Betmiga Prolonged pills 50mg 10pcs

Composition

of 1 tab. : – mirabegron 25 mg,50 mgsupport substances: macrogol 2000000, macrogol 8000, hydroxypropylcellulose, butylhydroxytoluene, purified water, magnesium stearate composition of the tablet shell: Opadray 03F43159 (hypromellose 2910 6 MPa-s, macrogol 8000, iron oxide yellow (E 172), iron oxide red (E 172)), Opadray 03F42192 (hypromellose 2910 6 MPa-s, macrogol 8000, iron oxide yellow (E 172)).

Pharmacological action

Selective beta-3-adrenergic receptor agonist. Mirabegron studies have demonstrated relaxation of bladder smooth muscles in rats and in an isolated human tissue preparation, as well as an increase in cAMP concentrations in bladder tissues 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 previously received m-holinoblockers for the treatment of overactive bladder (GMP), and in patients without a history of previous m-holinoblockers therapy. Mirabegron was also effective in patients with HMP who stopped treatment with m-holinoblockers due to lack of effect. A 12-week study in men with lower urinary tract symptoms (LUTs) and infravesical obstruction (IVO) demonstrated the safety and good tolerability of mirabegron at doses of 50 and 100 mg 1 time/day, as well as the absence of mirabegron’s effect on cystometric parameters. Changes in pulse rate and blood pressure during treatment are reversible and disappear after its cancellation. Pharmacokineticsafter oral use, mirabegron is absorbed into the bloodstream and reaches Cmax in blood plasma between three and four hours after use. 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 mean Cmax and AUC values increased more than proportionally to the dose. Css is achieved after 7 days of taking mirabegron once a day. After repeated use of 1 time/day, the Css of mirabegron in blood plasma is approximately 2 times higher than those after a single dose of the drug. Mirabegron is intensively distributed in the body. Vd under stable conditions (Vss) is approximately 1670 L. Mirabegron binds (approximately 71%) to plasma proteins, and also shows moderate affinity for albumin and alpha-1 acid glycoprotein. Mirabegron is distributed to red blood cells. Concentrations of 14C-mirabegron in red blood cells were 2 times higher than in plasma (as shown by in vitro studies). There are many pathways of mirabegron metabolism in the body, including dealkylation, oxidation, (direct) glucuronidation, and amide hydrolysis. After a single use of C-mirabegron, the main circulating component is mirabegron. Two main metabolites of mirabegron were detected in human blood plasma: both are glucuronides (phase II metabolites) and account for 16% and 11% of the total drug concentration, respectively. These metabolites have no pharmacological activity. Despite the involvement of CYP2D6 and CYP3A4 isoenzymes in the oxidative pathway of mirabegron metabolism in vitro, in vivo the role of these isoenzymes in total 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 renal excretion 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 in a daily dose of 25 mg to 12.2% after taking a daily dose of 100 mg. After taking 160 mg of C-mirabegron in healthy volunteers, approximately 55% of the radiolabel was detected in the urine and 34% in the feces. The fraction of unchanged mirabegron was approximately 45% of the total isotope-labeled drug in the urine, indicating the presence of metabolites. Most of the isotope-labeled drug in feces was represented by unchanged mirabegron.

Indications

Overactive bladder (OAB) with symptoms of urinary incontinence, frequent urination, and an urgent urge to urinate.

Use during pregnancy and lactation

Pregnancy

The amount of data on the use of mirabegron in pregnant women is limited. Animal studies have shown reproductive toxicity. Mirabegron is not recommended during pregnancy and in women of childbearing age who do not use contraception.

Breast-feeding period

In rodents, mirabegron is excreted in breast milk, therefore, humans also have a risk of getting the drug into breast milk. There are no studies on the effect of mirabegron on breast milk production, mirabegron excretion in breast milk, or exposure to the baby. Mirabegron should not be used in women who are breast-feeding.

Fertility

In animal studies, the effect of mirabegron on fertility in non-lethal doses was not revealed.

It has not been established whether mirabegron affects human fertility.

Contraindications

• End-stage renal disease (eGFR<15 ml/min/1.73 m 2, or patients who have shown the kidney dialysis);
• renal failure severe (eGFR 15-29 ml/min/1.73 m 2) while the use of strong inhibitors of CYP3A isoenzyme;
• severe stage of liver failure (class C on a scale child-Pugh);
• severe uncontrolled hypertension, defined as systolic blood pressure ≥180 mm Hg. St. and/or diastolic blood pressure ≥110 mm Hg. St. ;
• moderate stage liver failure (class b on a scale child-Pugh) while the use of strong inhibitors of CYP3A isoenzyme;
• children’s age (the lack of data on efficacy and safety);
• pregnancy and lactation;
• hypersensitivity to the Active ingredient.

