Tiotropium native
Tiotropium-native: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Tiotropium-nativ
ATX code: R03BB04
Active ingredient: tiotropium bromide (Tiotropium Bromide)
Manufacturer: JSC Pharmstandard-Leksredstva (Russia); Nativa LLC (Russia)
Description and photo update: 2019-08-07
Prices in pharmacies: from 1861 rubles.
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Tiotropium-native is a bronchodilator, long-acting m-cholinergic receptor blocker.
Release form and composition
The drug is available in the form of capsules with powder for inhalation: No. 3, with a hard transparent shell, colorless or with a yellow tint, the contents of the capsules are almost white or white powder (10 pcs. In blisters, in a cardboard box 1, 3 or 6 packs complete with or without inhalation device and instructions for the use of Tiotropium-native).
1 capsule contains:
- active substance: tiotropium bromide monohydrate - 22.5 mcg (equivalent to tiotropium content - 18 mcg);
- auxiliary components: lactose monohydrate, sodium benzoate;
- capsule shell: hypromellose.
Pharmacological properties
Pharmacodynamics
Tiotropium-native is a bronchodilator. Its active ingredient, tiotropium bromide, is a long-acting m-anticholinergic blocker with the same affinity for different subtypes of muscarinic receptors from M 1 to M 5. Relaxation of airway smooth muscle results from inhibition of M 3 receptors. The bronchodilatory (bronchodilatory) effect depends on the dose of tiotropium bromide and lasts for 24 hours. This prolonged action is associated with a very slow dissociation of the active substance from M 3-receptors compared to ipratropium bromide. Tiotropium bromide is an N-quaternary anticholinergic agent, therefore, when administered by inhalation, it has a selective local effect and does not cause systemic undesirable m-anticholinergic reactions in the recommended therapeutic doses. Dissociation of tiotropium bromide from M 3 receptors occurs more slowly than from M 2. In chronic obstructive pulmonary disease (COPD), the pronounced long-term bronchodilating effect of the drug is due to its high affinity for receptors and slow dissociation. After inhalation of tiotropium bromide, bronchodilation is a consequence of not systemic, but local action.
A single dose of tiotropium bromide significantly improves lung function after 0.5 hours, providing an increase in forced expiratory volume in 1 second (FEV 1) and forced vital capacity (FVC) for 24 hours. A pronounced bronchodilatory effect is achieved after 72 hours, pharmacodynamic equilibrium occurs within 168 hours after starting therapy. There is a significant increase in the morning and evening peak expiratory flow rate (PEF).
With prolonged (within a year) use, the effectiveness of Tiotropium-native in relation to bronchodilation does not decrease.
Throughout the entire period of treatment with tiotropium bromide, there is a significant decrease in dyspnea, an improvement in exercise tolerance, a significant decrease in the frequency of exacerbations of COPD and an increase in the period until the first exacerbation, a significant decrease in the number of hospitalizations of patients with exacerbation of COPD, and an increase in the period until the first hospitalization. The use of tiotropium bromide for four years leads to a permanent improvement in FEV 1, while there is no change in the rate of annual decline in FEV 1.
Compared with taking salmeterol, during treatment with tiotropium bromide, the risk of death is reduced by 16%, the period before the first exacerbation with a decrease in the risk of exacerbations increases by 17%.
Pharmacokinetics
After inhalation of tiotropium bromide, its absolute bioavailability is about 19%, which indicates a high bioavailability of the fraction reaching the lungs. The maximum concentration of the substance in the blood plasma (C max) is reached in 5–7 minutes. In patients with COPD, the C max of tiotropium bromide in the equilibrium state is about 12 pg / ml and decreases rapidly, this indicates its inherent multi-compartment type of distribution. The basal concentration of tiotropium bromide in blood plasma at steady state is about 1.71 pg / ml.
Plasma protein binding - 72%. The volume of distribution is 32 l / kg. Tiotropium bromide does not overcome the blood-brain barrier.
The degree of biotransformation is negligible. As a result of non-enzymatic cleavage by ether bonds, ethanol-N-methylscopine and dithienyl glycolic acid are formed, which do not bind to muscarinic receptors. The metabolism of the active substance can be disrupted with the simultaneous use of gestodene, quinidine, ketoconazole, which are inhibitors of the isoenzymes CYP2D6 and CYP3A4, which indicates their participation in the metabolism of tiotropium bromide. The drug, used even in supertherapeutic concentrations, does not inhibit CYP isoenzymes 1A1, 1A2, 3A4, 2B6, 2C9, 2C19, 2D6 or 2E1 in liver microsomes.
After inhalation, T 1/2 (half-life) of tiotropium bromide can be from 27 to 45 hours. Renal clearance exceeds creatinine clearance, indicating tubular secretion of tiotropium bromide. Pharmacokinetic equilibrium in patients with COPD against the background of the use of Tiotropium-native 1 time per day is achieved on day 7, while no cumulation is observed.
Within the therapeutic dose range, tiotropium bromide exhibits linear pharmacokinetics.
