Siberia instructions for use. Medicinal reference book geotar

Inhalation.
The drug is a capsule with powder for inhalation, which should be used only for inhalation through the mouth using a special device for inhalation Breezhaler, which is included in the package. The drug should not be taken orally. Capsules with powder for inhalation should be stored in a blister and removed from it immediately before use.
The recommended dose of Sibri Breezhaler is 50 mcg (content of 1 caps.) 1 time per day. Inhalation of the drug is carried out daily 1 time per day at the same time. If an inhalation is missed, the next dose should be inhaled as soon as possible. Patients should be instructed not to use more than 1 dose (50 micrograms) per day.
Before starting the use of Sibri Breezhaler, patients should be instructed about correct use inhaler.
If there is no improvement in respiratory function, you should make sure that the patient is using the drug correctly. The drug should be inhaled, not swallowed.
Special groups of patients.
Renal failure. In patients with mild to moderate renal impairment, the recommended dose of Sibri Breezhaler may be used. In patients with severe renal impairment or end-stage renal disease requiring hemodialysis, Sibri Breezhaler should be used at the recommended dose only if the intended benefit outweighs the potential risk.
Liver failure. Special clinical studies in patients with impaired liver function have not been conducted. The drug Sibri Breezhaler is excreted mainly by renal excretion, so a significant increase in exposure in patients with impaired liver function is not expected. In patients with impaired liver function, the recommended dose of Sibri Breezhaler may be used.
Elderly age. Sibri Breezhaler can be used at the recommended dose in patients 75 years of age and older.
Instructions for use of the inhaler.
Each package of Sibri Breezhaler contains:
- 1 inhalation device - Breezhaler;
- blisters with capsules with powder for inhalation.
Capsules with powder for inhalation should not be taken orally.
The inhalation device Breezhaler, which is in the package, is intended for use only with the capsules of the drug.
For inhalation of the capsules in the package, only the Breezhaler inhalation device is used.
Do not use the drug capsules with any other inhalation device and, in turn, do not use Breezhaler for inhalation of other drugs.
Throw away Breezhaler after 30 days of use.
How to use an inhaler
1. Remove cover.
2. Open the Breezhaler: to open the inhaler, hold it firmly by the base and tilt the mouthpiece.
3. Prepare a capsule: separate 1 bl. From the blister pack, tearing off the case along the perforation; take 1 bl. And remove the protective film from it to release the capsule; do not squeeze the capsule through the protective film.
4. Take out the capsule: the capsules should be stored in a blister and taken out only immediately before use; wipe your hands dry and remove the capsule from the blister; do not swallow the capsule.
5. Insert the capsule into the Breezhaler: put the capsule into the capsule chamber; never put the capsule directly into the mouthpiece.
6. Close Breezhaler: tightly close the inhaler; when it closes all the way, you should hear a click.
7. Pierce the capsule: hold the Breezhaler in an upright position so that the mouthpiece is pointing up; simultaneously press all the way down on both buttons; when piercing the capsule, a click should be heard; do not press the buttons to pierce the capsule more than 1 time.
8. Completely release the Breezhaler inhaler buttons on both sides.
9. Exhale; before inserting the mouthpiece into your mouth, exhale completely; never blow into the mouthpiece.
10. Inhale the drug: hold Breezhaler in your hand so that the buttons are left and right (and not top and bottom); put the mouthpiece of the Breezhaler inhaler into your mouth and squeeze your lips tightly around it; take a quick, even, deep breath; do not press the buttons of the lancing device.
11. Pay attention. When inhaled through the inhaler, a characteristic rattling sound should be heard, created by the rotation of the capsule in the chamber and spraying the powder. The patient may feel a sweetish taste of the drug in the mouth. If a rattling sound is not heard, this may mean that the capsule is stuck in the chamber of the inhaler. In this case, open the inhaler and carefully release the capsule by tapping on the base of the device. To release the capsule, do not press the buttons to pierce the capsule. Repeat steps 9 and 10 if necessary.
12. Hold your breath: if a characteristic sound is heard during inhalation, hold your breath as long as possible (so as not to experience discomfort) and at the same time remove the mouthpiece from your mouth; then exhale. Open Breezhaler and see if there is any powder left in the capsule. If powder remains in the capsule, close Breezhaler and repeat steps 9–12. Most people can empty a capsule in 1 or 2 inhalations. For some people, for a short time after inhalation medicinal product there is a cough, you should not worry about it. If there is no powder left in the capsule, then the patient has received the full dose of the drug.
13. Remove the capsule: after taking a daily dose of Sibri Breezhaler, tilt the mouthpiece, remove the empty capsule by tapping on the inhaler and discard it. Close the mouthpiece of the Breezhaler inhaler and close the Breezhaler cap. Do not store capsules in the Breezhaler inhaler.
Important information.
Do not swallow powder capsules for inhalation.
Use only Breezhaler, which is in the package.
Capsules should be stored in a blister and removed immediately before use.
Never insert a capsule into the mouthpiece of a Breezhaler inhaler.
Do not press the lancing device more than once.
Never blow into the mouthpiece of a Breezhaler inhaler.
Always pierce the capsule before inhalation.
Do not wash Breezhaler. Keep it dry (td; How to clean Breezhaler).
Do not disassemble Breezhaler.
Starting a new package of the drug, always use the new Breezhaler that is in the package for inhalation of the capsules.
Do not store capsules in the Breezhaler inhaler.
Always store capsule blisters and Breezhaler in a dry place.
Additional Information.
In very rare cases, a small amount of the contents of the capsules may enter the mouth.
Do not worry when inhaling or swallowing the drug.
When piercing the capsule more than 1 time, the risk of breaking it increases.
How to clean Breezhaler.
Clean Breezhaler once a week. Wipe the mouthpiece inside and out with a clean, dry cloth. Never use water to clean the Breezhaler inhaler. Keep it dry.

