Betmiga Tablets, box, 30 pcs., 50 mg, for oral administration

Betmiga Tablets, box, 30 pcs., 50 mg, for oral administration

Pharmacological properties

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 mm Hg 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.

Betmiga

- hypersensitivity to the active substance or any of the excipients of the drug;

- children's age (lack of data on effectiveness and safety);

- pregnancy and breastfeeding;

- end-stage renal failure (eGFR)

- 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);

- moderate stage of liver failure (class B on the Child-Pugh scale) with simultaneous use of strong inhibitors of the CYP3A isoenzyme.

The drug is prescribed with caution to the following categories of patients:

Patients with renal and liver failure.

Patients with severe renal failure should be treated with caution and the dose should not exceed 25 mg/day.

Patients with mild to moderate renal failure concomitantly taking strong CYP3A inhibitors should be treated with caution and the dose should not exceed 25 mg/day.

Patients with moderate liver failure should be treated with caution and the dose should not exceed 25 mg/day.

Patients with mild hepatic impairment (Child-Pugh Class A) concomitantly taking strong CYP3A inhibitors should be treated with caution and the dose should not exceed 25 mg/day.

Patients with uncontrolled severe hypertension

Since no studies have been conducted with the drug in patients with uncontrolled severe arterial hypertension (systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg), the drug is not recommended for use in this category of patients.

There are only limited data regarding the use of the drug in patients suffering from stage 2 hypertension (systolic blood pressure>160 mm Hg and/or diastolic blood pressure>100 mm Hg).

Patients with congenital or acquired QT prolongation

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.

Caution should be used 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 Type 1C 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.

Pregnancy

There are limited data on the use of mirabegron during pregnancy. Results from animal reproductive toxicity studies do not indicate direct or indirect negative effects of mirabegron. To prevent possible negative effects on the fetus, the use of the drug should be avoided in pregnant women and women of childbearing age who are not using contraception.

Lactation 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. The drug should not be used by women during breastfeeding.

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

4

Your rating: No Average rating: 4 (2 votes)