Mirabegron

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Mirabegron
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]

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Overview

Mirabegron is a beta-3 adrenergic agonist that is FDA approved for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. Common adverse reactions include hypertension, nasopharyngitis, urinary tract infection and headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Bladder muscle dysfunction - overactive, With symptoms of urge urinary incontinence, urgency, and urinary frequency
  • Dosing Information
  • The recommended starting dose of Myrbetriq is 25 mg once daily with or without food. Myrbetriq 25 mg is effective within 8 weeks. Based on individual patient efficacy and tolerability the dose may be increased to 50 mg once daily.
  • Myrbetriq should be taken with water, swallowed whole and should not be chewed, divided, or crushed.
  • Dose Adjustments in Specific Populations
  • The daily dose of Myrbetriq should not exceed 25 mg once daily in the following populations:
  • Patients with severe renal impairment (CL cr 15 to 29 mL/min or eGFR 15 to 29 mL/min/1.73 m 2).
  • Patients with moderate hepatic impairment (Child-Pugh Class B).
  • Myrbetriq is not recommended for use in patients with end stage renal disease (ESRD), or in patients with severe hepatic impairment (Child-Pugh Class C).

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

  • There is limited information regarding Off-Label Guideline-Supported Use of Mirabegron in adult patients.

Non–Guideline-Supported Use

  • There is limited information regarding Off-Label Non–Guideline-Supported Use of Mirabegron in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Mirabegron in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Mirabegron in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Mirabegron in pediatric patients.

Contraindications

  • None.

Warnings

5.1 Increases in Blood Pressure

Myrbetriq can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. Myrbetriq is not recommended for use in patients with severe uncontrolled hypertension (defined as systolic blood pressure greater than or equal to 180 mm Hg and/or diastolic blood pressure greater than or equal to 110 mm Hg) [see Clinical Pharmacology (12.2)].

In two, randomized, placebo-controlled, healthy volunteer studies, Myrbetriq was associated with dose-related increases in supine blood pressure. In these studies, at the maximum recommended dose of 50 mg, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mm Hg greater than placebo.

In contrast, in OAB patients in clinical trials, the mean increase in systolic and diastolic blood pressure at the maximum recommended dose of 50 mg was approximately 0.5 - 1 mm Hg greater than placebo. Worsening of pre-existing hypertension was reported infrequently in Myrbetriq patients.

5.2 Urinary Retention in Patients with Bladder Outlet Obstruction and in Patients Taking Antimuscarinic Medications for OAB

Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medications for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in Myrbetriq patients; however, Myrbetriq should be administered with caution to patients with clinically significant BOO. Myrbetriq should also be administered with caution to patients taking antimuscarinic medications for the treatment of OAB [see Clinical Pharmacology (12.2)].

5.3 Patients Taking Drugs Metabolized by CYP2D6

Since mirabegron is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates such as metoprolol and desipramine is increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone.

Adverse Reactions

Clinical Trials Experience

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In three, 12 week, double-blind, placebo-controlled, safety and efficacy studies in patients with overactive bladder (Studies 1, 2, and 3), Myrbetriq was evaluated for safety in 2736 patients [see Clinical Studies (14)]. Study 1 also included an active control. For the combined Studies 1, 2, and 3, 432 patients received Myrbetriq 25 mg, 1375 received Myrbetriq 50 mg, and 929 received Myrbetriq 100 mg once daily. In these studies, the majority of the patients were Caucasian (94%), and female (72%) with a mean age of 59 years (range 18 to 95 years).

Myrbetriq was also evaluated for safety in 1632 patients who received Myrbetriq 50 mg once daily (n=812 patients) or Myrbetriq 100 mg (n=820 patients) in a 1 year, randomized, fixed dose, double-blind, active controlled, safety study in patients with overactive bladder (Study 4). Of these patients, 731 received Myrbetriq in a previous 12 week study. In Study 4, 1385 patients received Myrbetriq continuously for at least 6 months, 1311 patients received Myrbetriq for at least 9 months, and 564 patients received Myrbetriq for at least 1 year.

The most frequent adverse events (0.2%) leading to discontinuation in Studies 1, 2 and 3 for the 25 mg or 50 mg dose were nausea, headache, hypertension, diarrhea, constipation, dizziness and tachycardia.

Atrial fibrillation (0.2%) and prostate cancer (0.1%) were reported as serious adverse events by more than 1 patient and at a rate greater than placebo.

Table 1 lists adverse reactions, derived from all adverse events, that were reported in Studies 1, 2 and 3 at an incidence greater than placebo and in 1% or more of patients treated with Myrbetriq 25 mg or 50 mg once daily for up to 12 weeks. The most commonly reported adverse reactions (greater than 2% of Myrbetriq patients and greater than placebo) were hypertension, nasopharyngitis, urinary tract infection and headache.