Active substance:
Glycopyrronium bromide (Glycopyrronii bromidum)

ATX
A03AB02 Glycopyrronium bromide

Pharmacological group
m-anticholinergic [m-anticholinergics]

Nosological classification (ICD-10)
J44 Chronic obstructive pulmonary disease other

Compound
Capsules with powder for inhalation 1 caps.
active substance: glycopyrronium base 50 mcg (equivalent to 63 mcg glycopyrronium bromide)$
Excipients: lactose monohydrate - 24.9 mg; magnesium stearate - 0.037 mg $
capsule shell: hypromellose - 45.59 mg; water - 2.7 mg; carrageenan - 0.42 mg; sodium chloride - 0.18 mg; dye "Sunset" yellow (E110) - 0.12 mg; black ink (shellac, iron dye black oxide, propylene glycol, sodium hydroxide)/

Description of the dosage form
Capsules: hard No. 3 with a transparent cap and an orange body, marked "?" under the black stripe on the cap and "GPL50" written in black ink above the black stripe on the body. The contents of the capsules are white or almost white powder.

pharmachologic effect
Pharmacological action - bronchodilating, m-anticholinergic.

Pharmacodynamics
Sibri® Breezhaler® inhalation long-term active drug. The mechanism of action of glycopyrronium bromide (m-anticholinergic blocker) is based on blocking the bronchoconstrictor action of acetylcholine on smooth muscle cells. respiratory tract, resulting in a bronchodilatory effect. Five subtypes of muscarinic receptors (M1–5) have been identified in the human body. Only M1–3 subtypes are known to be involved in physiological function respiratory system. Glycopyrronium bromide, being a muscarinic receptor antagonist, has a high affinity specifically for the M1-3 subtype receptors. At the same time, glycopyrronium bromide has 4–5 times greater selectivity for the M1 and M3 receptor subtypes compared to the M2 receptor subtype. This leads to a rapid onset of a therapeutic effect after inhalation of the drug, which is confirmed by clinical studies. The duration of action of the drug after inhalation is due to the long-term maintenance of the therapeutic concentration of the drug in the lungs, as evidenced by the longer T1 / 2 of the drug after inhalation use compared to intravenous administration. Numerous clinical studies have shown that against the background of the use of glycopyrronium bromide in patients with COPD, lung function improves significantly (assessment was carried out using changes in forced expiratory volume in 1 min (FEV1): therapeutic effect occurs within the first 5 minutes after inhalation, with a significant increase in FEV1 from baseline in the range of 0.091 to 0.094 l, the bronchodilating effect of glycopyrronium bromide after inhalation persists for more than 24 hours. clinical research, there is no evidence of the development of tachyphylaxis to the bronchodilatory effect of the drug against the background of regular use up to 52 weeks.
There were no changes in heart rate and the duration of the QTc interval against the background of the use of the drug Sibri® Breezhaler® at a dose of 200 mcg in patients with COPD.

