Instructions for use of SPIRIVA
Tiotropium is a quaternary ammonium compound, sparingly soluble in water.
After inhalation in powder form over a therapeutic dose range, it exhibits linear pharmacokinetics.
Suction
When administered by inhalation, the absolute bioavailability of tiotropium is 19.5%, which indicates the high bioavailability of the drug fraction reaching the lungs. Cmax in blood plasma is achieved 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 solution form had an absolute bioavailability of 2-3%.
Distribution
Plasma protein binding - 72%. Vd - 32 l/kg. At steady state, Cmax in blood plasma in patients with COPD is 17-19 pg/ml 5 minutes after inhalation of powder at a dose of 18 mcg and decreases rapidly. Css in blood plasma was 3-4 pg/ml.
Does not penetrate the BBB. After long-term administration of the drug once a day in patients with COPD, the equilibrium state of pharmacokinetic parameters is achieved after 2-3 weeks, with no further cumulation observed.
Metabolism
The degree of biotransformation is insignificant. Tiotropium is broken down nonenzymatically to the alcohol N-methylscopine and dithienylglycolic acid, which do not bind to muscarinic receptors.
Metabolic disorders are possible with the use of inhibitors of the cytochrome P450 system isoenzymes 2D6 and 3A4 (quinidine, ketoconazole, gestodene). Tiotropium, even at supratherapeutic concentrations, does not inhibit cytochrome P450 isoenzymes 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1 or 3A4 in human liver microsomes.
Removal
After inhalation administration, terminal T1/2 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 CC, indicating tubular secretion of the drug.
Tiotropium is excreted mainly in the urine unchanged - 74%.
Pharmacokinetics in special clinical situations
In elderly patients, a decrease in the renal clearance of tiotropium is observed (326 ml/min in patients with COPD under 58 years of age, to 163 ml/min in patients with COPD over 70 years of age), which is apparently due to a decrease in renal function with age. After inhalation, urinary excretion of tiotropium is reduced from 14% (young healthy volunteers) to 7% (patients with COPD), but no significant changes in plasma concentrations were observed in elderly patients with COPD when inter- and intra-individual variability was taken into account (after inhalation powder increases AUC0-4 by 43%).
If renal function is impaired after inhalation use, the concentration of the drug in the blood plasma increases and renal clearance decreases. With mild renal impairment (creatinine clearance 50-80 ml/min), often observed in elderly patients, the increase in plasma tiotropium concentration is insignificant.
It is expected that hepatic impairment will not have a significant effect on the pharmacokinetics of tiotropium because the drug is mainly excreted in the urine and the formation of pharmacologically active metabolites is not associated with the participation of enzymes.
Spiriva® respimat®
The recommended therapeutic dose is 2 inhalation doses of Respimat® inhaler spray (5 mcg/dose) 1 time/day, at the same time of day.
In elderly patients, patients with impaired liver function and patients with minor impaired renal function (creatinine clearance 50-80 ml/min)
you can use the drug Spiriva® Respimat® at the recommended dose.
However, the use of the drug in patients with moderate or significant renal impairment (creatinine clearance less than 50 ml/min)
should be carefully monitored.
COPD does not usually occur in children. Safety and effectiveness of the drug Spiriva® Respimat® in children
have not been studied.
Rules for using the Spiriva® Respimat® inhaler
Before using the inhaler for the first time, you must carry out the steps listed below under numbers 1-6.
Inserting a cartridge
1. With the green cap closed, press the locking button and remove the transparent sleeve down.
2. Remove the cartridge from the packaging. Insert the thin end into the inhaler until it locks into place. To ensure that the cartridge is fully inserted, gently press the cartridge onto a hard surface. Once the cartridge is inserted into the inhaler, there is no need to remove it.
3. Put the transparent sleeve back on. After this, the sleeve should no longer be removed.
Preparing to use your inhaler for the first time
4. The inhaler should be held vertically with the green cap on. You need to turn the transparent sleeve in the direction of the red arrows indicated on the label until it clicks (half a turn).
