Bretaris Genuair inhalation powder dispenser 322mcg/dose 60 doses 1pc

Composition

Powder for inhalation

Active ingredient:

clidinium bromide;

Auxiliary substances:

lactose monohydrate.

Pharmacological action

Clinical efficacy studies have shown that Bretaris Generic provides clinically significant improvement in lung function (measured by forced expiratory volume per second [FEV 1]) for more than 12 hours after morning and evening use, which was manifested within 30 minutes after the first dose (an increase in FEV 1 compared to baseline is 124-133 ml). Maximum bronchodilation was achieved within 1-3 hours after taking the dose, with an average peak improvement in FEV1 relative to the baseline level of 227-268 ml at steady state.

Electrophysiology of the heart

When aclidinium bromide (200 mcg or 800 mcg) was administered to healthy volunteers once a day for 3 days, no effect on the QT interval (corrected by the Friederitz or Bazett method or individually) was observed.

There was also no clinically significant effect of Bretaris Generic on heart rate during 24-hour Holter monitoring in 336 patients (164 of whom received Bretaris Generic® twice daily at a dose of 322 mcg) after 3 months of use of the drug.

Clinical efficacy

The Bretaris ® Generic Phase III clinical trial program included 269 patients treated with Bretaris® Generic at a dose of 322 mcg twice daily in one 6-month randomized trial with placebo control, and 190 patients treated with Bretaris® Generic at a dose of 322 mcg twice daily in another 3-month randomized trial with placebo control. Efficacy was assessed by the dynamics of lung function and clinical symptoms, such as shortness of breath, diagnosis-related health status, the use of emergency medications, and the presence of exacerbations. In long-term safety studies, Bretaris ® Generic® has been shown to be effective for bronchodilators with a duration of use of more than 1 year.

Bronchodilation

During the 6-month study, patients treated with Bretaris® Generic® at a dose of 322 mcg twice daily showed clinically significant improvement in lung function (measured by FEV). The maximum bronchodilatory effect was manifested from the first day and persisted during the 6-month treatment period. After 6 months of therapy, average improvement before taking the morning dose (minimum) FEV] compared to placebo was 128 ml (95% CI=85-170; p

Similar observations were made for Bretaris ® Generic® during the 3-month study.

Disease-specific health status and symptomatic improvement

Bretaris ® Generic provided clinically significant improvements in shortness of breath (assessed using the Transient Dyspnea Index [TDI]) and disease-related health status (assessed using the St. George’s Hospital Respiratory Questionnaire [SGRQ]). The table below shows a reduction in symptoms after 6 months of Bretaris Generic treatment.

Variable

Treatment

Improvement over placebo P

-value

Bretaris* “_

“”®Placebo Generic

Transient dyspnea index

Percentage of patients with minimal clinically significant difference 3

56,9

45,5

1,68-multiple

increase

in probability

of 0.004

Average change from baseline

1.9

0.9

1.0 units

St. George’s Hospital Respiratory Questionnaire

Percentage of patients with minimal clinically important

difference57

.3 41.0

1.87-fold

increase

in probability

Average change from baseline

-7.4

-2,8

– 4,6 units

a) Minimum clinically important difference (MCID) of at least 1 unit change in the Transient Dyspnea Index.

b) Minimum Clinically significant difference (MCID) of at least 4 units of change on the St. George’s Hospital Respiratory Questionnaire.

c) Odds ratio, an increase in the probability of achieving the minimum clinically important difference compared to placebo.

Patients treated with Bretaris ® Generic® required fewer emergency medications than patients treated with placebo (a decrease of 0.95 injections per day for 6 months [p=0.005]). Bretaris ® Generic also improved daytime symptoms of COPD (shortness of breath, cough, and sputum formation), as well as night and early morning clinical symptoms.

A pooled analysis of the effectiveness of 6-month and 3-month placebo-controlled trials showed a significant reduction in the incidence of moderate and severe exacerbations (requiring antibiotic or glucocorticoid therapy or leading to hospitalization) when taking 322 mcg of aclidinium twice daily compared to placebo (frequency per patient per year: 0.31 vs. 0.44, respectively; p=0.0149).

Exercise tolerance

In a 3-week, randomized, cross-sectional, placebo-controlled clinical trial with Bretaris ® Generic, there was a statistically significant 58-second increase in exercise duration compared to placebo (95% CI=9-108; p=0.021; pre-treatment values: 486 seconds).