Pharmacokinetics
Absorption. After inhalation, glycopyrronium bromide is rapidly absorbed into the systemic circulation and reaches Cmax in blood plasma after 5 minutes. The absolute bioavailability of glycopyrronium bromide after inhalation is approximately 40%. About 90% of the systemic exposure of glycopyrronium bromide is due to absorption in the lungs and 10% to absorption in the gastrointestinal tract. Absolute bioavailability after oral administration glycopyrronium bromide is estimated at 5%. Against the background of regular inhalations (1 time per day), the equilibrium state of glycopyrronium bromide is achieved within 1 week. Cmax of glycopyrronium bromide in the equilibrium state (inhalation 50 mcg 1 time per day) and the concentration of glycopyrronium bromide in the blood plasma immediately before taking the next dose are 166 and 8 pg / ml, respectively. Urinary excretion at steady state compared with the first administration suggests that systemic accumulation is dose-independent over the dose range of 25–200 μg.
Distribution. After intravenous administration, Vss of glycopyrronium bromide was 83 liters and Vd in the terminal phase was 376 liters. The apparent Vd in the terminal phase after inhalation was 7310 l, which reflects the slower elimination of the drug after inhalation. In vitro, the binding of glycopyrronium bromide to human plasma proteins was 38–41% at a concentration of 1–10 ng/mL. These concentrations are at least 6 times higher than those in the equilibrium state achieved in plasma against the background of the use of the drug at a dose of 50 mcg 1 time per day.
Metabolism. It has been noted that hydroxylation of glycopyrronium bromide leads to the formation of various mono- and bis-hydroxylated metabolites, and direct hydrolysis leads to the formation of carboxylic acid derivatives (M9). In vitro studies have shown that CYP isoenzymes contribute to the oxidative biotransformation of glycopyrronium bromide. Hydrolysis to M9 appears to be catalyzed by enzymes of the cholinesterase family. Since in vitro studies did not reveal the metabolism active ingredient in the lungs and M9 makes a minor contribution to the circulation (4% of Cmax and AUC of glycopyrronium bromide) after IV administration, it is assumed that M9 is formed from the absorbed fraction of the active substance from the gastrointestinal tract (after inhalation) by first-pass hydrolysis and / or during the primary passage through the liver. After inhalation or IV administration, only a minimal amount of M9 was detected in the urine (≤0.5% of the administered dose). Glucuronic conjugates and/or sulfates of glycopyrronium bromide have been detected in human urine after repeated inhalations at approximately 3% of the dose. In vitro inhibition studies demonstrated that glycopyrronium bromide was not significantly involved in the inhibition of CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 isoenzymes, the MDR1, MRP2, or MXR transporters, and the OATP1B1, OATP1B3, OAT1 transporters. OST1 or OST2. In vitro enzyme induction studies did not reveal a significant induction of glycopyrronium bromide for any of the cytochrome P450 isoenzymes tested, nor for UGT1A1 and the MDR1 and MRP2 transporters.
Withdrawal. Excretion of glycopyrronium bromide by the kidneys reaches 60-70% of the total plasma clearance, 30-40% is excreted in other ways - with bile or due to metabolism. After single and repeated inhalations of glycopyrronium bromide in the range of 50 to 200 mcg once a day in healthy volunteers and patients with COPD, the mean renal clearance was in the range of 17.4–24.4 l/h. Active tubular secretion contributes to the renal excretion of glycopyrronium bromide. Up to 20% of the dose taken is found in the urine unchanged. The plasma concentration of glycopyrronium bromide decreases in a multi-phase manner. The mean terminal T1 / 2 is longer after the inhalation route of administration (33–57 hours) than after intravenous administration (6.2 hours) and oral administration (2.8 hours). The nature of the elimination suggests prolonged absorption in the lungs and / or penetration of glycopyrronium bromide into the systemic circulation during and 24 hours after inhalation. In patients with COPD, the systemic exposure, as well as the total urinary excretion of glycopyrronium bromide at steady state, increased proportionally to the dose in the range from 50 to 200 mcg.

Special patient groups
A population pharmacokinetic analysis of data in patients with COPD revealed that body weight and age are not factors influencing inter-individual differences in the systemic exposure of the drug. Sibri® Breezhaler® at a dose of 50 mcg once a day can be safely used in any age group and at any body weight.
Gender, smoking and baseline FEV1 do not have a visible effect on the systemic exposure of glycopyrronium bromide.
Impaired liver function. Clinical studies in patients with impaired liver function have not been conducted. Excretion of glycopyrronium bromide occurs mainly due to excretion by the kidneys. It is expected that impairment of hepatic metabolism of glycopyrronium bromide will not lead to a clinically significant increase in systemic exposure.
Impaired kidney function. The systemic exposure of glycopyrronium bromide depends on the state of renal function. A moderate increase in total systemic exposure (AUC) up to 1.4 times was observed in patients with mild to moderate renal impairment. medium degree severity and up to 2.2 times in patients with severe renal impairment or end-stage renal disease. The use of a population pharmacokinetic analysis led to the conclusion that in patients with COPD and impaired renal function of mild to moderate severity (estimated by glomerular filtration rate (GFR ≥30 ml / min / 1.73 m2), Sibri® Breezhaler® can be used in the recommended doses.

