Spiriva - instructions for use, dose, side effects, contraindications

Active substanceTiotropium bromideTiotropium bromide

Similar drugsTo uncover

Spiriva®

capsules d / inhal.

Boehringer Ingelheim International GmbH Germany

Spiriva® Respimat®

solution d / inhal.

Boehringer Ingelheim International GmbH Germany

Tiotropium-native

capsules d / inhal.

NATIVA, LLC Russia

Dosage form: & nbspcapsules with powder for inhalation

Composition:

1 capsule contains the active ingredient: tropotropy bromide monohydrate 0.0225 mg equivalent tiotropium 0.0180 mg All other substances: lactose monohydrate. 200 M 5.2025 mg; lactose monohydrate micronized 0.2750 mg.

Capsule composition (mg / capsule): Macrogol 2.4000 mg. Nondiocarbamine (E132) 0.0120 mg. gitan dioxide (E171) 1.0240 mg. iron oxide yellow (E172) 0.0120 mg. gelatin 44.5160 mg

Description:

Hard gelatin capsules are light greenish-blue, opaque. The contents of the capsules are white powder.

Pharmacotherapeutic group:M-holinoblokator

ATX: & nbsp

R.03.B.B Holinblockers

R.03.B.B.04 Tiotropium bromide

Pharmacodynamics:

Tiotropium bromide is an antimuscarinic drug of long-acting m-cholinoblocker, often called anticholinergic in clinical practice. It has the same affinity for different subtypes of muscarinic receptors from Mi up to M₅. The result of inhibition of M₃- The receptors in the respiratory tract is the relaxation of smooth muscles. The bronchodilator effect is dose dependent and persists for at least 24 hours.A considerable duration of action is probably connected with a very slow dissociation from M₃- receptors, in comparison with ipratropium bromide. With the inhalation route of administration tiotropium bromide as N-quaternary athe anticholinergic agent has a local selective effect, while at therapeutic doses it does not cause systemic m-cholinoblocking side effects. Dissociation from Mg-receptors occurs faster than from M3. High affinity for receptors and slow dissociation cause a pronounced and prolonged bronchodilator effect in patients with chronic obstructive pulmonary disease. The bronchodilation after inhalation of tiotropium bromide is a consequence of local rather than systemic effect.

It was shown that SPIRIVA significantly increases lung function (forced expiratory volume in 1 second FEV1, forced vital capacity of FVC lungs) 30 minutes after a single dose for 24 hours. Pharmacodynamic equilibrium was achieved during the first week, and pronounced bronchodilator effect was observed on day 3.SPIRIVA® significantly increases the morning and evening peak flow rate of exhalation, measured by patients. The bronchodilator effect of Spiriva ⁸, evaluated during 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, it was shown that SPIRIVA significantly improved exacerbations (0.09 versus 0.13, the ratio risks: 0.73; 95% CI from 0.66 to 0.82; P <0.001)

Pharmacokinetics:

Tiotropium is a quaternary ammonium the compound is moderately soluble in water.

Suction: With inhalation method The absolute bioavailability of tiotropium is 19.5%, indicating that the fraction of the drug reaching the lungs is highly bioavailable. Tiotropium in solution with oral administration has an absolute bioavailability of 2-3%. Eating does not affect the absorption of tiotropium. Maximum tiotropium concentration in plasma (cmax) after Inhalation is achieved after 5-7 minutes. At the stage of dynamic equilibrium, the peak concentration of tiotropium in the blood plasma in patients with COPD is 12.9 pg / ml and rapidly decreases.This indicates a multi-compartmental type of drug distribution. At the stage of dynamic equilibrium, the basal concentration of tiotropium in the blood plasma is 1.71 pg / ml

Distribution. 72% of the accepted dose The drug binds to plasma proteins and the volume of distribution is 32 l / kg.

Studies have shown that tiotropium does not penetrates the blood-brain barrier.

Biotransformation: Power biotransformation is insignificant. it is confirmed by the fact that after intravenous introduction of the drug to healthy young volunteers, 74% unchanged substance. Tiotropium is digested in a non-fermental way to alcohol N-methylskopine and dithienylglycolic acid, which do not bind to muscarinic receptors. In studies it was shown that the drug (<

20 % of the dose after intravenous administration) is metabolized by cytochrome P450, this process depends on oxidation and subsequent conjugation with glutathione to form various metabolites. Metabolic disorders can occur with the use of inhibitors CYP 450 2D6 and ZA4 (quinidine, ketoconazole and gestodene). In this way CYP 450 2D6 and 3A4 are included in the metabolism of the drug. Tiotropium does not inhibit cytochrome P450, 1A1, 1A2, 2B6, 2C9, 2C19 even in super therapeutic concentrations, 2D6, 2E1, or FOR in the microsomes of the human liver.

