Pharmacodynamics and pharmacokinetics
Pharmacodynamics
The active substance is a selective β2-adrenergic receptor agonist , the effect of which is long-lasting with a single dose. It is a full agonist of β2-adrenergic receptors and its effect on them is 24 times stronger than on β1-adrenergic receptors . The mechanism of action is associated with stimulation of adenylate cyclase , under the influence of which ATP is converted into cyclic AMP . An increase in the content of the latter causes relaxation of the bronchial muscles.
The indacaterol molecule has a high affinity for cell membrane lipids, therefore, remaining in them, it acts for 24 hours. The effect is rapid (like salbutamol ) and long-lasting. The maximum effect occurs 2-4 hours after application. Provides significant improvement in lung function throughout the day, reduction of shortness of breath and good exercise tolerance. tachyphylaxis is observed when taking this drug for 1 year . There was no dependence of the effect on the time of inhalation (morning or evening).
Pharmacokinetics
After inhalation, Cmax in the blood is reached within 15 minutes. Bioavailability is 43%. Serum concentration increases with repeated use and Css is achieved within 12-14 days. Unchanged serum indacaterol Its metabolites are also present in the blood. The intestines were excreted (90% of the dose), excretion through the kidneys was insignificant. Serum concentration decreases stepwise. T1/2 - 45.5 - 126 hours. Pharmacokinetics do not change significantly in patients with moderate liver dysfunction.
Buy Onbrez Breezhaler capsules for inhalation 150 mcg No. 30 + inhaler in pharmacies
Onbrez Breezhaler Buy Onbrez Breezhaler in pharmacies Onbrez Breezhaler in the medicine directory DOSAGE FORMS capsules with powder for inhalation 150 µg
MANUFACTURERS Novartis Pharma Stein AG (Switzerland)
GROUP Bronchodilators - beta-agonists
COMPOSITION Active substance: indacaterol 150 mcg.
INTERNATIONAL NON-PROPENTED NAME Indacaterol
PHARMACOLOGICAL ACTION Indacaterol is a selective long-acting 2-adrenergic receptor agonist (within 24 hours) with a single dose. The pharmacological action of β2-adrenergic receptor agonists, including indacaterol, is associated with stimulation of intracellular adenylate cyclase, an enzyme that catalyzes the conversion of ATP to cyclic 3′,5′-adenosine monophosphate (cyclic AMP). An increase in cyclic AMP content leads to relaxation of bronchial smooth muscles. Indacaterol is an almost complete 2-adrenergic receptor agonist; the stimulating effect of the drug on 2-adrenergic receptors is 24 times stronger than on 1-adrenergic receptors, and 20 times stronger than on 3-adrenergic receptors. After inhalation, the drug has a rapid and long-lasting bronchodilator effect. Provides a sustained significant improvement in lung function (increased forced expiratory volume in the first second, FEV1) for 24 hours. The maximum effect is observed 2-4 hours after inhalation. When using indacaterol, there was no dependence of the bronchodilator effect on the time of inhalation of the drug during the day (morning or evening). Reduces dynamic and static hyperinflation (increased lung volumes at the end of spontaneous expiration) in patients with moderate and severe COPD. When using the drug, there is a statistically significant increase in inspiratory capacity and FEV1, a decrease in shortness of breath, and an improvement in exercise tolerance. After single or repeated inhalations, the average time to reach maximum concentration in the blood serum is about 15 minutes. After a single inhalation, the absolute bioavailability of indacaterol is about 43%. Systemic exposure results from absorption of the drug in the lungs and intestines. Serum concentration increases with repeated use of the drug. Of the metabolites of the drug in the blood serum, the hydroxylated derivative of indacaterol is determined to the greatest extent. Next, hydroxylated indacaterol and phenolic O-glucuronide of indacaterol predominate. Later, diastereomers of the hydroxylated derivative, indacaterol N-glucuronide, and C- and N-dealkylated products are detected. UGT1A1 is the only isoenzyme that metabolizes indacaterol to the phenolic O-glucuronide. Hydroxylation of indacaterol occurs mainly via the CYP3A4 isoenzyme. It has also been established that indacaterol is a substrate for the membrane transporter of P-glycoprotein (P-gp) molecules, but has low affinity. The amount of unchanged indacaterol excreted in the urine is less than 2% of the dose. Renal clearance of indacaterol averaged 0.46-1.20 l/h. Considering that the serum clearance of indacaterol is 23.3 L/h, it is obvious that excretion of the drug through the kidneys is insignificant (approximately 2-5% of systemic clearance). When taken orally, indacaterol was excreted mainly through the intestines (90% of the dose): unchanged (54% of the dose) and in the form of hydroxylated metabolites (23% of the dose).
INDICATIONS FOR USE Long-term maintenance therapy of bronchial obstruction in patients with COPD.
CONTRAINDICATIONS Age under 18 years (efficacy and safety have not been established); pregnancy; breastfeeding period; hypersensitivity to any of the components of the drug. The drug should be prescribed with caution to patients with concomitant cardiovascular disorders (coronary artery disease, acute myocardial infarction, arrhythmias, arterial hypertension), with convulsive disorders, thyrotoxicosis, diabetes mellitus, as well as in patients with a history of inadequate response to the action of 2-adrenergic receptor agonists .
