Tiotropium-Native caps 18mcg #30

Tiotropium-Native instruction

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Composition and form of the preparation

Capsules with powder for inhalation solid No. 3, with a slightly yellowish hue, clear, colorless; the contents of the capsules are white or almost white powder.
1 caps.
tiotropium bromide monohydrate 22.5 μg
which corresponds to a tiotropium content of 18 μg
Excipients: sodium benzoate - 20 mcg, lactose monohydrate - 10 mg.
Solid Capsules №3: hypromellose - 100%.
10 pieces. - contour-packed cells (1) together with the device for inhalation or without it. - packs cardboard.
10 pieces. - contoured cellular packaging (3) together with the device for inhalation or without it. - packs cardboard.
10 pieces. - contoured cellular packaging (6) together with the device for inhalation or without it. - packs cardboard.

pharmachologic effect

A bronchodilator is a blocker of long-acting m-cholinergic receptors.
Has the same affinity for different subtypes of m-cholinergic receptors from M1 to M5. As a result of inhibition of M3 receptors in the airways, the smooth muscle relaxes. The bronchodilator effect is dose dependent and persists for at least 24 hours. Significant duration of action is probably associated with a very slow release from association with M3 receptors, as compared to ipratropium bromide. When inhaled tiotropium bromide, as an anticholinergic agent 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 M2 receptors occurs faster than from the bond with the M3 receptors. High affinity for receptors and slow release from communication with them cause intensive and prolonged bronchodilator effect in patients with COPD.
Bronchodilation after inhalation of tiotropium bromide is a consequence of local rather than systemic action.
In clinical studies, it was shown that 30 minutes after a single dose of tiotropium bromide for 24 hours significantly improves lung function (increased FEV1 and FVC). Pharmacodynamic equilibrium was achieved during the 1 st week, and pronounced bronchodilator effect was observed on the 3rd day. Tiotropium bromide significantly increases the morning and evening peak flow rate of exhalation, measured by patients. During the year there was no tolerance of bronchodilator effect.
Tiotropium bromide significantly reduces the frequency of exacerbations of COPD and prolongs the period until the moment of the first exacerbation compared with placebo. Significantly improves the quality of life, which is observed throughout the treatment period. Tiotropium bromide significantly reduces the number of hospitalizations associated with exacerbation of COPD, and increases the time until the first hospitalization.

Pharmacokinetics

Tiotropium bromide is a quaternary ammonium compound, sparingly soluble in water.
Tiotropium bromide has a linear pharmacokinetics within therapeutic limits after intravenous administration and inhalation of dry powder.
With inhalation, the absolute bioavailability of tiotropium bromide is 19.5%, which indicates a high bioavailability of the fraction of Tiotropium-Native reaching the lungs. Cmax in blood plasma is reached 5 minutes after inhalation. Tiotropium bromide is poorly absorbed from the digestive tract. For the same reason, eating does not affect the absorption of tiotropium. When ingested tiotropium bromide in the form of a solution, the absolute bioavailability was 2-3%.
Binding to plasma proteins - 72%. Vd is 32 l / kg. In the equilibrium state, Cmax in blood plasma in patients with COPD is 17-19 pg / ml 5 min after inhalation of the powder at a dose of 18 mcg and rapidly decreases. Css in blood plasma was 3-4 pg / ml.
Does not penetrate the BBB.
The degree of biotransformation is insignificant. Tiotropium bromide is cleaved non-enzymatically to alcohol N-methylscopic and dithienylglycolic acid, which do not bind to muscarinic receptors.
A metabolic disorder is possible with the use of inhibitors of isoenzymes CYP2D6 and 3A4 (quinidine, ketoconazole, gestodene). Thus, the isozymes CYP2D6 and 3A4 are included in the metabolism of the drug. Tiotropium bromide does not inhibit cytochrome P450 isoenzymes 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1 or 3A4 in human liver microsomes even in super therapeutic concentrations.
After inhalation, the terminal T1 / 2 is 5-6 days. The total clearance for IV induction to healthy young volunteers is 880 ml / min, with an individual variability of 22%. Tiotropium bromide after intravenous administration is excreted, mainly with urine unchanged - 74%. After inhalation of the powder, renal excretion is 14%, the rest, not absorbed in the intestine, is excreted with feces. Renal clearance of tiotropium bromide exceeds QC, which indicates tubular secretion of Tiotropium-Native. After a long administration of the drug 1 time / day in patients with COPD, the equilibrium state of the pharmacokinetic parameters is achieved after 2-3 weeks, with no further cumulation observed.
In elderly patients, there is a decrease in renal clearance of tiotropium bromide (326 ml / min in patients with COPD to 58 years, to 163 ml / min in patients with COPD over 70 years), which is apparently due to a decrease in kidney function with age. After inhalation, the excretion of tiotropium bromide in urine decreases from 14% (young healthy volunteers) to 7% (patients with COPD), but in elderly patients with COPD no significant changes in plasma concentration were observed when inter- and intra-individual variability powder inhalation increase AUC0-4 by 43%).
If the renal function is disturbed after inhalation and / or administration, the concentration of Tiotropium-Native in the blood plasma increases and the kidney clearance decreases. With mild renal impairment (CK 50-80 ml / min), often observed in elderly patients, an increase in tiotropium bromide concentration in the blood plasma is insignificant (after IV introduction, the AUC0-4 increase by 39%). In patients with COPD with an average or severe decrease in renal function (CK <50 ml / min) after iv injection of ipratropium bromide, a double increase in plasma concentration (82% increase in AUC0-4) was observed compared with plasma concentrations blood, determined after the inhalation of dry powder.

