mirabegron

General

Pronunciation:
mye-ra-beg-ron

Trade Name(s)

• Myrbetriq

Ther. Class.

urinary tract antispasmodics

Pharm. Class.

beta-adrenergic agonists

Indications

• Overactive bladder, including urge urinary incontinence, urgency, and frequency (either as monotherapy or in combination with solifenacin).
• Pediatric neurogenic detrusor overactivity.

Action

• Acts as a selective beta-3 adrenergic agonist.
• Increases bladder capacity by relaxing detrusor smooth muscle during storage phase of bladder fill-void cycle.

Therapeutic Effect(s):

• Decreased symptoms of overactive bladder.
• Improved bladder capacity in neurogenic detrusor overactivity.

Pharmacokinetics

Absorption: 29–35% absorbed following oral administration.

Distribution: Widely distributed.

Metabolism and Excretion: Extensively metabolized, 6% excreted unchanged in urine (25-mg dose); remainder excreted in urine and feces as metabolites.

Half-life: Adults:  50 hr;  Children:  26–31 hr.

TIME/ACTION PROFILE (effects on bladder)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Severe uncontrolled hypertension;
• End-stage renal disease (eGFR <15 mL/min/1.73 m²  or requiring dialysis);
• Severe hepatic impairment.

Use Cautiously in:

• Hypertension;
• Bladder outlet obstruction/concurrent antimuscarinics (↑ risk of urinary retention);
• Concurrent use of antimuscarinics used to treat overactive bladder;
• OB:  Safety not established in pregnancy;
• Lactation: Safety not established in breastfeeding;
• Pedi:  Children <3 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

CV: ↑ BP, tachycardia

EENT: nasopharyngitis

GI: constipation, diarrhea, nausea

GU: urinary tract infection

Neuro: dizziness, headache

Misc: ANGIOEDEMA

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• May ↑ levels and risk of toxicity of  CYP2D6 substrates, including  desipramine,  flecainide,  metoprolol,  propafenone, and  thioridazine.
• May ↑ levels and risk of toxicity of  digoxin ; use lowest effective level of digoxin/monitor serum levels.

Route/Dosage

The extended-release tablets and extended-release oral suspension are NOT interchangeable and should NOT be combined.

Overactive Bladder

PO (Adults): 25 mg once daily; may ↑ to 50 mg once daily, if needed, after 4–8 wk.

Renal Impairment 
PO (Adults): eGFR 15–29 mL/min/m² :  25 mg once daily (max dose = 25 mg/day).

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment:  25 mg once daily (max dose = 25 mg/day).

Neurogenic Detrusor Overactivity

PO (Children  ≥3 yr and ≥35 kg): Extended-release tablets:  25 mg once daily; may ↑ to 50 mg once daily, if needed, after 4–8 wk.  Extended-release oral suspension (granules):  48 mg once daily; may ↑ to 80 mg once daily, if needed after 4–8 wk.

PO (Children  ≥3 yr and 22–<35 kg): Extended-release oral suspension (granules):  32 mg once daily; may ↑ to 64 mg once daily, if needed after 4–8 wk.

PO (Children  ≥3 yr and 11–<22 kg): Extended-release oral suspension (granules):  24 mg once daily; may ↑ to 48 mg once daily, if needed after 4–8 wk.

Renal Impairment 
PO (Children  ≥3 yr and ≥35 kg): eGFR 15–29 mL/min/m² :  Extended-release tablets: 25 mg once daily (max dose = 25 mg/day); Extended-release oral suspension (granules): 48 mg once daily (max dose = 48 mg/day).

Renal Impairment 
PO (Children  ≥3 yr and 22–<35 kg): eGFR 15–29 mL/min/m² :  Extended-release oral suspension (granules): 32 mg once daily (max dose = 32 mg/day).

Renal Impairment 
PO (Children  ≥3 yr and 11–<22 kg): eGFR 15–29 mL/min/m² :  Extended-release oral suspension (granules): 24 mg once daily (max dose = 24 mg/day).

Hepatic Impairment 
PO (Children  ≥3 yr and ≥35 kg): Moderate hepatic impairment:  Extended-release tablets: 25 mg once daily (max dose = 25 mg/day); Extended-release oral suspension (granules): 48 mg once daily (max dose = 48 mg/day).

Hepatic Impairment 
PO (Children  ≥3 yr and 22–<35 kg): Moderate hepatic impairment:  Extended-release oral suspension (granules): 32 mg once daily (max dose = 32 mg/day).

Hepatic Impairment 
PO (Children  ≥3 yr and 11–<22 kg): Moderate hepatic impairment:  Extended-release oral suspension (granules): 24 mg once daily (max dose = 24 mg/day).

Availability (generic available)

Extended-release tablets: 25 mg, 50 mg

Extended-release oral suspension (granules): 8 mg/mL

Assessment

• Assess for urinary urgency, frequency, urge incontinence, and urinary retention periodically during therapy.
• Monitor BP prior to starting and periodically during therapy; may ↑ BP.
• Monitor for signs and symptoms of angioedema (swelling of face, lips, tongue, or larynx).  If airway symptoms occur,  discontinue mirabegron and treat symptomatically.

Implementation

• Tablets and granules are different products. Do not interchange, substitute, or combine.
• PO Administer without regard to food.
  •  DNC: Swallow tablets whole with water; do not break, crush, or chew. 
• Pediatric patients weighing ≥35 kg may use tablets or granules.
• Administer granules for patients weighing <35 kg. Prepare granules as an extended-release oral suspension. Tap the closed bottle to loosen granules. Add 100 mL of water to bottle, shake vigorously for 1 min, let stand for 10–30 min, and then shake again for 1 min. Repeat shaking for 1 min if granules have not dispersed. Take with food. Store at room temperature for ≤28 days after reconstitution.

Patient/Family Teaching

• Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy.
• Instruct patient to take a missed dose as soon as remembered. If >12 hr since missed dose omit and take next dose at scheduled time.
• Advise patient to have BP checked periodically during therapy to monitor for hypertension.
• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to notify health care provider if difficulty emptying bladder occurs.
• Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
• Advise patient to immediately discontinue mirabegron and notify health care provider if difficulty breathing or upper airway swelling occurs.
• Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Decreased urinary frequency, urgency, and urge incontinence.