5. Remove the green cap.
6. Point the inhaler down. Press the dose button. Close the green cap.
Repeat steps 4, 5 and 6 until an aerosol cloud appears.
Then repeat steps 4, 5 and 6 three more times to ensure the inhaler is ready for use.
The Spiriva® Respimat® inhaler is now ready for use.
The implementation of these steps does not reduce the number of doses of the drug. Once prepared, the Spiriva® Respimat® inhaler delivers 30 doses (60 inhalations).
Using an inhaler
I. Hold the inhaler upright with the green cap on to prevent accidental release of the medication. Turn the transparent sleeve in the direction of the red arrows indicated on the label until it clicks (half a turn).
II. Remove the green cap. Exhale slowly and deeply. Cover the end of the mouthpiece tightly with your lips. The air hole of the inhaler must be free. Point the inhaler towards the back of the throat.
While inhaling slowly and deeply through your mouth, press the dose button and continue inhaling as long as possible. Hold your breath for 10 seconds or as long as comfortable.
III. Repeat steps I-II to obtain the full dose. This inhaler should only be used once a day.
Close the green cap of the inhaler until you use it again.
If the Spiriva® Respimat® inhaler has not been used for more than 7 days, you should point it down before use and press the dose button once. If the inhaler has not been used for more than 21 days, repeat steps 4-6 until an aerosol cloud is obtained. Then repeat steps 4-6 three more times.
Determining when to start using a new inhaler
The Spiriva® Respimat® inhaler contains 30 doses (60 inhalations). The dose indicator shows approximately how much of the drug is left. When the inhaler pointer points to the red area of the scale, this means there is approximately 7 days of medication left (14 inhalations). During this time, you must obtain a prescription for a new Spiriva® Respimat® inhaler.
When the inhaler pointer reaches the end of the red area of the scale (i.e. when 30 doses have been used), this means that the inhaler is empty. The inhaler will be automatically blocked. From this point on, turning the transparent sleeve will not be possible.
After the first use, the Spiriva® Respimat® inhaler must be discarded no later than after 3 months, even if not the entire amount of the medicine has been used.
Caring for your inhaler
The mouthpiece and metal part of the atomizer must be cleaned with a damp, soft cloth at least once a week. Slight discoloration of the mouthpiece does not affect the functioning of the inhaler. If necessary, wipe the outside of the inhaler with a damp cloth.
Side effects of Spiriva
Many of these side effects can be attributed to the anticholinergic properties of Spiriva. The incidence rates given below are based on the incidence of adverse reactions reported in 5437 patients treated with tiotropium in 19 placebo-controlled clinical studies with treatment periods ranging from 4 weeks to 1 year. From the central nervous system (≥0.1%, but ≤1%): dizziness. From the organ of vision (≥0.01%, but ≤0.1%): blurred vision, increased intraocular pressure; glaucoma*. From 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 the use of 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 goes away with continued treatment; (0.1% but ≤1%): oral candidiasis; (≥0.01% but ≤0.1%): constipation, gastroesophageal reflux disease; intestinal obstruction*, including paralytic ileus, dysphagia. From the immune system, skin and subcutaneous tissues (≥0.01%, but ≤0.1%): skin rash, urticaria, itching and other allergic reactions (including immediate allergic reactions). From the genitourinary system (≥0.01%, but ≤0.1%): urinary disturbance and urinary retention (usually in predisposed men), urinary tract infection. *The frequency of manifestations is unknown (5437 patients did not experience a single adverse reaction to the drug).
Spiriva overdose, symptoms and treatment
High doses of Spiriva may cause anticholinergic effects, although in a study there were no systemic anticholinergic side effects when administered to healthy volunteers at single doses up to 282 mcg. Bilateral conjunctivitis and dry mouth were noted after inhalation of 141 mcg of tiotropium per day; with continued treatment, signs of conjunctivitis disappeared. When the drug was repeatedly administered to patients with COPD at a daily dose of 36 mcg for 4 weeks, only a feeling of dry mouth was noted.