SIDE EFFECTS When using the drug in therapeutic doses, the following adverse events were most often observed: nasopharyngitis, cough, upper respiratory tract infections and muscle spasms. Most of the above-mentioned adverse events were mild or moderate in severity, the incidence of these adverse events decreased with further use. From the respiratory system: often - cough, sore throat, rhinorrhea. From the musculoskeletal system: often - muscle spasm, myalgia, bone pain. From the nervous system: infrequently - dizziness, paresthesia. From the cardiovascular system: often - ischemic heart disease; infrequently - atrial fibrillation. From the digestive system: often - dry mouth. Metabolic disorders: often - hyperglycemia/newly diagnosed diabetes mellitus. General disorders: often - peripheral edema, pain in the chest (non-cardiogenic); infrequently - discomfort in the chest area. In clinical studies, within 15 seconds after inhalation of the drug, patients (in 17-20% of cases) developed a sporadic cough lasting about 5 seconds. The occurrence of cough after inhalation of the drug slightly bothered patients and did not require discontinuation of treatment with the drug (since cough is a symptom of COPD, and only in 6.6% of cases patients associated cough with the use of the drug). There was no connection between cough observed immediately after inhalation of the drug and the development of bronchospasm, exacerbation of COPD, worsening of COPD and decreased effectiveness of the drug.
INTERACTIONS Drugs that prolong the QT interval. As with the use of other β2-adrenergic receptor agonists, QT interval prolongation is possible during drug therapy. Since this effect of indacaterol on the length of the QT interval may be potentiated by other drugs, the drug should be administered with caution to patients receiving MAO inhibitors, tricyclic antidepressants, or other drugs that prolong the QT interval. Prolongation of the QT interval increases the risk of developing ventricular arrhythmia. Sympathomimetic drugs. Concomitant use of indacaterol with sympathomimetics (either alone or as part of combination therapy) may increase the risk of adverse events. The drug should not be used simultaneously with other long-acting β2-adrenergic receptor agonists or with drugs containing long-acting β2-adrenergic receptor agonists. Hypokalemia. Concomitant use with methylxanthine derivatives, corticosteroids or diuretics that remove potassium may enhance possible hypokalemia caused by 2-adrenergic receptor agonists. 2-adrenergic receptor blockers. Since β2-adrenergic blockers may weaken the effect or interfere with the action of β2-adrenergic agonists, Onbrez® Breezhaler® should not be used concomitantly with β2-adrenergic blockers (including eye drops). If it is necessary to use both classes of drugs, it is preferable to use cardioselective 2-adrenergic receptor blockers, however, they must be used with caution. Interaction at the level of the CYP3A4 isoenzyme and the membrane transporter P-glycoprotein. The interaction of indacaterol with specific inhibitors of the CYP3A4 isoenzyme and P-glycoprotein, such as ketoconazole, erythromycin and verapamil, has been studied. Concomitant use of indacaterol with verapamil resulted in a 1.4-2-fold increase in AUC and a 1.5-fold increase in maximum concentration. When using indacaterol with erythromycin, there was an increase in AUC by 1.4 - 1.6 times and maximum concentration by 1.2 times. Combination therapy with indacaterol and ketoconazole caused a 2-fold and 1.4-fold increase in AUC and maximum concentration, respectively. This increase in exposure due to drug interactions did not lead to a change in the safety profile. No drug interactions were observed when indacaterol was used with other drugs. In vitro studies have shown that indacaterol has little potential for interaction with drugs at the level of enzyme metabolism or at the level of membrane transporters with systemic exposure achieved at therapeutic doses.
METHOD OF APPLICATION AND DOSAGE For inhalation use only! Inhalation of the drug is carried out daily, once a day at the same time. The recommended dose of the drug is 150 mcg (contents of 1 capsule 150 mcg) 1 time per day (1 inhalation per day). The dose of the drug can be increased only on the recommendation of a doctor.
OVERDOSE Symptoms: after a single use of the drug in patients with COPD at a dose 10 times higher than the maximum therapeutic dose, a moderate increase in heart rate, an increase in blood pressure and a prolongation of the QTc interval were observed. The most likely symptoms of a drug overdose are tachycardia, tremor, palpitations, headache, nausea, vomiting, drowsiness, ventricular arrhythmia, metabolic acidosis, hypokalemia and hyperglycemia (caused by increased systemic beta2-adrenomimetic action). Treatment: supportive and symptomatic therapy is indicated. In severe cases, patients must be hospitalized. If necessary, it is possible to use cardioselective beta-blockers. Cardioselective beta-blockers should be used with caution, only under strict medical supervision, since their use can provoke the development of bronchospasm.
