decreases rapidly. This indicates a multi-compartment distribution of the drug. At the stage of dynamic equilibrium, the basal concentration of tiotropium in blood plasma is 1.71 pg / ml

Distribution. 72% of the taken dose of the drug binds to plasma proteins and the volume of distribution is 32 l / kg. Studies have shown that tiotropium does not cross the blood-brain barrier.

Biotransformation: The degree of biotransformation is negligible. This is confirmed by the fact that after intravenous administration of the drug to healthy young volunteers, 74% of the unchanged substance is found in the urine. Tiotropium is cleaved in a non-enzymatic manner to the alcohol N-methylscopine and dithienyl glycolic acid, which do not bind to muscarinic receptors.

Studies have shown that the drug (< 20 % от дозы после внутривенного применения) метаболизируется цитохромом P450, этот процесс зависит от оксидации и последующей коньюгации с глютатионом с образованием различных метаболитов. Нарушение метаболизма может иметь место при использовании ингибиторов CYP 450 2D6 и 3А4 (хинидина, кетоконазола и гестодена). Таким образом, CYP 450 2D6 и 3А4 включаются в метаболизм препарата. Тиотропий даже в сверхтерапевтических концентрациях не ингибирует цитохром Р450, 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1, или 3А в микросомах печени человека.

Withdrawal: The half-life of tiotropium after inhalation varies from 27 to 45 hours. The total clearance for intravenous administration to healthy young volunteers is 880 ml / min. Tiotropium after intravenous administration is mainly excreted by the kidneys unchanged (74%). After inhalation of dry powder at the stage of dynamic equilibrium, renal excretion is 7% per day of the dose, the remaining non-absorbed part is excreted through the intestines. The renal clearance of tiotropium exceeds the clearance of creatinine, which indicates the tubular secretion of the drug. After long-term administration of the drug once a day by patients with COPD, the pharmacokinetic equilibrium is achieved on day 7, with no further accumulation observed.

Tiotropium has linear pharmacokinetics within therapeutic limits, regardless of the dosage form of the drug. Elderly patients:

In patients with COPD and mild renal impairment (creatinine clearance 50-80 ml / min), inhalation of tiotropium once a day at the stage of dynamic equilibrium led to an increase in AUC 0-6 by 1.8-30%. The C max value remained the same as in patients with normal renal function (creatinine clearance\u003e 80 ml / min). In patients with COPD and moderate or severe renal impairment (creatinine clearance< 50 мл/мин) внутривенное введение тиотропия приводило к двукратному увеличению концентрации препарата в плазме (значение AUC 0- 4ч увеличивалось на 82 % а значение C max увеличивалось на 52 %) по сравнению с пациентами с ХОБЛ и нормальной функцией почек. Аналогичное повышение концентрации тиотропия в плазме отмечалось и после ингаляции сухого порошка.

Patients with impaired liver function: It is assumed that liver failure will not have a significant effect on the pharmacokinetics of tiotropium, since tiotropium is mainly excreted by the kidneys, and by non-enzymatic cleavage of ether bonds, with the formation of metabolites that do not bind to muscarinic receptors.

Indications
Spiriva is indicated as supportive therapy in patients with COPD, including chronic bronchitis and emphysema (supportive therapy for persistent dyspnea and to prevent exacerbations).

Contraindications
Hypersensitivity to atropine or its derivatives (for example, ipratropium or oxytropium) or to the components of this drug (in particular, to lactose monohydrate, which contains milk protein, due to lactase deficiency, lactose intolerance, glucose-galactose malabsorption); I trimester of pregnancy; children under 18 years old.

Carefully

Angle-closure glaucoma, prostatic hyperplasia, bladder neck obstruction.

Pregnancy and lactation

As a precautionary measure, it is preferable to refrain from using SPIRIVA during pregnancy.