Excretion: 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 basically excreted by the kidneys unchanged (74%). After inhalation of dry powder at the stage of dynamic equilibrium, renal excretion is 7% per day from the dose, the remaining non-sucked part is excreted through the intestine. Renal clearance of tiotropium exceeds the creatinine clearance, which indicates tubular secretion preparation. After long-term administration of the drug once a day in patients with COPD, the pharmacokinetic balance is reached on day 7, with no accumulation observed thereafter.

Tiotropium has a linear pharmacokinetics in therapeutic limits regardless of the dosage form of the drug.

Elderly patients: In elderly patients the decrease in renal clearance of tiotropium (365 ml / min in patients with COPD younger than 65 years, up to 271 ml / min in patients with COPD older than 65 years) is observed.These changes did not lead to a corresponding increase in the values of the area under the curve "concentration / time" (AUCo-b) or Cmax.

Patients with impaired renal function: Have patients with COPD and mild renal impairment (creatinine clearance 50-80 ml / min) inhalational application of tiotropium once a day at the stage of dynamic equilibrium led to an increase in the value of AUCo-b at 1,8- thirty %. The value of Sm_Ohremained the same as in patients with normal renal function (creatinine clearance> 80 ml / min). In patients with COPD and moderate or severe impairment of renal function (creatinine clearance <50 mL / min), intravenous tiotropium resulted in a two-fold increase in plasma drug concentration (value AUCo-44 increased by 82% and the value of Cm_Ohincreased by 52%) compared with patients with COPD and normal function kidney. A similar increase in concentration powder.

Patients with impaired liver function: It is suggested 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 the ester bonds, with the formation of metabolites that do not bind to muscarinic receptors.

Indications:

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

Contraindications:

Hypersensitivity to atropine or its derivatives (for example, ipratropium or oxytropy) or to the components of this (in particular, to lactose monohydrate, which contains milk protein, due to deficiency of lactase, lactose intolerance, glucose-galactose malabsorption);

I trimester of pregnancy; children under 18 years.

Pregnancy and lactation:

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

As a precaution, it is preferable to refrain from using SPIRIVA during pregnancy. There are no clinical data on the use of tiotropium in breast-feeding women. In pre-clinical studies, data were obtained that a small amount of tiotropium is excreted into breast milk.

SPIRIVA should not be used in pregnant or breast-feeding women, unless the expected benefit does not exceed the possible risk to the fetus or child.

Dosing and Administration:

When using Spiriva in the form of inhalations with the aid of the HandyHaler device, it is recommended to use one capsule per day at the same time.

The drug should not be swallowed.

Older patients should take Spirivu in recommended doses.

Patients with impaired renal function can use Spiri at recommended doses. However, careful monitoring of patients with moderate or severe renal failure receiving Spiriva in combination with other drugs that are mainly excreted by the kidneys is necessary.

Patients with hepatic impairment may take Spirivu at recommended doses.

Instructions for using the HandyHaler appliance *

The HandyHaler * was specially developed for Spiriva. It should not be used to take other medicines. You can use your HandyHaler * for one year.

Instrument HandyHaler "includes:

1) dust cap;

2) mouthpiece;

3) base;

4) a puncturing button;

5) the central chamber.

Using the HandyHaler *

Open the dust cap by lifting it upwards.

Then open the mouthpiece.

Take the Spiriva capsule from the blister (just before use) and put it in the central chamber, as shown in the figure.

It does not matter which side of the capsule is placed in the camera.

Close the mouthpiece firmly until it clicks, and leave the dust cap open.

Hold KhandyHaler * mouthpiece up, push the piercing button once to the end and then release.

Thus, an opening is formed through which the drug is released from the capsule during inspiration.

Exhale completely.

Caution: never exhale into the mouthpiece.

Take HandyHaler * in the mouth and tightly press the lips around the mouthpiece. Keep your head straight, inhale slowly and deeply, but at the same time with enough force to hear the vibration of the capsule. Breathe in until the lungs are completely filled; then hold your breath until you feel discomfort, while taking out HandyHaler® from your mouth. Continue to breathe calmly.

Repeat the procedure, which will completely empty the capsule.

Open the mouthpiece again. Remove and discard the used capsule.

Close the mouthpiece and dust cap.

Purge KhandiHalera * once a month.

