Ultibro brizhaler capsules 50mkg + 110mkg №30

Mechanism of action

Sibri Brizhaler - long-acting inhalation drug. Glycopyrronium bromide - (m-holinoblokator), whose mechanism of action is based on blocking the bronchoconstrictor action of acetylcholine on the smooth muscle cells of the respiratory tract, which leads to the bronchodilatory effect. In humans, 5 subtypes of muscarinic receptors (M1-5) were detected. 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 for receptors of the subtype M1-3. At the same time, glycopyrronium bromide has a 4-5 times greater selectivity for the M1 and M3 receptor subtype, compared with the M2 receptor subtype. This leads to the rapid emergence of a therapeutic effect after inhalation of the drug, which is confirmed by clinical studies. The duration 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 is significantly improved (the assessment was carried out by changing the forced expiratory volume in 1 minute (FEV1)): 5 minutes after inhalation, with a significant increase in FEV) from baseline values ​​in the range of 0.091 l to 0.094 l, the bronchodilatory effect of glycopyrronium bromide persists for more than 24 hours after inhalation. According to clinical studies, there is no evidence of the development of tachyphylaxis to the bronchodilating 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 during the use of the drug Sibri Bryzhaler in a dose of 200 mcg in patients with COPD.

Indications

- supportive 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;

- children's and teenage age up to 18 years;

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

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

Carefully

Angle-closure glaucoma, diseases associated with urinary retention, severe renal failure (GFR below 30 ml / min / 1.73 m²), including end-stage renal disease requiring hemodialysis (Sibri preparation^® Brizhaler^® should be used only if the expected benefit outweighs the potential risk); unstable coronary artery disease, myocardial infarction in history, cardiac arrhythmias, prolongation of the QT interval_c (QT corrected> 0.44 s).

Use during pregnancy and lactation

In preclinical studies it was shown that the drug has no teratogenic effect after inhalation. Due to the lack of clinical data on the use of the drug Sibri^® Brizhaler^® in pregnant women, the drug can be used during pregnancy only if the intended use for the patient exceeds the potential risk to the fetus.

It is not known whether glycopyrronium bromide passes into breast milk in humans. Use of the drug Sibri^® Brizhaler^® 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.

Composition

The composition of the capsule: hypromellose - 45.59 mg, water - 2.7 mg, carrageenan - 0.42 mg, sodium chloride - 0.18 mg, sunset sunflower yellow (E110) - 0.12 mg.

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

Dosage and administration

For inhalation use only!

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 Brizhaler^®which is included in the package. The drug can 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 the drug Sibri^® Brizhaler^® makes 50 mkg (contents of 1 capsule) 1 time / day. Inhalation of the drug is carried out daily 1 time / day at the same time. In case of missing inhalation, the next dose should be taken as soon as possible. Patients should be instructed not to take more than 1 dose of the drug (50 mcg) per day.

Before starting to use the drug Sibri^® Brizhaler^® Patients should be instructed in the proper use of the inhaler.

In the absence of an improvement in respiratory function, you should ensure that the patient is using the drug correctly. The drug should be inhaled, not swallowed.

In patients with impaired renal mild and moderate severitySibri^® Brizhaler^® can be used in the recommended dose. In patients with severe renal impairment or end-stage renal disease requiring hemodialysis, Sibri^® Brizhaler^®should be used at the recommended dose only if the intended benefit outweighs the potential risk.

Special clinical studies in patients with impaired liver function was not conducted. Glycopyrronium bromide 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 Sibri^® Brizhaler^® can be used in the recommended dose.

Patients aged 75 and older in Sibri^® Brizhaler^® can be used in the recommended dose.

Side effects

The safety profile of the drug Sibri^® Brizhaler^® characterized by symptoms associated with m-anticholinergic effects, including dry mouth (2.2%), while other effects on the gastrointestinal tract and signs of urinary retention were infrequent.