Indications for Sibri® Breezhaler®
Maintenance therapy of bronchial conduction disorders in patients with chronic obstructive pulmonary disease.

Contraindications
hypersensitivity to glycopyrronium bromide or any other components that make up the drug;
simultaneous reception with inhalation drugs containing other m-anticholinergics;
galactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose);
age up to 18 years.
Carefully: angle-closure glaucoma; diseases accompanied by urinary retention; severe renal failure (GFR below 30 ml / min / 1.73 m2), including end-stage renal failure requiring hemodialysis (Sibri® Breezhaler® should be used only if the expected benefit outweighs the potential risk); unstable ischemic disease hearts; a history of myocardial infarction; violations heart rate; prolongation of the QTc interval (QT corrected >0.44 s).

Use during pregnancy and lactation
In preclinical studies, the absence of a teratogenic effect in the drug after inhalation use was shown. Due to the lack of clinical data on the use of Sibri® Breezhaler® in pregnant women, the drug can be used during pregnancy only if the expected benefit to the patient outweighs the potential risk to the fetus.
It is not known whether glycopyrronium bromide penetrates into breast milk in a person. The use of Sibri® Breezhaler® for breastfeeding should only be considered if the benefit to the mother outweighs any potential risk to the infant.
Neither reproductive toxicity studies nor other animal studies suggest that the drug may affect fertility in men or women.

Interaction
The simultaneous use of glycopyrronium bromide and inhaled indacaterol, a beta2-adrenergic agonist, does not affect the pharmacokinetics of both drugs.
In clinical studies in healthy volunteers, cimetidine, an inhibitor of organic cation transporters that affect the renal clearance of glycopyrronium bromide, increased the total exposure (AUC) of glycopyrronium bromide by 22% and reduced renal clearance by 23%. Based on these indicators, no clinically significant interaction is expected with the simultaneous use of Sibri® Breezhaler® with cimetidine or other cation transporter inhibitors.
In vitro studies have shown that Sibri® Breezhaler® probably does not affect the metabolism of other drugs.
Inhibition or induction of the metabolism of glycopyrronium bromide does not lead to significant changes systemic exposure of the drug.

Dosage and administration
Inhalation.
The drug is a capsule with a powder for inhalation, which should be used only for inhalation through the mouth using a special device for inhalation Breezhaler®, which is included in the package. The drug should not be taken orally. Capsules with powder for inhalation should be stored in a blister and removed from it immediately before use.
The recommended dose of Sibri® Breezhaler® is 50 mcg (content of 1 capsule) 1 time per day. Inhalation of the drug is carried out daily 1 time per day at the same time. If an inhalation is missed, the next dose should be taken as soon as possible. Patients should be instructed not to take more than 1 dose (50 mcg) per day.
Before starting the use of Sibri® Breezhaler®, patients should be instructed on the correct use of the inhaler.
If there is no improvement in respiratory function, you should make sure that the patient is using the drug correctly. The drug should be inhaled, not swallowed.

Special patient groups
Renal failure. In patients with mild to moderate renal impairment, the recommended dose of Sibri® Breezhaler® may be used. In patients with severe renal impairment or end-stage renal disease requiring hemodialysis, Sibri® Breezhaler® should be used at the recommended dose only if the intended benefit outweighs the potential risk.
Liver failure. Special clinical studies in patients with impaired liver function have not been conducted. The drug Sibri® Breezhaler® is excreted mainly by renal excretion, therefore, a significant increase in exposure in patients with impaired liver function is not expected. In patients with impaired liver function, the recommended dose of Sibri® Breezhaler® can be used.
Elderly patients. Sibri® Breezhaler® can be used at the recommended dose in patients aged 75 years and older.
Instructions for use of the Breezhaler® inhalation device
Each package of Sibri® Breezhaler® contains:
- 1 Breezhaler® inhalation device;
- blisters with capsules with powder for inhalation.
Capsules with powder for inhalation should not be taken orally.
The inhalation device Breezhaler®, which is in the package, is intended for use only with the capsules of the drug.
For inhalation of the capsules in the package, only the Breezhaler® inhalation device is used.
Do not use the drug capsules with any other inhalation device and, in turn, do not use Breezhaler® for inhalation of other drugs.
After 30 days of use, Breezhaler® should be discarded.

