The International Continence Society definition of overactive bladder (OAB) is, “urinary urgency, usually accompanied by frequency, nocturia, with or without urge urinary incontinence.”[1] It is important to understand that OAB isn't an exact disease, but rather, a symptom complex with multiple, distinct etiologies. It is an incredibly embarrassing condition, and many patients are uncomfortable discussing it with their providers. The treatment of OAB includes a three-step algorithm starting with lifestyle modification, then, medication, and lastly, minimally invasive intervention. Lifestyle and behavioral modification including paying close attention to fluid consumption and bladder irritants, bladder training, and pelvic muscle floor therapy. The second line includes using anticholinergics or beta-3 adrenoceptor agonist. The third line consists of the injection of onabotulinum-toxin A, sacral neuromodulation, and percutaneous posterior tibial nerve stimulation.

The medications used in OAB typically are the antimuscarinics. However, given their broad side-effect profile, they have to be used cautiously, especially in patients with acute angle-closed glaucoma, older patients, and chronic constipation. Mirabegron, a beta-3 adrenoceptor agonist, has been shown to have high safety and efficacy profile by large random placebo-controlled clinical trials. Mirabegron is used for the treatment of urgency, urge urinary incontinence, and increased urinary frequency found in the overactive bladder.[2] It received approval from the US Food and Drug Administration (FDA) in June 2012 for the treatment of this condition.[3] Mirabegron has been reported to have better tolerance and compliance by patients as compared to the antimuscarinics. In this article, we will cover the use of mirabegron. We will pay close attention to the mechanism of action, routes of administration/combination therapy, adverse effects, contraindications, monitoring, and coordination between health team providers.

The human bladder expresses various sympathetic and parasympathetic receptors to help regulate micturition. Activation of the parasympathetic system will result in bladder contraction. Receptors positively affecting bladder contraction and micturition include the M2 and M3 receptor subtypes, which function via the parasympathetic nervous system.[4] These receptors work to increase intracellular calcium and down-regulate cyclic-adenosine respectively, which will increase muscle contraction. Negatively affecting micturition predominantly includes the sympathetic beta-3 adrenergic receptors.[5] Mirabegron is a beta-3 receptor agonist which will cause detrusor muscle relaxation. Animal studies have shown that beta-3 receptor agonists exhibit a dose-dependent detrusor relaxation (mediated via up-regulation of cyclic-adenosine) during the storage phase of micturition.[3] In this way, mirabegron can aid in the symptomatic relief of OAB.

Mirabegron is a once daily orally administered drug.[3] It is available in 25 mg or 50 mg strengths. The lower strength tablet is recommended as a starting dose and for patients with severe renal or moderate hepatic impairment, and the higher dose tablet is recommended for patients to take with or without food if they tolerate the lower dose.[3] Other therapeutic routes of administration (intravenous, rectal, enteral, epidural, intracerebral, etc.,) for mirabegron are not FDA approved in the treatment of OAB. Mirabegron may take 4 to 8 weeks before patients see improvements in their symptoms.

In addition to monotherapy, combination therapy with low dose mirabegron (25 mg) and a low dose of solifenacin (5 mg), an anti-muscarinic, has been shown to have significant improvement of urinary urgency and urgency incontinence when compared to monotherapy. Three large double-blind, randomized controlled trials (Symphony, Beside, and Synergy) have shown the safety and efficacy of combination therapy. Recently, the FDA has approved combination therapy for patients with urinary urgency.

Side effects of mirabegron are generally mild and tolerable. One study showed that the adverse effects of mirabegron include hypertension (most commonly), nasopharyngitis, and urinary tract infection.[6]  Dry mouth (a common side effect of the anti-muscarinics) is six-fold less in mirabegron[6] which is because mirabegron does not affect the muscarinic receptors in the salivary glands. Other side effects include tachycardia, constipation, headache, back pain, dizziness, palpitations, atrial fibrillation, urticarial reaction, joint pain, and joint swelling.[7] Mirabegron is considered a very safe and effective drug. Mirabegron may also be more useful in the elderly population as the neurocognitive concerns of anti-muscarinic therapy may not be as much of a problem; however, this requires further investigation.

If patients are currently on mirabegron therapy, it is essential to monitor their blood pressure. Mirabegron use correlates with hypertension, and its contraindication includes severe uncontrolled hypertension and pregnancy.[8] Analysis of hypertension should depend on the discretion of the clinician. Resistant hypertension is defined as blood pressure that that remains elevated above 140/90 despite the use of three different anti-hypertensive drugs at the most tolerated doses, one of which being a diuretic.[9] In this light, the optimization of blood pressure should be a consideration before initiating mirabegron therapy.