It is excreted through the kidneys within 24 hours up to 7% of the dose, through the intestines - the rest.
In elderly patients with COPD against the background of a decrease in renal clearance (up to 365 ml / min in patients with COPD under 65 years of age and up to 271 ml / min in patients with COPD from 65 years of age and older), the corresponding variation in such characteristics of tiotropium bromide as C max and AUC 0-6h (area under the pharmacokinetic curve "concentration - time" for the period from 0 to 6 hours) in the blood does not occur.
Features of pharmacokinetics in patients with impaired renal function:
- mild renal failure with creatinine clearance (CC) 50-80 ml / min: inhalation of tiotropium bromide once a day in an equilibrium state causes an increase in the AUC value of 0-6 hours to 30%, while C max does not change;
- moderate or severe renal failure (CC less than 50 ml / min): there is a twofold increase in the concentration of the substance in the blood plasma compared with patients with normal renal function.
In case of impaired liver function, a significant change in the pharmacokinetics of tiotropium bromide is unlikely, due to its preferential excretion by the kidneys and the formation of metabolites using non-enzymatic cleavage of ether bonds.
Indications for use
The use of Tiotropium-native is indicated as a maintenance therapy in patients with COPD, including those with chronic bronchitis and emphysema (to prevent exacerbations and with persistent shortness of breath).
Contraindications
Absolute:
- lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;
- I trimester of pregnancy;
- age up to 18 years;
- hypersensitivity to atropine (including ipratropium, oxytropium and its other derivatives) and other components of the drug.
Caution should be exercised when prescribing Tiotropium-native to patients with angle-closure glaucoma, bladder neck obstruction, prostatic hyperplasia, moderate and severe renal failure (CC less than 50 ml / min).
It is not recommended to use tiotropium bromide during pregnancy or lactation, unless the expected therapeutic effect for the mother outweighs the possible threat to the fetus or child.
Tiotropium-native, instructions for use: method and dosage
The capsules are not intended for oral administration. You cannot swallow them!
Tiotropium-native is used in the form of inhalations using the Inhaler CDM inhaler.
The Inhaler CDM inhaler is a single-dose device for administering a drug by inhalation - a plastic device about 6 cm high. It is very easy to use, equipped with a movable upper part and a retractable capsule compartment that allow you to dose and inhale very small doses of the drug while performing active inhalation through the mouthpiece.
For the correct dosage of Tiotropium-native when using the Inhaler CDM inhaler, the following sequence of actions must be observed:
- Remove the transparent cap from the device.
- Firmly holding the inhaler with one hand, with the index finger of the other hand, press on the "press" inscription in the moving part of the device and move the capsule compartment in the opposite direction.
- After opening the compartment, insert the capsule with the drug into a special slot (depression).
- While holding the Inhaler CDM in an upright position, make sure the capsule is in the correct position in the slot and close the compartment. To do this, press it with your thumb in the opposite direction until it stops. A click sound indicates that the device is ready for inhalation.
- To pierce the capsule inside the device, you must press the mouthpiece with force (the arrow on the body should disappear beyond the boundaries of the lower part of the device to the upper line) and release it. At this moment, access to the contents of the capsule opens into the mouthpiece lumen.
- You must exhale before inhalation. You cannot breathe out through the mouthpiece.
- Squeezing the mouthpiece of the device with your teeth and clasping it tightly with your lips, take a deep and strong breath through your mouth. At this moment, a vibrating sound of a rotating capsule inside the inhaler is heard, which indicates the dispersion of the drug. After taking a deep breath, hold your breath for at least 10 seconds (or as much as possible).
- Then the device is removed from the mouth and a slow exhalation is made, then they continue to breathe normally.
- To ensure that the entire dose of the drug is inhaled, inhalation with the capsule already inserted into the device can be repeated.
During the procedure, the device must be held strictly in an upright position, without covering the holes located on the sides of the mouthpiece with your fingers.
Do not press on the mouthpiece while inhaling, so as not to block the movement of the capsule.
After inhalation, the capsule compartment is opened, the empty capsule is taken out, and the device is closed. The mouthpiece should be closed with a cap. Use a dry cloth to clean the outside of the mouthpiece.
Recommended dosage: 1 capsule per day, preferably always at the same time.
For elderly patients and with impaired renal and / or liver function, dose adjustment is not required.
Patients with moderate or severe renal failure receiving Tiotropium-native in combination with other drugs that are excreted mainly by the kidneys should be closely monitored.