Using an inhaler
1. Remove cover.
2. Open Breezhaler®: To open the inhaler, hold it firmly by the base and tilt the mouthpiece.
3. Prepare a capsule: separate 1 bl. from the blister pack, tearing it off along the perforation; take one blister and remove the protective film from it to release the capsule; do not squeeze the capsule through the protective film.
4. Take out the capsule: the capsules should be stored in a blister and taken out only immediately before use; wipe your hands dry and remove the capsule from the blister; do not swallow the capsule.
5. Insert the capsule into the Breezhaler®: put the capsule into the capsule chamber; never put the capsule directly into the mouthpiece.
6. Close Breezhaler®: tightly close the inhaler; when it closes all the way, you should hear a click.
7. Pierce the capsule: hold Breezhaler® in a vertical position so that the mouthpiece is pointing up; simultaneously press all the way down on both buttons; when piercing the capsule, a click should be heard; do not press the buttons to pierce the capsule more than once.
8. Completely release the Breezhaler® inhaler buttons on both sides.
9. Exhale; before inserting the mouthpiece into your mouth, exhale completely; never blow into the mouthpiece.
10. Inhale the drug: hold Breezhaler® in your hand so that the buttons are left and right (and not top and bottom); put the mouthpiece of the Breezhaler® inhaler into your mouth and tightly squeeze your lips around it; take a quick, even, deep breath; do not press the buttons of the lancing device.
11. Pay attention. When inhaled through the inhaler, a characteristic rattling sound should be heard, created by the rotation of the capsule in the chamber and spraying the powder. The patient may feel a sweetish taste of the drug in the mouth. If a rattling sound is not heard, this may mean that the capsule is stuck in the chamber of the inhaler. In this case, open the inhaler and carefully release the capsule by tapping on the base of the device. To release the capsule, do not press the buttons to pierce the capsule. Repeat steps 9 and 10 if necessary.
12. Hold your breath: if a characteristic sound is heard during inhalation, hold your breath as long as possible (so as not to experience discomfort), and at the same time remove the mouthpiece from your mouth; then exhale. Open Breezhaler® and see if there is any powder left in the capsule. If powder remains in the capsule, close Breezhaler® and repeat steps 9–12. Most people can empty a capsule in 1 or 2 inhalations. Some people have a cough for a short time after inhalation of the drug, but you should not worry about this. If there is no powder left in the capsule, then the patient has received the full dose of the drug.
13. Remove the capsule: after taking a daily dose of Sibri® Breezhaler®, tilt the mouthpiece, remove the empty capsule by tapping on the inhaler and discard it. Close the mouthpiece of the Breezhaler® inhaler and close the Breezhaler® cap. Do not store capsules in the Breezhaler® inhaler.
The following must be remembered:
Do not swallow powder capsules for inhalation.
Use only Breezhaler®, which is in the package.
Capsules should be stored in a blister and removed immediately before use.
Never insert a capsule into the mouthpiece of the Breezhaler® inhaler.
Do not press the lancing device more than once.
Never blow into the mouthpiece of the Breezhaler® inhaler.
Always pierce the capsule before inhalation.
Do not wash Breezhaler®. Keep it dry (see How to clean Breezhaler®).
Do not disassemble Breezhaler®.
Starting a new package of the drug, always use the new Breezhaler®, which is in the package, for inhalation of capsules.
Do not store capsules in the Breezhaler® inhaler.
Always store capsule blisters and Breezhaler® in a dry place.
Additional Information
In very rare cases, a small amount of the contents of the capsules may enter the mouth.
Do not worry when inhaling or swallowing the drug.
When piercing the capsule more than once, the risk of breaking it increases.
How to clean Breezhaler®
Clean Breezhaler® once a week. Wipe the mouthpiece inside and out with a clean, dry cloth. Never use water to clean the Breezhaler® inhaler. Keep it dry.