Drug interactions Spiriva
Although formal drug interaction studies have not been conducted, tiotropium bromide has been used concomitantly with other drugs (sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids used in the treatment of COPD) without developing side effects. There is insufficient information on the use of other anticholinergic drugs in combination with Spiriva: a single dose of ipratropium bromide during long-term use of Spiriva in patients with COPD and healthy volunteers was not associated with an increase in the number of adverse reactions, changes in vital signs or ECG results. The use of Spiriva in combination with other medicinal products containing anticholinergics has not been studied and is therefore not recommended.
Special instructions for the use of Spiriva
During pregnancy and breastfeeding. There are no clinical data regarding the safety of the use of Spiriva during pregnancy, however, experimental studies have not revealed any 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 during breastfeeding, 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 child. Based on the fact that there is no experience with the use of Spiriva in the treatment of children, the drug is recommended for use only in adults. Spiriva is a bronchodilator that is prescribed once a day for maintenance therapy and is not used to relieve acute bronchospasm attacks. As with other anticholinergic drugs, 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 regarding the correct use of Spiriva capsules. Do not allow the powder to get into your eyes, which can provoke an attack of angle-closure glaucoma. Signs of angle-closure glaucoma may include pain or discomfort in the eyes, blurred vision, the appearance of a halo around objects or colored spots in front of the eyes in combination with conjunctival or corneal hyperemia. Consultation with an ophthalmologist is required as the use of miotic eye drops may not be effective. Spiriva should not be used more than once a day. Spiriva capsules should only be used with the HandyHaler device. The drug contains 5.5 mg of lactose monohydrate per capsule. Impact on the ability to drive vehicles and operate mechanical devices. No research was carried out. Dizziness or blurred vision may affect your ability to operate vehicles or use mechanical equipment.
Spiriva Respimat 2.5 mcg/inhalation 4 ml No. 1 solution for inhalation. included with inhaler
SPIRIVA® RESPIMAT® Trade name Spiriva® Respimat® International nonproprietary name Tiotropium bromide Dosage form Solution for inhalation complete with Respimat inhaler, 2.5 mcg/inhalation Composition 1 inhalation contains the active substance - tiotropium bromide 2.5 mcg (equivalent to 3.124 mcg tiotropium bromide monohydrate) 2 inhalations correspond to 1 therapeutic dose excipients: benzalkonium chloride, disodium edetate, 1M hydrochloric acid, purified water. Description Transparent, colorless liquid. Pharmacotherapeutic group Other inhaled drugs for the treatment of obstructive airway diseases. Anticholinergics. Tiotropium bromide. ATC code R03BB04 Pharmacological action Pharmacokinetics Tiotropium bromide is a non-chiral quaternary ammonium compound, moderately soluble in water. About 40% of the inhalation dose is deposited in the lungs, the remaining amount in the gastrointestinal tract (GIT). Suction. After inhalation, about 33% of the inhalation dose enters the systemic circulation. Tiatropium bromide is poorly absorbed through the gastrointestinal tract (10-15%) due to the chemical structure (quaternary ammonium compound) and in vitro studies. The absolute bioavailability of tiotropium bromide solutions for oral administration is 2-3%. Eating does not affect the absorption of tiotropium bromide. At steady state, the peak plasma concentration of tiotropium bromide in patients with chronic obstructive pulmonary disease (COPD) is 10.5-11.7 pg/ml 10 minutes after taking a dose of 5 μg using the RESPIMAT inhaler and then rapidly decreases in accordance with the multicompartmental model . The equilibrium minimum concentration of tiotropium bromide in blood plasma is 1.49-1.68 pg/ml. The equilibrium maximum concentration of tiotropium bromide in blood plasma, equal to 5.15 pg/ml, was achieved 5 minutes after administration of the drug at a therapeutic dose in patients with bronchial asthma. Distribution. The binding of the drug to plasma proteins is 72%, and the volume of distribution is 32 l/kg. Preclinical studies have shown that tiotropium bromide does not penetrate the blood-brain barrier to any