Betmiga, 10 pcs., 50 mg, extended-release film-coated tablets

Betmiga tablets ppo prolong 50 mg No. 10

Compound

Active substance: mirabegron - 50 mg. Excipients: macrogol 2,000,000 - 70 mg, macrogol 8000 - 119.6 mg, hyprolose - 7.5 mg, butylated hydroxytoluene - 0.4 mg, magnesium stearate - 2.5 mg.

Pharmacokinetics

Following oral administration, mirabegron is absorbed into the bloodstream and reaches Cmax in plasma between three and four hours after administration. Studies have shown an increase in absolute bioavailability from 29% to 35% after increasing the dose from 25 to 50 mg. In this case, the average Cmax value and AUC value increased more than proportionally to the dose. Css is achieved after 7 days of taking mirabegron once a day. After repeated use once a day, the Css of mirabegron in the blood plasma are approximately 2 times higher than those after a single dose of the drug.

Mirabegron is intensively distributed in the body. Vd in stable conditions (Vss) is approximately 1670 l. Mirabegron is approximately 71% protein bound in plasma and also exhibits moderate affinity for albumin and alpha-1 acid glycoprotein. Mirabegron is distributed to red blood cells. Concentrations of 14C-mirabegron in erythrocytes were 2 times higher than in plasma (as shown by in vitro studies).

There are many ways mirabegron is metabolized in the body, incl. dealkylation, oxidation, (direct) glucuronidation and amide hydrolysis. After a single administration of C-mirabegron, the main circulating component is mirabegron. Two main metabolites of mirabegron were found in human plasma: both are glucuronides (phase II metabolites) and constitute, respectively, 16% and 11% of the total drug concentration. These metabolites do not have pharmacological activity.

Despite the participation of the CYP2D6 and CYP3A4 isoenzymes in the oxidative pathway of mirabegron metabolism in vitro, in in vivo conditions the role of these isoenzymes in the overall elimination is small.

The total plasma clearance is about 57 l/h. The final T1/2 is approximately 50 hours. Renal clearance is approximately 13 l/h, which corresponds to almost 25% of the total clearance. The main mechanisms of excretion by the kidneys are active tubular secretion and glomerular filtration. The amount of unchanged mirabegron excreted in the urine is dose-dependent and varies from 6.0% after taking the drug at a daily dose of 25 mg to 12.2% after taking a daily dose of 100 mg. After administration of 160 mg of C-mirabegron to healthy volunteers, approximately 55% of the radiolabel was detected in urine and 34% in feces. The unchanged mirabegron fraction accounted for approximately 45% of the total isotopically labeled drug in urine, indicating the presence of metabolites. Most of the isotopically labeled drug in the feces was represented by unchanged mirabegron.

Indications for use

Overactive bladder (OAB) with symptoms of urinary incontinence, frequent urination and urinary urgency.

Contraindications

• hypersensitivity to the active substance or any of the excipients;
• children's age (lack of data on effectiveness and safety);
• pregnancy and breastfeeding;
• end-stage renal failure (eGFR < 15 ml/min/1.73 m2 or patients in whom hemodialysis is indicated);
• severe stage of renal failure (eGFR 15-29 ml/min/1.73 m2) with simultaneous use of strong inhibitors of the CYP3A isoenzyme;
• severe stage of liver failure (Class C on the Child-Pugh scale);
• severe uncontrolled hypertension, defined as systolic pressure ≥180 mmHg and/or diastolic pressure ≥110 mmHg;
• moderate stage of liver failure (Class B on the Child-Pugh scale) with simultaneous use of strong inhibitors of the CYP3A isoenzyme.

Directions for use and doses

Taken orally.

A single dose is 25-50 mg, depending on renal function and concurrent therapy. Frequency of administration: 1 time/day.

Patients with renal and liver failure

The following table shows the recommended daily doses for patients suffering from renal or hepatic impairment, with or without CYP3A inhibitors.