Clinical data on the use of tiotropium in women who are breastfeeding are not available. In preclinical studies, data have been obtained that, a small amount of tiotropium is excreted in breast milk.

SPIRIVA should not be used in pregnant or breastfeeding women, unless the expected benefit outweighs the potential risk to the fetus or baby.

Method of administration and dosage
Inhalation
When using Spiriva in the form of inhalations using the HandiHaler ® device, it is recommended to use one capsule per day at the same time.

The drug does not need to be swallowed.

Elderly patients should take Spiriva at the recommended doses. Patients with impaired renal function can use Spiriva at the recommended doses. However, careful monitoring of patients with moderate or severe renal insufficiency receiving Spiriva is necessary (as is the case with other drugs, which are mainly excreted by the kidneys). Patients with hepatic impairment can take Spiriva at the recommended doses.

Instructions for using the HandiHaler ® device

The HandiHaler® has been specially designed for Spiriva. It should not be used to take other medicines. You can use your HandiHaler ® for one year.

HandiHaler ® device includes:

dustproof cap;
mouthpiece;
base;
piercing button;
central camera.

Using the HandiHaler device

Open the dust cap by pushing the piercing button fully and then releasing

Open the dust cap fully by lifting it up. Then open the mouthpiece by lifting it up.

Remove the Spiriva capsule from the blister (just before use) and place it in the central chamber as shown in the figure. It does not matter which side the capsule is placed in the chamber.

Close the mouthpiece tightly until it clicks, leave the dust-proof cap open.

While holding HandiHaler ® with the mouthpiece up, press the piercing button fully once and then release.
Thus, an opening is formed through which the drug is released from the capsule during inhalation.

Exhale completely.
Warning: never exhale into the mouthpiece.

Take HandiHaler® in your mouth and press your lips tightly around the mouthpiece. Keeping your head straight, inhale slowly and deeply, but at the same time with sufficient force to hear the vibration of the capsule. Inhale until the lungs are full; then hold your breath until you feel discomfort while removing HandiHaler® from your mouth. Continue breathing calmly again. Repeat procedures 6 and 7 to completely empty the capsule.

Open the mouthpiece again. Remove and discard the used capsule. Close the mouthpiece and dust cap for storing your HandiHaler.

Clean HandiHalera ® once a month.

Open the mouthpiece and dust cap. Then open the base of the instrument by lifting the piercing button. Rinse the inhaler thoroughly in warm water until the powder is completely removed. Wipe the HandiHaler ® with a paper towel and, with the mouthpiece, base and dust cap open, leave to air dry for 24 hours. After cleaning the device according to the instructions, it will be ready for the next use. If necessary, the outside of the mouthpiece can be cleaned with a damp but not wet cloth.

Opening the blister
Peel off the blister strip along the perforated line.

Open the blister strip just before use so that one capsule is completely visible. If the second capsule was accidentally opened (exposed to air), do not use it.

Take out the capsule.

Capsules must not be exposed to high temperatures, neither in the device nor in the blister. the action of sunlight, etc. The capsule contains a small amount of powder - therefore, the capsule is not completely filled.

Side effects

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

Metabolic and nutritional disorders

dehydration*

Gastrointestinal disorders

often (≥1% and< 10 %) - сухость во рту, обычно легкой степени выраженности;

infrequently (≥0.1% and< 1 %) - стоматиты; запор, гастроэзофагеальный рефлюкс;

rarely (≥0.01% and< 0,1 %) - кандидоз ротоглотки, гингивиты, глосситы; кишечная

obstruction, including paralytic ileus, dysphagia.

Respiratory, Chest and Mediastinal Disorders

infrequently (≥0.1% and< 1 %) - дисфония, кашель, фарингиты;

rarely (≥0.01% and< 0,1 %) - пародоксальный бронхоспазм, ларингиты, синуситы, носовое кровотечение.