significant extent. Biotransformation. After intravenous administration, 74% of the substance is excreted unchanged in the urine, which indicates a low degree of biotransformation. Tiotropium bromide ester is non-enzymatically cleaved into alcohol (N-methylscopine) and dithienylglycolic acid, which do not bind to muscarinic receptors. In vitro studies have shown that some of the drug (<20% of the dose after intravenous administration) is metabolized by cytochrome P450 (CYP)-dependent oxidation and subsequent conjugation with glutathione to form various phase II metabolites. This enzymatic mechanism can be slowed down by CYP 2D6 (and 3A4) inhibitors, quinidine, ketoconazole and gestodine. Thus, CYP 2D6 and 3A4 are involved in the metabolic pathway through which a smaller portion of the dose is eliminated. Tiotropium bromide, even at supratherapeutic concentrations, does not inhibit CYP 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1 or 3A in human liver microsomes. Excretion. The terminal half-life of tiotropium bromide after inhalation is approximately 5-6 days in healthy volunteers and patients with COPD, and 34 hours in patients with bronchial asthma. The total clearance after intravenous administration is 880 ml/min with 22% interindividual variability. After inhalation, excretion in urine is 20.1-29.4% of the dose in healthy volunteers, in patients with bronchial asthma within 24 hours - 11.9% (0.595 mcg) of the dose. The remaining amount of the drug that is not absorbed in the intestine is excreted through the gastrointestinal tract. The renal clearance of tiotropium bromide exceeds the clearance of creatinine, indicating excretion in the urine. Linearity/nonlinearity. Tiotropium bromide exhibits linear pharmacokinetics over the therapeutic dose range. Elderly patients. As with all drugs primarily excreted by the kidneys, there is a decrease in the renal clearance of tiotropium bromide in the elderly (326 ml/min in patients with COPD aged < 58 years and up to 163 ml/min in patients with COPD aged > 70 years). , which may be explained by decreased renal function. Urinary excretion of tiotropium bromide after inhalation decreased from 14% (in young healthy volunteers) to about 7% (in patients with COPD); however, there is no significant change in plasma concentrations with age among patients with COPD, taking into account inter- and intra-individual variability. No age differences were found in the effects of tiotropium bromide in patients with bronchial asthma. Patients with impaired renal function. As with other drugs that undergo predominantly renal excretion, patients with impaired renal function experience increased plasma concentrations of the drug and decreased renal clearance after intravenous administration and dry powder inhalation. Mild renal impairment (creatinine clearance 50-80 ml/min), often observed in elderly patients, is accompanied by a slight increase in plasma tiotropium bromide concentrations (39% increase in AUC0-4h after intravenous administration). In COPD patients with moderate to severe renal impairment (creatinine clearance <50 mL/min), intravenous tiotropium bromide resulted in a doubling of plasma concentrations (82% increase in AUC0-4h), which was confirmed by plasma concentrations after inhalation of the solution using the RESPIMAT inhaler. . In patients with bronchial asthma and mild renal impairment (creatinine clearance 50-80 ml/min), inhalation of tiotropium bromide did not lead to significant increases in drug concentrations compared to patients with normal renal function. Patients with impaired liver function. Impaired liver function does not have a significant effect on the pharmacokinetics of tiotropium bromide. Tiotropium bromide is primarily excreted by the kidneys (up to 74% in young healthy volunteers) and by simple non-enzymatic cleavage of the ester into pharmacologically inactive derivatives. Pediatric patients. Pediatric patients were not enrolled in COPD programs but were studied in the cystic fibrosis (CF) clinical program along with adult patients. 