Download - Mirabegron
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Myrbetriq™ - mirabegron
Manufacturer: Astellas Pharma
FDA Approval Date: 6/28/2012
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Myrbetriq™ - mirabegron
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
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Myrbetriq™ - mirabegron
Clinical Application
• 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
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Myrbetriq™ - mirabegron
Clinical Application
• 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
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Myrbetriq™ - mirabegron
Drug Facts
• Pharmacology• Beta3 adrenergic agonist
• Agonizes beta3 receptors of the bladder detrusor muscle leading to relaxation
• Minimal intrinsic activity on beta1 and beta2
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Myrbetriq™ - mirabegron
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
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Myrbetriq™ - mirabegron
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
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Myrbetriq™ - mirabegron
Drug Interactions
• Drug Interactions – Precipitant Drugs • No significant interactions
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Myrbetriq™ - mirabegron
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
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Myrbetriq™ - mirabegron
Monitoring Parameters
• Efficacy Monitoring• Decrease in incontinence episodes• Decrease in micturitions / day
• Toxicity Monitoring• Pulse• Blood Pressure
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Myrbetriq™ - mirabegron
Prescription Information
• Dosing• 25mg daily for 8 weeks, then 50mg daily
• Cost• Expected to be available mid-October 2012
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Myrbetriq™ - mirabegron
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
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Myrbetriq™ - mirabegron
Literature Review: Scorpio
• 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
US FDA Myrbetriq NDA 2011
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Myrbetriq™ - mirabegron
Literature Review: Scorpio
• 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)
US FDA Myrbetriq NDA 2011
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Myrbetriq™ - mirabegron
Literature Review: Scorpio
US FDA Myrbetriq NDA 2011
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
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Myrbetriq™ - mirabegron
Literature Review: Scorpio
US FDA Myrbetriq NDA 2011
Mean Number of Incontinence Episodes per 24 hours at final visit
Mirabegron 50mg
Mirabegron 100mg
Tolterodine SR 4mg
Adj. mean diff. vs placebo
from baseline-0.41 -0.29 -0.10
p-value p=0.003 p=0.01 NS
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Myrbetriq™ - mirabegron
Literature Review: Scorpio
US FDA Myrbetriq NDA 2011
Mean Volume Voided (mL) per Micturition at final visit
Mirabegron 50mg
Mirabegron 100mg
Tolterodine SR 4mg
Adj. mean diff. vs placebo
from baseline11.9 13.2 12.6
p-value p<0.001 p<0.001 p<0.001
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Myrbetriq™ - mirabegron
Literature Review: Scorpio
• 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
US FDA Myrbetriq NDA 2011
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Myrbetriq™ - mirabegron
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
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Myrbetriq™ - mirabegron
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