Overdose
There is no data on an overdose of Sibri® Breezhaler®.
In patients with COPD, regular inhalation administration of Sibri® Breezhaler® in a total dose of 100 and 200 mcg once a day for 28 days was well tolerated.
Acute intoxication in case of accidental ingestion of a capsule of Sibri® Breezhaler® is unlikely due to the low oral bioavailability of glycopyrronium bromide (about 5%).
Plasma Cmax and total systemic exposure after intravenous administration of 150 μg glycopyrronium bromide (equivalent to 120 μg glycopyrronium) in healthy volunteers were approximately 50 and 6 times higher, respectively, than plasma Cmax and total systemic exposure at steady state achieved when using the drug Sibri® Breezhaler® inhalation at the recommended doses (50 mcg 1 time per day). Signs of an overdose were not detected.

special instructions
The drug Sibri® Breezhaler® is not recommended for the relief of acute episodes of bronchospasm.
Hypersensitivity reactions
Cases of the development of immediate-type hypersensitivity reactions have been reported after the use of Sibri® Breezhaler®. If there are signs that indicate the development allergic reaction, incl. angioedema (including difficulty breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, the drug should be discontinued and alternative therapy should be selected.
Paradoxical bronchospasm
As in cases of other inhalation therapy, the use of the drug Sibri® Breezhaler® can lead to paradoxical bronchospasm, which can be life-threatening. In the event of paradoxical bronchospasm, the use of Sibri® Breezhaler® should be immediately discontinued and alternative therapy applied.
M-anticholinergic effect
Like other m-anticholinergic drugs, Sibri® Breezhaler® should be used with caution in patients with angle-closure glaucoma or urinary retention.
Patients should be informed about the signs and symptoms of an acute attack of angle-closure glaucoma and the need to stop using Sibri® Breezhaler®, and immediately inform their doctor if any of these signs or symptoms develop.
severe kidney failure
Patients with impaired renal function (GFR less than 30 ml/min/1.73 m2), including patients with end-stage disease requiring hemodialysis, should be closely monitored for possible adverse drug reactions. Sibri® Breezhaler® is intended for the maintenance treatment of patients with COPD. Due to the fact that patients over the age of 40 years significantly predominate in the general COPD population, when using the drug in patients under 40 years of age, spirometric confirmation of the diagnosis of COPD is required.

Impact on ability to drive vehicles and work with mechanisms
The drug Sibri® Breezhaler® does not adversely affect the ability to drive vehicles, mechanisms.

Release form
Capsules with powder for inhalation, 50 mcg. In a blister pack of polyamide/aluminum/PVC and aluminum foil, 6 pcs. 1, 2, 4 or 5 bl. together with a device for inhalation (Breezhaler®) in a cardboard box.
Multipack. 3 packs of 5 bl. together with a device for inhalation (Breezhaler®), 4 packs of 4 bl. together with a device for inhalation (Breezhaler®) or 25 packs of 1 bl. c together with a device for inhalation (Breezhaler®).

Manufacturer
Novartis Pharma AG, Switzerland.
Manufactured by: Novartis Pharma Stein AG. Lichtstrasse 35, 4056 Basel, Switzerland.
Manufacturer's address: Novartis Pharma Stein AG. Switzerland, 4332 Stein, Schaffhauserstrasse.

Terms of dispensing from pharmacies
On prescription.

Storage conditions of Sibri® Breezhaler®
In a dry place, at a temperature not exceeding 25 °C.
Keep out of the reach of children.

Shelf life of Sibri® Breezhaler®
2 years.
Do not use after the expiry date stated on the packaging.

Compound

Capsules with powder for inhalation, hard, size No. 3, with a transparent cap and an orange body, with a special marking "Novartis logo" under the black stripe on the cap and the inscription "GPL50" in black ink above the black stripe on the body; the contents of the capsules are white or almost white powder.

1 caps.-glycopyrronium bromide 63 mcg, which corresponds to the content of glycopyrronium base 50 mcg

Excipients: lactose monohydrate - 24.9 mg, magnesium stearate - 0.037 mg.

Capsule composition: hypromellose - 45.59 mg, water - 2.7 mg, carrageenan - 0.42 mg, sodium chloride - 0.18 mg, dye sunset yellow (E110) - 0.12 mg.

Ink composition: shellac, black iron oxide, propylene glycol, sodium hydroxide.

Release form

6 pcs. - blisters made of Polyamide/Aluminum/PVC-Aluminum (5) complete with a device for inhalation (breather) - packs of cardboard.

pharmachologic effect

Sibri Breezhaler is an inhaled long-acting drug. Glycopyrronium bromide - (m-anticholinergic blocker), the mechanism of action of which is based on blocking the bronchoconstrictor action of acetylcholine on the smooth muscle cells of the respiratory tract, which leads to a bronchodilating effect. Five subtypes of muscarinic receptors (M1-5) have been identified in the human body. It is known that only the M1-3 subtypes are involved in the physiological function of the respiratory system.