Cardiovascular disorders

infrequently (≥0.1% and< 1 %) - мерцательная аритмия;

rarely (≥0.01% and< 0,1 %) - тахикардия (включая суправентрикулярную тахикардию), ощущение сердцебиения.

Kidney and urinary tract disorders

infrequently (≥0.1% and< 1 %) - затрудненное мочеиспускание и задержка мочеиспускания (у мужчин с предрасполагающими факторами); дизурия;

rarely (≥0.01% and< 0,1 %) - инфекции мочевыводящих путей.

Allergic reactions

infrequently (≥0.1% and< 1 %) - сыпь;

rarely (≥0.01% and< 0,1 %) - крапивница, зуд, реакции повышенной чувствительности,

including immediate reactions. Angioneurotic edema *.

Skin disorders

skin infections and skin ulcers, dry skin *.

The musculoskeletal system and related connective tissue diseases

swelling of the joints *.

Nervous system disorders

infrequently (≥0.1% and< 1 %) - головокружение;

rarely (≥0.01% and< 0,1 %) - бессонница.

Violations of the organ of vision infrequently

(≥0.1% and< 1 %) - нечеткое зрение;

rarely (≥0.01% and< 0,1 %) - повышение внутриглазного давления, глаукома.

* in the combined database of clinical trials, these adverse reactions were not identified; there were only isolated reports of these adverse reactions with the widespread use of the drug, however, the connection with the m-anticholinergic effect of SPIRIVA has not been proven; the frequency of these rare events is difficult to assess.

Overdose

When using high doses, manifestations of anticholinergic action are possible. However, systemic anticholinergic side effects were not detected after a single inhalation dose of up to 282 μg of tiotropium when taken to healthy volunteers.

Bilateral conjunctivitis combined with dry mouth was observed in healthy volunteers after repeated administration of a single daily dose of 141 μg, which disappeared with continued treatment. In a study that examined the effect of repeated doses of tiotropium in COPD patients who received a maximum of 36 mcg for more than 4 weeks, dry mouth was the only side effect.

Acute intoxication associated with accidental ingestion of capsules is unlikely due to the low bioavailability of the drug.

Interaction with other medicinal products
It is possible to use tiotropium in combination with other drugs commonly used to treat COPD: sympathomimetics, methylxanthines, oral and inhaled glucocorticosteroids. Combined use with long-acting beta2-agonists, inhaled glucocorticosteroids and their combinations does not affect the effect of tiotropium.

Limited information about the joint use with anticholinergic drugs was obtained from 2 clinical studies: a single administration of one dose of ipratropium bromide against the background of constant administration of Spiriva in patients with COPD (64 patients) and in healthy volunteers (20 people) did not lead to a decrease in adverse reactions, changes in vital parameters and electrocardiogram. However, chronic concomitant use of anticholinergics and Spiriva has not been studied and is therefore not recommended.

special instructions
Spiriva - as a bronchodilator used once a day for maintenance treatment, should not be used as initial therapy for acute attacks of bronchospasm, i.e. in urgent cases.

After inhalation of Spiriva powder, immediate hypersensitivity reactions may develop.
Inhalation of the drug can lead to bronchospasm.

Patients with moderate or severe renal impairment (creatinine creatinine clearance< 50мл/мин) при приеме СПИРИВЫ следует тщательно наблюдать, как это необходимо и в других случаях назначения лекарств, экскретирующихся преимущественно почками.

Patients should be familiar with the rules for using Spiriva capsules. Do not let the powder get into your eyes. Eye pain or discomfort, blurred vision, visual halos combined with eye redness, conjunctival congestion and corneal edema may indicate an acute attack of angle-closure glaucoma. If any combination of these symptoms develops, you should immediately consult a specialist. The use of drugs that cause miosis is not an effective treatment in this case.

Spirivu should not be used more than once a day.
Spiriva capsules should only be used with the HandiHaler® device.
One dose / capsule contains 5.5 mg of lactose monohydrate.

