Description
Release form
Capsules with powder for inhalation, solid, size No. 3, with a transparent lid and an orange body, with a special marking, the Novartis logo under the black stripe on the cap and the GPL50 inscription in black ink over the black stripe on the body contains the contents of the capsules in white or almost white powder.
Pharmacological action
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 smooth muscle cells of the respiratory tract, which leads to a bronchodilating effect. In the human body, 5 subtypes of muscarinic receptors (M1-5) have been identified. It is known that only subtypes M1-3 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 subtype M1-Z. Moreover, glycopyrronium bromide has a 4-5-fold higher 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, as 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, which is confirmed 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 significantly improves (assessment was carried out by changing the forced expiratory volume in 1 min (FEV1)): the therapeutic effect occurs during the first 5 minutes after inhalation, with a significant increased 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 bronchodilating effect of the drug with regular use up to 52 weeks.
No changes in heart rate (HR) and QTc duration were observed with the use of Sibri Breezhaler at a dose of 200 mcg in patients with COPD.
Indications
– supportive care for bronchial conduction disorders in patients with chronic obstructive pulmonary disease.
Contraindications
– hypersensitivity to glycopyrronium bromide or any other components that are part of the drug
– children and adolescents under 18 years of age
– concomitant use with inhaled drugs containing other m-anticholinergic lactose deficiency, lactose deficiency, glucose-galactose malabsorption (the drug contains lactose).
Precautions
Angle-closure glaucoma, diseases associated with urinary retention, severe renal failure (GFR below 30 ml / min / 1.73 m2), including end-stage renal failure requiring hemodialysis (Sibri ® Breezhaler ® should only be used if if the expected benefit exceeds the potential risk) unstable coronary heart disease, a history of myocardial infarction, heart rhythm disturbances, lengthening of the QTc interval (QT adjusted> 0.44 s).
Use during pregnancy and lactation
Preclinical studies have shown that the drug does not have a teratogenic effect after inhalation. 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 intended benefit to the patient outweighs the potential risk to the fetus.
It is not known whether glycopyrronium bromide passes into breast milk in humans. The use of Sibri ® Breezhaler ® during breastfeeding should only be considered if the benefits to the mother outweigh any potential risk to the baby.
Neither reproductive toxicity studies nor other animal studies suggest that the drug may affect fertility in men or women.
Composition
Composition of the capsule: hypromellose – 45.59 mg, water – 2.7 mg, carrageenan – 0.42 mg, sodium chloride – 0.18 mg, dye sunny sunset yellow (E110) – 0.12 mg.
Ink composition: shellac, dye iron oxide black, propylene glycol, sodium hydroxide.
Dosage and administration
For inhalation only!
The drug is a capsule with inhalation powder, which should be used only for inhalation through the mouth with the help of 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 immediately before use.
The recommended dose of Sibri ® Breezhaler ® is 50 mcg (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 skipping 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 using Sibri ® Breezhaler ®, patients should be instructed in the proper use of the inhaler.
If there is no improvement in respiratory function, make sure that the patient is using the drug correctly. The drug should be inhaled, not swallowed.
In patients with impaired renal function of mild to moderate severity, Sibri ® Breezhaler ® can be used in the recommended dose. In patients with severe renal impairment or end-stage renal disease requiring hemodialysis, Sibri ® Breezhaler ® should be used in the recommended dose only if if the intended benefit exceeds the potential risk.
No specific clinical studies have been conducted in patients with impaired liver function. 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 ® Breezhaler ® can be used in the recommended dose.
In patients 75 years of age and older, Sibri ® Breezhaler ® can be used at the recommended dose.
Side effects
The safety profile of Sibri® Breezhaler® is characterized by symptoms associated with m-anticholinergic action, including dry mouth (2.2%), while other gastrointestinal effects and signs of urinary retention were infrequent.
Adverse drug reactions associated with local drug tolerance included pharyngeal irritation, nasopharyngitis, rhinitis and sinusitis. In recommended doses, the Sibri® Brizkhaler® preparation does not affect blood pressure and heart rate.
The safety and tolerability of Sibri® Breezhaler® was investigated in 1353 patients with COPD at a recommended dose of 50 mcg 1 time / day. Of these, 842 patients were treated for at least 26 weeks and 351 for at least 52 weeks.
Determination of the frequency of adverse drug reactions: very often (? 1/10) often (? 1/100, <1/10) infrequently (? 1/1000, <1/100) rarely (? 1/10 000, 1/1000 ) is very rare (<1/10 000). Infectious and parasitic diseases: often – nasopharyngitis infrequently – rhinitis, cystitis. From the side of metabolism: infrequently – hyperglycemia. From the side of the psyche: often – insomnia. From the nervous system: often – headache infrequently – hypesthesia. From the cardiovascular system: infrequently – atrial fibrillation, palpitations. From the respiratory system, chest and mediastinal organs: infrequently – congestion in the sinuses, productive cough, pharyngeal irritation, nosebleeds. From the digestive system: often – dry mouth, gastroenteritis infrequently – dyspepsia, dental caries. From the skin and subcutaneous tissues: infrequently – skin rash. From 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 trial lasting 12 months, the following additional adverse events were identified, which were more common with Sibri® Breezhaler® compared with placebo: nasopharyngitis (9.0% vs 5.6%), vomiting (1.3% vs 0.7%), muscle pain (1.1% vs 0.7%), neck pain (1.3 % versus 0.7%), diabetes mellitus (0.8% against 0%). Undesirable drug reactions obtained during post-marketing research and according to the literature: since the data are reported on a voluntary basis from a population of uncertain size, it is not possible to determine their frequency (frequency is unknown) – angioedema. In elderly patients over 75 years of age, the incidence of urinary tract infections and headache with Sibri® Brizkhaler® 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 your doctor. Drug 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 transporters of organic cations that affect renal clearance of glycopyrronium bromide, increased total exposure (AUC) of glycopyrronium bromide by 22% and decreased 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 glycopyrronium bromide metabolism does not lead to significant changes in the systemic exposure of the drug. Overdose There is no data on an overdose of Sibri ® Brizkhaler ®. In patients with COPD, regular inhalation administration of the Sibri ® Brizkhaler ® preparation at a total dose of 100 and 200 mcg once a day for 28 days was well tolerated. Acute intoxication with accidental ingestion of a Sibri ® Brizkhaler ® capsule is unlikely due to the low bioavailability of glycopyrronium bromide when administered orally (about 5%). Cmax 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 Cmax in plasma and total systemic exposure in equilibrium achieved with the use of Sibri ® Breezhaler ® inhaled in recommended doses (50 mcg 1 time / day). There were no signs of overdose. Storage conditions The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25 ° C. Expiration Expiration is 2 years. Deystvuyuschee substances Hlykopyrronyya bromide, Yndakaterol pharmacy terms of prescription Form of Treatment kapsul Appointment Vzrosl m on purpose doctor Indications Low learning, Bronchial asthma, Bronchospasm Possible product names Ultibro Breezhaler capsules with powder for inhalation 50 mcg + 110 mcg in a set with an inhaler 30pcs.