Other adverse reactions reported by less than 1% of patients treated with Myrbetriq in Studies 1, 2, or 3 included:

Cardiac disorders: palpitations, blood pressure increased [see Clinical Pharmacology (12.2)]

Eye Disorders: glaucoma [see Clinical Pharmacology (12.2)]

Gastrointestinal disorders: dyspepsia, gastritis, abdominal distension

Infections and Infestations: sinusitis, rhinitis

Investigations: GGT increased, AST increased, ALT increased, LDH increased

Renal and urinary disorders: nephrolithiasis, bladder pain

Reproductive system and breast disorders: vulvovaginal pruritus, vaginal infection

Skin and subcutaneous tissue disorders: urticaria, leukocytoclastic vasculitis, rash, pruritus, purpura, lip edema

Table 2 lists the rates of the most commonly reported adverse reactions, derived from all adverse events in patients treated with Myrbetriq 50 mg for up to 52 weeks in Study 4. The most commonly reported adverse reactions (>3% of Myrbetriq patients) were hypertension, urinary tract infection, headache, and nasopharyngitis.

In Study 4, in patients treated with Myrbetriq 50 mg once daily, adverse reactions leading to discontinuation reported by more than 2 patients and at a rate greater than active control included: constipation (0.9%), headache (0.6%), dizziness (0.5%), hypertension (0.5%), dry eyes (0.4%), nausea (0.4%), vision blurred (0.4%), and urinary tract infection (0.4%). Serious adverse events reported by at least 2 patients and exceeding active control included cerebrovascular accident (0.4%) and osteoarthritis (0.2%). Serum ALT/AST increased from baseline by greater than 10-fold in 2 patients (0.3%) taking Myrbetriq 50 mg, and these markers subsequently returned to baseline while both patients continued Myrbetriq.

In Study 4, serious adverse events of neoplasm were reported by 0.1%, 1.3%, and 0.5% of patients treated with Myrbetriq 50 mg, Myrbetriq 100 mg and active control once daily, respectively. Neoplasms reported by 2 patients treated with Myrbetriq 100 mg included breast cancer, lung neoplasm malignant and prostate cancer.

In a separate clinical study in Japan, a single case was reported as Stevens-Johnson syndrome with increased serum ALT, AST and bilirubin in a patient taking Myrbetriq 100 mg as well as an herbal medication (Kyufu Gold).

Postmarketing Experience

Because these spontaneously reported events are from the worldwide postmarketing experience, from a population of uncertain size, the frequency of events and the role of mirabegron in their causation cannot be reliably determined.

The following events have been reported in association with mirabegron use in worldwide postmarketing experience:

Urologic: urinary retention [see Warnings and Precautions (5.2)]

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mirabegron in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Mirabegron during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Mirabegron with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Mirabegron with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Mirabegron with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Mirabegron with respect to specific gender populations.

Race

There is no FDA guidance on the use of Mirabegron with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Mirabegron in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Mirabegron in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Mirabegron in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Mirabegron in patients who are immunocompromised.

Administration and Monitoring

Administration

Dosing Information

  • The recommended starting dose of Myrbetriq is 25 mg once daily with or without food. Myrbetriq 25 mg is effective within 8 weeks. Based on individual patient efficacy and tolerability the dose may be increased to 50 mg once daily.
  • Myrbetriq should be taken with water, swallowed whole and should not be chewed, divided, or crushed.

Dose Adjustments in Specific Populations

  • The daily dose of Myrbetriq should not exceed 25 mg once daily in the following populations:
  • Patients with severe renal impairment (CL cr 15 to 29 mL/min or eGFR 15 to 29 mL/min/1.73 m 2).
  • Patients with moderate hepatic impairment (Child-Pugh Class B).
  • Myrbetriq is not recommended for use in patients with end stage renal disease (ESRD), or in patients with severe hepatic impairment (Child-Pugh Class C).

DOSAGE FORMS AND STRENGTHS

  • Myrbetriq extended-release tablets are supplied in two different strengths as described below:
  • 25 mg oval, brown, film coated tablet, debossed with the Astellas logo (Astellas logo) and “325”
  • 50 mg oval, yellow, film coated tablet, debossed with theAstellas logo (Astellas logo) and "355"

Monitoring

There is limited information regarding Monitoring of Mirabegron in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Mirabegron in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Mirabegron in the drug label.

Pharmacology

There is limited information regarding Mirabegron Pharmacology in the drug label.

Mechanism of Action

Structure

File:Mirabegron01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Mirabegron in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Mirabegron in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Mirabegron in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Mirabegron in the drug label.

How Supplied

Storage

There is limited information regarding Mirabegron Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Mirabegron in the drug label.

Precautions with Alcohol

  • Alcohol-Mirabegron interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Myrbetriq

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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