SPECIAL INSTRUCTIONS Bronchial asthma. Due to the lack of data on the long-term use of indacaterol in patients with bronchial asthma, the drug should not be used in this category of patients. Paradoxical bronchospasm. Like any other inhalation therapy, the use of the drug can lead to the development of paradoxical bronchospasm, which poses a threat to the patient's life. If paradoxical bronchospasm occurs, treatment with the drug should be immediately discontinued and alternative therapy should be prescribed. Worsening of the underlying disease. The drug cannot be used to relieve acute bronchospasm, i.e. Do not use as emergency therapy. If the course of COPD worsens during treatment with the drug, it is necessary to re-evaluate the patient’s condition and revise the treatment regimen for the disease. Effect on the cardiovascular system. In some patients, the drug, like other 2-adrenergic receptor agonists, can affect the cardiovascular system (increase heart rate, blood pressure). If adverse events occur, it may be necessary to discontinue drug therapy. In addition, the following electrocardiographic changes may be observed when beta-2 adrenergic agonists are used: T wave flattening, QT prolongation, and ST segment depression (however, the clinical significance of these changes has not been established). When using the drug in clinical studies (in recommended therapeutic doses), no significant prolongation of the QT interval was observed compared to placebo. Hypokalemia. Some patients may experience significant hypokalemia when using β2-adrenergic agonists, leading to the development of adverse effects from the cardiovascular system. A decrease in serum potassium concentration is usually transient and does not require correction. In patients with severe COPD, hypokalemia may be exacerbated by hypoxia and concomitant therapy, which in turn may increase the likelihood of developing arrhythmias. Hyperglycemia. Inhalation of high doses of 2-adrenergic receptor agonists may increase plasma glucose levels. When using the drug in patients with diabetes mellitus, the concentration of glucose in the blood plasma should be regularly monitored. In clinical studies, patients receiving the drug (in recommended doses) experienced an increase in the incidence of clinically significant hyperglycemia by an average of 1-2% compared to placebo.
STORAGE CONDITIONS The drug should be stored in a dry place, out of reach of children, at a temperature not exceeding 30 C.
Side effects
Most common adverse reactions:
- nasopharyngitis , sinusitis ;
- sore throat, nasal discharge;
- cough;
- dry mouth;
- muscle spasms, muscle and bone pain;
- tachycardia , ischemic heart disease ;
- hyperglycemia;
- peripheral edema.
Less common adverse reactions:
- dizziness;
- atrial fibrillation;
- paresthesia;
- discomfort in the chest.
Onbrez Breezhaler, instructions for use (Method and dosage)
Intended for inhalation use only. To deliver the drug, a Breezhaler metered-dose inhaler is used. Inhalation is carried out 1 time/day, preferably at the same time. In rare cases, the contents of the capsules may enter the mouth in small quantities, but this should not worry the patient. Do not use to relieve bronchospasm as an emergency aid.
Capsules with powder must be stored in a blister, removed only before use and monitor their integrity. The recommended dose is 150 mcg - 1 inhalation per day. The dose is increased according to the doctor's recommendation.
In severe COPD, inhalations are performed with a dose of 300 mcg once a day. This dose is the maximum allowable. There is no dose adjustment in elderly people.
The drug capsules cannot be used with another inhalation device. You need to clean the device once a week by wiping the mouthpiece with a dry cloth without using water. In some patients, blood pressure and heart rate , which may require discontinuation of treatment.
Onbrez Breezhaler caps with powder for ing 300 mcg N 30 + Breezhaler M 1
Active substance.
Indacaterol
Dosage form:
capsules with powder for inhalation
Compound.
1 capsule with powder for inhalation contains:
active ingredient: 194 mcg or 389 mcg of indacaterol maleate (corresponding to 150 mcg or 300 mcg of indacaterol);
excipients: lactose monohydrate 24.806 mg/24.611 mg;
capsule shell: gelatin 49.0 mg/49.0 mg, black ink (for 150 mg capsules) and blue ink (for 300 mg capsules), which includes shellac (E904), black iron oxide dye (E172), water purified, propylene glycol (E1520).
The blue ink also contains brilliant blue dye (E133), aluminum varnish, and titanium dioxide (El71).
Description.
150 mcg capsules: hard gelatin capsules No. 3 with a transparent, colorless cap and body, marked under a black stripe on the cap and the inscription “IDL 150” in black ink above the black stripe on the body.
300 mcg capsules: hard gelatin capsules No. 3 with a transparent, colorless cap and body, marked under a blue stripe on the cap and the inscription “IDL 300” in blue ink above the blue stripe on the body.
The contents of the capsules are white or almost white powder.
Pharmacotherapeutic group: Bronchodilator - selective beta2-adrenergic agonist
Indacaterol is a selective, long-acting beta2-adrenergic receptor agonist (for 24 hours) with a single dose.
The pharmacological action of beta2-adrenergic agonists, including indacaterol, is associated with stimulation of intracellular adenylate cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic 3′,5′-adenosine monophosphate (cyclic AMP). An increase in cyclic AMP content leads to relaxation of bronchial smooth muscles. Indacaterol is an almost complete beta2-adrenergic receptor agonist; the stimulating effect of the drug on beta2-adrenergic receptors is 24 times stronger than on beta1-adrenergic receptors, and 20 times stronger than on beta3-adrenergic receptors.
After inhalation, the drug has a rapid and long-lasting bronchodilator effect.
Indacaterol provides a sustained, significant improvement in lung function (increased forced expiratory volume in 1 second, FEV1) over 24 hours. The drug is characterized by a rapid onset of action (within 5 minutes after inhalation), comparable to the effect of salbutamol, a short-acting beta2-adrenergic receptor agonist . The maximum effect of indacaterol is observed 2-4 hours after inhalation. In patients receiving indacaterol for 1 year, there was no development of tachyphylaxis to the bronchodilator effect of the drug. When using indacaterol, there was no dependence of the bronchodilator effect on the time of inhalation of the drug during the day (morning or evening).
Indacaterol reduces dynamic and static hyperinflation (increased lung volumes at the end of spontaneous expiration) in patients with moderate to severe chronic obstructive pulmonary disease (COPD). When using the drug, there is a statistically significant increase in inspiratory capacity and FEV1, a decrease in shortness of breath, and an improvement in exercise tolerance. There is also a significant reduction in the risk of exacerbations of COPD (increasing the time until the next exacerbation), reducing the need for inhaled short-acting beta2-adrenergic receptor agonists and improving the quality of life of patients (assessed using a certified questionnaire from St. George's Hospital).
