Ultibro Breezhaler - Instructions For Use, Price, Analogues, Reviews

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Ultibro Breezhaler

Ultibro Breezhaler: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Ultibro Breezhaler

ATX code: R03AL04

Active ingredient: indacaterol (Indacaterol) + glycopyrronium bromide (Glycopyrronium bromide)

Producer: Novartis Pharma, AG (Novartis Pharma, AG) (Switzerland)

Description and photo update: 2019-09-07

Prices in pharmacies: from 1890 rubles.

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Ultibro Breezhaler is a combined inhaled bronchodilator.

Release form and composition

Dosage form - capsules with powder for inhalation: transparent, solid, colorless, size No. 3, black marking on the lid in the form of a company logo, on the body under a double blue stripe the inscription "IGP110.50", made in blue ink; the capsules contain a white or almost white powder (in a cardboard box of 1, 2, 5, 8, 15 or 25 blisters of 6 capsules, complete with a breathaler - a device for inhalation, as well as instructions for the use of Ultibro Breezhaler).

Active ingredients in 1 capsule:

• glycopyrronium base - 0.05 mg (glycopyrronium bromide - 0.063 mg);
• indacaterol base 0.11 mg (indacaterol maleate 0.143 mg).

Auxiliary components (1 capsule):

• powder: magnesium stearate - 0.037 mg; lactose monohydrate - 24.757 mg;
• capsule shell: potassium chloride - 0.18 mg; hypromellose - 45.7 mg; carrageenan - 0.42 mg; water - 2.7 mg;
• black ink: shellac, dye black iron oxide (E 172), propylene glycol, potassium hydroxide, water;
• blue ink: indigo carmine (E 132), shellac, titanium dioxide, propylene glycol.

Pharmacological properties

Pharmacodynamics

Ultibro Breezhaler is one of the long-acting inhaled combination drugs. The active substances - glycopyrronium bromide and indacaterol, contribute to the relaxation of the smooth muscles of the bronchi, while due to a different mechanism of action, a mutual strengthening of the bronchodilating effect is noted.

Glycopyrronium bromide is a long-acting inhaled m-cholinergic blocker, which is intended for maintenance therapy of bronchial conduction disorders in patients with COPD (chronic obstructive pulmonary disease). The mechanism of its action is due to the blocking of the bronchoconstrictor action of acetylcholine on the smooth muscle cells of the respiratory tract, due to which the bronchodilatory effect is obtained.

In the human body, five subtypes of muscarinic receptors have been identified (M _1–5). It was found that only the M _1–3 subtypes are involved in the physiological function of the respiratory system. Glycopyrronium bromide has a 4–5 times greater selectivity for M ₁ and M ₃ receptor subtypes, compared to the M ₂ subtype. After inhalation of the drug, this factor contributes to the rapid development of the therapeutic effect, which is confirmed by clinical studies.

The persistence of the bronchodilating effect of glycopyrronium bromide after inhalation occurs for 24 hours. The duration of exposure to the drug is based on the long-term maintenance of the therapeutic concentration of the substance in the lungs, which is confirmed by a longer T _1/2 (half-life) after inhalation, compared with intravenous administration.

Indacaterol is an ultra-long-acting selective β ₂ -adrenomimetic (with a single dose - within 24 hours). The pharmacological effect of indacaterol, like other β ₂ -adrenomimetics, is based on the stimulation of intracellular adenylate cyclase. It is an enzyme that catalyzes the conversion of ATP to cyclic 3 ', 5'-AMP (cyclic AMP). With an increase in its content, relaxation of the smooth muscles of the bronchi is noted. Indacaterol is an almost complete β ₂ -adrenoreceptor agonist; the stimulating effect of the drug on β ₂ -adrenergic receptors is 24 times higher than that of β ₁ -adrenergic receptors and 20 times higher than that of β ₃-adrenergic receptors. The substance after inhalation has a long and rapid bronchodilating effect.

The density of M ₃ -cholinergic receptors and β ₂ -adrenergic receptors in the peripheral and central airways differs, therefore β ₂ -adrenomimetics relax the peripheral airways better, while M-anticholinergics have a more significant effect in relation to the central airways. Thus, thanks to the combination of the two active components of Ultibro Breezhaler, an optimal expansion of the bronchi is noted throughout the entire lower respiratory tract system.

The therapeutic effect of Ultibro Breezhaler develops 5 minutes after inhalation, it remains at a constant level for 24 hours, which allows for a lasting significant improvement in lung function.

