MYRBETRIQ Rx

Indication(s):

Treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Pharmacology:

Mirabegron is an agonist of the human beta-3 adrenergic receptor. It relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of beta-3 AR which increases bladder capacity.

Clinical Trials:

Myrbetriq was evaluated in three, 12-week, double-blind, randomized, placebo-controlled, parallel group, multicenter studies in patients with OAB with symptoms of urge urinary incontinence, urgency, and urinary ­frequency (Studies 1, 2, and 3). Entry criteria required that patients had symptoms of OAB for at least 3 months duration, at least 8 micturitions per day, and at least 3 episodes of urgency with or without incontinence over a 3 day period. The population included both naïve patients who had not received prior antimuscarinic pharmacotherapy (48%) and those who had received prior antimuscarinic pharmacotherapy (52%).

In Study 1, patients were randomized to placebo, Myrbetriq 50mg, Myrbetriq 100mg, or an active control once daily. In Study 2, patients were randomized to placebo, Myrbetriq 50mg or Myrbetriq 100mg once daily. In Study 3, patients were randomized to placebo, Myrbetriq 25mg or Myrbetriq 50mg once daily.

The co-primary efficacy endpoints in all 3 trials were (1) change from baseline to end of treatment (Week 12) in mean number of incon­ti­nence episodes per 24 hours and (2) change from baseline to end of treatment in mean number of micturitions per 24 hours, based on a 3-day micturition diary. An important ­secondary ­endpoint was the change from baseline to end of treatment in mean volume voided per micturition.

At Week 12, treatment with Myrbetriq 25mg and 50mg resulted in statistically significant improvement in efficacy parameters of incontinence episodes and number of urinations per 24 hours. In treatment with Myrbetriq 25mg, incontinence episodes were reduced by 1.36 episodes from a baseline of 2.65, a statistically significant reduction of 0.40 vs. placebo. The number of urinations was reduced by 1.65 urinations from a baseline of 11.68, a statistically significant reduction of 0.47 vs. placebo. In treatment with Myrbetriq 50mg, incontinence episodes were reduced by 1.49 episodes from a baseline of 2.71, a statistically significant reduction of 0.40 vs. placebo. Number of urinations was reduced by 1.75 urinations from a baseline of 11.70, a statistically significant reduction of 0.55 vs. placebo.

Legal Classification:

Rx

Adults:

Swallow whole. Initially 25mg once daily. May increase to 50mg once daily as needed or tolerated. Severe renal impairment or moderate hepatic impairment: max 25mg once daily. End-stage renal disease (ESRD) or severe hepatic impairment: not recommended.

Children:

Not established.

Warnings/Precautions:

Severe uncontrolled hypertension: not recommended. Monitor blood pressure periodically. Significant bladder outlet obstruction, patients taking antimuscarinic drugs for OAB: risk of urinary retention. Pregnancy (Category C). Nursing mothers: not recommended.

Interaction(s)

May potentiate CYP2D6 substrates (eg, metoprolol, desipramine). Adjust dose and monitor esp. with narrow therapeutic index drugs metabolized by CYP2D6 (eg, thioridazine, flecai­nide, propafenone). Concomitant digoxin: use lowest digoxin dose initially (monitor and titrate).

Adverse Reaction(s)

Hypertension, nasopharyngitis, urinary tract infection, headache.

How Supplied:

Tabs—30, 90

LAST UPDATED:

1/9/2013