Utromeg Tablet 25mg

Product Information

UTROMEG

Utromeg®

Mirabegronß

Presentation

Utromeg 25 mg Tablet: Brown, barrel shaped tablet; each film coated modified release tablet contains Mirabegron INN 25 mg.

Utromeg 50 mg Tablet: Yellow, Barrel shaped tablet; each film coated modified release tablet contains Mirabegron INN 50 mg.

Indications

Utromeg (Mirabegron) is indicated for the symptomatic treatment of urgency, increased micturition frequency and urgency

incontinence as may occur in adult patients with overactive bladder (OAB) syndrome.

Dosage and administration

Adults including elderly: The recommended starting dose is one Utromeg 25 mg (Mirabegron 25 mg) tablet once daily with or without

food. Based on individual patient efficacy and tolerability the dose may be increased to two Utromeg 25 mg (Mirabegron 25 mg)

tablet once daily or one Utromeg 50 mg (Mirabegron 50 mg) tablet once daily. 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 Utromeg

(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.

Method of administration: Utromeg (Mirabegron) tablet is to be taken once daily, with liquids, swallowed whole and is not to be

chewed, divided, or crushed.

Contraindications, warning, etc

Contra-indications: 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 ³180 mm Hg and/or diastolic blood pressure ³110

mm Hg. Precautions: Renal impairment: Mirabegron has not been studied in patients with end stage renal disease (GFR < 15

mL/min/1.73 m2 or patients requiring haemodialysis) and therefore, it is not recommended for use in this patient population. Data

are limited in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2); based on a pharmacokinetic study a dose

reduction to 25 mg is recommended in this population. Mirabegron is not recommended for use in patients with severe renal

impairment (GFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors. Hepatic impairment: Mirabegron has not

been studied in patients with severe hepatic impairment (Child-Pugh Class C) and, therefore, it is not recommended for use in this

patient population. Mirabegron is not recommended for use in patients with moderate hepatic impairment (Child-Pugh Class B)

concomitantly receiving strong CYP3A inhibitors. Hypertension: Mirabegron can increase blood pressure. Blood pressure should be

measured at baseline and periodically during treatment with Mirabegron, especially in hypertensive patients. Data are limited in

patients with stage 2 hypertension (systolic blood pressure ? 160 mm Hg or diastolic blood pressure ³100 mm Hg). Patients with

congenital or acquired QT prolongation: Caution should be exercised when administering Mirabegron in patients with congenital or

acquired QT prolongation. Patients with bladder outlet obstruction and patients taking antimuscarinics medications for OAB: A

controlled clinical safety study in patients with bladder outlet obstruction (BOO) did not demonstrate increased urinary retention

in patients treated with Mirabegron; however, Mirabegron should be administered with caution to patients with clinically

significant bladder outlet obstruction. Mirabegron should also be administered with caution to patients taking antimuscarinic

medications for the treatment of OAB. Drug-interactions: Effect of enzyme inhibitors: Mirabegron exposure (AUC) was increased

1.8-fold in the presence of the strong inhibitor of CYP3A/P-gp ketoconazole in healthy volunteers. No dose-adjustment is needed

when Mirabegron is combined with inhibitors of CYP3A and/or P-gp. However, in patients with mild to moderate renal impairment or

mild hepatic impairment concomitantly receiving strong CYP3A inhibitors, such as itraconazole, ketoconazole, ritonavir and

clarithromycin, the recommended dose is 25 mg once daily with or without food. Mirabegron is not recommended in patients with

severe renal impairment or patients with moderate hepatic impairment concomitantly receiving strong CYP3A inhibitors. Effect of

enzyme inducers: Substances that are inducers of CYP3A or P-gp decrease the plasma concentrations of Mirabegron. No dose

adjustment is needed for Mirabegron when administered with therapeutic doses of rifampicin or other CYP3A or P-gp inducers. Effect

of Mirabegron on CYP2D6 substrates: In healthy volunteers, the inhibitory potency of Mirabegron towards CYP2D6 is moderate and the

CYP2D6 activity recovers within 15 days after discontinuation of Mirabegron. Multiple once daily dosing of Mirabegron IR resulted

in a 90% increase in Cmax and a 229% increase in AUC of a single dose of metoprolol. Multiple once daily dosing of Mirabegron

resulted in a 79% increase in Cmax and a 241% increase in AUC of a single dose of desipramine. Caution is advised if Mirabegron is

co-administered with medicinal products with a narrow therapeutic index and significantly metabolised by CYP2D6, such as

thioridazine, Type 1 C antiarrhythmics (e.g., flecainide, propafenone) and tricyclic antidepressants (e.g., imipramine,

desipramine). Caution is also advised if Mirabegron is co-administered with CYP2D6 substrates that are individually dose titrated.

Effect of Mirabegron on transporters: Mirabegron is a weak inhibitor of P-gp. Mirabegron increased Cmax and AUC by 29% and 27%,

respectively, of the P-gp substrate digoxin in healthy volunteers. For patients who are initiating a combination of Mirabegron and

digoxin, the lowest dose for digoxin should be prescribed initially. Serum digoxin concentrations should be monitored and used for

titration of the digoxin dose to obtain the desired clinical effect.

Other interactions: No clinically relevant interactions have been observed when Mirabegron was co-administered with therapeutic

doses of solifenacin, tamsulosin, warfarin, metformin or a combined oral contraceptive medicinal product containing

ethinylestradiol and levonorgestrel. Dose-adjustment is not recommended.

Use in Pregnancy and lactation: There are limited amount of data from the use of Mirabegron in pregnant women. Studies in animals

have shown reproductive toxicity. Mirabegron is not recommended during pregnancy and in women is planning to be pregnant.

Mirabegron is excreted in the milk of rodents and therefore is predicted to be present in human milk. No studies have been

conducted to assess the impact of Mirabegron on milk production in humans, its presence in human breast milk, or its effects on

the breast-fed child. Mirabegron should not be administered during breast-feeding. Fertility: There were no treatment-related

effects of Mirabegron on fertility in animals. The effect of Mirabegron on human fertility has not been established.

Side effects: The most common side effects 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%).

Overdose: Mirabegron has been administered to healthy volunteers at single doses up to 400 mg. At this dose, adverse events

reported included palpitations and increased pulse rate exceeding 100 beats per minute (bpm). 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 overdose, pulse rate, blood pressure, and

ECG monitoring is recommended.

Pharmaceutical precautions

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

Packaging quantity

Utromeg 25 mg tablet: Carton containing 10 tablets in alu-alu blister.

Utromeg 50 mg tablet: Carton containing 10 tablets in alu-alu blister.

Manufactured by

UniMed & UniHealth Manufacturers Ltd.

B K Bari, Gazipur, Bangladesh

® Registered Trademark