Brand name: Myrbetriq
Drug class: Selective beta-3 Adrenergic Agonists
Chemical name: 2-Amino-N-[4-[2-[[(2R)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-4-thiazoleacetamide
Molecular formula: C₂₁H₂₄N₄O₂S
CAS number: 223673-61-8

Introduction

Genitourinary smooth muscle relaxant; a selective β₃-adrenergic agonist.

Uses for Mirabegron

Overactive Bladder

Management of overactive bladder for relief of symptoms associated with voiding (e.g., urge urinary incontinence, urgency, frequency).

May be an appropriate alternative in patients with overactive bladder in whom antimuscarinic agents are ineffective or cannot be tolerated because of adverse anticholinergic effects.

Mirabegron Dosage and Administration

Administration

Oral Administration

Administer orally once daily with water without regard to meals.

Swallow tablets whole; do not chew, divide, or crush.

Dosage

Adults

Overactive Bladder

Oral

Initially, 25 mg once daily. May increase to 50 mg once daily according to response and tolerance.

Prescribing Limits

Adults

Overactive Bladder

Oral

Maximum 50 mg daily.

Special Populations

Hepatic Impairment

Dosage adjustment not necessary in patients with mild hepatic impairment (Child-Pugh class A).

Maximum 25 mg daily in patients with moderate hepatic impairment (Child-Pugh class B). (See Special Populations under Pharmacokinetics.)

Use not recommended in patients with severe hepatic impairment (Child-Pugh class C). (See Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage adjustment not necessary in patients with mild or moderate renal impairment (Cl_Cr 30–89 mL/minute).

Maximum 25 mg daily in patients with severe renal impairment (Cl_Cr 15–29 mL/minute). (See Special Populations under Pharmacokinetics.)

Use not recommended in patients with end-stage renal disease (ESRD) (Cl_Cr <15 mL/minute or when hemodialysis required). (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No specific dosage recommendations at this time. (See Geriatric Use under Cautions.)

Gender

Dosage adjustment not necessary based on gender.

Cautions for Mirabegron

Contraindications

• Manufacturer states none known.

Warnings/Precautions

Cardiovascular Effects

Increased BP reported. Worsening of preexisting hypertension reported infrequently. Increases in SBP and DBP appeared to be dose related and reversible upon discontinuance of therapy.

Measure BP periodically, especially in patients with preexisting hypertension. Avoid use in patients with severe uncontrolled hypertension (i.e., SBP ≥180 mm Hg, DBP ≥110 mm Hg).

Causes only minimal QT_c interval prolongation and slight increases in HR in healthy individuals.

Genitourinary Effects

Urinary retention reported in patients with bladder outflow obstruction and in those receiving antimuscarinic agents for treatment of overactive bladder during postmarketing surveillance. Use with caution in such patients.

Interactions with Drugs Metabolized by Hepatic Microsomal Enzymes

Possible increase in systemic exposure to substrates of CYP2D6 when used concomitantly with mirabegron. (See Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes under Interactions.) Appropriate monitoring recommended; dosage adjustment may be necessary, especially in patients receiving CYP2D6 substrates with a narrow therapeutic index. (See Specific Drugs under Interactions.)

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats and detected in nursing pups; not known whether distributed into human milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Pharmacokinetics not substantially affected by patient age. No substantial differences in safety and efficacy relative to younger adults; dosage adjustment not necessary.

Hepatic Impairment

Increased plasma concentrations of mirabegron reported in patients with moderate hepatic impairment (Child-Pugh class B). (See Hepatic Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Not evaluated in patients with severe hepatic impairment (Child-Pugh class C); use not recommended in such patients.

Renal Impairment

Increased plasma concentrations of mirabegron reported in patients with severe renal impairment (Cl_Cr 15–29 mL/minute). (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Not evaluated in patients with ESRD (Cl_Cr <15 mL/minute or when hemodialysis required); use not recommended in such patients.

Common Adverse Effects

Hypertension, nasopharyngitis, urinary tract infection, headache.

Drug Interactions

Substrate of CYP isoenzymes 3A4 and 2D6, butyrylcholinesterase, UGT, P-glycoprotein (P-gp), and organic cation transporters (OCT) 1, 2, and 3.

Moderate, time-dependent inhibitor of CYP2D6 and weak inhibitor of CYP3A. Does not induce CYP1A2 or 3A. At high concentrations, inhibits P-gp-mediated drug transport. Not expected to cause clinically important inhibition of OCT-mediated drug transport.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6: Pharmacokinetic interaction (increased plasma concentrations of CYP2D6 substrates). Monitor appropriately and adjust dosage if necessary in patients receiving concomitant therapy with mirabegron and CYP2D6 substrates, especially such drugs with a narrow therapeutic index.

Substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2E1: Pharmacokinetic interaction unlikely. Inhibition of these enzymes not observed at clinically relevant concentrations.

Specific Drugs

Mirabegron Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is 29 or 35% following mirabegron dosages of 25 or 50 mg, respectively.

Peak plasma concentrations achieved at approximately 3.5 hours after oral administration.

Steady-state concentrations achieved within 7 days of once-daily dosing.