At the 26th week of treatment, there is an increase in FEV1 (forced expiratory volume in the first second) by an average of 320 ml compared with patients who received placebo, and by 110 ml compared with patients who received therapy separately with glycopyrronium bromide, indacaterol or tiotropium bromide … There is also a decrease in functional residual lung capacity and residual lung volume.

Against the background of the use of Ultibro Breezhaler, there is a decrease in shortness of breath, physical activity is better tolerated. There was also a significant decrease in the risk of exacerbations of COPD (the time until the next exacerbation increases), a decrease in the need for inhaled short-acting β ₂ -adrenomimetics, and an improvement in the quality of life of patients (as assessed based on the certified questionnaire of St. George's Hospital).

Based on the results of clinical studies, Ultibro Breezhaler, when used in therapeutic and supratherapeutic doses, has no clinically significant effect on heart rate, QT interval length, serum glucose concentration and potassium content.

Pharmacokinetics

The average time to reach C _max (maximum concentration of the substance) of indacaterol and glycopyrronium bromide in blood plasma after inhalation was 5 and 15 minutes, respectively.

AUC (area under the concentration-time curve) of glycopyrronium bromide in equilibrium when using Ultibro Breezhaler corresponds to that when the substance is inhaled alone.

According to a study that examined the effectiveness of inhalation delivered to the lungs when using Ultibro Breezhaler, the dose of indacaterol corresponds to the use of 0.15 mg of indacaterol alone. AUC of a substance in an equilibrium state when using Ultibro Breezhaler corresponds or may be slightly lower than that when inhaled 0.15 mg of indacaterol alone. The absolute bioavailability is: indacaterol - 47-66%, glycopyrronium bromide - about 40%.

There is no information on the use of Ultibro Breezhaler in patients with severe hepatic impairment.

In patients with severe impairment of renal function or end-stage chronic renal failure, in which hemodialysis is required, Ultibro Breezhaler can be used only in cases where the expected benefit is higher than the possible risk.

Glycopyrronium bromide

After inhalation, the substance is rapidly absorbed and reaches C _max in blood plasma in 5 minutes. Approximately 90% of the systemic exposure to glycopyrronium bromide is due to absorption in the lungs and 10% in the gastrointestinal tract. The absolute bioavailability of the substance after inhalation is estimated at 40% of the dose received. Against the background of daily inhalations (1 time per day), C _ss (equilibrium concentration) of glycopyrronium bromide is reached in 7 days. AUC of a substance in an equilibrium state is 1.4-1.7 times higher than after the first inhalation. With _{max of the} substance in equilibrium and its plasma concentration in the blood at the end of the dosing period are 166 and 8 pg / ml, respectively.

V _ss (volume of distribution in the equilibrium state) after intravenous administration of glycopyrronium bromide was 83 L, and V _z (volume of distribution in the terminal phase) was 376 L. V _z / F (apparent volume of distribution in the terminal phase after inhalation) is 7310 liters, which is a reflection of the slower elimination of the substance after inhalation. The connection of glycopyrronium bromide with human blood plasma proteins at a concentration of 1–10 ng / ml is 38–41%.

It is noted that as a result of the hydroxylation of glycopyrronium bromide, the formation of various mono- and bis-hydroxylated metabolites occurs, and as a result of direct hydrolysis - derivatives of carboxylic acid (M ₉). According to the results of the study, CYP isoenzymes contribute to the oxidative biotransformation of glycopyrronium bromide. Probably, hydrolysis to M _{9 is} catalyzed by enzymes of the cholinesterase family. In the course of the studies, the metabolism of the active substance in the lungs was not revealed, but it was found that M ₉ makes an insignificant contribution to the circulation. Based on this, it is assumed that M ₉is formed from the fraction of the active substance absorbed from the gastrointestinal tract (after inhalation) by first-pass hydrolysis and / or by primary passage through the liver.