*mild stage: eGFR 60 - 89 ml/min/1.73 m2;
moderate stage: eGFR 30 - 59 ml/min/1.73 m2; severe stage: eGFR 15 - 29 ml/min/1.73 m2 ** mild stage: class A on the Child-Pugh scale; moderate stage: class B on the Child-Pugh scale

Storage conditions

Store at a temperature not exceeding 30 °C, out of the reach of children.

Best before date

3 years. The drug should not be used after the expiration date indicated on the packaging.

special instructions

Mirabegron at therapeutic doses did not demonstrate clinically significant prolongation of the QT interval in the studies conducted. However, since patients taking drugs that may cause QT prolongation did not participate in these studies with mirabegron, the effect on these patients is not known. This category of patients should take mirabegron with caution.

Mirabegron should be used with caution in combination with drugs that have a narrow therapeutic index and drugs that are significantly metabolized by CYP2D6, such as thioridazine, drugs for the treatment of class 1 C arrhythmias (for example, flecainide, propafenone) and tricyclic antidepressants (for example, imipramine, desipramine). Mirabegron should also be taken with caution when co-administered with drugs that are metabolized by the CYP2D6 isoenzyme and the dose of which must be individually determined.

During post-marketing surveillance of the use of mirabegron in patients with bladder outlet obstruction (VFO) and in patients already taking anticholinergic drugs for the treatment of OAB, cases of urinary retention were observed. A controlled clinical safety study in patients with IFO did not find an increase in urinary retention in patients receiving mirabegron; however, mirabegron should be used with caution in patients with clinically significant IFO.

Mirabegron should also be used with caution in patients already taking anticholinergic drugs for the treatment of OAB.

Mirabegron may increase blood pressure. It is recommended to measure blood pressure before starting treatment and periodically during treatment with mirabegron, especially in patients with arterial hypertension.

Description

Selective beta3-adrenergic receptor agonist. A drug that reduces the tone of smooth muscles of the urinary tract.

Dosage form

Extended-release, yellow, oval, biconvex film-coated tablets, engraved with “355” and a graphic logo on one side; the kernel is white or almost white.

Use in children

The use of the drug in children is prohibited, because There are no data on effectiveness and safety.

Action

Selective agonist of β3-adrenergic receptors. Studies with mirabegron have demonstrated relaxation of bladder smooth muscle in rats and in isolated human tissue, as well as an increase in cAMP concentrations in bladder tissue in rats. Thus, mirabegron improves the reservoir function of the bladder by stimulating β3-adrenergic receptors located in its wall.

Studies have demonstrated the effectiveness of mirabegron both in patients who have previously received anticholinergic drugs for the treatment of overactive bladder (OAB), and in patients without a history of previous anticholinergic therapy.

Mirabegron was also effective in patients with OAB who discontinued treatment with anticholinergic drugs due to lack of effect.

A 12-week study in men with lower urinary tract symptoms (LUTS) and bladder outlet obstruction (IBO) demonstrated the safety and good tolerability of mirabegron in doses of 50 and 100 mg once a day, as well as the absence of mirabegron’s effect on cystometric parameters.

Changes in heart rate and blood pressure during treatment are reversible and disappear after treatment is discontinued.

Side effects

Infections and infestations: often - urinary tract infection; uncommon - vaginal infection, cystitis.

From the organ of vision: rarely - swelling of the eyelids.

From the cardiovascular system: often - tachycardia; infrequently - rapid heartbeat, atrial fibrillation, increased blood pressure

From the digestive system: often - nausea; infrequently - dyspepsia, gastritis, increased activity of GGT, AST, ALT; rarely - swelling of the lips.

From the skin and subcutaneous tissue: uncommon - urticaria, rash, macular rash, papular rash, itching; rarely - leukocystoclastic vasculitis, purpura, angioedema.

From the musculoskeletal system: infrequently - swelling of the joints.