Indications

As maintenance therapy in patients with COPD, including chronic bronchitis and emphysema (maintenance therapy with persistent dyspnea and to prevent exacerbations).

Contraindications

I trimester of pregnancy; children and adolescents under 18; hypersensitivity to tiotropium bromide; increased sensitivity to atropine or its derivatives (including to ipratropium and oxotropy).

Dosage

Apply in the form of inhalations 1 time / day. The dose depends on the dosage form used.

Side effects of Tiotropium-Native

On the part of the digestive system: a slight dry mouth, often disappears with continued treatment (≥ 1% and <10%); candidiasis of the oral cavity (≥ 0.1% and <1%); constipation, gastroesophageal reflux (≥ 0.01% and <1%); in isolated cases - intestinal obstruction (including paralytic ileus), dysphagia.
On the part of the respiratory system: dysphonia, bronchospasm, cough and local irritation of the pharynx (≥ 0.1% and <1%); nasal bleeding (≥ 0.01% and <1%).
From the cardiovascular system: tachycardia, palpitations (≥ 0.01% and <1%); in single cases - supraventricular tachycardia, atrial fibrillation.
From the side of the central nervous system: dizziness (≥ 0.1% and <1%).
From the urinary system: difficulty urinating and urinary retention in men with predisposing factors, urinary tract infections (≥ 0.01% and <1%).
Allergic reactions: rash, hives, itching, hypersensitivity reactions, including immediate-type reactions (≥ 0.01% and <1%); in isolated cases - angioedema.
Other: in single cases - blurred vision, increased intraocular pressure (≥ 0.01% and <1%); glaucoma.
Most of the above adverse reactions may be associated with the anticholinergic action of tiotropium bromide.

Drug Interactions

The constant combined use of anticholinergics and tiotropium bromide has not been studied and is therefore not recommended.

special instructions for Tiotropium-Native

With caution should be used with zakratougolnoy glaucoma, prostatic hyperplasia, obstruction of the neck of the bladder.
It is not intended for relief of acute attacks of bronchospasm.
After inhalation, it is possible to develop immediate-type hypersensitivity reactions.
The process of inhalation can cause bronchospasm.
During the period of treatment, the condition of patients with renal insufficiency should be carefully monitored (CK ≤ 50 ml / min).

Impact on the ability to drive vehicles and manage mechanisms

Studies to study the effect of the drug on the ability to drive vehicles and control mechanisms have not been conducted. Causes of dizziness and blurred vision while using Tiotropium-Native may have a negative effect on the above ability.

Pregnancy and lactemia

Contraindicated in the first trimester of pregnancy.
In the second and third trimesters of pregnancy and during lactation, tiotropium bromide should be used only in cases where the expected benefit of therapy for the mother exceeds the potential risk to the fetus or infant.

Terms of sell

To buy Tiotropium-Native you don't need a prescription.