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

Effect of enzyme inhibitors: In healthy volunteers, mirabegron exposure (AUC) was raised 1.8-fold in the presence of the potent CYP3A/P-gp inhibitor ketoconazole. When Mirabegron is taken with CYP3A and/or P-gp inhibitors, there is no need to modify the dosage. The suggested dose is 25 mg once day with or without meals in patients with mild to moderate renal impairment or mild hepatic impairment who are also taking strong CYP3A inhibitors such itraconazole, ketoconazole, ritonavir, and clarithromycin. Patients with severe renal impairment or moderate hepatic impairment who are also taking powerful CYP3A inhibitors should not take mirabegron.

Effect of enzyme inducers: Substances that induce CYP3A or P-gp reduce Mirabegron plasma concentrations. When Mirabegron is used with therapeutic dosages of rifampicin or other CYP3A or P-gp inducers, there is no need to modify the dose.

Mirabegron’s effect on CYP2D6 substrates: Mirabegron’s inhibitory potency against CYP2D6 is modest in healthy volunteers, and CYP2D6 activity recovers within 15 days after stopping Mirabegron. Multiple once-daily Mirabegron IR doses resulted in a 90 percent rise in Cmax and a 229 percent increase in AUC when compared to a single dose of metoprolol.

Mirabegron’s effect on transporters: Mirabegron is a mild P-gp inhibitor. In healthy individuals, mirabegron raised the Cmax and AUC of the P-gp substrate digoxin by 29% and 27%, respectively. When starting a patient on a combination of Mirabegron and digoxin, the lowest digoxin dose should be administered first. To achieve the intended therapeutic impact, serum digoxin concentrations should be monitored and utilized to titrate the digoxin dosage.

Contraindications

Patients with hypersensitivity to the active ingredient or any of the excipients, as well as severe uncontrolled hypertension (systolic blood pressure 180 mm Hg and/or diastolic blood pressure 110 mm Hg), should not use Mirabegron.

Side Effect

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

End-stage renal disease (GFR 15 mL/min/1.73 m2 or patients requiring haemodialysis): Mirabegron has not been investigated in patients with end-stage renal disease (GFR 15 mL/min/1.73 m2 or patients requiring haemodialysis), thus it is not indicated for use in this patient population. Patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) have limited data; a dosage decrease to 25 mg is advised in this population based on a pharmacokinetic study. Mirabegron is not advised for individuals who are using powerful CYP3A inhibitors and have significant renal impairment (GFR 15 to 29 mL/min/1.73 m2).

Mirabegron has not been tested in individuals with severe hepatic impairment (Child-Pugh Class C), thus it is not indicated for usage in this patient group. Mirabegron is not advised for individuals who are using powerful CYP3A inhibitors and have significant hepatic impairment (Child-Pugh Class B).

Therapeutic Class

BPH/ Urinary retention/ Urinary incontinence

Storage Conditions

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

Pharmaceutical Name

General Pharmaceuticals Ltd.