From the reproductive system: infrequently - vulvovaginal itching

*Detected during post-marketing use

Use during pregnancy and breastfeeding

Pregnancy

There is limited data on the use of mirabegron in pregnant women. Animal studies have shown reproductive toxicity. Mirabegron is not recommended during pregnancy or in women of childbearing age who are not using contraception.

Breastfeeding period

In rodents, mirabegron is excreted in breast milk, therefore, in humans there is also a risk of the drug passing into breast milk. There are no studies examining the effect of mirabegron on breast milk production, the excretion of mirabegron in breast milk and the effect on the child. Mirabegron should not be used in women during breastfeeding.

Fertility

Animal studies have not shown any effect of mirabegron on fertility at non-lethal doses.

It has not been established whether mirabegron affects fertility in humans.

Interaction

Mirabegron is a moderate, time-dependent inhibitor of CYP2D6 and a weak inhibitor of CYP3A. At high concentrations, mirabegron inhibited drug transport via P-glycoprotein.

Clinically significant interactions between mirabegron and medicinal products that inhibit, activate or are a substrate of one of the CYP isoenzymes or transporters are not expected, with the exception of the inhibitory effect of mirabegron on the metabolism of CYP2D6 isoenzyme substrates.

Mirabegron concentration (AUC) increased 1.8-fold under the influence of the strong CYP3A/P-gp inhibitor ketoconazole in healthy volunteers. Dose adjustment of mirabegron is not required when taken together with inhibitors of the CYP3A or P-gp isoenzyme. However, in patients with mild to moderate renal impairment (eGFR 30-89 ml/min/1.73 m2) or mild hepatic impairment (Child-Pugh class A) taking strong CYP3A inhibitors such as itraconazole, ketoconazole, ritonavir and clarithromycin, the recommended daily dose of mirabegron is 25 mg, regardless of meals.

Substances that induce CYP3A or P-gp isoenzymes reduce the plasma concentration of mirabegron.

In healthy volunteers, mirabegron moderately inhibits the CYP2D6 isoenzyme, the activity of which is restored 15 days after discontinuation of mirabegron. Daily dosing of mirabegron resulted in a 90% increase in Cmax and 229% increase in AUC for a single dose of metoprolol. Daily dosing of mirabegron resulted in a 79% increase in Cmax and 241% increase in AUC for a single dose of desipramine. Mirabegron should be used with caution in combination with drugs that have a narrow therapeutic index and drugs that are significantly metabolized by CYP2D6, such as thioridazine, drugs for the treatment of class I C arrhythmias (for example, flecainide, propafenone) and tricyclic antidepressants (for example, imipramine, desipramine). Mirabegron should also be taken with caution when co-administered with drugs that are metabolized by the CYP2D6 isoenzyme and the dose of which must be individually determined.

Mirabegron is a weak inhibitor of the P-gp protein. Mirabegron increased Cmax and AUC by 29% and 27%, respectively, when administered with digoxin to healthy volunteers. For patients starting to take mirabegron and digoxin at the same time, digoxin should be taken at the lowest dose. In this case, it is necessary to monitor the concentrations of digoxin in the blood plasma and select a further effective dose of digoxin based on the results of control tests. The potential for P-gp inhibition by mirabegron should be taken into account when mirabegron is administered concomitantly with drugs transported by P-gp proteins, such as dabigatran.

The increased effect of mirabegron when taken together with other drugs is expressed in an increase in heart rate.

Overdose

Doses up to 400 mg have been used in single doses of mirabegron to healthy volunteers.
When using this dose level, adverse events were recorded in the form of rapid heartbeat (in 1 out of 6 volunteers) and an increase in heart rate of more than 100 beats/min (in 3 out of 6 volunteers). With repeated (over 10 days) use of the drug in daily doses of up to 300 mg, an increase in heart rate and an increase in systolic blood pressure were recorded in healthy volunteers.

In case of overdose, symptomatic and supportive therapy is indicated. Monitoring of pulse rate, blood pressure and ECG is necessary.

Impact on the ability to drive vehicles and operate machinery

Betmiga does not have a clinically significant effect on the ability to drive vehicles and operate machinery.