Adverse drug reactions associated with local tolerance of the drug included pharyngeal irritation, nasopharyngitis, rhinitis, and sinusitis. In the recommended doses of the drug Sibri^® Brizhaler^® does not affect blood pressure and heart rate.

Safety and tolerability of the drug Sibri^® Brizhaler^® was studied when used in 1353 patients with COPD at the recommended dose of 50 mcg 1 time / day. Of these, 842 patients were treated for at least 26 weeks and 351 - at least 52 weeks.

Determination of the frequency of undesirable drug reactions: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10,000, 1/1000); very rarely (<1/10 000).

Infectious and parasitic diseases: often - nasopharyngitis; infrequently - rhinitis, cystitis.

On the part of metabolism: infrequently - hyperglycemia.

On the part of the psyche: often - insomnia.

From the nervous system: often - headache; infrequently - hypesthesia.

Cardiovascular: infrequently - atrial fibrillation, palpitations.

On the part of the respiratory system, organs of the chest and mediastinum: infrequently - congestion in the sinuses, productive cough, irritation of the pharynx, nosebleeds.

On the part of the digestive system: often - dry mouth, gastroenteritis; infrequently - dyspepsia, dental caries.

On the part of the skin and subcutaneous tissues: infrequently - skin rash.

On the part of the musculoskeletal system: infrequently - pain in the limbs, pain in the skeletal muscles of the chest.

From the urinary system: often - urinary tract infection; infrequently - dysuria, urinary retention.

General disorders: infrequently - fatigue, asthenia.

In a clinical study lasting for 12 months, the following additional adverse events were identified that occurred more frequently with the use of Sibri^® Brizhaler^® compared to placebo: nasopharyngitis (9.0% versus 5.6%), vomiting (1.3% versus 0.7%), muscle pain (1.1% versus 0.7%), pain in the neck (1.3% versus 0.7%), diabetes (0.8% against 0%).

Undesirable drug reactions obtained during post-marketing research and according to the literature: since the data are reported voluntarily from a population of uncertain size, it is not possible to determine their frequency (frequency unknown) - angioedema.

Elderly patients older than 75 years, the frequency of urinary tract infections and headache with the use of the drug Sibri^®Brizhaler^® was higher than in the placebo group (3.0% versus 1.5% and 2.3% versus 0%, respectively).

If any of the above side effects are exacerbated or any other side effects occur, the patient should inform the physician.

Drug interaction

The simultaneous use of glycopyrronium bromide and inhaled indacaterol, beta agonist₂-adrenoreceptors, does not affect the pharmacokinetics of both drugs.

In clinical studies in healthy volunteers, cimetidine, an inhibitor of organic cation transporters that affect 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 simultaneous use of the drug Sibri.^® Brizhaler^® with cimetidine or other cation transporter inhibitors. In vitro studies have shown that the drug Sibri^® Brizhaler^® probably does not affect the metabolism of other drugs.

Inhibition or induction of the metabolism of glycopyrronium bromide does not lead to significant changes in the systemic exposure of the drug.

Overdose

No data on drug overdose Sibri^® Brizhaler^®.

In patients with COPD, regular inhalation administration of the drug Sibri^®Brizhaler^® in the total dose of 100 and 200 mg once a day for 28 days was well tolerated. Acute intoxication upon accidental ingestion of the capsule of the drug Sibri^® Brizhaler^® unlikely due to the low bioavailability of glycopyrronium bromide when administered orally (about 5%).

C_max in plasma and total systemic exposure after iv administration of 150 μg glycopyrronium bromide (equivalent to 120 μg glycopyrronium) in healthy volunteers were approximately 50 and 6 times higher, respectively, than C_maxin blood plasma and overall systemic exposure in the equilibrium state, achieved with the use of the drug Sibri^® Brizhaler^® inhalation at recommended doses (50 mcg 1 time / day). Signs of overdose were not detected.

Storage conditions

The drug should be kept out of the reach of children, in a dry place at a temperature not exceeding 25 ° C.