When Bretaris® Generic was used, there was a statistically significant reduction in excessive lung overextension at rest (functional residual capacity [FEU]=0.197 l [95% CI=0.321,0.072; p=0.002]; residual volume [RV]=0.238 L [95% CI=0.396,0.079; p=: 0.004]), as well as an improvement in minimum inspiratory capacity (by 0.078 L; 95% CI=0.01,0.145; p=0.025) and decreased shortness of breath during exercise (Borg scale) (by 0.63 Borg units; 95% CI= 1.11,0.14; p=0.012).

Absorption

Aclidinium bromide is rapidly absorbed from the lungs, reaching its maximum plasma concentration within 5 minutes after inhalation in healthy volunteers, and usually within the first 15 minutes in patients with COPD. The fraction of the inhaled dose that reached the systemic circulation as unchanged aclidinium is very low, less than 5%.

The maximum plasma concentration achieved after inhalation of dry powder in patients with COPD at a single dose of 400 mcg of aclidinium bromide was approximately 80 pg / ml. Steady-state plasma concentrations were reached within 7 days when taken twice daily and, given the short half-life, steady-state concentrations may be reached shortly after the first dose. Accumulation during repeated use at steady-state concentrations was not observed.

Distribution

The total amount of aclidinium bromide entering the lungs through the Bretaris Generic inhaler was approximately 30% of the measured dose.

The binding of aclidinium bromide to plasma proteins in vitro, most likely corresponds to the binding of metabolites to proteins, due to the rapid hydrolysis of aclidinium bromide in plasma, the binding to plasma proteins was 87% for the carboxylic acid metabolite and 15% for the alcohol metabolite. The main plasma protein that binds aclidinium bromide is albumin.

Biotransformation

Aclidinium bromide is rapidly and actively hydrolyzed to its pharmacologically inactive alcohol derivatives and carboxylic acid derivatives. There is both chemical hydrolysis (nonenzymatic) and enzymatic, with the participation of esterases. The main esterase involved in hydrolysis in humans is butyrylcholinesterase. The level of the acidic metabolite in the blood plasma after inhalation is approximately 100 times higher than the level of the alcohol metabolite and the unchanged Active ingredient.

Low absolute bioavailability of aclidinium bromide by inhalation (

Biotransformation involving cytochrome P450 (CYP450) isoenzymes plays a minor role in the overall metabolic clearance of aclidinium bromide.

In vitro studies have shown that aclidinium bromide at a therapeutic dose or its metabolites do not inhibit or induce any cytochrome p450 isoenzymes (CYP450) and do not inhibit the activity of esterases (carboxylesterase. acetylcholinesterase and butyrylcholinesterase). In vitro studies have shown that aclidinium bromide or its metabolites are not substrates or inhibitors of P-glycoprotein.

Deduction

The final half-life of aclidinium bromide is about 2-3 hours.

After intravenous use of 400 micrograms of radiolabeled aclidinium bromide to healthy volunteers, about 1% of the dose was excreted unchanged in the urine.

Up to 65% of the dose was excreted as metabolites in the urine and up to 33% as metabolites in the faeces.

After inhalation of 200 mcg and 400 mcg of aclidinium bromide to healthy volunteers and patients with COPD, a very small amount, about 0.1% of the dose taken, was excreted unchanged in the urine, indicating that renal clearance plays a minor role in the total clearance of aclidinium from blood plasma.

Linearity / non-linearity

Aclidinium bromide has linear and time-independent pharmacokinetics in the therapeutic range.

Pharmacokinetic/pharmacodynamic ratio

Given that aclidinium bromide has a local effect in the lungs and is rapidly degraded in plasma, there is no direct relationship between pharmacokinetics and pharmacodynamics.

Special patient groups

Elderly patients

The pharmacokinetic properties of aclidinium bromide in patients with moderate to severe COPD are similar in patients aged 40-59 years and in patients aged 70 years and older. Therefore, no dose adjustment is required in elderly patients with COPD.

Patients with impaired liver function

No trials were performed in patients with hepatic impairment. Since aclidinium bromide is primarily metabolized by chemical and enzymatic degradation in plasma, it is highly unlikely that impaired liver function alters its systemic effects. No dose adjustment is required in patients with COPD and hepatic impairment.

Patients with impaired renal function

No significant differences in pharmacokinetics were found in patients with normal and impaired renal function. Therefore, no dose adjustment or additional monitoring is required in patients with COPD and impaired renal function.