Indications:
Long-term maintenance therapy for bronchial obstruction in patients with chronic obstructive pulmonary disease (COPD).
Overdose
Symptoms of overdose appeared when taking a dose 10 times the therapeutic dose. At the same time, there was an increase in heart rate , blood pressure and changes in the ECG in the form of prolongation of the QT .
The most common symptoms of overdose: tachycardia , palpitations, ventricular arrhythmia , tremor , headache , drowsiness , nausea, vomiting, hypokalemia and hyperglycemia .
Symptomatic therapy is indicated. Use beta-blockers (cardioselective) with caution, since their use sometimes provokes bronchospasm .
ULTIBRO BREEZHALER
Pharmacokinetics
Absorption
After inhalation of the drug Ultibro® Breezhaler®, the average time to reach maximum concentrations (Cmax) of glycopyrronium bromide and indacaterol in blood plasma was 15 minutes and 5 minutes, respectively. The AUC of glycopyrronium bromide at steady state when using the drug Ultibro® Breezhaler® corresponds to that when inhaling glycopyrronium bromide alone.
According to an in vitro study that examined the effectiveness of inhalation, the dose of indacaterol delivered to the lungs with Ultibro® Breezhaler® is equivalent to the use of indacaterol alone at a dose of 150 mcg. The AUC of indacaterol at steady state when using the drug Ultibro® Breezhaler® corresponds to or may be slightly lower than that when indacaterol is inhaled separately at a dose of 150 mcg. The absolute bioavailability of indacaterol when using the drug Ultibro® Breezhaler® ranges from 47% to 66%, glycopyrronium bromide - about 40%.
Glycopyrronium bromide
After inhalation, glycopyrronium bromide is rapidly absorbed and reaches Cmax in blood plasma within 5 minutes. About 90% of the systemic exposure of glycopyrronium bromide is due to absorption in the lungs, and 10% is due to absorption in the gastrointestinal tract. The absolute bioavailability of glycopyrronium bromide after inhalation is estimated at 40% of the delivered dose. With regular inhalations (once a day), Css glycopyrronium bromide is achieved within 1 week. The AUC of glycopyrronium bromide at steady state was 1.4-1.7 times higher than after the first inhalation. Cmax of glycopyrronium bromide at steady state (with inhalation of the recommended dose 1 time per day) and the concentration of glycopyrronium bromide in blood plasma at the end of the dosing period are 166 pg/ml and 8 pg/ml, respectively.
Indacaterol
The average time to reach Cmax of indacaterol in the blood serum is about 15 minutes after a single or repeated inhalations. Serum concentrations of indacaterol increase with repeated use of the drug. The equilibrium concentration of the substance in the blood (Css) is achieved within 12-15 days of using the drug. When the drug is inhaled at a dose of 60 to 480 mcg (dose delivered to the lungs) with a frequency of 1 time per day for 14 days, the coefficient of accumulation of indacaterol, estimated by the area under the “primary passage” curve through the liver. After inhalation or intravenous administration, only minimal amounts of M9 were detected in urine (<0.5% of the administered dose). Glucuronic and/or sulfate conjugates of glycopyrronium bromide have been detected in human urine after repeated inhalations at approximately 3% of the delivered dose. In vitro inhibition studies have shown that glycopyrronium bromide does not have a significant ability to inhibit the activity of the isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4/5, the transport proteins MDR1, MRP1 or MXR, which mediate the elimination of drugs from cells, and also transporter proteins OATP1B1, OATP1B3, O ATI, OATZ, OCT1 or OCT2. In vitro enzyme induction studies have not revealed that glycopyrronium bromide has a clinically significant ability to induce cytochrome P450 isoenzymes, the UGT1A1 enzyme, and the MDR1 and MRP2 transporter proteins.
Indacaterol
When radiolabeled indacaterol is administered orally, unchanged indacaterol is the major serum component and accounts for approximately 1/3 of the drug's daily AUC. Of the metabolites of indacaterol in blood serum, the hydroxylated derivative of indacaterol is determined to the greatest extent. The phenolic O-glucuronide of indacaterol and hydroxylated indacaterol are found in smaller quantities. In addition, diastereomers of the hydroxylated derivative, indacaterol N-glucuronide, and C- and N-dealkylation products were detected.
The UGT1A1 isoenzyme is the only isoenzyme that metabolizes indacaterol to the phenolic O-glucuronide. Hydroxylation of indacaterol occurs mainly via the CYP3A4 isoenzyme. It has also been established that indacaterol is a low-affinity substrate for the membrane transporter of P-glycoprotein (P-gp) molecules.
Removal
Glycopyrronium bromide
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 through metabolism. In healthy volunteers and patients with COPD who received glycopyrronium in doses of 50 to 200 mcg once a day and once or repeatedly, the average renal clearance of glycopyrronium ranged from 17.4 to 24.4 l/h. Excretion of glycopyrronium bromide through the kidneys is due to active tubular secretion. Up to 23% of the dose is found unchanged in the urine. The concentration of glycopyrronium bromide in the blood plasma decreases multiphasically. The mean terminal half-life is longer after inhalation (33-57 hours) than after IV (6.2 hours) or oral administration (2.8 hours). The nature of elimination suggests prolonged absorption in the lungs and/or penetration of glycopyrronium bromide into the systemic circulation during and after 24 hours after inhalation.