Side effects
- from the respiratory system, chest and mediastinal organs: infrequently - cough, dysphonia, pharyngitis; rarely - laryngitis, sinusitis, paradoxical bronchospasm, epistaxis;
- from the gastrointestinal tract: often - dry mouth (more often mild); infrequently - oropharyngeal candidiasis, constipation, gastroesophageal reflux; rarely - gingivitis, glossitis, nausea, stomatitis, dysphagia, intestinal obstruction (including paralytic ileus); frequency not established - caries;
- from the side of metabolism and nutrition: the frequency is not established - dehydration;
- from the immune system: rarely - hypersensitivity reactions (including immediate reactions, Quincke's edema), urticaria; frequency not established - anaphylactic reactions;
- from the nervous system: infrequently - a violation of taste, dizziness, headache; rarely - insomnia;
- on the part of the organ of vision: infrequently - blurred vision; rarely - increased intraocular pressure, glaucoma;
- from the heart: infrequently - atrial fibrillation; rarely - palpitations, tachycardia (including supraventricular or supraventricular tachycardia);
- from the musculoskeletal system: frequency not established - joint swelling;
- from the urinary system: infrequently - dysuria, difficulty urinating, urinary retention (in the presence of predisposing factors in men); rarely - urinary tract infections;
- dermatological reactions: infrequently - rash; rarely - itching; frequency not established - dry skin, skin infections, skin ulcers.
Overdose
A symptom of an overdose of tiotropium bromide may be a slight manifestation of systemic anticholinergic action. In case of accidental ingestion of capsules, acute intoxication is unlikely.
Against the background of inhalation use of the substance at a dose of up to 340 mcg once or at a dose of up to 170 mcg for 7 days in healthy volunteers, in addition to dry mouth, no other adverse reactions were observed.
Treatment: if necessary, symptomatic therapy is performed.
special instructions
Tiotropium-native is not intended for the initial treatment of acute attacks of bronchospasm as an ambulance, since it is a long-acting bronchodilator for maintenance therapy.
It should be borne in mind that after inhalation of tiotropium bromide, immediate hypersensitivity reactions may develop, as well as, as in the case of the use of other inhaled drugs, paradoxical bronchospasm.
When prescribing capsules, the doctor must make sure that the patient is familiar with the rules for using the inhaler and precisely follows the sequence of all steps during the procedure.
Do not allow the contents of the capsules to get into the eyes due to the risk of an attack of angle-closure glaucoma. During the appointment of Tiotropium-native, the patient should be informed that if symptoms such as blurred vision, discomfort or pain in the eye appear, the appearance of visual halos in combination with redness of the eyes, corneal edema and conjunctival congestion, they should immediately consult a doctor. The use of drugs that cause miosis is not effective in this case.
Tiotropium bromide does not affect the results of doping tests in athletes.
Influence on the ability to drive vehicles and complex mechanisms
During the period of application of Tiotropium-native, if it is necessary to perform potentially hazardous activities that require increased attention and speed of psychomotor reactions, patients should be careful. In the event of dizziness, headache or blurred vision, they are advised to refrain from driving vehicles and complex mechanisms.
Application during pregnancy and lactation
The use of Tiotropium-native in the first trimester of pregnancy is contraindicated.
Due to the limited information about the effect of tiotropium bromide in humans on the course of pregnancy, fetal development, childbirth and postnatal development of the child, as a precautionary measure, it is recommended to refrain from using Tiotropium-native during the entire period of gestation.
The results of preclinical studies confirm the excretion of small amounts of tiotropium bromide in breast milk.
It is possible to prescribe Tiotropium-native to pregnant women or during breastfeeding only in cases where, in the opinion of the doctor, the expected benefit from therapy to the mother outweighs the possible risk to the fetus or child.
Pediatric use
The use of Tiotropium-native for the treatment of patients under the age of 18 is contraindicated.
With impaired renal function
With caution, Tiotropium-native should be prescribed to patients with moderate and severe renal failure (CC less than 50 ml / min).
In case of impaired renal function, the usual dosage regimen is used.
For violations of liver function
For the treatment of patients with impaired liver function, dose adjustment of Tiotropium-native is not required.
Use in the elderly
For elderly patients, correction of the Tiotropium-native dosage regimen is not required.
Drug interactions
The use of Tiotropium-native has been shown as part of combination therapy with drugs such as sympathomimetics, methylxanthines, oral and inhaled glucocorticosteroids, which are usually used in COPD. The therapeutic effect of tiotropium bromide when used simultaneously with inhaled glucocorticosteroids, long-acting beta2-adrenergic agonists, or their combination is not impaired.
The constant use of Tiotropium-native in conjunction with other anticholinergics is not recommended due to the lack of information on the safety and effectiveness of this combination.
Analogs
The analogues of Tiotropium-native are Spiriva, Spiriva Respimat, Ipratropium-Nativ, Sibri Brizhailer, etc.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 25 ° C in a dark place.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Tiotropium-native
Reviews of Tiotropium-native are rare and ambiguous in nature. Some patients indicate the effectiveness of the drug, a decrease in the frequency and severity of attacks, and the absence of unwanted side reactions. However, in some patients, the use of capsules caused a worsening of the condition.
Price for Tiotropium-native in pharmacies
The price of Tiotropium-native for a package containing 10 capsules can be from 569 rubles, 30 capsules - from 1708 rubles, 60 capsules - from 3416 rubles.
Tiotropium-native: prices in online pharmacies
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Drug name Price Pharmacy |
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Tiotropium-native 18 mcg capsules with powder for inhalation 30 pcs. 1861 RUB 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!