Impact on the ability to drive a car or operate machinery.
There have been no studies examining this effect. Dizziness and blurred vision while taking the drug can have this effect.

Release form
Powder capsules for inhalation 18 mcg.
10 capsules in a PVC / aluminum foil blister. 1,3 or 6 blisters complete with a HandiHaler inhaler, or without an inhaler, with instructions for use, are placed in a cardboard box.

Storage conditions
At a temperature not higher than 25 ° C. Do not freeze. Keep out of the reach of children!

Shelf life
24 months.
Do not use after the expiration date stated on the package.
After opening, use the blister within 9 days.

Terms of dispensing from pharmacies
With a doctor's prescription.

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co.KG, Germany Binger Strasse 173 55216 Ingelheim am Rhein, Germany

You can get additional information about the drug, as well as send your claims and information about adverse events to the following address in Russia

OOO Boehringer Ingelheim 125171, Moscow, Leningradskoe shosse, 16A, building 3

When administered by inhalation, tiotropium, as an anticholinergic agent of the N-quaternary structure, has a local selective effect, while at therapeutic doses it does not cause systemic anticholinergic side effects. The release of tiotropium from binding to M2 receptors is faster than from binding to M3 receptors.

The high affinity for the receptors and the slow release from the connection with them cause an intense and long-lasting bronchodilating effect in patients with chronic obstructive pulmonary disease (COPD). Bronchodilation after inhalation of tiotropium is a local and not a systemic effect.

In clinical studies, it has been shown that Spiriva significantly improves lung function (forced expiratory volume in 1 sec / FEV1 / and forced vital capacity / FVC /) 30 minutes after a single dose for 24 hours.

Pharmacodynamic equilibrium was achieved during the 1st week, and a pronounced bronchodilatory effect was observed on the 3rd day. Spiriva significantly increases the morning and evening peak expiratory flow rate measured by patients. The bronchodilating effect of Spiriva, assessed throughout the year, did not reveal manifestations of tolerance.

Spiriva significantly reduces the frequency of exacerbations of COPD and increases the period to the moment of the first exacerbation, compared with placebo. Significantly improves the quality of life, which is observed during the entire period of treatment. Spiriva significantly reduces the number of hospitalizations associated with exacerbation of COPD, and increases the time until the first hospitalization.

Pharmacokinetics
Tiotropium is a quaternary ammonium compound, moderately soluble in water. After inhalation in powder form in the therapeutic dose range, it is characterized by linear pharmacokinetics.

When administered by inhalation, the absolute bioavailability of tiotropium is 19.5%, which indicates a high bioavailability of the fraction of the drug reaching the lungs. C max in blood plasma is reached 5 minutes after inhalation. Tiotropium is poorly absorbed from the gastrointestinal tract. For the same reason, food intake does not affect the absorption of tiotropium.

When taken orally tiotropium in the form of a solution, the absolute bioavailability was 2-3%. Plasma protein binding - 72%. Vd - 32 l / kg. In the equilibrium state, C max in blood plasma in patients with COPD is 17-19 pg / ml 5 minutes after inhalation of the powder at a dose of 18 μg and decreases rapidly. Css in blood plasma was 3-4 pg / ml. Does not penetrate the BBB.

The degree of biotransformation is negligible. Tiotropium is cleaved non-enzymatically to alcohol-N-methylscopine and dithienyl glycolic acid, which do not bind to muscarinic receptors. A metabolic disorder is possible with the use of inhibitors of isoenzymes of the cytochrome P450 system CYP2D6 and 3A4 (quinidine, ketoconazole, gestodene).

Tiotropium, even at supertherapeutic concentrations, does not inhibit cytochrome P450 isoenzymes 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1 or 3A4 in human liver microsomes.

After inhalation, terminal T 1/2 is 5-6 days. After inhalation of the powder, renal excretion is 14%, the rest, not absorbed in the intestine, is excreted in the feces. The renal clearance of tiotropium exceeds the CC, which indicates the tubular secretion of the drug.