In the urine after inhalation or intravenous administration, a minimum amount of M _{9 is found} (<0.5% of the dose). Sulfate and / or glucurone conjugates of glycopyrronium bromide were detected in urine after repeated inhalation in a volume of approximately 3% of the delivered dose. According to studies of inhibition of the substance, glycopyrronium bromide has a pronounced ability to suppress the activity of isoenzymes CYP2D6, CYP1A2, CYP2A6, CYP2C8, CYP2C19, CYP2C9, CYP2E1 or CYP3A4 / 5, transport proteins MRP1, MDR1 or MXR, which also mediate drug excretion from cells transporters OATZ, OATI, OATP1VZ, OATP1B1, OST1 or OST2 does not possess. Enzyme induction studies in glycopyrronium bromide clinically significant ability to induce cytochrome P ₄₅₀ isoenzymes, MDR1 and MRP2 transporter proteins and the UGT1A1 enzyme were not detected.

Most of the dose (60–70% of the total plasma clearance) is excreted by the kidneys, from 30 to 40% is excreted by other routes - through metabolism or with bile. The average renal clearance of glycopyrronium in healthy volunteers and patients with COPD who receive glycopyrronium at a dose of 0.05–0.2 mg once a day, both once and repeatedly, is in the range of 17.4–24.4 l / h.

Excretion of the substance through the kidneys is associated with active tubular secretion. Unchanged in urine is detected up to 23% of the dose. The plasma concentration of glycopyrronium bromide in the blood decreases in a multiphase manner. The average final T _1/2 is longer after inhalation and is 33-57 hours (after intravenous and oral administration - 6.2 and 2.8 hours, respectively). By the nature of elimination, it can be assumed that the substance has long-term absorption in the lungs and / or enters the systemic circulation during and after 24 hours from the moment of inhalation.

The total excretion by the kidneys and the AUC of glycopyrronium bromide at steady state in patients with COPD increase proportionally when using a dose in the range of 0.05–0.2 mg.

Clinical studies in patients with hepatic insufficiency have not been conducted. Excretion of glycopyrronium bromide occurs mainly due to excretion by the kidneys. It is assumed that a deterioration in the metabolism of glycopyrronium bromide in the liver will not lead to a clinically significant increase in AUC.

Renal failure affects the AUC of glycopyrronium bromide. A moderate increase in AUC up to 1.4 times is observed in patients with mild / moderate renal failure, in severe renal failure and in patients with end-stage, this value increases to 2.2 times. With mild to moderate renal failure, no dosage adjustment is required.

Indacaterol

C _max indacaterol in serum after a single / repeated inhalation achieved in 15 minutes on average. The serum concentration of indacaterol in the blood increases with repeated use of Ultibro Breezhaler. C _ss in the blood is reached within 12-15 days of therapy. When inhaled in the dose range of 0.06-0.48 mg (the dose that is delivered to the lungs) with a frequency of once a day for 14 days, the cumulation coefficient of indacaterol, estimated by the AUC of the drug on the 1st and 14th-15th days is 2.9-3.8.

After intravenous administration, the V _{z of} indacaterol is 2557 L, which indicates that the substance has a significant distribution. The connection with human plasma and serum proteins is approximately 95%.

With oral administration of radioactively labeled indacaterol, the main component of serum is an unchanged substance, it is about 1/3 of the daily AUC of the drug. To the greatest extent of the metabolites of indacaterol in the blood serum, its hydroxylated derivative is determined. In smaller amounts, hydroxylated indacaterol and phenolic O-glucuronide of indacaterol are detected. Also identified: N-glucuronide of indacaterol, diastereomers of the hydroxylated derivative, and N- and C-dealkylation products.

The only isoenzyme that metabolizes indacaterol to phenolic O-glucuronide is the UGT1A1 isoenzyme. Hydroxylation of the substance occurs mainly with the help of the isoenzyme CYP3A4. It has also been determined that indacaterol is a low affinity substrate for the membrane transporter of P-gp (P-glycoprotein) molecules.

The amount of unchanged indacaterol, which is excreted by the kidneys, is up to 2.5% of the delivered dose. The average renal clearance of the substance is from 0.46 to 1.2 l / h. The serum clearance of indacaterol is 18.8–23.3 l / h, so it is obvious that the substance is excreted through the kidneys only slightly (approximately 2–5% of the systemic clearance). After oral administration, indacaterol is excreted mainly through the intestine as an unchanged substance and as hydroxylated metabolites (54 and 23% of the dose, respectively).

The serum concentration of indacaterol in the blood decreases in a multiphase manner with an average endpoint T _{1/2 of} 45.5–126 hours. The effective T _1/2, which is calculated on the basis of the accumulation of indacaterol with repeated use, is in the range of 40–52 hours, which is consistent with the established time to reach equilibrium (12 to 15 days).