5 minutes after inhalation of 5 mcg tiotropium bromide, the steady-state plasma tiotropium bromide concentration in CF patients aged ≥ 5 years was 10.1 pg/mL and decreased rapidly. Levels in patients with CF aged <5 years using a mask and adapter were 3-4 times lower than in patients with CF aged 5 years or older. Exposure to tiotropium bromide in CF patients aged <5 years was dependent on body weight. Pharmacokinetic/pharmacodynamic interactions. There is no direct relationship between pharmacokinetics and pharmacodynamics. Pharmacodynamics Mechanism of action Tiotropium bromide is a specific long-acting muscarinic receptor antagonist. Has similar affinity for subtypes M1-M5. In the respiratory tract, tiatropium bromide competitively and reversibly binds to M3 receptors of bronchial smooth muscle, counteracting the cholinergic (bronchoconstrictor) effect of acetylcholine, which leads to relaxation of bronchial smooth muscle. The bronchoprotective effect depends on the dose and lasts for more than 24 hours. Tiotropium bromide, being an N-quaternary anticholinergic agent, when administered inhaled, has a local selective effect (on the bronchi) in an acceptable range of therapeutic doses even before the appearance of systemic anticholinergic effects. Pharmacodynamic effects Dissociation of tiotropium from M3 receptors occurs very slowly, indicating a significantly longer dissociation half-life than ipratropium. Dissociation of tiotropium from M2 receptors occurs faster than from M3 receptors, which causes greater selectivity (kinetically controlled) for receptors of the M3 subtype compared to M2. High activity, slow dissociation of the drug from connection with receptors, selectivity during local inhalation administration of the drug determine a pronounced and long-term bronchodilator effect in patients with COPD and bronchial asthma. Clinical Efficacy and Safety in COPD The Phase III clinical trial program included the following clinical outcome measures in COPD: measures of pulmonary function, dyspnea, health-related quality of life, and effect on exacerbations. In clinical studies, SPIRIVA RESPIMAT, administered once daily, provided significant improvements in lung function (forced expiratory volume in one second and forced vital capacity) within 30 minutes after the first dose (mean improvement in FEV1 at 30 minutes: 0.113 L ; 95% confidence interval (CI): 0.102 – 0.125 l, p < 0.0001). Stable improvement in pulmonary function was maintained over 24 hours (mean improvement in FEV1: 0.122 L; 95% CI: 0.106 - 0.138 L, p < 0.0001), and pharmacodynamic steady state was achieved within one week. The drug significantly improved morning and evening MEF (maximum expiratory volume flow) and led to a reduction in the use of rescue bronchodilators. The bronchodilator effect of SPIRIVA RESPIMAT was maintained for one year without any signs of tolerance. Long-term studies lasting 1 year demonstrated the following clinical results with the use of SPIRIVA RESPIMAT: - significant reduction in shortness of breath, the improvement was maintained throughout the entire treatment period - clinically significant improvement in quality of life according to the average overall patient score - reduction in the number of exacerbations (attacks) of COPD and a significant reduction in risk hospitalization due to exacerbation of COPD. Clinical efficacy and safety in asthma The Phase III clinical trial program in persistent asthma included measurements of lung function as well as severe exacerbations. Results showed a clinically significant improvement in lung function when taking SPIRIVA RESPIMAT as an adjunct to background treatment. At week 24, the mean improvement in peak and trough FEV1 was 0.110 L and 0.093 L, respectively. The improvement in lung function was maintained for 24 hours. Treatment of patients with symptoms of bronchial asthma with additional use of tiotropium bromide reduced the risk of severe exacerbations of bronchial asthma by 21%. The risk reduction in the average number of severe asthma exacerbations/patient per year was 20%. This was supported by a 31% reduction in the risk of asthma progression and a 24% reduction in the risk of the average number of asthma progressions/patient per year. Pediatric patients There are no data on use in pediatric patients with COPD and bronchial asthma. Clinical efficacy and safety in cystic fibrosis (CF) The CF clinical research program included studies in patients 5 months of age and older. The results showed that signs and symptoms considered to be manifestations of CF were numerically, but not statistically significantly, increased with tiotropium bromide, especially in patients aged ≤ 11 years. Indications for use - maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) for symptomatic relief - adjunctive maintenance treatment of adult patients with bronchial asthma (who have had one or more severe exacerbations during the past year during combination treatment with inhaled corticosteroids and long-acting β2-agonists) . Method of administration and