After long-term administration of the drug 1 time / day in patients with COPD, the equilibrium state of pharmacokinetic parameters is achieved after 2-3 weeks, while no further cumulation is observed. Tiotropium is excreted mainly in the urine unchanged - 74%.
- Pharmacokinetics in special clinical situations
  In elderly patients, there is a decrease in renal clearance of tiotropium (326 ml / min in patients with COPD up to 58 years old, up to 163 ml / min in patients with COPD over 70 years old), which is apparently due to a decrease in renal function with age. After inhalation, urinary tiotropium excretion decreases from 14% (young healthy volunteers) to 7% (patients with COPD), however, in elderly patients with COPD, no significant changes in plasma concentration were observed, if we take into account the inter- and intraindividual variability (after inhalation powder increase in AUC0-4 by 43%).
  
  In case of impaired renal function after inhalation use, the concentration of the drug in the blood plasma increases and renal clearance decreases. With a mild decrease in renal function (CC 50-80 ml / min), often observed in elderly patients, the increase in the concentration of tiotropium in the blood plasma is insignificant.
- From the urinary system
  Difficulty urinating and urinary retention (in men with predisposing factors).
- Allergic reactions
  Hypersensitivity reactions, including isolated cases of angioedema.
- Others
  Blurred vision, acute glaucoma are possible.
Most of the above adverse reactions can be associated with the anticholinergic effect of Spiriva.

Interaction
It is possible to prescribe Spiriva in combination with other drugs commonly used to treat COPD: sympathomimetics, methylxanthine derivatives, oral and inhaled corticosteroids.

Overdose
- Symptoms: minor manifestations of systemic anticholinergic action are possible - dry mouth, accommodation disturbances, increased heart rate. After inhalation of a single dose of up to 282 μg, no systemic anticholinergic effects were observed in healthy volunteers. After repeated administration of a single daily dose of 141 μg in healthy volunteers, bilateral conjunctivitis was observed in combination with dry mouth, which disappeared with continued treatment. In a study examining the effects of tiotropium with repeated use in patients with COPD who received a maximum of 36 mcg of the drug for more than 4 weeks, dry mouth was the only side effect. Acute intoxication associated with accidental ingestion of capsules inside is unlikely due to the low bioavailability of the drug.
- Treatment: symptomatic.

Precautionary measures
The drug Spiriva is not intended to relieve acute attacks of bronchospasm. After inhalation of Spiriva powder, immediate allergic reactions may develop.

Use with caution in patients with angle-closure glaucoma, prostatic hyperplasia, or bladder neck obstruction.

The inhalation process can cause bronchospasm. Elderly patients should take the drug in the recommended doses.

In case of impaired renal function, patients can use Spiriva in recommended doses. However, when Spiriva is prescribed in combination with other drugs that are excreted mainly by the kidneys, it is necessary to monitor the condition of patients. Patients with moderate or severe renal impairment (creatinine clearance ≤ 50 ml / min) should be closely monitored.

Patients with hepatic impairment can take the drug in the recommended doses.

Patients should be familiarized with the rules for using the inhaler.

Do not let the powder get into your eyes. Eye pain or discomfort, blurred vision, visual halos in combination with eye redness, conjunctival congestion and corneal edema may indicate an acute attack of angle-closure glaucoma. If any combination of these symptoms develops, the patient should immediately see a doctor. The use of only drugs that cause miosis is not an effective treatment in this case.

Formula: C19H22BrNO4S2, chemical name: (1R, 2R, 4S, 5S, 7S) -7-9,9-dimethyl-3-oxa-9-azoniatricyclo nonane bromide monohydrate.
Pharmacological group: vegetotropic agents / anticholinergics / m-anticholinergics.
Pharmachologic effect: bronchodilating, anticholinergic.