Glycopyrronium bromide, being an antagonist of muscarinic receptors, has a high affinity specifically for receptors of the M1-3 subtype. At the same time, glycopyrronium bromide has a 4-5 times greater selectivity for the M1 and M3 receptor subtypes compared to the M2 receptor subtype. This leads to a rapid onset of a therapeutic effect after inhalation of the drug, which is confirmed by clinical studies. The duration of action of the drug after inhalation is due to the long-term maintenance of the therapeutic concentration of the drug in the lungs, as evidenced by the longer half-life of the drug after inhalation, compared with intravenous administration. Numerous clinical studies have shown that against the background of the use of glycopyrronium bromide in patients with chronic obstructive pulmonary disease (COPD), pulmonary function improves significantly (assessed using changes in forced expiratory volume in 1 min (FEV1)): the therapeutic effect occurs during the first 5 minutes after inhalation, with a significant increase in FEV) from baseline in the range of 0.091 l to 0.094 l, the bronchodilating effect of glycopyrronium bromide after inhalation persists for more than 24 hours. According to clinical studies, there is no evidence of the development of tachyphylaxis to the bronchodilatory effect of the drug against the background of regular use up to 52 weeks.

There were no changes in heart rate (HR) and the duration of the QTc interval against the background of

Indication for use

- maintenance therapy of bronchial conduction disorders in patients with chronic obstructive pulmonary disease.

Methods of application and doses

For inhalation use only!

The drug is a capsule with a powder for inhalation, which should be used only for inhalation through the mouth using a special device for inhalation Breezhaler, which is included in the package. The drug should not be taken orally. Capsules with powder for inhalation should be stored in a blister and removed from it immediately before use.

The recommended dose of Sibri Breezhaler is 50 mcg (contents of 1 capsule) 1 time per day. Inhalation of the drug is carried out daily 1 time per day at the same time. If an inhalation is missed, the next dose should be taken as soon as possible. Patients should be instructed not to take more than 1 dose (50 micrograms) per day.

In the case of the appointment of Sibri Breezhaler, patients should be instructed on the correct use of the inhaler.

Use in patients with kidney failure

In patients with mild to moderate renal insufficiency, the recommended dose of Sibri Breezhaler may be used. In patients with severe renal insufficiency or end-stage kidney disease requiring hemodialysis, Sibri Breezhaler should be used at the recommended dose only if the expected benefit outweighs the potential risk.

Use in patients with hepatic impairment

No specific clinical studies have been conducted in patients with hepatic impairment. The drug Sibri Breezhaler is excreted mainly by renal excretion, so a significant increase in exposure in patients with hepatic insufficiency is not expected. In patients with impaired liver function, the recommended dose of Sibri Breezhaler may be used.

Use in elderly patients

Sibri Breezhaler can be used at the recommended dose in patients aged 75 years and older.

Directions for use

Each package of Sibri Breezhaler contains:

One inhalation device - Breezhaler

Blisters with capsules with powder for inhalation

Capsules with powder for inhalation should not be taken orally!

The inhalation device Breezhaler, which is in the package, is intended for use only with the capsules of the drug.

For inhalation of the capsules in the package, only the Breezhaler inhalation device is used.

Do not use the drug capsules with any other inhalation device and, in turn, do not use Breezhaler for inhalation of other drugs.

Throw away Breezhaler after 30 days of use.

How to use an inhaler

Remove the cover.

Open Breezhaler.

To open the inhaler, grasp the base firmly and tilt the mouthpiece.

Prepare the capsule:

Separate one blister from the blister pack by tearing it off at the perforation.

Take one blister and remove the protective film from it to release the capsule.

Do not squeeze the capsule through the protective film.

Take out the capsule:

Capsules should be stored in a blister and removed only immediately before use. Dry your hands and remove the capsule from the blister. Do not swallow the capsule.

Insert capsule into Breezhaler:

Put the capsule into the capsule chamber.

Never put a capsule directly into the mouthpiece.

Close Breezhaler:

Close the inhaler tightly. When it closes all the way, you should hear a "click".

Pierce the capsule:

Hold the Breezhaler upright with the mouthpiece pointing up.

Press all the way down on both buttons at the same time. When piercing the capsule, a “click” should be heard.

Do not press the buttons to pierce the capsule more than once.

Fully release the Breezhaler inhaler buttons on both sides.

Breathe out:

Exhale completely before inserting the mouthpiece into your mouth.

Never blow into the mouthpiece.

Inhale medication:

Hold the Breezhaler in your hand so that the buttons are left and right (not top and bottom), as shown in the picture.

Put the mouthpiece of the Breezhaler inhaler into your mouth and close your lips tightly around it.

