2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. Myrbetriq™ - mirabegron
Drug Interactions
• Drug Interactions – Precipitant Drugs
• No significant interactions
10. Myrbetriq™ - mirabegron
Monitoring Parameters
• Efficacy Monitoring
• Decrease in incontinence episodes
• Decrease in micturitions / day
• Toxicity Monitoring
• Pulse
• Blood Pressure
11. Myrbetriq™ - mirabegron
Prescription Information
• Dosing
• 25mg daily for 8 weeks, then 50mg daily
• Cost
• Expected to be available mid-October 2012
12. 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
13. 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
14. 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
15. Myrbetriq™ - mirabegron
Literature Review: Scorpio
Mean Number of Micturitions per 24 hours
at final visit
Mirabegron Mirabegron Tolterodine
50mg 100mg SR 4mg
Adj. mean diff.
vs placebo -0.60 -0.44 -0.25
from baseline
p-value p<0.001 p=0.005 NS
US FDA Myrbetriq NDA 2011
16. Myrbetriq™ - mirabegron
Literature Review: Scorpio
Mean Number of Incontinence Episodes per 24
hours at final visit
Mirabegron Mirabegron Tolterodine
50mg 100mg SR 4mg
Adj. mean diff.
vs placebo -0.41 -0.29 -0.10
from baseline
p-value p=0.003 p=0.01 NS
US FDA Myrbetriq NDA 2011
17. Myrbetriq™ - mirabegron
Literature Review: Scorpio
Mean Volume Voided (mL) per Micturition
at final visit
Mirabegron Mirabegron Tolterodine
50mg 100mg SR 4mg
Adj. mean diff.
vs placebo 11.9 13.2 12.6
from baseline
p-value p<0.001 p<0.001 p<0.001
US FDA Myrbetriq NDA 2011
18. 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
19. 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
20. 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