Betmiga, 10 pcs., 50 mg, extended-release film-coated tablets

Pharmaceutical group: Drugs for the treatment of urological diseases / Pharmaceutical action: Mirabegron is a powerful selective beta3-adrenergic receptor agonist. Studies with mirabegron have demonstrated relaxation of bladder smooth muscle in rats and in isolated human tissue, as well as an increase in cAMP concentrations in bladder tissue in rats. Thus, mirabegron improves the reservoir function of the bladder by stimulating beta3-adrenergic receptors located in its wall. Studies have demonstrated the effectiveness of mirabegron both in patients who have previously received M-anticholinergics for the treatment of overactive bladder (OAB), and in patients without a history of previous therapy with M-anticholinergics. Mirabegron was also effective in patients with OAB who discontinued M-anticholinergic treatment due to lack of effect. Urodynamics. A 12-week study in men with lower urinary tract symptoms (LUTS) and bladder outlet obstruction (IVO) demonstrated the safety and good tolerability of mirabegron at doses of 50 and 100 mg once daily, and no effect of mirabegron on cystometric parameters. Effect on QT interval. At doses of 50 mg and 100 mg, mirabegron had no effect on the heart rate-corrected QT interval (QTcI value), which was recorded in the analysis for groups by gender and for the entire group of patients. The effect of repeated oral administration of mirabegron at a therapeutic dose (50 mg once daily) and supratherapeutic doses (100 and 200 mg once daily) on QTcI was studied in a separate study (TQT study) (n = 164 healthy male volunteers and n = 153 healthy female volunteers). In both men and women receiving mirabegron 50 and 100 mg, the upper limit of the one-sided 95% confidence interval for the largest time-matched difference from placebo in QTcI did not exceed 10 ms at any time point. Effect on pulse rate and blood pressure in patients with OAB. In a 12-week, double-blind, placebo-controlled, phase 3 study in patients with OAB (mean age 59 years) receiving mirabegron 50 mg once daily, there was an increase in baseline mean difference from placebo in heart rate (by 1 bpm) ) and systolic blood pressure/diastolic blood pressure (SBP/DBP) (by about 1 mmHg or less). Changes in heart rate and blood pressure during treatment are reversible and disappear after discontinuation of the drug. Effect on intraocular pressure (IOP). 56 days after starting treatment with mirabegron at a dose of 100 mg once daily, no increase in IOP was observed in healthy volunteers. A phase I study (n = 310) assessed the effect of mirabegron on IOP using Goldmann applanation tonometry: mirabegron 100 mg did not differ from placebo in the effect size with respect to the mean change in baseline mean individual IOP values ​​at day 56. Pharmacokinetics: Absorption. Following oral administration, mirabegron is absorbed into the bloodstream and reaches its maximum plasma concentration (Cmax) between three and four hours after administration. Studies have shown an increase in absolute bioavailability from 29% to 35% after increasing the dose from 25 mg to 50 mg. In this case, the average Cmax value and the AUC value increased more than in proportion to the dose. Equilibrium concentrations are achieved after 7 days of taking mirabegron once a day. After repeated once-daily administration, plasma concentrations of mirabegron at steady state are approximately twice as high as those after a single dose of the drug. The effect of food intake on drug absorption. Phase 3 studies demonstrated the same effectiveness and safety of treatment when taking mirabegron during and outside meals. Thus, the recommended dose of mirabegron can be taken both during and outside meals. Distribution. Mirabegron is intensively distributed in the body. The volume of distribution under stable conditions (Vss) is approximately 1670 l. Mirabegron is approximately 71% protein bound in plasma and also exhibits moderate affinity for albumin and alpha-1 acid glycoprotein. Mirabegron is distributed to red blood cells. Concentrations of 14C-labeled mirabegron in erythrocytes were 2 times higher than in plasma (as shown in in vitro studies). Metabolism. There are many pathways for mirabegron metabolism in the body, including dealkylation, oxidation, (direct) glucuronidation and amide hydrolysis. After a single administration of 14C-mirabegron, the main circulating component is mirabegron. Two main metabolites of mirabegron were found in human plasma: both are glucuronides (phase II metabolites) and constitute, respectively, 16% and 11% of the total drug concentration. These metabolites do not have pharmacological activity. Despite the participation of the enzymes CYP2D6 and CYP3A4 in the oxidative pathway of mirabegron metabolism in vitro, in vivo the role of these isoenzymes in the overall elimination is small. Excretion. The total clearance (Cltotal) of the drug is approximately 57 l/hour. The terminal half-life (t1/2) is approximately 50 hours. Renal clearance (Clren) is approximately 13 l/hour, which corresponds to almost 25% of the Cltot value. The main mechanisms of excretion by the kidneys are active tubular secretion and glomerular filtration. The amount of unchanged mirabegron excreted in the urine is dose-dependent and varies from 6.0% after taking the drug at a daily dose of 25 mg to 12.2% after taking a daily dose of 100 mg. After administration of 160 mg of 14C-mirabegron to healthy volunteers, approximately 55% of the tracer was detected in urine and 34% in feces. The unchanged mirabegron fraction accounted for approximately 45% of the total isotopically labeled drug in urine, indicating the presence of metabolites. Most of the isotopically labeled drug in the feces was represented by unchanged mirabegron. Features of pharmacokinetics in certain categories of patients: Age. In elderly patients, there is no need for dose adjustment. In studies, Cmax and AUC values ​​for mirabegron and its metabolites were similar in older (≥ 65 years) and younger volunteers (18-45 years). Floor. No dose adjustment is required depending on the gender of the patient. Race. No dose adjustment is required depending on the patient's race. Race does not affect the pharmacokinetics of the drug.