AUC of a substance in an equilibrium state increases in proportion to the delivered dose in the range of 0.12–0.48 mg.

Systemic exposure of indacaterol increases in proportion to the dose increase when used in the range of 0.15–0.6 mg. Systemic exposure of a substance is associated with its absorption in the gastrointestinal tract and lungs.

In patients with mild / moderate liver dysfunction, pharmacokinetic parameters do not significantly change. The use of indacaterol in patients with severe hepatic dysfunction has not been studied.

The experience of using indacaterol in blacks is limited.

Indications for use

Ultibro Breezhaler is prescribed for long-term maintenance therapy of bronchial obstruction disorders in patients with COPD in order to relieve symptoms and reduce the number of exacerbations.

Contraindications

Absolute:

• galactose intolerance, lactase deficiency or glucose-galactose malabsorption;
• combined use with drugs containing other long-acting M-anticholinergics or long-acting β ₂ -adrenomimetics;
• age up to 18 years;
• individual intolerance to the components of the drug.

Relative (Ultibro Breezhaler is prescribed under medical supervision):

• diseases accompanied by urinary retention;
• severe renal failure (in patients with a glomerular filtration rate below 30 ml / min / 1.73 m ²), including end-stage renal failure, which requires hemodialysis;
• severe liver dysfunction;
• cardiovascular diseases, including ischemic heart disease (including unstable angina pectoris), acute myocardial infarction (including a burdened history), cardiac arrhythmias, arterial hypertension, lengthening of the QTc interval (corrected QT> 0.44 s), congenital lengthening of the QT interval;
• seizure disorders;
• diabetes;
• thyrotoxicosis;
• angle-closure glaucoma;
• burdened history of inadequate response to the action of β ₂ -adrenomimetics;
• combined use with drugs that prolong the QT interval (antiarrhythmic drugs IA and III classes, tricyclic and tetracyclic antidepressants, antipsychotics, macrolides, antifungal drugs, imidazole derivatives, some antihistamines, including terfenadine, astemizole, drugs for the anesthesia group), barbiturates;
• pregnancy and lactation.

Ultibro Breezhaler, instructions for use: method and dosage

Ultibro Breezhaler is intended for oral inhalation using a breathaler (a special device for inhalation) that is included in the kit. The drug cannot be taken orally. The capsules should be stored in a blister and removed immediately before use.

The recommended dose of Ultibro Breezhaler is 1 capsule once a day. Inhalation should be done daily at the same time. If a dose is missed, it should be taken as soon as possible. Do not use more than 1 dose per day.

If, against the background of Ultibro Breezhaler therapy, an improvement in respiratory function does not occur, it is necessary to make sure that it is used correctly. The drug must be inhaled, not swallowed.

How to use the inhaler:

1. Remove the cover and, holding the inhaler by the base and tilting the mouthpiece in the direction of the arrow, open the device.
2. With clean, dry hands, remove the capsule from the blister, release it from the protective film (do not squeeze the capsule through the film) and insert it into the Breezhaler, placing it in a specially designated place (do not put it in the mouthpiece).
3. Close Breezhaler (you should hear a click).
4. Pierce the capsule: holding the device strictly vertically, simultaneously press the buttons of the piercing device on both sides (a click should occur at the moment of piercing the capsule) and release them. You cannot press the buttons again.
5. Exhale completely (do not blow into the mouthpiece).
6. Place the mouthpiece in your mouth and wrap your lips tightly around it. Take a quick, even and deepest breath. During inhalation, a sweetish taste of the agent may be felt in the mouth and a characteristic rattling sound will be heard, produced during the rotation of the capsule in the chamber and the spraying of the powder. The absence of a characteristic sound may mean that the capsule is stuck in the inhaler chamber. If this happens, you need to carefully remove it, slightly tapping on the base of the device. Do not press the side buttons repeatedly to eject the capsule.
7. If there is a characteristic sound, indicating the correct execution of the procedure, hold your breath as long as possible (without leading to unpleasant sensations), at this time the mouthpiece can be removed.
8. Exhale.
9. Open the inhaler and check the capsule for powder residue. If there is still powder in the capsule, close the Breezhaler and repeat the inhalation procedure. For the complete release of the capsule, most patients usually need 1–2 inhalations. The absence of powder in the capsule indicates a full dose. In some cases, after inhalation, a cough is noted for a short period, which is not a reason for worry.
10. After inhalation, open Breezhaler by tilting the mouthpiece, remove the empty capsule and discard it, then close the mouthpiece and inhaler.

