1. โดย เภสัชกรณัฐวุฒิ จรีบุญ สมโภช

4. OAB affects 33 million people in the United States (17% of American adults) more common in women and in older people negative impact on quality of life –psychological (anxiety and depression) –social consequences (restricted activities) Most patients have symptoms for years and it is common for patients to only seek treatment after an extended period of symptoms

5. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) having to void more than 8 times in a day or more than 2-3 times/night (nocturia) may be associated with the loss of large or small amounts of urine (urge incontinence), but not all patients with OAB experience urinary incontinence In summary, there are 4 symptom characteristics to OAB; urgency, frequency, nocturia and urgency incontinence (in the absence of UTI, other obvious pathology, or factors)

6. usually results from an involuntary increase in bladder pressure due to bladder smooth muscle (detrusor) over-activity

7. Treatment Options Behavioral therapy –Bladder retraining Medication –Anticholinergic Drug –B3-adrenocepter Agonist Minimally invasive therapies –Botulinum A-toxin –Neuromodulation Surgery

14. Mirabegron is a first-in-class agonist of beta 3-adrenoceptors Approved In June 2012 by USFDA Mirabegron relaxes smooth muscles (bladder) through activation of beta 3-AR increasing of the voiding interval inhibition of bladder contraction during filling

15. Mirabegron

17. Pharmacokinetics plasma protein binding = 71% terminal elimination half life = 50 h Time for maximum concentration (Tmax) = 3–4 h metabolized to 10 metabolites no significant drug-drug interaction moderate CYP2D6 inhibitor

18. Clinical Efficacy European–Australian multicentre, randomized, double-blind, parallel-group, placebo and active controlled phase III trial (SCORPIO trial) The study enrolled 1978 patients with OAB who, after a 2-week placebo run-in period, were randomized to receive one of the following once daily for 12 weeks: placebo (n = 494) mirabegron 50 mg (n = 493) mirabegron 100 mg (n = 496) [Khullar et al. 2011]

19. Clinical Safety and Adverse events

20. September 2015,serious cases of hypertension and increased blood pressure have been reported in patients on mirabegron treatment Mirabegron is now contraindicated in patients with severe uncontrolled hypertension defines as SBP > 180 mmHg and/or DPB ≥ 110 mmHg

21. Proposed dose: 50 mg daily or 25 mg only in severe renal or moderate hepatic impairment Formulation: Oral Controlled Absorption System (OCAS) tablets