Instructions for use MAGNEKARD tablets 75 mg

Pregnancy

Low doses (up to 100 mg/day)

Clinical studies indicate that doses up to 100 mg/day are safe for use in certain conditions in pregnant women that require special monitoring.

Doses 100-500 mg/day

There is insufficient clinical experience with the use of ASA in doses of 100-500 mg/day, so it is necessary to follow the recommendations for doses of 500 mg/day and above.

Dose 500 mg/day or higher

III trimester

Prostaglandin synthesis inhibitors are contraindicated in the third trimester of pregnancy, because their use can lead to the following conditions in the fetus:

• cardiac toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• impaired renal function, which can lead to renal failure and, consequently, a decrease in the amount of amniotic fluid.

The use of prostaglandin synthesis inhibitors at the end of pregnancy can lead to:

• prolonged bleeding due to decreased platelet aggregation, which can occur even when used in very low doses;
• inhibition of uterine contractions, which can lead to a delay or prolonged labor.

I and II trimester

Prostaglandin synthesis inhibitors should be used only when absolutely necessary in the first and second trimesters of pregnancy; the dose should be low and the duration of use as short as possible.

Suppression of prostaglandin synthesis may adversely affect pregnancy and/or intrauterine development of the embryo. Data from epidemiological studies show an increased risk of spontaneous abortion and congenital heart defects of the child and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of congenital heart defects increases from less than 1% to 1.5%. The risk is believed to be associated with increasing dose and duration of treatment. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased losses before and after embryo implantation. In addition, an increase in cases of defects was noted, incl. cardiovascular system, in animals that were exposed to inhibitors of prostaglandin synthesis during the period of organogenesis. In connection with the above, acetylsalicylic acid at a dose of 100 mg/day or higher doses is contraindicated in the third trimester of pregnancy.

Breast-feeding

Application experience is insufficient. Before prescribing acetylsalicylic acid, the benefits of treatment should be assessed taking into account the potential risk to the child.

Fertility

ASA is not recommended for women wishing to become pregnant, because inhibition of prostaglandin synthesis is believed to reduce fertility. If the use of ASA is necessary, treatment should be as short as possible and in as low doses as possible. The effect on fertility is reversible.