When using the inhaler, patients should remember a few basic rules:

• avoid swallowing capsules;
• do not blow into the mouthpiece;
• store capsules in a blister, and not in Breezhaler, take them out just before the procedure;
• use only the device that is included in the package;
• store capsules and Breezhaler in a dry place;
• do not wash Breezhaler or disassemble it;
• do not put the capsule in the mouthpiece, do not forget to pierce it before inhalation;
• press the lancing device no more than once;
• use a new Breezhaler when starting a new package;
• clean the inhaler with a clean dry cloth once a week.

Side effects

Adverse reactions when using Ultibro Breezhaler are characterized by symptoms that are typical for M-anticholinergics and β ₂ -adrenomimetics used as monotherapy. Most often (more than 3% of cases), the development of cough and pain in the oropharynx (including sore throat) is noted.

When inhaled in recommended doses in patients with COPD, Ultibro Breezhaler has no clinically significant systemic β ₂ -adrenomimetic effect. On average, the heart rate changed by no more than 1 beat per minute, and tachycardia occurred rarely and with a lower frequency than in the placebo group. The incidence of hypokalemia and significant prolongation of the QTc interval (> 450 ms) is similar to that in the placebo group.

Possible adverse reactions that occurred when using Ultibro Breezhaler 1 time per day in patients with COPD during registration clinical trials lasting 6 and 12 months (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare):

• immune system: infrequently - hypersensitivity;
• respiratory system: often - pain in the oropharynx, cough, sore throat; infrequently - nosebleeds;
• infectious and parasitic diseases: very often - an upper respiratory tract infection; often - rhinitis, sinusitis, urinary tract infection, nasopharyngitis;
• metabolism and nutrition: infrequently - hyperglycemia, diabetes mellitus;
• psyche: infrequently - insomnia;
• kidneys and urinary tract: infrequently - urinary retention, bladder obstruction;
• nervous system: often - headache, dizziness; infrequently - paresthesia;
• organ of vision: infrequently - glaucoma ¹;
• skin and subcutaneous tissue: infrequently - itching / rash;
• musculoskeletal and connective tissue: often - pain in bones and muscles; infrequently - myalgia, muscle spasms;
• heart: infrequently - tachycardia, ischemic heart disease, palpitations, atrial fibrillation;
• digestive system: often - dental caries, dyspepsia; infrequently - dryness of the oral mucosa;
• general disorders: often - chest pain, fever ¹; infrequently - fatigue, peripheral edema.

¹ New side reactions that developed during the use of Ultibro Breezhaler and were not observed with the use of each of the active substances separately.

When used as monotherapy glycopyrronium bromide or indacaterol, the following violations were noted:

• respiratory system: infrequently - paradoxical bronchospasm;
• musculoskeletal and connective tissue: infrequently - pain in the limbs;
• digestive system: often - gastroenteritis.

In most cases, when using Ultibro Breezhaler, dry mouth was mild. The development of cough was noted often, but this disorder was usually mild.

Ischemic heart disease and hypersensitivity reactions were noted with a frequency of 0.4 and 0.1%, respectively (0.3 and 0% in patients from the placebo group).

Overdose

After 14 days of using Ultibro Breezhaler at doses several times higher than therapeutic, in patients with COPD, an increase in the incidence of ventricular extrasystole was noted. Unstable ventricular tachycardia was generally observed in four patients, with the longest episode lasting 9 contractions (4 seconds).

It has been suggested that an overdose of Ultibro Breezhaler will exhibit symptoms that are typical of an overdose of β ₂ -adrenomimetics (including tremor, tachycardia, palpitations, headache, drowsiness, nausea, vomiting, ventricular arrhythmia, metabolic acidosis, hyperglycaemia), and - cholinoblockers (including increased intraocular pressure, which is accompanied by eye pain, redness of the eyes or blurred vision, difficulty urinating, constipation).

Glycopyrronium bromide

In patients with COPD, with regular inhalation administration of glycopyrronium once a day in a total dose of 0.1 and 0.2 mg for a course of 4 weeks, there was a good tolerance.

If the capsule is accidentally swallowed, acute intoxication of the substance is unlikely, which is associated with its low bioavailability after oral administration (approximately 5%).

