FDA approves Lorcaserin and Mirabegron extended-release tablets.
(Belviq, Arena Pharmaceuticals GmbH)
Safety. In clinical trials of lorcaserin lasting at least 1 year, the most common adverse reactions occurring in >5% of patients without type 2 diabetes were headache, dizziness, fatigue, nausea, dry mouth, and constipation. In patients with type 2 diabetes, the most common adverse reactions were hypoglycemia, headache, back pain, cough, and fatigue. Other safety concerns included serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions, hypoglycemia (due to weight loss in type 2 diabetes), valvular heart disease, cognitive impairment, psychiatric disorders (i.e., euphoria, hallucination, and dissociation), heart rate decreases (of ~1.2 to 2.0 beats per minute), decreases in red and white blood cell counts, and priapism.
Dosing. The recommended dose of lorcaserin is 10 mg administered orally twice daily with or without food. Patients should be evaluated within 12 weeks for response; those who do not lose ≥5% of baseline body weight should discontinue lorcaserin. Due to the risk of serotonin syndrome or NMS-like reactions, coadministration of lorcaserin along with other serotonergic drugs (i.e., SSRIs, SNRIs, MAOIs, triptans, bupropion, dextromethorphan, and St. John's Wort, among others) should be undertaken with extreme caution.
Mirabegron extended-release tablets
(Myrbetriq, Astellas Pharma US)
An estimated 33 million Americans suffer from overactive bladder (OAB). On June 28, 2012, FDA approved the beta-3 adrenergic agonist mirabegron (Myrbetriq) for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency. Mirabegron works by relaxing the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle.
Efficacy. Mirabegron was evaluated in three 12-week, double-blind, randomized, placebo-controlled, multicenter clinical trials of overactive-bladder patients with symptoms of urge urinary incontinence, urgency, and urinary frequency. Results showed that mirabegron 25 mg and 50 mg statistically significantly reduced the number of times a patient had an incontinence episode (adjusted mean difference from placebo; -0.41 for 50 mg in study 1, -0.34 for 50 mg in study 2, and -0.40 to -0.42 for 25 mg and 50 mg, respectively, in study 3) and the number of times a patient urinated (adjusted mean difference from placebo; -0.60 for 50 mg in study 1, -0.61 for 50 mg in study 2, and -0.47 to -0.42 for 25 mg and 50 mg, respectively, in study 3) during a 24-hour period.
Safety. The most common reported adverse reactions (occurring in >2% of subjects and more often than placebo) during the above-mentioned clinical trials of mirabegron were hypertension, nasopharyngitis, urinary tract infection, and headache. Mirabegron can increase blood pressure, and therefore, periodic blood pressure determinations are recommended (especially in hypertensive patients). Mirabegron is not recommended for use in patients with severe uncontrolled hypertension. A higher risk of urinary retention is present in patients suffering from bladder outlet obstruction or taking antimuscarinic drugs for OAB.
Dosing. The recommended starting dose of mirabegron is 25 mg once daily, with or without food. If the 25 mg dose is not effective within 8 weeks, the dose may be increased to 50 mg once daily. Patients with severe renal impairment (CrCl 15 to 29 mL/min) or moderate hepatic impairment (Child-Pugh Class B) should not receive doses >25 mg once daily. Mirabegron should not be administered to patients with end-stage renal disease or severe hepatic impairment. Mirabegron is a moderate CYP2D6 inhibitor and caution should be used when administering it concomitantly with drugs metabolized by CYP2D6 (i.e., metoprolol, despiramine, digoxin).
Craig I. Coleman is associate professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Conn., and director of the Pharmacoeconomics and Outcomes Studies Group, Hartford Hospital.