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Meet the new Beta 3 Agonist: Mirabegron (Myrbetriq®)

By: Steve P. Soman

Mirabegron (Mybetriq®), known also by the brand name Betanis®in Japan, is a new once daily oral drug.   First in its class, it is a selective β(3)-adrenoceptor agonist that improves symptoms associated with over active bladder (OAB) such as urinary incontinence, urgency, and urinary frequency by enhancing storage function and relaxing the urinary bladder.1,2  The medication was approved by the Food and Drug Administration (FDA) on June 28, 2012 and is expected to be available by sometime in October of 2012.3

The mechanism of action of mirabegron as a selective beta 3 adrenergic receptor agonist relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activating this receptor and thus increasing the bladder capacity.2  The recommended starting dose is 25 mg once daily and based on efficacy and patient tolerance, may increase to 50mg once daily.2  The 25mg dose is effective within 8 weeks of initiating therapy.  Mirabegron needs to be dose adjusted at 25 mg once daily for severe renal impairment (CrCl of 15 to 29 mL/min) or in moderate hepatic impairment (Child-Pugh Class B).2  It is not recommended in end stage renal disease or in severe hepatic impairment (Child-Pugh Class C) due to lack of available safety data.2  The product is available as 25mg and 50mg extended release tablets that may not be crushed, chewed, or cut.

Precaution should be used when treating patients with uncontrolled hypertension (>180/110 mmHg) as the drug can raise blood pressure.2  In two randomized placebo controlled studies with healthy volunteers dosed with 50mg, the blood pressure increase was 3.5 mm Hg/1.5 mm Hg greater than placebo.2  In another clinical trial using patients with OAB, the blood pressure increase was 0.5 mm Hg/1 mm Hg greater than placebo.2

Multiple clinical trials evaluating adverse effect were conducted using mostly Caucasian female population with a mean age of 59 years old.2 The most commonly reported adverse reactions were hypertension, nasopharyngitis, urinary tract infection, and headache.  Other important side effects that are not frequent (<1%) but important to note in geriatric patients are constipation, tachycardia, diarrhea, abdominal pain and fatigue.2,4 The drug may also raise AST/ALT levels from baseline but in the study, these markets returned to baseline while the patients continued taking mirabegron 50mg therapy.2

The drug also has the potential for drug interactions through the cytochrome P-450 system, more specifically CYP 2D6.  Mirabegron is a CYP 2D6 inhibitor, so drugs using the same pathway should be monitored and dose adjusted to prevent occurrence of adverse reactions or toxicity.4  There is increased systemic exposure of metoprolol (Toprol XL®, Lopressor®) and desipramine (Norpramin®, Pertofane®) seen when co-administered with mirabegron due to this interaction.2  Mirabegron also uses the CYP 3A4 pathway (minor) along with dealkylation, glucuronidation, and amide hydrolysis in its metabolism.2  These pathways allow for more theoretical interactions with medications that use the same metabolic pathway.

When mirabegron and digoxin (Lanoxin®) are coadministered, there is a noted 27% increase in digoxin AUC and 29% increase in digoxin Cmax, so treating patient with the lowest dose of digoxin and titrating the dose to desired clinical effect while monitoring serum digoxin levels is recommended.2,5  Mirabegron lacks safety data in pregnancy and thus is category C and should only be used if the benefits outweigh the risks.

Mirabegron generally reaches maximum plasma concentrations (Cmax) within 3.5 hours.2  The bioavailability (F) is 29% at 25mg dose and 35% at 50mg dose.  The drug reaches steady state within seven days of once daily dosing.  A high fat meal can reduce the absorption of mirabegron which is seen in a 45% reduced Cmax and 17% reduced area under the curve (AUC).2  Mirabegron is 71% bound of plasma proteins with a volume of distribution at steady state (Vss) of 1670L.2  The half-life of mirabegron is 50 hours.  It is eliminated through the urine and feces, 55% and 35% respectively.2  Approximately 25% of the drug is excreted unchanged renally, and the renal clearance rate is around 13L/hour.2

There is limited postmarking data available on this medication since it is newly approved however worldwide post marketing experience from an undefined population demographics (size etc.) without specific information of frequency or role of mirabegron in the side effect reported that patients on the medication experienced urinary retention.2

A multi-centered study from UK, Spain, and Dubai concludes that mirabegron may be used as a treatment for OAB in patients intolerant of or who have a suboptimal response to anti-muscarinic agents such as tolterodine SR (Detrol LA®).6,7  Mirabegron (Mybetriq®) is still a new agent, so more monitoring and safety evaluation is required before its role in therapy can be well defined.


  1. Grasescardo, J. Mirabegron for the treatment of overactive bladder. Drugs Today. 48.1 (Jan 2012): 25-32. Web. 22 Jul 2012. Available at:
  2. Mybetriq®  [package insert].  Astellas Pharma US, Inc. Accessed 16 Jul 2012.
  3. Lexi-Comp OnlineTM. Mybetriq (Lexi Drugs). Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; Accessed 19 Jul 2012
  4. Traynor, Kate. Mirabegron Approved for Overactive Bladder. Pharmacy News Archive. American Society of Health-System Pharmacists, July 2, 2012. Web. 20 Jul 2012.
  5. New Drugs Online Report for Mirabegron. UKMI New Drugs Online. UK Medicines Information, June 12, 2012. Web. 18 Jul 2012.
  6. Khullar V, Cambronero J, et al. The efficacy and tolerability of mirabegron, a potent and selective b3 adrenoceptor agonist, compared with placebo and tolterodine slow release in patients with overactive bladder – results from a European-Australian Phase III trial . Study Abstract Documents. International Continence Society, n.d. Web. 25 Jul 2012. Accessed 25 Jul 2012
  7. Ellsworth, Pamela. Treatment of Overactive Bladder Symptoms Beyond Antimuscarinics. PostGraduate Medicine – Current and Future Therapies. Division of Urology, Warren Alpert School of Medicine, Brown University, n.d. Web. 25 Jul 2012. Accessed 25 Jul 2012
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