dosage The drug SPIRIVA RESPIMAT is intended only for inhalation and only through the RESPIMAT inhaler. Adults - the recommended dose is two injections of the solution through the RESPIMAT inhaler, corresponding to 5 mcg of tiotropium bromide, once a day, at the same time of day. Do not exceed the recommended dose. In the treatment of bronchial asthma, maximum benefit will be achieved after using several doses of SPIRIVA RESPIMAT. Elderly patients should use SPIRIVA RESPIMAT at the recommended dose. Patients with impaired renal function should use SPIRIVA RESPIMAT at the recommended dose. However, in patients with moderate or acute renal impairment (creatinine clearance ≤ 50 ml/min), SPIRIVA RESPIMAT should only be used if the expected benefit outweighs the potential risk (see Precautions). Patients with impaired liver function can use SPIRIVA RESPIMAT at the recommended dose. Pediatric patients. There are no data on the use of the drug for COPD and bronchial asthma in children and adolescents under 18 years of age. The effectiveness and safety of the drug have not been established. Cystic fibrosis. The effectiveness and safety of the drug have not been established. To ensure correct use of the drug, patients should be instructed on how to use the inhaler. Instructions for use of the drug SPIRIVA RESPIMAT Please read the instructions and follow them carefully. SPIRIVA RESPIMAT inhaler and SPIRIVA RESPIMAT cartridge 1. Installing the cartridge. Before using the inhaler for the first time, you must carry out the steps shown below in Fig. 1-6. 1 1. With the green cap (A) closed, press the safety catch (E) while pushing out the clear base (G). 2a 2. Remove the cartridge (H) from the package. Insert the narrow end of the cartridge into the inhaler until it locks into place (Fig. 2a). To ensure proper installation of the cartridge, gently press the cartridge onto a hard surface (Fig. 2b). The cartridge is not fully inserted into the inhaler if the silver ring on the bottom of the cartridge is visible. 2b Once the cartridge is inserted into the inhaler, do not remove it. 3 3. Put the transparent base (G) back on. After this, the base should no longer be removed. 2. Preparing the SPIRIVA RESPIMAT inhaler for first use. 4 4. Hold the SPIRIVA RESPIMAT inhaler upright with the green cap (A) closed. Turn the clear base (G) in the direction of the black arrows on the label until it clicks (half a turn). 5 5. Open the green cap (A) until it clicks fully open. 6 6. Point the SPIRIVA RESPIMAT inhaler downwards. Press the dose button (D). Close the cap (A). Repeat steps 4, 5 and 6 until a visible cloud of aerosol appears. Repeat steps 4, 5, and 6 three more times to ensure the inhaler is ready to use. The SPIRIVA RESPIMAT inhaler is now ready for use. The above steps do not affect the number of doses of the drug. After installing the cartridge, the SPIRIVA RESPIMAT inhaler allows you to release 30 doses of the drug (60 injections). 3. Daily use of the SPIRIVA RESPIMAT inhaler You should use this inhaler only ONCE a day. Give TWO INJECTIONS each time you use. I I. Hold the SPIRIVA RESPIMAT inhaler upright with the green cap (A) closed to prevent accidental release of a dose of medication. Turn the transparent base (G) in the direction of the black arrows on the label until it clicks (half a turn). II II. Open the green cap (A) until it clicks fully open. Exhale fully and slowly, and then wrap your lips tightly around the end of the mouthpiece without blocking the air hole of the inhaler (C). Point the SPIRIVA RESPIMAT inhaler towards the back of your throat. While inhaling slowly and deeply through your mouth, press the dose button (D) and continue to inhale slowly for as long as possible. Hold your breath for 10 seconds or as long as is comfortable. III. Repeat steps I and II to obtain the full dose (2 injections). This inhaler should only be used ONCE per day. Close the green cap until you next use your SPIRIVA RESPIMAT inhaler. If the inhaler has not been used for more than 7 days, point it downwards and release 1 spray before use. If the inhaler has not been used for more than 21 days, repeat steps 4-6 until an aerosol cloud is obtained. Then repeat steps 4-6 three times. 