Mirabegron

Myrbetriq™ - mirabegron

Manufacturer: Astellas Pharma

FDA Approval Date: 6/28/2012


Clinical Application

• Indications:• Treatment of overactive bladder (OAB) with

symptoms of urgency, urge urinary incontinence and urinary frequency

• Place in therapy:• Patients unable to tolerate anticholinergic

agents for OAB • Patients for whom OAB significantly impacts

their quality of life



• Warnings/Precautions• May elevate blood pressure • Use cautiously in patients with bladder outlet

obstruction or taking antimuscarinic agents for OAB

• Monitor patients taking concomitant CYP2D6 object drugs for adverse reactions

• Cautiously initiate and titrate digoxin



• Pregnancy:• Category C

• Lactation:• Predicted to found in human breast milk• Discuss discontinuing nursing or

mirabegron to minimize potential serious adverse effects to nursing infant


Drug Facts

• Pharmacology• Beta3 adrenergic agonist

• Agonizes beta3 receptors of the bladder detrusor muscle leading to relaxation

• Minimal intrinsic activity on beta1 and beta2


Drug Facts

• Pharmacokinetics

• A – Bioavailability: 25-35%;

• D – Vd: 1670L; 70% protein bound

• M – Hepatic via dealkylation, amide hydrolysis, glucuronidation, oxidation, CYP2D6 (minor) CYP3A4 (minor)

• E – 55% urine (25% unchanged); 35% feces; t½: 50hr


Drug Interactions

• Drug Interactions – Object Drugs • Metoprolol (AUC 229%)• Desipramine (AUC 241%)• As a moderate CYP2D6 inhibitor, monitoring

of narrow therapeutic index drugs should be considered when starting mirabegron

• Thioridazine, flecainide, propafenone


Drug Interactions

• Drug Interactions – Precipitant Drugs • No significant interactions


Adverse Effects

• Common Adverse Effects

Adverse Effect Mirabegron 25mg (%)

Mirabegron 50mg (%)

Placebo (%)

Hypertension 11.3 7.5 7.6

Urinary Tract Infection 4.2 2.9 1.8

Nasopharyngitis 3.5 3.9 2.5

Headache 2.1 3.2 3.0


Monitoring Parameters

• Efficacy Monitoring• Decrease in incontinence episodes• Decrease in micturitions / day

• Toxicity Monitoring• Pulse• Blood Pressure


Prescription Information

• Dosing• 25mg daily for 8 weeks, then 50mg daily

• Cost• Expected to be available mid-October 2012


Literature Review: Scorpio

• Randomized double-blind, placebo- and active-controlled, European/Australian trial

• 2 week placebo run-in period followed by 12 week treatment period

• 1987 patients randomized equally to placebo, mirabegron 50mg, mirabegron 100mg or tolterodine SR 4mg

US FDA Myrbetriq NDA 2011



• Inclusion Criteria:• Mean age: 60 years• 99.1% White• 72.2% female• Mean BMI: 27.8 kg/m2

• 62.9% <65 years old• > 8 micturitions/24hrs AND >3 episodes of

urgency with or without incontinence/24hrs




• Primary Endpoints• Change in mean number of micturitions/ 24hrs

at final visit• Change in mean number of incontinence

episodes/24hrs at final visit

• Secondary Endpoints• Change in mean volume voided/micturition• Primary endpoints at week 4• Postvoid residual volume (PVR)





Mean Number of Micturitions per 24 hours at final visit

Mirabegron 50mg

Mirabegron 100mg

Tolterodine SR 4mg

Adj. mean diff. vs placebo

from baseline-0.60 -0.44 -0.25

p-value p<0.001 p=0.005 NS




Mean Number of Incontinence Episodes per 24 hours at final visit

Mirabegron 50mg

Mirabegron 100mg

Tolterodine SR 4mg


from baseline-0.41 -0.29 -0.10

p-value p=0.003 p=0.01 NS




Mean Volume Voided (mL) per Micturition at final visit

Mirabegron 50mg

Mirabegron 100mg

Tolterodine SR 4mg


from baseline11.9 13.2 12.6

p-value p<0.001 p<0.001 p<0.001



• Conclusions• Mirabegron demonstrated greater efficacy

than placebo for the primary endpoints• The improvement seen with tolterodine was

less than expected, which may be attributed to prior failure with antimuscarinic agents

• Older patients (> 65 years) showed a better treatment effect than younger patients



Summary

• Myrbetriq, mirabegron, is a beta3 agonist for the treatment of overactive bladder

• Dosage adjustments are recommended in patients with moderate hepatic or renal impairment

• Caution should be taken in patients with HTN• Place in therapy includes patients with significantly

impaired quality of life due to OAB who are unable to tolerate anticholinergic agents


References

1. www.myrbetriq.com

2. Include all article references in standard format.

3. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Myrbetriq NDA 202611 Medical Review, August 26, 2011. Retrieved August 24, 2012 from http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202611Orig1s000TOC.cfm

Mirabegron

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