Open the mouthpiece and the dust cap. Then open the base of the device by lifting the piercing button. Rinse the inhaler thoroughly in warm water until

complete removal of the powder. HandyHaler * wipe with a paper towel and leave it open for 24 hours with an open mouthpiece, base and a dust cap. After cleaning the device according to the instructions, it will be ready for the next use. If necessary, the outer surface of the mouthpiece can be cleaned with a damp but not wet cloth.

Neither in the device, nor in the blister, capsules should not be exposed to high temperatures, i.e. the action of solar rays, etc.

Side effects:

Adverse reactions of the drug were detected on based on the data obtained during the clinical trials and selected messages during the post-registration use of the drug.

Disorders from the metabolism and supply

dehydration *

Hgastrointestinal tract

often (> 1% and <10%) - dry mouth, usually mild degree of severity;

infrequently (> 0.1% and <1%) - stomatitis; constipation, gastroesophageal reflux;

rarely (> 0.01% and <0.1%) - candidiasis of the oropharynx, gingivitis, glossitis; intestinal obstruction, including paralytic ileus, dysphagia.

Disturbances from the respiratory system, chest and mediastinal organs infrequently (> 0.1% and <1%) - dysphonia, cough, pharyngitis;

rarely (> 0.01% and <0.1%) - paradoxical bronchospasm, laryngitis, sinusitis, nosebleeds.

Disorders from the cardiovascular system

infrequently (> 0,1% and <1%) - atrial fibrillation;

rarely (> 0.01% and <0.1%) - tachycardia (including supraventricular tachycardia), palpitations.

Disorders from the kidneys and urinary tract

infrequent (> 0.1% and <1%) - difficulty urinating and delayed urination (in men with predisposing factors); dysuria;

rarely (> 0.01% and <0.1%) - urinary tract infections.

Allergic reactions

infrequently (> 0.1% and <1 %) - a rash;

rarely (> 0.01% and <0.1%) - hives, itching, reactions of hypersensitivity, including reactions of immediate type.

Angioedema.

Disturbances from the skin skin infections and skin ulcers, dry skin *.

The musculoskeletal system and associated connective tissue diseases swelling of the joints.

Disturbances from the nervous system infrequently (> 0.1% and <1%) - dizziness; rarely (> 0.01% and <0.1%) - insomnia.

Disturbances on the part of the organ of sight infrequently (> 0.1% and <1%) - fuzzy vision; rarely (> 0.01% and <0.1%) - increased intraocular pressure, glaucoma.

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

Overdose:

The appearance of any serious anticholinergic symptoms is unlikely. There may be minor manifestations of systemic anticholinergic action, such as dry mouth, accommodation disorders, increased heart rate. Treatment is symptomatic.

However, systemic anticholinergic side effects were not detected after a single inhalation dose of up to 282 μg of tiotropium when taken by healthy volunteers.

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

Acute intoxication associated with the occasional ingestion of capsules is unlikely in view of the low bioavailability of the drug.

Interaction:

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

Limited information on combined use with anticholinergic drugs was obtained from 2Clinical trials: single administration of a single dose of ipratropium bromide against the background of a constant intake of SPIRIVA in patients with COPD (64 patients) and in healthy volunteers(20 man) did not lead to a decrease in adverse reactions, changes in vital parameters and electrocardiograms.However, the consistent joint use of anticholinergic drugs and SPIRIVA has not been studied, and therefore not recommended.

Special instructions:

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

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

As well as other anticholinergic drugs, Spiriva should be administered with caution to a patient with narrow-angle glaucoma, prostatic hyperplasia, or obstruction of the neck of the bladder.

Inhalation of the drug may lead to bronchospasm.

Patients with moderate or severe renal insufficiency (creatinine clearance <50ml / min) should be carefully observed when taking Spiriva, as is necessary in other cases of prescribing drugs excreted mainly by the kidneys.

Patients should be familiarized with the rules of using Spiriva® capsules with an inhaler. Do not let the powder get into the eyes.Pain in the eye or discomfort, blurred vision, visual aureoles in combination with red eyes, conjunctival stasis and corneal edema may indicate an acute attack of narrow-angle glaucoma. When developing any combination of these symptoms, you should immediately contact a specialist. The use of drugs that cause miosis, is not an effective method of treatment in this case.

Spiriva should not be used more than once a day.

Capsules Spiriva should only be used with a HandyHaler® device.

Form release / dosage:

capsules with powder for inhalation 18 μg

Packaging:10. 10. 30 or 60 capsules per pack, complete with a HandyHaler® inhaler or without an inhaler.

Storage conditions:

At a temperature of no higher than 25 ° C. Do not expose to freezing.

Keep out of the reach of children!

Shelf life:

24 months.

Do not use after the expiration date indicated on the package. After opening, use the blister for 9 days.

Terms of leave from pharmacies:On prescription