Overactive Bladder: Myths and Reality

The problem of overactive bladder (OAB) has long ceased to be just a medical problem and has become a social problem.
It is characterized by a low quality of life for patients, rare visits by patients to urologists, and ignorance of primary care physicians about the problem of OAB, which consequently complicates the provision of care to this group of patients. We asked Doctor of Medical Sciences, Prof. to share his extensive experience in diagnosing and treating OAB. Department of Urology, Russian State Medical University Grigory Georgievich Krivoborodov. – Grigory Georgievich, how long have you been working on the problem of GMP? What interested you in this problem?

G.G. Krivoborodov: We have been dealing with the problem of GMF for more than 15 years. We became interested as soon as the first foreign publications about GMF appeared. This is due to the fact that our clinic has traditionally been involved in urodynamic studies for a long time, and patients with OAB often need to perform them. Therefore, from the very beginning it was clear to us what form of urination disorder OAB belongs to. Everyone knows that there is a category of patients who complain of frequent urination, often urgent urination and/or urgent urinary incontinence. Previously, we could not find out the reason. We believed that the patients had a chronic inflammatory process of the bladder wall, which leads to urgent urination, although general urine tests and urine cultures showed the absence of any infection. Such patients are often referred to a psychoneurologist, believing that they have mental illnesses that cause such somatic problems. It has also been observed that 30–40% of patients with such unexplained frequency of urination have involuntary detrusor contractions on cystometry, which is now called detrusor overactivity. And then it became clear that such urgent and frequent urination is associated with special changes in the detrusor of the bladder. Such patients cannot accumulate a sufficient amount of urine in the bladder, since there is a sudden contraction of the bladder, which is manifested by urgent and frequent urination. It was after these observations that a new era of treatment for patients with frequent and urgent urination began in the world, and the condition began to be referred to as OAB. Until now, OAB has been somewhat of a mysterious disease. For example, the diagnosis of OAB is not included in the international classification of diseases, and some doctors use the synonym “urinary urgency and frequency syndrome.”

– What do you think is the prevalence of the GMP problem in Russia?

G.G. Krivoborodov: About 15% of the population of our country have urgent and frequent urination. I think it is important to emphasize that OAB is a common condition that is more common than well-known diseases such as diabetes, asthma and osteoporosis.

– There is a point of view that patients with urgent and frequent urination rarely seek help. Is it so?

G.G. Krivoborodov: This is a correct and important question. Despite the significant prevalence of OAB, patients rarely seek help from medical institutions. Most often, we detect OAB when we ask patients about it ourselves. The same problem of detecting OAB exists in other countries, in particular in the USA. The appeal of patients with symptoms of OAB and urge urinary incontinence leaves much to be desired.

– In practice, a situation often occurs that OAB is treated as chronic cystitis, leukoplakia of the bladder, and at the same time they are surprised at the “persistent” course of the disease, which gives rise to myths about incurability. Do all urologists know about the existence of OAB and, most importantly, how to correctly diagnose it?

G.G. Krivoborodov: I am absolutely sure that the vast majority of urologists in our country have sufficient knowledge about OAB. Probably, this is simply the reluctance of doctors to fully understand this problem and become interested in this category of patients. Despite the fact that over the past 10 years, doctors in our and other clinics have made great efforts to popularize the problem of OAB among doctors of various specialties, for some reason the detection of patients with urgent and frequent urination has not increased.

– What are the causes and pathogenesis of OAB?

G.G. Krivoborodov: Currently, we do not know the exact reasons for the development of OAB, which can reliably lead to the formation of a mechanism for urgent and frequent urination.

However, most authors tend to associate the appearance of OAB symptoms with detrusor ischemia, most often due to bladder outlet obstruction or arteriolosclerosis. Impaired blood circulation in the detrusor leads to its postsynaptic denervation with subsequent structural changes in the intercellular connections of myocytes. These structural changes are one of the reasons for the formation of detrusor hyperactivity with symptoms of urgency and frequent urination. In recent years, the mucous membrane of the bladder has been studied in detail. It was possible to establish that this seemingly insignificant formation is important in the regulation of bladder function. Further research may provide a new explanation of the mechanisms of formation of OAB symptoms.