Indacaterol
The amount of unchanged indacaterol excreted by the kidneys is less than 2.5% of the delivered dose. Renal clearance of indacaterol averaged 0.46-1.2 l/h. Considering that the serum clearance of indacaterol is 18.8-23.3 l/h, it is obvious that excretion of the drug through the kidneys is insignificant (approximately 2-5% of systemic clearance). When taken orally, indacaterol was excreted mainly through the intestines: unchanged (54% of the dose) and in the form of hydroxylated metabolites (23% of the dose).
The concentration of indacaterol in the blood serum decreases multiphasically with a mean terminal half-life (T1/2) ranging from 45.5 to 126 hours. The effective T1/2, calculated on the basis of the accumulation of indacaterol after repeated use, ranged from 40 to 52 hours. which is consistent with the established time to reach an equilibrium state (12-15 days).
The AUC of indacaterol at steady state increased proportionally to the delivered dose, ranging from 120 mcg to 480 mcg.
Linearity/nonlinearity
Glycopyrronium bromide
In patients with COPD, the AUC as well as the total renal excretion of glycopyrronium bromide at steady state increased in a dose-proportional manner ranging from 50 mcg to 200 mcg.
Indacaterol
Systemic exposure of indacaterol increases in proportion to increasing doses (from 150 to 600 mcg). Systemic exposure of the drug is due to its absorption both in the lungs and in the gastrointestinal tract.
Pharmacokinetics in special groups of patients.
Ultibro
®
Breezhaler®
Age, gender and body weight do not have a significant effect on the pharmacokinetics of the drug Ultibro® Breezhaler® in patients with COPD. There was a negative correlation between AUC and lean body mass (or body weight), however, since AUC did not change significantly and the predictive value of lean body mass is low, dosage adjustment based on this parameter is not recommended. Smoking and baseline FEV do not have a visible effect on the AUC of Ultibro® Breezhaler®.
Glycopyrronium bromide
Age and body weight are factors influencing interindividual differences in drug AUC. The recommended dose of glycopyrronium bromide can be safely used in any age group and at any body weight. Gender, smoking, and baseline FEV) had no apparent effect on the AUC of glycopyrronium bromide.
Indacaterol
Age (adult patients up to 88 years), gender and body weight (32-168 kg) do not affect the pharmacokinetics of indacaterol in patients with COPD.
Patients with liver dysfunction.
Ultibro
®
Breezhaler®
Based on the pharmacokinetic properties of each of the components used separately, the drug Ultibro® Breezhaler® can be used in the recommended dose in patients with mild to moderate liver dysfunction. There are no data on the use of the drug in patients with severe liver dysfunction.
Glycopyrronium bromide
Clinical studies have not been conducted in patients with liver failure. Elimination of glycopyrronium bromide occurs primarily through renal excretion. Impaired hepatic metabolism of glycopyrronium bromide is not expected to result in a clinically significant increase in AUC.
Indacaterol
The pharmacokinetics of indacaterol did not change significantly in patients with mild to moderate hepatic impairment. The use of the drug in patients with severe liver dysfunction has not been studied.
Free patients with impaired renal function
Ultibro
®
Breezhaler®
Based on the pharmacokinetic properties of each of the components used separately, the drug Ultibro® Breezhaler® can be used at the recommended dose in patients with mild to moderate renal impairment. In patients with severely impaired renal function or end-stage chronic renal failure (ESRD) requiring hemodialysis, Ultibro® Breezhaler® should be used only if the expected benefit outweighs the possible risk.
Glycopyrronium bromide
Renal impairment affects the AUC of glycopyrronium bromide. A moderate increase in AUC of up to 1.4-fold was observed in patients with mild to moderate renal impairment and up to 2.2-fold in patients with severe and end-stage renal impairment. The use of a population pharmacokinetic analysis led to the conclusion that in patients with COPD with concomitant mild to moderate renal failure (assessed by glomerular filtration rate (GFR) >30 ml/min/1.73 m2), glycopyrronium bromide can be used in recommended doses .
Indacaterol
Since indacaterol is excreted by the kidneys to a small extent, the pharmacokinetics of the drug in patients with impaired renal function have not been studied.
Ethnicity
Ultibro
®
Breezhaler®
There was no statistically significant effect of ethnicity on the AUC of both components.
Glycopyrronium bromide
No differences were found between ethnic subgroups.
Indacaterol
No differences were found between ethnic subgroups. Experience with the drug in people of the Black race is limited.
Interaction
The effect on the length of the QT is potentiated by tricyclic antidepressants and MAO . Prolongation of the QT carries a risk of ventricular arrhythmia .
Concomitant use with sympathomimetics increases the risk of adverse reactions.
Cannot be used with other β2-adrenergic receptor agonists .
Hypokalemia is enhanced by simultaneous use of corticosteroids methylxanthine derivatives , and diuretics.
β2-adrenergic receptor blockers (including eye drops) weaken the effect of the drug. Concomitant use with verapamil , erythromycin , and ketoconazole leads to an increase in Cmax .
Content
- Characteristics of onbrez breathhaler (caps. 150 mg d/ing. No. 30 (with inhaler))
Composition: Active substance: indacaterol 150 mcg.