Take a quick, even, deep breath. Do not press the lancing device buttons.

Note:

When you inhale through the inhaler, you should hear a characteristic rattling sound created by the rotation of the capsule in the chamber and the atomization of the powder. You may feel a sweetish taste of the drug in your mouth.

If you do not hear a rattling sound, this may mean that the capsule is stuck in the chamber of the inhaler.

In this case, open the inhaler and gently release the capsule by tapping on the base of the device. To release the capsule, do not press the capsule piercing buttons. Repeat steps 9 and 10 if necessary.

Hold your breath:

If you hear a characteristic sound while inhaling, hold your breath as long as possible (so as not to experience discomfort), and at the same time remove the mouthpiece from your mouth. After that, exhale.

Open Breezhaler and see if there is any powder left in the capsule. If powder remains in the capsule, close Breezhaler and repeat steps 9-12. Most people can empty a capsule in one or two inhalations.

Some people have a cough for a short time after inhaling the drug. If you cough, don't worry. If there is no powder left in the capsule, then you have received the full dose of the drug.

Take out the capsule:

After you have taken your daily dose of Sibri Breezhaler, tilt the mouthpiece, remove the empty capsule by tapping on the inhaler and discard it. Close the mouthpiece of the Breezhaler inhaler and close the Breezhaler cap.

Do not swallow powder capsules for inhalation.

Use only Breezhaler, which is in the package.

Capsules should be kept in a blister pack and removed immediately before use.

Never insert a capsule into the mouthpiece of a Breezhaler inhaler. Do not press the lancing device more than once.

Never blow into the mouthpiece of a Breezhaler inhaler.

Always roll the capsule before inhalation.

Do not wash Breezhaler. Keep it dry. See section "How to clean the Breezhaler". Do not disassemble Breezhaler.

When starting a new package of the drug, always use the new Breezhaler that is in the package for inhalation of the capsules.

Do not store capsules in the Breezhaler inhaler.

Always store capsule blisters and Breezhaler in a dry place.

Additional Information

In very rare cases, a small amount of the contents of the capsules may enter the mouth. Don't worry if you inhale it or swallow it.

Please note that if you pierce the capsule more than once, the risk of breaking it increases.

How to clean Breezhaler

Clean the Breezhaler once a week. Wipe the mouthpiece inside and out with a clean, dry cloth. Never use water to clean your Breezhaler inhaler. Keep it dry.

Contraindications

- hypersensitivity to glycopyrronium bromide or any other components that make up the drug;

- age up to 18 years;

- simultaneous administration with inhalation drugs containing other m-anticholinergics;

- galactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose).

Carefully

Angle-closure glaucoma, diseases accompanied by urinary retention, severe renal failure (GFR below 30 ml / min / 1.73 m2), including end-stage renal disease requiring hemodialysis (Sibri Breezhaler should be used only if the expected benefit exceeds the potential risk); unstable coronary heart disease (CHD), a history of myocardial infarction, cardiac arrhythmias, prolongation of the QTc interval (QT corrected > 0.44 s).

special instructions

Paradoxical bronchospasm

As with other inhalation therapy, the use of Sibri Breezhaler can lead to paradoxical bronchospasm, which can be life-threatening. In the event of paradoxical bronchospasm, the use of Sibri Breezhaler should be immediately discontinued and alternative therapy prescribed.

M-anticholinergic effect

Like other m-anticholinergics medicines Sibri Breezhaler should be used with caution in patients with angle-closure glaucoma or urinary retention.

Patients should be informed about the signs and symptoms of an acute attack of angle-closure glaucoma and the need to stop using Sibri Breezhaler, and immediately inform their doctor if any of these signs or symptoms develop.

severe kidney failure

Patients with severe renal insufficiency (GFR less than 30 ml/min/1.73 m2), including patients with end-stage disease requiring hemodialysis, should be closely monitored for possible adverse drug reactions.

Sibri Breezhaler is intended for the maintenance treatment of patients with COPD.

Due to the fact that patients over the age of 40 years significantly predominate in the general COPD population, when prescribing the drug to patients under 40 years of age, spirometric confirmation of the diagnosis of COPD is required.

Impact on ability to perform potentially dangerous species activities requiring special attention and quick reactions (driving vehicles, working with moving mechanisms, etc.)

Sibri Breezhaler does not adversely affect the ability to drive vehicles and perform potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Storage conditions

In a dry place at a temperature not exceeding 25°C. Keep out of the reach of children. Shelf life - 2 years.

Note

Terms of dispensing from pharmacies

R.03.B.B.06 Glycopyrronium bromide