Mirabegron

Indications

Mirabegron is used for: Overactive bladder, with symptoms of urge urinary incontinence, urgency, and urinary frequency

Adult Dose

Overactive Bladder Indicated for overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency 25 mg PO qDay 25 mg dose is typically effective within 8 weeks May increase to 50 mg PO qDay based on individual efficacy and tolerability Hepatic impairment Moderate (Child-Pugh B): Not to exceed 25 mg/day Severe (Child Pugh C): Not recommended

Child Dose

Renal Dose

Renal impairment Severe (CrCl 15-29 mL/min): Not to exceed 25 mg/day ESRD: Not recommended

Administration

May be taken with or without food: Swallow whole, do not chew/divide/crush.

Contra Indications

Hypersensitivity. Severe uncontrolled HTN.

Precautions

End-stage renal disease, severe renal impairment; moderate (Child-Pugh Class B) & severe hepatic impairment (Child-Pugh Class C); severe uncontrolled HTN. Known history of QT prolongation or taking medicines known to prolong QT interval; bladder outlet obstruction & taking antimuscarinic medications for OAB. Women of childbearing potential not using contraception. Pregnancy & lactation. Childn <18 yr. Lactation: Unknown whether distributed in breast milk; excretion in breast milk possible; discontinue nursing or the drug taking into account the importance of the drug to the mother

Pregnancy-Lactation

Pregnancy There are no studies with the use in pregnant women to inform drug-associated risk for birth defects or miscarriage Animal data Administration to pregnant animals during organogenesis resulted in reversible skeletal variations (in rats) at 22-fold (via AUC) the maximum recommended human dose (MRHD) of 50 mg/day and decreased fetal body weights (in rabbits) at 14-fold the MRHD At maternally toxic exposures in rats (96-fold), decreased fetal weight and increased fetal mortality were observed and, in rabbits (36-fold), cardiac findings (fetal cardiomegaly and fetal dilated aortae) were observed Lactation There is no information on the presence of mirabegron in human milk, the effects on the breastfed child, or the effects on milk production Mirabegron-related material was present in rat milk and in the stomach of nursing pups following administrations of a single 10 mg/kg oral dose of 14C-labeled mirabegron to lactating rats

Interactions

Increased AUC of strong CYP3A/P-gp inhibitors eg, ketoconazole, itraconazole, ritonavir, clarithromycin. Decreased plasma conc by CYP3A/P-gp inducers. Increased Cmax & AUC of metoprolol, despiramine & digoxin. Thioridazine, type 1C antiarrhythmics (eg flecainide, propafenone), TCAs. Potential P-gp inhibition of dabigatran.

Adverse Effects

Side effects of Mirabegron : >10% Elevated BP occurring predominantly in patients with preexisting hypertension (7-11%) 1-10% Dry mouth (3-9%), Nasopharyngitis (3-4%), UTI (3-6%), Headache (2-4%), Influenza (2-3%), Constipation (2-3%), Dizziness (2%), Arthralgia (2%), Cystitis (2%), Back pain (1-3%), Sinusitis (1-3%), URTI (1-2%), Arthralgia (1-2%), Diarrhea (1-2%), Tachycardia (1-2%), Fatigue (1%), Abdominal pain (0-1%), Reports of neoplasms (0-1%) <1% Cardiac disorders (eg, palpitations, elevated BP), Eye Disorders (eg, glaucoma, blurry vision), GI disorders (eg, dyspepsia, gastritis, abdominal distension), Rhinitis, Elevations in GGT, AST, ALT, LDH, Renal and urinary disorders (eg, nephrolithiasis, bladder pain), Reproductive system disorders (eg, vulvovaginal pruritis, vaginal infection) Skin and subcutaneous tissue disorders (eg, urticaria, leukocytoclastic vasculitis, rash, pruritus, purpura, lip edema) Stevens-Johnson syndrome associated with increased serum ALT, AST and bilirubin

Mechanism of Action

Beta-3 adrenergic receptor agonist which causes relaxation of the detrusor smooth muscle of the urinary bladder and increases bladder capacity.