Miragon 25 Tablet

Mirabegron is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency Mirabegron, in combination with the muscarinic antagonist solifenacin succinate, is indicated for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency

BPH/ Urinary retention/ Urinary incontinence

Mirabegron is a potent and selective beta 3-adrenoceptor agonist. Mirabegron showed relaxation of bladder smooth muscle in rat and human isolated tissue, increased cyclic adenosine monophosphate (cAMP) concentrations in rat bladder tissue and showed a bladder relaxant effect in rat urinary bladder function models. Mirabegron increased mean voided volume per micturition, and decreased the frequency of non-voiding contractions, without affecting voiding pressure or residual urine in rat models of bladder overactivity. In a monkey model, mirabegron showed decreased voiding frequency. These results indicate that mirabegron enhances urine storage function by stimulating beta 3-adrenoceptors in the bladder. During the urine storage phase, when urine accumulates in the bladder, sympathetic nerve stimulation predominates. Noradrenaline is released from nerve terminals, leading predominantly to beta adrenoceptor activation in the bladder musculature and hence bladder smooth muscle relaxation. During the urine voiding phase, the bladder is predominantly under parasympathetic nervous system control. Acetylcholine, released from pelvic nerve terminals, stimulates cholinergic M2 and M3 receptors, inducing bladder contraction. The activation of the M2 pathway also inhibits beta 3-adrenoceptor induced increases in cAMP. Therefore beta 3-adrenoceptor stimulation should not interfere with the voiding process. This was confirmed in rats with partial urethral obstruction, where mirabegron decreased the frequency of non-voiding contractions without affecting the voided volume per micturition, voiding pressure or residual urine volume.

Recommended starting dose: 25 mg once daily, alone or in combination with solifenacin succinate 5 mg, once daily. Based on individual efficacy and tolerability, may increase dose to 50 mg once daily, alone or in combination with solifenacin succinate 5 mg, once daily. Swallow whole with water, with or without food, do not chew, divide or crushPatients with Severe Renal Impairment or Patients with Moderate Hepatic Impairment: Maximum dose is 25 mg Mirabegron once daily Patients with End Stage Renal Disease (ESRD) or Patients with Severe Hepatic Impairment: Not recommended

The effect of co-administered medicinal products on the pharmacokinetics of mirabegron and the effect of mirabegron on the pharmacokinetics of other medicinal products was studied in single- and multiple-dose studies. Most drug-drug interactions were studied using a dose of mirabegron 100 mg given as oral controlled absorption system (OCAS) tablets. Interaction studies of mirabegron with metoprolol and with metformin used mirabegron immediate-release (IR) 160 mg. Clinically relevant drug interactions between mirabegron and medicinal products that inhibit, induce or are a substrate for one of the CYP isozymes or transporters are not expected, except for the inhibitory effect of mirabegron on the metabolism of CYP2D6 substrates.

Mirabegron is contraindicated in patients with: Hypersensitivity to the active substance or to any of the excipients. Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg.

The most common adverse reactions reported for patients treated with Mirabegron 50 mg during the three 12-week phase 3 double-blind, placebo-controlled studies are tachycardia and urinary tract infections. The frequency of tachycardia was 1.2% in patients receiving Mirabegron 50 mg. Tachycardia led to discontinuation in 0.1% patients receiving Mirabegron 50 mg. The frequency of urinary tract infections was 2.9% in patients receiving Mirabegron 50 mg. Urinary tract infections led to discontinuation in none of the patients receiving Mirabegron 50 mg. Serious adverse reactions included atrial fibrillation (0.2%).

Renal and Hepatic Impairment: Mirabegron has not been studied in patients with end stage renal diseaseGender: No dose adjustment is necessary according to gender.Children: The safety and efficacy of mirabegron in children below 18 years of age have not yet been established. No data are available.

Mirabegron has been administered to healthy volunteers at single doses up to 400 mg. At this dose, adverse events reported included palpitations (1 of 6 subjects) and increased pulse rate exceeding 100 beats per minute (bpm) (3 of 6 subjects). Multiple doses of mirabegron up to 300 mg daily for 10 days showed increases in pulse rate and systolic blood pressure when administered to healthy volunteers. Treatment for overdose should be symptomatic and supportive. In the event of an overdosage, pulse rate, blood pressure and ECG monitoring is recommended.

Store in a cool and dry place, protected from light.