Aclidinium bromide is a competitive, selective muscarinic receptor antagonist (also called an anticholinergic), with a longer binding time to Mz receptors than to M2 receptors. Mz-receptors mediate the contraction of airway smooth muscle. Inhaled aclidinium bromide acts topically in the lungs, as an antagonist of Mz-receptors of airway smooth muscle and causes bronchial dilation. Preclinical in vitro and in vivo studies have demonstrated rapid, dose-dependent, and long-term inhibition of acetylcholine-induced bronchospasm by aclidinium bromide. Aclidinium bromide is rapidly degraded in plasma, so the number of systemic anticholinergic side effects is low.

Indications

bronchodilating therapy

Contraindications

• Hypersensitivity;
• Age up to 18 years (efficacy and safety have not been established);
• Galactose intolerance, lactase deficiency, or glucose-galactose malabsorption (the drug contains lactose).

Side effects

The most common side effects associated with the use of Bretaris Generic are headache (6.6%) and nasopharyngitis (5.5%).

The frequency of side effects is based on an estimate of the overall incidence of side effects (i. e., events associated with the use of Bretaris Generic) observed with the use of Bretaris Generic at a dose of 322 mcg (636 patients) in a pool analysis of one 6-month and two 3-month randomized clinical trials with placebo control.

The frequency of side effects is defined as follows: very common (≥1/10), common (≥1/100 to

Infectious and parasitic diseases: often – sinusitis, nasopharyngitis.

From the immune system: rarely – hypersensitivity reactions; frequency unknown-angioedema.

Nervous system disorders: often – headache; infrequently-dizziness.

From the side of the visual organ: infrequently – blurred vision.

From the cardiovascular system: infrequently-tachycardia, palpitations.

Respiratory, thoracic and mediastinal disorders: often-cough; infrequently-dysphonia.

From the gastrointestinal tract: often – diarrhea; infrequently-dryness of the oral mucosa, stomatitis.

Skin and subcutaneous tissue disorders: infrequently – rash, itching of the skin.

From the side of the kidneys and urinary tract: infrequently-urinary retention.

Interaction

Concomitant use of aclidinium bromide with other M-holinoblockers has not been studied and is not recommended.

Despite the lack of in vivo studies, the use of aclidinium bromide for inhalation is possible in combination with other COPD medications, including sympathomimetics, bronchodilators, methylxanthines, and inhaled or oral corticosteroids.

In vitro studies have shown that aclidinium bromide at a therapeutic dose or its metabolites do not interact with drugs that are substrates of P-glycoprotein or drugs that are metabolized by cytochrome p450 isoenzymes (CYP450) and esterases.

How to take, course of use and dosage

Introduction to the Bretarisgenueyr inhaler :

Remove the Generic inhaler from the bag and check out its components.

To use the Bretaris Generic inhaler after removing the cap, you need to take 2 steps::

Step 1. Press and release the green button and exhale completely, but not into the inhaler.

Step 2. Wrap your lips tightly around the mouthpiece and inhale deeply and strongly through the inhaler.

After inhalation, do not forget to put on a protective cap.

Getting started

Before using it for the first time, open the sealed bag along the label and remove the Generic inhaler.

When you are about to take a dose of medication, remove the protective cap by slightly squeezing the arrows on each side and pulling outwards.

Make sure that nothing blocks the mouthpiece.

Hold the Generic inhaler horizontally with the mouthpiece facing you, with the green button facing straight up.

Step 1. Press and release the green button.

Do not hold down the green button.

Stop and check; make sure that the dose is ready for inhalation.

Make sure that the color control window turns green.

The green color of the control window confirms that the drug is ready for inhalation.

If the color control window remains red, press and lower the green button again (see Step 1).

Step 2. Wrap your lips tightly around the mouthpiece of the Generic inhaler and inhale deeply and deeply through the mouthpiece.

Such a strong, deep breath delivers the drug through the inhaler to the lungs.

Caution: Do not hold the device with the green down button pressed during inhalation.

As you inhale, you will hear a “click” indicating the correct use of the Generic inhaler.

To make sure that you have taken the entire dose, continue to breathe, even after you hear the “click” of the inhaler.

Remove the Generic inhaler from your mouth and hold your breath long enough to feel comfortable, then slowly exhale through your nose.

