Generic

Mirabegron

Indications

Mirabegron is used to treat the symptoms of overactive bladder (OAB) syndrome in adults, including urgency, increased micturition frequency, and urgency incontinence.

Pharmacology

Mirabegron is the first agonist for the beta-3 adrenoceptor. Mirabegron works in two ways: it raises the levels of cyclic adenosine monophosphate (cyclic AMP) and leads to relaxation of the detrusor smooth muscle during the storage phase of the urine bladder fill-void cycle by activating beta-3 adrenoceptors, which improves bladder capacity.

Dosage & Administration

Adults including elderly: The recommended starting dose is Mirabegron 25 mg tablet once daily with or without food. Based on individual patient efficacy and tolerability the dose may be increased to Mirabegron 50 mg tablet once daily.

Renal or hepatic impairment:

• Patients with severe renal impairment (ClCr 15 to 29 mL/min or eGFR 15 to 29 mL/min/1.73 m2) or moderate hepatic impairment (Child-Pugh Class B), the daily dose of Mirabegron should not exceed 25 mg tablet once daily.
• Mirabegron has not been studied in patients with end stage renal disease (GFR <15 mL/min/1.73 m2 or patients requiring haemodialysis) or severe hepatic impairment (Child Pugh Class C) and it is therefore not recommended for use in these patient populations.

Gender: No dose adjustment is necessary according to gender.

Paediatric population: The safety and efficacy of Mirabegron in children below 18 years of age have not yet been established.

Mirabegron tablet is to be taken once daily, with liquids, swallowed whole and is not to be chewed, divided, or crushed.

Interaction

The effect of enzyme inhibitors: In healthy volunteers, when the strong CYP3A/Pgp inhibitor ketoconazole is present, the exposure to Mirabegron (AUC) increased by 1.8 times. When Mirabegron is used in combination with CYP3A and/or Pgp inhibitors, there is no need to adjust the dose. However, for patients with mild to moderate renal insufficiency or mild liver insufficiency who also receive strong CYP3A inhibitors (such as itraconazole, ketoconazole, ritonavir, and clarithromycin), the recommended dose It is 25 mg, once a day, with or without meals. Mirabegron is not recommended for patients with severe renal insufficiency or patients with moderate hepatic insufficiency, while receiving strong CYP3A inhibitor therapy. The effect of

enzyme inducer: CYP3A or Pgp inducer substances will reduce the plasma concentration of Mirabegron. When administered with therapeutic doses of rifampicin or other CYP3A or Pgp inducers, there is no need to adjust the dose of Mirabegron.

Effect of Mirabegron on CYP2D6 substrates: In healthy volunteers, Mirabegron has a moderate inhibitory effect on CYP2D6, and CYP2D6 activity is restored within 15 days after stopping Mirabegron. The administration of Mirabegron IR multiple times a day resulted in a 90% increase in Cmax and a 229% increase in AUC. Multiple administrations of Mirabegron once a day resulted in a 79% increase in Cmax and a 241% increase in AUC. If Mirabegron has a narrow therapeutic index and is significantly metabolized by CYP2D6 (such as thioridazine, type 1 C antiarrhythmic drugs (such as flecainide, propafenone) and tricyclic antidepressants (such as Caution should be taken when imipramine and desipramine are used in combination. If Mirabegron is co-administered with a CYP2D6 substrate titrated in a single dose, caution is also advised.

Effect of Mirabegron on transporters: Mirabegron is a weak inhibitor of Pgp. In healthy volunteers, Mirabegron increased the Cmax and AUC of the Pgp digoxin substrate by 29% and 27%, respectively. For patients starting to use Mirabegron and Digoxin in combination, the lowest dose of Digoxin should be prescribed initially. Serum digoxin concentration should be monitored and used to titrate the digoxin dose to obtain the desired clinical effect.

Other Interactions: When Mirabegron was co-administered with therapeutic doses of solinacin, tamsulosin, warfarin, metformin, or combined oral contraceptives containing ethinyl estradiol and levonorgestrel, no clinically relevant interaction was observed. No dosage adjustment is recommended.

Contraindications

Mirabegron is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients and severe uncontrolled hypertension defined as systolic blood pressure 180 mm Hg and/or diastolic blood pressure 110 mm Hg.

Side Effects

Tachycardia and urinary tract infections were the most prevalent adverse events observed in individuals treated with Mirabegron 50 mg during the three 12-week phase 3 double-blind, placebo-controlled trials. Patients using Mirabegron 50 mg had a 1.2 percent chance of developing tachycardia. In 0.1 percent of individuals using Mirabegron 50 mg, tachycardia caused them to stop taking it. Patients using Mirabegron 50 mg had a 2.9 percent chance of getting a urinary tract infection. None of the individuals using Mirabegron 50 mg had to stop taking it because of urinary tract infections. Atrial fibrillation was one of the most serious side effects (0.2 percent ).

Pregnancy & Lactation

There is a scarcity of information about Mirabegron’s usage in pregnant women. Reproductive toxicity has been demonstrated in animal studies. Mirabegron should not be used during pregnancy or by women who are expecting to get pregnant. Mirabegron is excreted in rat milk, therefore it’s likely to be found in human milk as well. There have been no research on Mirabegron’s influence on human milk production, its presence in human breast milk, or its effects on the breast-fed infant. Mirabegron should not be given to a breastfeeding mother. Mirabegron had no effect on fertility in animals when used as a therapy. Mirabegron’s effect on human fertility has yet to be determined.

Precautions & Warnings

Renal impairment: Mirabegron has not been studied in patients with end-stage renal disease (GFR <15 ml / min / 1.73 m2 or patients requiring hemodialysis), so it is not recommended for use in this population. There are limited data on patients with severe renal insufficiency (GFR 15-29 ml / min / 1.73 m2); according to pharmacokinetic studies, it is recommended to reduce the dose to 25 mg in this population. It is not recommended to use Mirabegron in patients with severe renal impairment (GFR 15-29 ml / min / 1.73 m2) who are also using strong CYP3A inhibitors.

Hepatic impairment: Mirabegron has not been studied in patients with severe hepatic impairment (ChildPugh grade C), so it is not recommended for use in this patient population. Mirabegron is not recommended for patients with moderate hepatic impairment (ChildPugh Class B) who are also using strong CYP3A inhibitors.

Hypertension: Mirabegron can raise blood pressure. Blood pressure should be measured regularly at the beginning of treatment and during treatment with Mirabegron, especially in patients with hypertension. There are limited data for patients with stage 2 hypertension (systolic blood pressure 160 mmHg or diastolic blood pressure 100 mmHg).

Patients with congenital or acquired prolonged QT interval: Be cautious when using Mirabegron in patients with congenital or acquired prolonged QT interval.

patients with bladder outlet obstruction and patients taking antimuscarinic drugs for OAB: A controlled clinical safety study of patients with bladder outlet obstruction (BOO) did not show increased urinary retention in patients treated with Mirabegron; however, Mirabegron should be used with caution in patients with clinically significant bladder outlet obstruction. Mirabegron should also be used with caution in patients taking antimuscarinic medications for OAB.

Therapeutic Class

BPH/ Urinary retention/ Urinary incontinence

Storage Conditions

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

Pharmaceutical Name

Healthcare Pharmaceuticals Ltd.