Pharmacological action: Indacaterol is a selective agonist of long-acting 2-adrenergic receptors (within 24 hours) with a single dose.
The pharmacological action of β2-adrenergic receptor agonists, including indacaterol, is associated with stimulation of intracellular adenylate cyclase, an enzyme that catalyzes the conversion of ATP to cyclic 3′,5′-adenosine monophosphate (cyclic AMP).
An increase in cyclic AMP content leads to relaxation of bronchial smooth muscles.
Indacaterol is an almost complete 2-adrenergic receptor agonist; the stimulating effect of the drug on 2-adrenergic receptors is 24 times stronger than on 1-adrenergic receptors, and 20 times stronger than on 3-adrenergic receptors.
After inhalation, the drug has a rapid and long-lasting bronchodilator effect.
Provides a sustained significant improvement in lung function (increased forced expiratory volume in the first second, FEV1) over 24 hours.
The maximum effect is observed 2-4 hours after inhalation.
When using indacaterol, there was no dependence of the bronchodilator effect on the time of inhalation of the drug during the day (morning or evening).
Reduces dynamic and static hyperinflation (increased lung volumes at the end of spontaneous expiration) in patients with moderate and severe COPD.
When using the drug, there is a statistically significant increase in inspiratory capacity and FEV1, a decrease in shortness of breath, and an improvement in exercise tolerance.
After single or repeated inhalations, the average time to reach maximum concentration in the blood serum is about 15 minutes.
After a single inhalation, the absolute bioavailability of indacaterol is about 43%.
Systemic exposure results from absorption of the drug in the lungs and intestines.
Serum concentration increases with repeated use of the drug.
Of the metabolites of the drug in the blood serum, the hydroxylated derivative of indacaterol is determined to the greatest extent.
Next, hydroxylated indacaterol and phenolic O-glucuronide of indacaterol predominate.
Later, diastereomers of the hydroxylated derivative, indacaterol N-glucuronide, and C- and N-dealkylated products are detected.
UGT1A1 is the only isoenzyme that metabolizes indacaterol to the phenolic O-glucuronide.
Hydroxylation of indacaterol occurs mainly via the CYP3A4 isoenzyme.
It has also been established that indacaterol is a substrate for the membrane transporter of P-glycoprotein (P-gp) molecules, but has low affinity.
The amount of unchanged indacaterol excreted in the urine is less than 2% of the dose.
The renal clearance of indacaterol averaged 0.
46-1.
20 l/h.
Considering that the serum clearance of indacaterol is 23.
3 l/h, it is obvious that excretion of the drug through the kidneys is insignificant (approximately 2-5% of systemic clearance).
When taken orally, indacaterol was excreted mainly through the intestines (90% of the dose): unchanged (54% of the dose) and in the form of hydroxylated metabolites (23% of the dose).
Indications for Use: Long-term maintenance therapy of bronchial obstruction in patients with COPD.
Directions for Use: For inhalation use only! Inhalation of the drug is carried out daily, once a day at the same time.
The recommended dose of the drug is 150 mcg (contents of 1 capsule 150 mcg) 1 time per day (1 inhalation per day).
The dose of the drug can be increased only on the recommendation of a doctor.
Interaction: Drugs that prolong the QT interval.
As with the use of other β2-adrenergic receptor agonists, QT interval prolongation is possible during drug therapy.
Since this effect of indacaterol on the length of the QT interval may be potentiated by other drugs, the drug should be administered with caution to patients receiving MAO inhibitors, tricyclic antidepressants, or other drugs that prolong the QT interval.
Prolongation of the QT interval increases the risk of developing ventricular arrhythmia.
Sympathomimetic drugs.
Concomitant use of indacaterol with sympathomimetics (either alone or as part of combination therapy) may increase the risk of adverse events.
The drug should not be used simultaneously with other long-acting β2-adrenergic receptor agonists or with drugs containing long-acting β2-adrenergic receptor agonists.
Hypokalemia.
Concomitant use with methylxanthine derivatives, corticosteroids or diuretics that remove potassium may enhance possible hypokalemia caused by 2-adrenergic receptor agonists.
2-adrenergic receptor blockers.
Since β2-adrenergic blockers may weaken the effect or interfere with the action of β2-adrenergic agonists, Onbrez® Breezhaler® should not be used concomitantly with β2-adrenergic blockers (including eye drops).
If it is necessary to use both classes of drugs, it is preferable to use cardioselective 2-adrenergic receptor blockers, however, they must be used with caution.
Interaction at the level of the CYP3A4 isoenzyme and the membrane transporter P-glycoprotein.
The interaction of indacaterol with specific inhibitors of the CYP3A4 isoenzyme and P-glycoprotein, such as ketoconazole, erythromycin and verapamil, has been studied.
Concomitant use of indacaterol with verapamil resulted in 1.
4-2-fold increase in AUC and 1.
5-fold increase in maximum concentration.
When indacaterol was used with erythromycin, an increase in AUC of 1 was observed.
4 — 1.
6 times and a maximum concentration of 1.
2 times.
Combination therapy with indacaterol and ketoconazole caused 2-fold and 1-fold.
4-fold increase in AUC and maximum concentration, respectively.
This increase in exposure due to drug interactions did not lead to a change in the safety profile.
No drug interactions were observed when indacaterol was used with other drugs.
In vitro studies have shown that indacaterol has little potential for interaction with drugs at the level of enzyme metabolism or at the level of membrane transporters with systemic exposure achieved at therapeutic doses.