After intravenous administration of 0.15 mg of glycopyrronium bromide in healthy volunteers, C _max and AUC were approximately 50 and 6 times higher than these values in the equilibrium state achieved with inhalation of glycopyrronium in recommended doses. At the same time, no signs of overdose were detected.

Indacaterol

In patients with COPD, after a single use of indacaterol at a dose 10 times the maximum therapeutic dose, there was a moderate increase in heart rate, lengthening of the QTc interval and an increase in blood pressure.

Therapy

When signs of overdose appear, supportive and symptomatic treatment is performed. In severe cases, patients are hospitalized. If necessary, selective β-blockers can be used, but only with caution and under strict medical supervision, since this can cause the development of bronchospasm.

special instructions

Ultibro Breezhaler is recommended for use in relieving acute episodes of bronchospasm.

The drug is intended for maintenance treatment in patients with COPD. Due to the fact that patients over 40 years of age predominate in the general population of COPD, in the case of the appointment of Ultibro Breezhaler to patients under this age, spirometric confirmation of the diagnosis is required.

When using active ingredients as monotherapy, cases of immediate hypersensitivity reactions have been reported. If symptoms appear that indicate the development of an allergic reaction (in the form of difficulty breathing or swallowing, swelling of the tongue, face and lips, hives, skin rash), it is necessary to cancel Ultibro Breezhaler and choose an alternative treatment.

There is no information on the use of the drug in patients with bronchial asthma, therefore, Ultibro Breezhaler therapy is not prescribed to patients in this group. With the use of long-acting β ₂ -adrenomimetics in the treatment of bronchial asthma, the likelihood of developing serious adverse events associated with bronchial asthma (including death) increases.

During clinical trials of the drug, cases of paradoxical bronchospasm were not observed. However, against the background of therapy with other inhalation agents, the development of this disorder was observed, which potentially poses a threat to life. If it occurs, Ultibro Breezhaler should be immediately canceled, with an alternative treatment prescribed.

There are no data on the use of the drug in angle-closure glaucoma, so therapy should be carried out with caution. You need to know about the symptoms and signs of an acute attack of angle-closure glaucoma, in case of a disorder, you need to cancel the use of Ultibro Breezhaler and consult a doctor.

The human heart contains mainly β ₁ -adrenergic receptors, β ₂ -adrenergic receptors are presented mainly in the smooth muscles of the bronchi, while their share in the human heart is 10-50% of all adrenergic receptors. The exact function of β ₂ -adrenergic receptors in the heart has not been precisely established, but their presence suggests that even highly selective β ₂ -adrenergic agonists can affect the heart.

The use of β ₂ -adrenomimetics can have a clinically significant effect on the cardiovascular system (manifested as an increase in heart rate, increase in blood pressure, etc.). With the development of adverse reactions from the cardiovascular system, Ultibro Breezhaler can be canceled.

Also, during therapy with β ₂ -adrenomimetics, the following electrocardiographic changes can be observed: lengthening of the QT interval, flattening of the T wave and depression of the ST segment (it has not been established what clinical significance these changes have). In clinical trials, the use of Ultibro Breezhaler in recommended therapeutic doses did not lead to the development of a significant lengthening of the QT interval, in comparison with placebo.

In some patients, the use of β ₂ -adrenomimetics can cause significant hypokalemia, leading to the development of side effects from the cardiovascular system. Usually, a decrease in serum potassium concentration in the blood is transient and does not require correction. In patients with COPD, severe hypokalemia may be associated with hypoxia and concomitant treatment, which, in turn, may increase the risk of arrhythmias. When conducting clinical studies of the use of Ultibro Breezhaler in the recommended therapeutic doses, clinically significant effects of hypokalemia were not observed.

In the case of inhalation of high doses of β ₂ -adrenomimetics, an increase in plasma glucose levels in the blood is possible. Patients with diabetes mellitus during the period of Ultibro Breezhaler therapy need to regularly monitor the plasma concentration of glucose in the blood. When conducting clinical studies in patients who received the drug in the recommended doses, an increase in the incidence of clinically significant hyperglycemia was observed in comparison with the placebo group. The safety and efficacy of Ultibro Breezhaler in patients with uncompensated diabetes mellitus have not been studied.

Influence on the ability to drive vehicles and complex mechanisms

Ultibro Breezhaler has little or no effect on the ability to drive.

Application during pregnancy and lactation

Ultibro Breezhaler during pregnancy / lactation can be used only in cases where the expected benefit is higher than the possible risk.