Note: some patients, depending on their individual characteristics, may experience a slight sweet or bitter taste when inhaling this drug. Do not take an additional dose if you do not feel any taste after inhalation.

Stop and check: Make sure that you have inhaled correctly.

Make sure that the control window turns red. This confirms that you have correctly inhaled the full dose.

If the color control window remains green, inhale deeply and strongly through the mouthpiece again (see Step 2).

If the window still doesn’t change its color to red, it’s possible that you may have forgotten to release the green button before inhaling, or you may have inhaled incorrectly. If this is the case, try again.

Make sure you release the green button and take a strong, deep breath through the mouthpiece.

Note: If you are still unable to perform the inhalation correctly after several attempts, contact your doctor.

As soon as the window turns red, put a protective cap on the mouthpiece.

When you need a new Generic Inhaler

The Generic inhaler is equipped with a dose indicator that shows approximately how many doses are left in the inhaler. The dose indicator slowly goes down, showing the intervals before the dose is reached. 10 (60,50,40,30,20,10,0). Each Generic inhaler contains at least 30 or 60 doses, depending on the type of package.

When the red-striped ribbon appears on the dose indicator, it means that you are nearing the last dose and you need to purchase a new Generic inhaler.

Overdose

High doses of aclidinium bromide may lead to symptoms associated with anticholinergic activity.

However, a single inhaled dose of aclidinium bromide up to 6000 mcg in healthy volunteers did not lead to systemic adverse anticholinergic effects. There were no clinically significant side effects after 7-day treatment with aclidinium bromide in doses up to 800 mcg 2 times / day in healthy volunteers.

The development of acute intoxication with an accidental overdose of aclidinium bromide is unlikely due to the low bioavailability when taken orally and the inhaled dosage method of the drug Bretaris Generic.

Treatment: symptomatic.

Special instructions

Asthma

Bretaris Generic should not be used for asthma; no clinical studies have been conducted on the use of aclidinium bromide for the treatment of asthma.

Paradoxical bronchospasm

As with other inhalation therapy, the use of Bretaris Generic can cause paradoxical bronchospasm. If this occurs, then treatment with Bretaris Generic should be discontinued and other therapy should be considered.

Increasing symptoms of the disease

Aclidinium bromide is intended for the maintenance treatment of patients with COPD and should not be used as an emergency medication. If the patient has experienced a change in the severity of COPD symptoms during aclidinium bromide treatment, which requires additional emergency therapy, the patient’s condition should be re-evaluated and the treatment strategy reviewed.

Impact on the cardiovascular system

The safety profile in relation to the cardiovascular system is characterized by the presence of anticholinergic action.

Like other m-holinoblockers, Bretaris Generic should be used with caution in patients who have had a myocardial infarction in the previous 6 months, with unstable angina, first diagnosed with arrhythmia in the previous 3 months, or in patients who were hospitalized for heart failure of functional classes III and IV according to the New York Heart Association classification in the previous 12 months, since such patients were excluded from clinical studies, and anticholinergic effects may affect for the course of these diseases.

Anticholinergic effects

Dryness of the oral mucosa observed with the use of anticholinergic drugs may be associated with the development of dental caries over time.

Due to the presence of anticholinergic effects, aclidinium bromide should be administered with caution in patients with angle-closure glaucoma (although direct contact with the eyes is very unlikely), prostatic hyperplasia and bladder neck obstruction. Patients should be informed about the signs and symptoms of an acute attack of angle-closure glaucoma and the need to stop using the drug and consult a doctor if they occur.

Bretaris Generic is intended for the maintenance treatment of patients with COPD. Due to the fact that the general population of COPD is significantly dominated by patients over the age of 40 years, when prescribing the drug to patients under 40 years of age, spirometric confirmation of the diagnosis of COPD is required.

Influence on the ability to drive vehicles and other mechanisms

Aclidinium bromide can have an impact on the ability to drive vehicles and other mechanisms. Given the possibility of developing side effects such as headache, dizziness, blurred vision, care should be taken when driving vehicles, other mechanisms, as well as when engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

 In a dark place, at a temperature not exceeding 25 °C.

Shelf life

2 years

Active ingredient

Aclidinium bromide

Conditions of release from pharmacies

By prescription

Dosage form

powder for inhalation

Purpose

For adults as directed by your doctor

Indications

Chronic obstructive pulmonary disease, Bronchial asthma, Bronchospasm