– Are there any standards in the treatment of OAB? Not European, but ours, Russian?

G.G. Krivoborodov: Unfortunately, there are no state standards yet. There is a desire of individual doctors dealing with this problem to share their knowledge with other doctors. Thus, on the initiative of the Astellas company, an expert council on GMF was created, of which I am a member. The purpose of this council was to create recommendations for the diagnosis and treatment of OAB, based on international and domestic experience.

Such recommendations are available in brochure form. This helps doctors correctly and timely diagnose and treat patients with OAB.

– Are there cases of spontaneous “miraculous” cure and self-healing with this syndrome?

G.G. Krivoborodov: Unfortunately, in my practice I do not remember a single case of “miraculous” healing of a patient from OAB. OAB is often a serious disease. It requires timely and adequate treatment. Patients with OAB should be warned that this is a chronic disease that requires constant monitoring, treatment and contact with a doctor. Even in the early stages of the disease, existing treatment methods, including drug therapy, pelvic floor muscle exercises, behavioral therapy, electrical stimulation and neuromodulation, do not allow the patient to feel completely healthy. This is due to the fact that after stopping treatment, the vast majority of patients experience a relapse of symptoms of the disease.

– What treatment methods for OAB exist?

G.G. Krivoborodov: We must be very careful with the treatment of this category of patients. The lack of a positive treatment result often forms in the patient a negative attitude towards the doctor and leads to the loss of hopes for improvement of the condition. Therefore, it is difficult for me to understand what some doctors are guided by when prescribing untested treatment methods to patients with OAB. We can, of course, use new medications in patients with a form of OAB refractory to treatment with anticholinergics. The use of such drugs with as yet unproven effectiveness is possible only within the framework of clinical trials. In other words, every experiment must have a scientific basis, it must be based on something.

The first and main method of treating patients with OAB is drug therapy with anticholinergics (drugs that block M-cholinergic receptors of the bladder and increase storage capacity). First-line therapy drugs are Vesicare and Spazmex. Currently, the standard for selecting therapy is drugs that do not require dosage titration, and the patient receives the most effective dose of the drug from the first day of treatment. It is important to remember that OAB therapy is long-term, and the patient, if he wants to improve the quality of life, must be treated constantly, as happens, for example, with hypertension.

Approximately 70% of patients with OAB have an idiopathic form of detrusor overactivity, when there are no neurological diseases, and we currently do not know its causes. In case of idiopathic detrusor overactivity, the choice is made towards drugs that do not require dose titration. The drug of choice in this situation is solifenacin (Vesicare). The effectiveness and safety of Vesicare has been confirmed by a number of international clinical studies, according to which taking the drug significantly reduces the severity of all symptoms of OAB and leads to an improvement in the quality of life of patients. An important advantage of Vesicare is the ability to vary the dose depending on the severity of symptoms (5 or 10 mg/day), as well as ease of use (once a day).

In neurological patients with supraspinal lesions, OAB also occurs in the form of neurogenic detrusor hyperactivity. We know very well that with brain injuries (bruises, contusions, injuries), multiple sclerosis, Parkinson's disease, hemorrhagic and ischemic strokes of the brain, urgent and frequent urination often occurs. In such cases, we can diagnose neurogenic detrusor overactivity. For neurogenic detrusor overactivity, the drug trospium chloride (Spasmex) is advantageous. Spazmex does not penetrate the blood-brain barrier and therefore does not cause side effects from the central nervous system, which is a big advantage when using this drug specifically in the category of patients with neurological disorders.

– What can you say about transdermal and intravesical forms of drugs for the treatment of OAB? Are they promising, will these drugs find their place in the treatment of OAB?

G.G. Krivoborodov: There are no transdermal, sublingual, or intravesical forms of drugs on sale in Russia. As far as I know, they are not widely used in other countries either.