4. When it is necessary to purchase a new SPIRIVA RESPIMAT inhaler The SPIRIVA RESPIMAT inhaler contains 60 injections (30 therapeutic doses). The dose indicator shows the approximate amount of drug remaining. If the indicator points to the red area of the scale, then there is approximately 7 days of drug left (14 injections). During this time, you must obtain a new prescription for SPIRIVA RESPIMAT. If the dose indicator has reached the end of the red area of the scale (i.e. all 30 doses have been used), then the Spiriva Respimat inhaler is empty. The inhaler will be automatically blocked. From this point on, turning the transparent base will not be possible. No later than three months after the first use, the SPIRIVA RESPIMAT inhaler must be discarded, even if not all of the medicine has been used. How to care for your SPIRIVA RESPIMAT inhaler It is necessary to clean the mouthpiece and the metal part of the nebulizer only with a damp cloth or cloth at least once a week. Slight discoloration of the mouthpiece does not affect the functionality of the inhaler. If necessary, the inhaler is wiped in the outside with a damp cloth. Side effects many of the following undesirable phenomena can be a result of anticholinergic properties of bromide thyrophy. Side effects are determined at the following frequency: very often: ≥ 1/10; Often: ≥ 1/100 <1/10; infrequently: ≥ 1/1.000 <1/100; rarely: ≥ 1/10,000 <1/1.000; Very rarely: <1/10,000; It is unknown: it is impossible to evaluate on the basis of available data. Class of the system of organs frequency in COPD Frequency for bronchial asthma disorders by metabolism and nutrition dehydration is unknown unknown from the nervous system of dizziness infrequently infrequently headache infrequently insomnia, it is not commonly impaired by the glaucom organs of vision, rarely unknown an increase in intra -shallow pressure is rarely unknown. It is rarely unknown from the heart of the heart of the atrial fibrillation is not commonly unexpected by the rapid heartbeat infrequently supraventricular tachycardia is not often unexpectedly unexpected by tachycardia, it is not often not known violations of the respiratory system, the chest and mediastinum of the cough. Infrequently, infrene bleeding is not frequently not frequently dysphony rarely not often bronchospasm. One hundred laryngitis rarely It is not known that sinusitis is unknown unknown from the gastrointestinal tract, dryness in the mouth often often constipation of the oral cavity rarely rarely rarely dysphagia infrequently unexpectedly unknown gastroesophageal reflux disease is rarely unknown to the teeth, rarely, rarely, is rarely unknown, rarely rarely stomans intestinal obstruction, including paralytic intestinal impassability. It is not known nausea that is unknown unknown from the skin of the skin, violations of the immune system, the rash rarely rarely itching rarely rarely angion -European edema is rarely rarely rarely rare to infect/skin ulcers rarely unknown, is rarely unknown with hypersensitivity (including immediate reaction) unknownly anaphylactic The reaction is unknown unknown from the skeletal-muscular and connective tissue of the joint edema of the joint is unknown unknown from the kidneys and urinary tract, the urination delay is not often unknown to the urinary tract is rarely unknown to the infections of the patients is rarely unknown with the age of the patient. Contraindications - hypersensitivity to thiotropy bromide, atropine or its derivative (ipetropia, oxytropy) or to any component of this drug - children and adolescence under 18 years of age, drugs are allowed to use bromide tiotropy together with other drugs usually used in the treatment of COP and asthma, including Treatment with sympathomy bronchigators, methylxantins, oral and inhalation steroids, antihistamine agents, mucolytic, modifiers of leukotrienes, cromons and anti-Ige antibodies without clinical signs of drug interaction. The joint use of Spiriv Respimat with other anticholinergic drugs is not recommended. Special instructions of the drug Spiriv respond, which is a bronchoditional supporting agent for taking once a day, should not be used as the starting therapy of acute bouts of bronchospasm or to relieve acute symptoms. In the event of acute attacks, high-speed beta-2 agonists should be used. Spiriva Respimat should not be used as monotherapy (first -line drug) for the treatment of bronchial asthma. Patients suffering from bronchial asthma are strongly recommended to continue anti -inflammatory therapy with inhalation corticosteroids without changes after the start of the drug Spiriv Respimat, even if symptoms are relieved. After taking Spiriv, responds can occur reactions of hypersensitivity of an immediate type. In connection with its anticholinergic activity, Spiriva should be used with caution in patients with closing glaucoma, prostate hyperplasia