Side Effects: When using the drug in therapeutic doses, the following adverse events were most often observed: nasopharyngitis, cough, upper respiratory tract infections and muscle spasms.
Most of the above-mentioned adverse events were mild or moderate in severity, the incidence of these adverse events decreased with further use.
From the respiratory system: often - cough, sore throat, rhinorrhea.
From the musculoskeletal system: often - muscle spasm, myalgia, bone pain.
From the nervous system: infrequently - dizziness, paresthesia.
From the cardiovascular system: often - ischemic heart disease; infrequently - atrial fibrillation.
From the digestive system: often - dry mouth.
Metabolic disorders: often - hyperglycemia/newly diagnosed diabetes mellitus.
General disorders: often - peripheral edema, pain in the chest (non-cardiogenic); infrequently - discomfort in the chest area.
In clinical studies, within 15 seconds after inhalation of the drug, patients (in 17-20% of cases) developed a sporadic cough lasting about 5 seconds.
The occurrence of cough after inhalation of the drug slightly bothered the patients and did not require discontinuation of treatment with the drug (since cough is a symptom of COPD, and only in 6.
In 6% of cases, patients associated cough with the use of the drug).
There was no connection between cough observed immediately after inhalation of the drug and the development of bronchospasm, exacerbation of COPD, worsening of COPD and decreased effectiveness of the drug.
Contraindications: Age under 18 years (efficacy and safety have not been established); pregnancy; breastfeeding; hypersensitivity to any of the components of the drug.
The drug should be prescribed with caution to patients with concomitant cardiovascular disorders (coronary artery disease, acute myocardial infarction, arrhythmias, arterial hypertension), with convulsive disorders, thyrotoxicosis, diabetes mellitus, as well as in patients with a history of inadequate response to the action of 2-adrenergic receptor agonists .
Overdose: Symptoms: after a single use of the drug in patients with COPD at a dose 10 times higher than the maximum therapeutic dose, a moderate increase in heart rate, an increase in blood pressure and a prolongation of the QTc interval were observed.
The most likely symptoms of a drug overdose are tachycardia, tremor, palpitations, headache, nausea, vomiting, drowsiness, ventricular arrhythmia, metabolic acidosis, hypokalemia and hyperglycemia (caused by increased systemic beta2-adrenomimetic action).
Treatment: supportive and symptomatic therapy is indicated.
In severe cases, patients must be hospitalized.
If necessary, it is possible to use cardioselective beta-blockers.
Cardioselective beta-blockers should be used with caution, only under strict medical supervision, since their use can provoke the development of bronchospasm.
Special Instructions: Bronchial asthma.
Due to the lack of data on the long-term use of indacaterol in patients with bronchial asthma, the drug should not be used in this category of patients.
Paradoxical bronchospasm.
Like any other inhalation therapy, the use of the drug can lead to the development of paradoxical bronchospasm, which poses a threat to the patient's life.
If paradoxical bronchospasm occurs, treatment with the drug should be immediately discontinued and alternative therapy should be prescribed.
Worsening of the underlying disease.
The drug cannot be used to relieve acute bronchospasm, because
e.
Do not use as emergency therapy.
If the course of COPD worsens during treatment with the drug, it is necessary to re-evaluate the patient’s condition and reconsider the treatment regimen for the disease.
Effect on the cardiovascular system.
In some patients, the drug, like other 2-adrenergic receptor agonists, can affect the cardiovascular system (increase heart rate, blood pressure).
If adverse events occur, it may be necessary to discontinue drug therapy.
In addition, the following electrocardiographic changes may be observed when beta-2 adrenergic agonists are used: T wave flattening, QT prolongation, and ST segment depression (however, the clinical significance of these changes has not been established).
When using the drug in clinical studies (in recommended therapeutic doses), no significant prolongation of the QT interval was observed compared to placebo.
Hypokalemia.
Some patients may experience significant hypokalemia when using β2-adrenergic agonists, leading to the development of adverse effects from the cardiovascular system.
A decrease in serum potassium concentration is usually transient and does not require correction.
In patients with severe COPD, hypokalemia may be exacerbated by hypoxia and concomitant therapy, which in turn may increase the likelihood of developing arrhythmias.
Hyperglycemia.
Inhalation of high doses of 2-adrenergic receptor agonists may increase plasma glucose levels.
When using the drug in patients with diabetes mellitus, the concentration of glucose in the blood plasma should be regularly monitored.
In clinical studies, patients receiving the drug (in recommended doses) experienced an increase in the incidence of clinically significant hyperglycemia by an average of 1-2% compared to placebo.
Analogues of Onbrez Breezhaler
Level 4 ATC code matches:
Formoterol Easyhaler
Fenoterol
Ventolin
Berotek
Foradil
Berotek , Spiriva , Ventolin , Astalin , Athymos , Oxis , Formoterol , Salbutamol .
Reviews about Onbrez Breezhaler
Chronic obstructive pulmonary diseases are characterized by slowly progressive bronchial obstruction. At the same time, the phenomena of respiratory failure increase, which causes permanent disability and disability. COPD is a pathology that requires continuous maintenance therapy throughout life. If this is not done, the number of exacerbations increases, the patient’s quality of life decreases, his condition worsens and the risk of death increases significantly. With this disease, it is important to simplify the treatment regimen, that is, reduce the drug intake to 1 time per day, which is optimal for patients.