– Does the course of OAB change in pregnant women? What are the features of the treatment of OAB in pregnant women?

G.G. Krivoborodov: Currently, there are no adequate treatment methods that could be used during pregnancy, with the exception of behavioral therapy. Anticholinergics, electrical stimulation, and botulinum toxin are contraindicated.

– Are patients with OAB able to work? Can a patient with OAB who is resistant to treatment be assigned a disability group?

G.G. Krivoborodov: In the vast majority of cases, existing treatment methods allow patients to work in their profession. Even in the most severe cases, we can use combination treatment (for example, a combination of intradetrusor injections of botulinum toxin type A with anticholinergic drugs) with a good prognosis for work ability.

– You have written many articles on the treatment of OAB. Are you planning to publish a monograph or book?

G.G. Krivoborodov: 6 years ago, in collaboration with my teacher, corresponding member of the Russian Academy of Medical Sciences, prof. Evsey Borisovich Mazo published a monograph on the diagnosis and treatment of patients with OAB. Over the past period, extensive experience has been accumulated regarding the treatment and rehabilitation of patients with various forms of urinary dysfunction, including, of course, OAB. Perhaps in the near future I will have the opportunity to share new data with colleagues.

Interviewed by Victoria Shaderkina, urologist

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Description of the drug BETMIGA

Mirabegron is a moderate, time-dependent inhibitor of CYP2D6 and a weak inhibitor of CYP3A. At high concentrations, mirabegron inhibited drug transport via P-glycoprotein.

Clinically significant interactions between mirabegron and medicinal products that inhibit, activate or are a substrate of one of the CYP isoenzymes or transporters are not expected, with the exception of the inhibitory effect of mirabegron on the metabolism of CYP2D6 isoenzyme substrates.

Mirabegron concentration (AUC) increased 1.8-fold under the influence of the strong CYP3A/P-gp inhibitor ketoconazole in healthy volunteers. Dose adjustment of mirabegron is not required when taken together with inhibitors of the CYP3A or P-gp isoenzyme. However, in patients with mild to moderate renal impairment (eGFR 30-89 ml/min/1.73 m2) or mild hepatic impairment (Child-Pugh class A) taking strong CYP3A inhibitors such as itraconazole, ketoconazole, ritonavir and clarithromycin, the recommended daily dose of mirabegron is 25 mg, regardless of meals.

Substances that induce CYP3A or P-gp isoenzymes reduce the plasma concentration of mirabegron.

In healthy volunteers, mirabegron moderately inhibits the CYP2D6 isoenzyme, the activity of which is restored 15 days after discontinuation of mirabegron. Daily dosing of mirabegron resulted in a 90% increase in Cmax and 229% increase in AUC for a single dose of metoprolol. Daily dosing of mirabegron resulted in a 79% increase in Cmax and 241% increase in AUC for a single dose of desipramine. Mirabegron should be used with caution in combination with drugs that have a narrow therapeutic index and drugs that are significantly metabolized by CYP2D6, such as thioridazine, drugs for the treatment of class I C arrhythmias (for example, flecainide, propafenone) and tricyclic antidepressants (for example, imipramine, desipramine). Mirabegron should also be taken with caution when co-administered with drugs that are metabolized by the CYP2D6 isoenzyme and the dose of which must be individually determined.

Mirabegron is a weak inhibitor of the P-gp protein. Mirabegron increased Cmax and AUC by 29% and 27%, respectively, when administered with digoxin to healthy volunteers. For patients starting to take mirabegron and digoxin at the same time, digoxin should be taken at the lowest dose. In this case, it is necessary to monitor the concentrations of digoxin in the blood plasma and select a further effective dose of digoxin based on the results of control tests. The potential for P-gp inhibition by mirabegron should be taken into account when mirabegron is administered concomitantly with drugs transported by P-gp proteins, such as dabigatran.

The increased effect of mirabegron when taken together with other drugs is expressed in an increase in heart rate.