The safety and efficacy profile of the drug in pregnant women has not been studied; there is also no information on the use of glycopyrronium bromide or indacaterol in this group of patients.

When conducting studies of early and late embryogenesis in rats, no effect of Ultibro Breezhaler, which was used in different doses, on the embryo or fetus was found. In rabbits and rats that received inhalations of glycopyrronium bromide, the development of teratogenic effects was also not found. An insignificant plasma concentration of glycopyrronium bromide in umbilical cord blood was registered 86 minutes after a single intramuscular injection at a dose of 0.006 mg / kg to women who underwent a cesarean section.

After subcutaneous administration in rabbits and rats, the teratogenic effect of indacaterol was not revealed. However, the substance had a toxic effect on the reproductive system, which manifested itself as an increase in the frequency of skeletal changes in rabbits.

It is not established whether the active substances of Ultibro Breezhaler penetrate into breast milk. However, both indacaterol and glycopyrronium bromide (including its metabolites) were found in the milk of lactating rats.

Indacaterol, due to its relaxing effect on the smooth muscles of the uterus, can slow down the process of childbirth.

Pediatric use

For patients under the age of 18, Ultibro Breezhaler is not prescribed.

With impaired renal function

Caution when using Ultibro Breezhaler is required for patients with diseases accompanied by urinary retention, patients with severe renal failure (with a glomerular filtration rate below 30 ml / min / 1.73 m ²), including end-stage renal failure, which requires hemodialysis.

For violations of liver function

Ultibro Breezhaler with severe liver dysfunction is prescribed with caution.

Drug interactions

With inhalation use of Ultibro Breezhaler under equilibrium conditions, the pharmacokinetic properties of both active components did not change.

Special studies of the interaction of Ultibro Breezhaler with other drugs have not been conducted. Information on potential interactions is based on information on possible interactions of each of its active ingredients.

According to the studies, glycopyrronium bromide, most likely, has no effect on the metabolism of other drugs.

The interaction of Ultibro Breezhaler with other drugs / substances containing long-acting M-anticholinergics has not been studied, therefore, the combined use is not recommended.

Given that β-blockers can weaken or interfere with the effects of β ₂ -adrenomimetics, combined use with β-blockers (including eye drops) is not recommended (except for compelling reasons for their simultaneous use).

If it is necessary to use both classes of drugs, preference should be given to selective β-blockers, however, therapy requires caution.

Other possible interactions:

• tricyclic antidepressants, monoamine oxidase inhibitors or other drugs that can lead to prolongation of the QT interval: combined use requires caution, since the effect on the length of the QT interval may increase, which leads to an increase in the likelihood of ventricular arrhythmia;
• sympathomimetics: against the background of combined use, the risk of adverse events may increase; simultaneous administration with drugs containing other long-acting β ₂ -adrenomimetics is not recommended;
• methylxanthine derivatives, glucocorticosteroids or diuretics that cause hypokalemia: there may be an increase in possible hypokalemia caused by β ₂ -adrenomimetics;
• specific inhibitors of the isoenzyme CYP3A4 and P-glycoprotein (erythromycin, ketoconazole, ritonavir, verapamil): a study was made of the drug interaction between indacaterol and these drugs; with combined therapy, a significant increase in AUC and C _{max was} noted, while this did not lead to a change in the safety profile.

Analogs

The analogues of Ultibro Breezhaler are: Berodual, Ditek, Berodual N, Astmasol-SOLOfarm, Ipraterol-Aeronativ, Fenipra, Inspirax, etc.

Terms and conditions of storage

Store in a place protected from moisture, at temperatures up to 25 ° C, in its original packaging. Keep out of the reach of children.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Ultibro Breezhaler

Reviews about Ultibro Breezhaler are mostly positive. The therapeutic effect develops quickly, in particular, it manifests itself in a pronounced decrease in shortness of breath. Some responses indicate the development of side effects. The cost is assessed as high.

Price for Ultibro Breezhaler in pharmacies

The approximate price for Ultibro Breezhaler (30 capsules) is 3197-3437 rubles.

Ultibro Breezhaler: prices in online pharmacies

Drug name Price Pharmacy

Ultibro Breezhaler 50 mcg + 110 mcg powder capsules for inhalation complete with Breezhaler inhaler 30 pcs. 1890 RUB Buy

Ultibro Breezhaler capsules for inhalation. 50μg + 110μg 30 pcs. 2976 RUB Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!