or obstruction of the neck of the bladder. The use of inhalation drugs can cause bronchospasm, induced by inhalation. Spiriva Respimat should be used with caution in patients with known heart rhythm disorders. Since the concentration in blood plasma increases with a decrease in the renal function of the drug Spiriv Respimat in patients with moderate or severe degree of renal failure (creatinine clearance ≤50 ml/min) should begin only if the expected benefit exceeds potential risk. Long -term experience in the use of Spiriv responds in patients with severe degree of renal failure is absent. Patients must be instructed regarding the proper intimate of Spimat and the inadmissibility of the drug entering the eye. Patients should be warned that this can lead to a deterioration in the acute closed -angle glaucoma, the appearance of pain or discomfort in the eyes, temporary fuzziness of vision, the presence of rainbow circles or colored spots in the field of view of eye redness due to conjunctive hyperemia and corneal of the cornea. In the event of any combination of these symptoms, you should immediately stop taking the drug and consult a specialist. Dryness in the mouth, observed with anticholinergic treatment, in the long term may be accompanied by tooth decay. The drug Spiriva Respimat should not be used more often than once a day. Cycle scydosis: Spiriva responda is not recommended for cystic fibrosis (MV), since thiotropy bromide can enhance the signs and symptoms of MV (for example, serious undesirable phenomena, pulmonary exacerbations, infections of the respiratory tract) Fermatibility, pregnancy and breastfeeding: Pregnancy. There is a limited amount of data from the use of tiotropy bromide in pregnant women. Preclinical studies do not indicate a direct or indirect toxic effect on the reproductive function with clinically significant doses. As a precaution, the drug should be avoided during pregnancy. Breastfeeding period. There is no sufficient data about whether thyotropy bromide penetrates into breast milk. Despite the results of preclinical studies, which showed that the release of tiotropy bromide with milk occurs only in small quantities, the use of a spiritual response in women breastfeeding is not recommended. Tiotropy bromide is a long -acting connection. The decision on the advisability of continuing/stopping breastfeeding or continuing/stopping treatment using the drug Spiriv responda should be taken taking into account the advantage of breastfeeding for the baby and a favorable therapeutic effect of Spiriv Respimate for a woman. Fertility. There is no data on the effects of thiotropy on fertility. Preclinical studies did not reveal any undesirable effects on the reproductive function. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms. Studies on the effect of the drug on the ability to drive vehicles and mechanisms were not carried out. The occurrence of dizziness or fuzzy vision can affect these types of activity. An overdose of symptoms: high doses of bromide thiotropy can cause signs and symptoms characteristic of anticholinergic drugs. At the same time, there were no systemic anticholinergic unwanted effects after taking a single inhalation dose of up to 340 mcg and there were no significant undesirable effects after a 14-day administration of up to 40 μg of inhalation doses of bromide, in addition to dry mouth/throat and sip of the nose and mucous membrane of the nose, as well as expressed Reducing salivation from the 7th day. The occurrence of acute intoxication in the case of unintentional swallowing a tiotropic solution for inhalation from the cartridge is unlikely, due to low oral bioavailability. Treatment: symptomatic therapy. The form of release and packaging of 4 ml of the drug is poured into cartridges embedded in aluminum cartridges for the responda system. A self -adhesive label is glued to the cartridge. 1 cartridge, complete with 1 inhaler, respond, together with the instructions for medical use in the state and Russian languages, are invested in a pack of cardboard. Store storage conditions at a temperature of not higher than 25 ° C, not freeze! Keep out of the reach of children! Storage period 3 years is the period of use after the opening of the cartridge 3 months. Do not use after the expiration date stated on the package. Conditions of vacation from pharmacies according to the recipe and the country of the manufacturer Beringer Ingelheim Pharma GMBH and K. KG, Germany, the owner of the registration certificate Beringer Ingelheim Internet, Germany