Side effects

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

From the side of the visual organ:  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.

Skin and subcutaneous tissue disorders:  infrequently – urticaria, rash, macular rash, papular rash, pruritus; rarely-leukocystoclastic vasculitis, purpura, angioedema.

Musculoskeletal disorders:  infrequently-swelling of the joints.

From the side of the reproductive system:  infrequently-vulvovaginal pruritus

*Detected during a post-marketing application

Interaction

Mirabegron is a moderate time-dependent inhibitor of the CYP2D6 isoenzyme and a weak inhibitor of the CYP3A isoenzyme. In high concentrations, mirabegron inhibited the transport of drugs carried out at the expense of P-glycoprotein. A clinically significant interaction between mirabegron and drugs that inhibit, activate, or are a substrate of one of the CYP isoenzymes or transporters is not expected, except for the inhibitory effect of mirabegron on the metabolism of substrates of the CYP2D6 isoenzyme. Mirabegron concentration (AUC) increased 1.8-fold under the influence of a strong inhibitor of the CYP3A/P-gp isoenzymes ketoconazole in healthy volunteers. No dose adjustment of mirabegron is required when co-administered with inhibitors of the CYP3A or P-gp isoenzyme. However, in patients with mild to moderate renal insufficiency (eGFR 30-89 ml/min/1.73 m2) or mild hepatic insufficiency (Child-Pugh class A), taking strong inhibitors of the CYP3A isoenzyme such as itraconazole, ketoconazole, ritonavir and clarithromycin, the recommended daily dose of mirabegron is 25 mg regardless of food intake. Substances that induce CYP3A or P-gp isoenzymes reduce the concentration of mirabegron in plasma. In healthy volunteers, mirabegron moderately inhibits the CYP2D6 isoenzyme, whose activity is restored 15 days after discontinuation of mirabegron. Daily use of mirabegron resulted in a 90% increase in Cmax and 229% in AUC for a single dose of metoprolol. Daily intake 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 the CYP2D6 isoenzyme, for example, 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 is subject to individual determination. Mirabegron is a weak inhibitor of the P-gp protein. Mirabegron increased Cmax and AUC by 29% and 27%, respectively, when administered with digoxin in healthy volunteers. For patients who start taking mirabegron and digoxin at the same time, digoxin should be taken at the lowest dose. At the same time, it is necessary to monitor the concentrations of digoxin in blood plasma and select a further effective dose of digoxin based on the results of control tests. The potential for inhibition of the P-gp protein by mirabegron should be taken into account when prescribing mirabegron together with drugs transported by P-gp proteins, for example, dabigatran.The increased effect of mirabegron when taken together with other drugs is expressed in an increase in the pulse rate.

How to take, course of use and dosage

Adults (≥18 years), including the elderly:

50 mg once a day inside, washed down with liquid, regardless of the time of meal.

The Betmiga tablet should be taken whole and should not be chewed, as this may affect the prolonged release of the Active ingredient.

Overdose

Symptoms:

A single dose of mirabegron was administered to healthy volunteers in doses up to 400 mg. When using this level of doses, adverse events were recorded in the form of rapid heartbeat (in 1 out of 6 volunteers) and an increase in the pulse rate of more than 100 beats / min (in 3 out of 6 volunteers).

With repeated (for 10 days) use of the drug in daily doses up to 300 mg in healthy volunteers, an increase in pulse rate and an increase in systolic blood pressure were recorded.

Treatment:

symptomatic and supportive care. Monitoring of pulse rate, blood pressure and ECG is necessary.

Special instructions

Mirabegron in therapeutic doses did not demonstrate clinically significant prolongation of the QT interval in the framework of the conducted studies.

However, since patients taking drugs that may cause prolongation of the QT interval did not participate in these studies using mirabegron, the effect on these categories of patients is not known. Mirabegron should be taken with caution in this category of patients.

Mirabegron should be used with caution in combination with drugs that have a narrow therapeutic index and drugs that are significantly metabolized by the CYP2D6 isoenzyme, for example, 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 is subject to individual determination.

During post-marketing surveillance of mirabegron use in patients with infravesical obstruction (IFO) and in patients already taking holinoblockers for the treatment of GMP, cases of urinary retention were noted. A controlled clinical safety study in patients with IFR did not find an increase in urinary retention in patients treated with mirabegron, however, mirabegron should be administered with caution in patients with clinically significant IFR.

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

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

Form of production

Oval tablets, film-coated, yellow in color, with an engraving “355” and a graphic image of the Astellas company logo on one side.

Active ingredient

Mirabegron

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets

Purpose

Adult Doctor’s prescription