This drug helps improve the quality of life of such patients: it provides a bronchodilator effect throughout the day, quickly (within 5 minutes) begins to act and is well tolerated. Breezhaler is a very convenient and easy-to-use device that increases the efficiency of inhalation. This fact is important for elderly patients, who note that they are satisfied with this device.
All these points are reflected in the reviews of patients. It was recommended to take the drug in the morning; in mild cases, 150 mcg, and in severe cases, 300 mcg. The drug reduces the severity of shortness of breath; the need for emergency medications reduces the frequency of exacerbations. Among the undesirable reactions, nasopharyngitis , cough (20 seconds after inhalation, not long-lasting), headache and infections of the upper respiratory tract are noted. They were regarded as mild reactions and did not require discontinuation of the drug.
“... I suffer from chronic obstructive bronchitis. When this drug was added to the treatment, the mucus began to clear better, it became easier to breathe, and there were no attacks during physical activity. I take it all the time.” “...Noted an advantage over inhalers, which need to be used 2 times a day.” “... They prescribed ONBRES, and after 4 days the shortness of breath decreased significantly. I took 30 inhalations and was amazed by the effect. I began to bear loads, almost without shortness of breath.” “... I have been suffering from COPD for 30 years. There were days when I inhaled Salbutamol every hour. I was amazed by the effect of this drug - the effect was on the second day. I AM BREATHING!!! And this is happiness! “... Onbrez has been prescribed for about a year. It increases blood pressure. For me there is nothing better than Spiriva.”
Instructions for use ONBREZ BREEZHALER
Hypersensitivity
There have been cases of immediate hypersensitivity reactions following the use of Onbrez Breezhaler. If signs indicating an allergic reaction appear (in particular, difficulty breathing or swallowing, swelling of the tongue, lips and face, hives, skin rash), use of the drug should be stopped immediately and alternative treatment prescribed.
Bronchial asthma
Onbrez Breezhaler should not be used for asthma due to the lack of data on the effects of long-term use of Onbrez Breezhaler in this disease.
Paradoxical bronchospasm
As with other inhaled therapy, the use of Onbrez Breezhaler can lead to paradoxical bronchospasm, which can be life-threatening. In this case, the use of Onbrez Breezhaler should be stopped immediately and alternative therapy should be initiated.
Increased severity of disease
Onbrez Breezhaler is not indicated at the beginning of the treatment of acute episodes of bronchospasm, i.e. as urgent therapy. If the severity of COPD increases while using Onbrez Breezhaler, the patient's health status and COPD treatment regimen should be re-evaluated. It is not recommended to exceed the daily dose of Onbrez Breezhaler above the established maximum dose.
Systemic effects
After using Onbrez Breezhaler in recommended doses, a clinically significant effect on the cardiovascular system is usually not observed, as with the use of other beta2-adrenergic receptor agonists, indacaterol should be used cautiously in patients with cardiovascular disease, especially with coronary insufficiency, cardiac arrhythmia and arterial hypertension, patients with seizure disorders or thyrotoxicosis, as well as patients who respond inadequately to the effects of beta2-adrenergic agonists.
Like other beta2-adrenergic agonists, indacaterol may cause clinically significant cardiovascular effects in some patients, as measured by increased heart rate, increased blood pressure, and/or other symptoms. In this case, it may be necessary to discontinue the drug. In addition, beta2-adrenergic agonists have been reported to cause ECG changes such as T-wave flattening, QT prolongation, and ST-segment depression. The clinical significance of these data is unknown.
In some patients, beta2-adrenergic agonists can cause severe hypokalemia, which may lead to adverse cardiovascular effects. The decrease in serum potassium is usually temporary and does not require replenishment. In patients with severe COPD, hypokalemia may be exacerbated by hypoxia and concomitant medications, which may increase the susceptibility to cardiac arrhythmias.
Inhaled use of high doses of beta2-adrenergic agonists may increase plasma glucose levels. After initiation of treatment with Onbrez Breezhaler, plasma glucose levels should be more carefully monitored in patients with diabetes.
In clinical studies, clinically significant changes in blood glucose levels of 1-2% were observed more often when using Onbrez Breezhaler at the recommended dose compared to the placebo group. Onbrez Breezhaler has not been studied in patients with poorly controlled diabetes mellitus.
As with other inhaled beta2-adrenergic drugs, Onbrez Breezhaler should not be used more frequently or in doses higher than recommended.
Onbrez Breezhaler should not be used with other long-acting beta2-adrenergic agonists or with medications containing long-acting beta2-adrenergic agonists.
Use in pediatrics
Studies on the use of Onbrez Breezhaler in children have not been conducted, since COPD does not occur in children.
Impact on the ability to drive vehicles and operate machinery
Onbrez Breezhaler may affect the ability to drive vehicles or operate machinery, so when using the drug it is recommended to refrain from driving vehicles and performing other work that requires concentration.
Onbrez Breezhalera price, where to buy
You can buy Onbrez Breezhaler at any pharmacy. The cost of 30 capsules of 150 mcg is 1540-1700 rubles.
- Online pharmacies in RussiaRussia
ZdravCity
- Onbrez Breezhaler capsules for inhalation.
150 mcg 30 pcs. Siegfried Barbera S.L. / Novartis Pharma GmbH RUB 1,585 order - Onbrez Breezhaler capsules for inhalation. 300 µg 30 pcs. Siegfried Barbera S.L. / Novartis Pharma GmbH
RUB 1,466 order