Steady-state concentrations following once-daily administration approximately twice as high as that observed following a single dose.

Onset

Symptomatic improvement observed within 4 or 8 weeks with once-daily dosages of mirabegron 50 or 25 mg, respectively.

Food

Peak plasma concentrations and AUC decreased by 45 and 17%, respectively, following administration of mirabegron 50 mg with a high-fat meal and by 75 and 51%, respectively, following a low-fat meal. However, safety and efficacy established when administered without regard to food. (See Administration under Dosage and Administration.)

Special Populations

Peak plasma concentrations and AUC were similar following multiple oral doses in geriatric individuals (≥65 years of age) compared with younger adults (18–45 years of age).

Mean peak plasma concentrations and AUC increased by 16 and 17%, respectively, in poor CYP2D6 metabolizers compared with extensive CYP2D6 metabolizers.

Peak plasma concentrations and AUC increased by approximately 40–50% in females compared with males. Systemic exposure about 20–30% higher in females compared with males after adjusting for differences in body weight.

Pharmacokinetics of mirabegron similar in white and black individuals. Increased exposure observed in Japanese individuals compared with North American individuals; extent of differences decreased when peak plasma concentrations and AUC normalized for dose and body weight.

Mild hepatic impairment (Child-Pugh class A): Mean peak plasma concentrations and AUC increased by 9 and 19%, respectively, compared with those observed in individuals with normal hepatic function.

Moderate hepatic impairment (Child-Pugh class B): Mean peak plasma concentrations and AUC increased by 175 and 65%, respectively, compared with those observed in individuals with normal hepatic function. (See Hepatic Impairment under Dosage and Administration.)

Severe hepatic impairment (Child-Pugh class C): Effect on pharmacokinetics not studied. (See Hepatic Impairment under Dosage and Administration.)

Mild renal impairment (estimated GFR 60–89 mL/minute per 1.73 m²): Mean peak plasma concentrations and AUC increased by 6 and 31%, respectively, compared with those observed in individuals with normal renal function.

Moderate renal impairment (estimated GFR 30–59 mL/minute per 1.73 m²): Mean peak plasma concentrations and AUC increased by 23 and 66%, respectively, compared with those observed in individuals with normal renal function. (See Renal Impairment under Dosage and Administration.)

Severe renal impairment (estimated GFR 15–29 mL/minute per 1.73 m²): Mean peak plasma concentrations and AUC increased by 92 and 118%, respectively, compared with those observed in individuals with normal renal function. Not studied in patients with ESRD (Cl_Cr <15 mL/minute) or in those requiring hemodialysis. (See Renal Impairment under Dosage and Administration.)

Distribution

Extent

Extensively distributed.

Distributed into erythrocytes; erythrocyte concentrations about twofold higher than plasma concentrations in vitro.

Distributed into milk in rats and detected in nursing pups. Not known whether distributed into human milk.

Plasma Protein Binding

Approximately 71% (moderate affinity for albumin and α₁-acid glycoprotein).

Elimination

Metabolism

Undergoes hepatic metabolism via multiple pathways involving dealkylation, oxidation, direct glucuronidation, and amide hydrolysis. CYP isoenzymes 2D6 and 3A4 may be involved in the oxidative metabolism of mirabegron but have limited role in overall drug elimination. Butyrylcholinesterase, UGT, and possibly alcohol dehydrogenase also appear to be involved in mirabegron metabolism.

Two major glucuronide metabolites represent 16 and 11% of total drug exposure, respectively; these metabolites pharmacologically inactive at the β₃-adrenergic receptor.

Elimination Route

Eliminated principally by renal clearance via active tubular secretion along with glomerular filtration.

Approximately 55 and 34% of total radioactivity was recovered in urine and feces, respectively; approximately 25% of the radioactive dose was recovered as unchanged drug excreted in urine and 0% in feces.

Half-life

Approximately 50 hours.

Stability

Storage

Oral

Extended-release Tablets

25°C (may be exposed to 15–30°C).

Actions

• Selective β₃-adrenergic agonist.

• Stimulates human β₁-adrenergic receptors at higher than recommended dosages (200 mg).

• Relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle resulting in increased bladder capacity via activation of β₃-adrenergic receptors.

• Increased intraocular pressure not observed in healthy individuals following once-daily administration.

Advice to Patients

• Importance of reading manufacturer’s patient information before initiating therapy and each time prescription is refilled.

• Importance of advising patients to swallow mirabegron tablets whole with water and not to chew, divide, or crush the tablets.

• If a dose is missed, omit the dose and take the next dose at the regularly scheduled time; do not take a double dose to make up for the missed dose.

• Risk of increased BP. Monitor BP periodically, especially in patients with preexisting hypertension.

• Risk of urinary retention, especially in patients with bladder outlet obstruction or in those receiving concomitant treatment with antimuscarinic agents. Consult a clinician if urinary retention occurs.

• Risk of urinary tract infection, tachycardia, rash, or pruritus. Consult a clinician if any of these adverse effects occur.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements as well as any concomitant illnesses.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Medical Disclaimer