Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H24N4O2S |
| Molecular Weight | 396.506 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC(CC(=O)NC2=CC=C(CCNC[C@H](O)C3=CC=CC=C3)C=C2)=CS1
InChI
InChIKey=PBAPPPCECJKMCM-IBGZPJMESA-N
InChI=1S/C21H24N4O2S/c22-21-25-18(14-28-21)12-20(27)24-17-8-6-15(7-9-17)10-11-23-13-19(26)16-4-2-1-3-5-16/h1-9,14,19,23,26H,10-13H2,(H2,22,25)(H,24,27)/t19-/m0/s1
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=20878594
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=20878594
Mirabegron (trade name Myrbetriq in the US and Betmiga in Europe) is a drug for the treatment of overactive bladder (OAB). It was developed by Astellas Pharma and was approved in the United States in July 2012. Originally developed as a treatment for diabetes, the development of mirabegron was later refocused to OAB. Mirabegron is an orally bioavailable agonist of the human beta-3 adrenergic receptor (ADRB3), with muscle relaxing, neuroprotective and potential antineoplastic activities. Upon oral administration, mirabegron binds to and activates ADRB3, which leads to smooth muscle relaxation. Mirabegron also restores sympathetic stimulation in mesenchymal stem cell (MSC) niches, inhibits JAK2-mutated hematopoietic stem cell (HSC) expansion and blocks the progression of myeloproliferative neoplasms (MPNs). Lack of sympathetic stimulation of the MSC and HSC niche is associated with the development of MPNs.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL246 |
22.4 nM [EC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | MYRBETRIQ Approved UseIndicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. Launch Date2012 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
12.8 ng/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MIRABEGRON plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
29.4 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25791612 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MIRABEGRON plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
177 ng × h/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MIRABEGRON plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
46.82 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25791612 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MIRABEGRON plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
41.5 h |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MIRABEGRON plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
28.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25791612 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MIRABEGRON plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
29% |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MIRABEGRON plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
healthy, 23.6 years (range: 20–27 years) n = 8 Health Status: healthy Age Group: 23.6 years (range: 20–27 years) Sex: M Population Size: 8 Sources: |
Other AEs: Pulse rate increased... Other AEs: Pulse rate increased (2%) Sources: |
400 mg single, oral Highest studied dose |
healthy, 23.8 years (range: 20–27 years) n = 6 Health Status: healthy Age Group: 23.8 years (range: 20–27 years) Sex: M Population Size: 6 Sources: |
|
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 58.0±13.7 years n = 167 Health Status: unhealthy Condition: overactive bladder Age Group: 58.0±13.7 years Sex: M+F Population Size: 167 Sources: |
Other AEs: Cardiac disorders, Eye disorders... Other AEs: Cardiac disorders (3%) Sources: Eye disorders (3.6%) Constipation (1.8%) Dyspepsia (2.4%) |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
Disc. AE: Constipation, Hypertension... AEs leading to discontinuation/dose reduction: Constipation (0.2%) Sources: Page: p. 300Hypertension (0.2%) Tachycardia (0.1%) Atrial fibrillation (0.5%) Palpitations (0.5%) Edema peripheral (0.5%) Pyrexia (0.5%) ALT increased (0.4%) AST increased (0.4%) Bilirubin increased (0.4%) Liver enzyme abnormal (0.4%) Hypertensive crisis (0.3%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Pulse rate increased | 2% | 200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
healthy, 23.6 years (range: 20–27 years) n = 8 Health Status: healthy Age Group: 23.6 years (range: 20–27 years) Sex: M Population Size: 8 Sources: |
| Constipation | 1.8% | 200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 58.0±13.7 years n = 167 Health Status: unhealthy Condition: overactive bladder Age Group: 58.0±13.7 years Sex: M+F Population Size: 167 Sources: |
| Dyspepsia | 2.4% | 200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 58.0±13.7 years n = 167 Health Status: unhealthy Condition: overactive bladder Age Group: 58.0±13.7 years Sex: M+F Population Size: 167 Sources: |
| Cardiac disorders | 3% | 200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 58.0±13.7 years n = 167 Health Status: unhealthy Condition: overactive bladder Age Group: 58.0±13.7 years Sex: M+F Population Size: 167 Sources: |
| Eye disorders | 3.6% | 200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 58.0±13.7 years n = 167 Health Status: unhealthy Condition: overactive bladder Age Group: 58.0±13.7 years Sex: M+F Population Size: 167 Sources: |
| Tachycardia | 0.1% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Constipation | 0.2% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Hypertension | 0.2% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Hypertensive crisis | 0.3% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| ALT increased | 0.4% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| AST increased | 0.4% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Bilirubin increased | 0.4% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Liver enzyme abnormal | 0.4% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Atrial fibrillation | 0.5% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Edema peripheral | 0.5% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Palpitations | 0.5% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
| Pyrexia | 0.5% Disc. AE |
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: Page: p. 300 |
unhealthy, adult n = 2736 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 2736 Sources: Page: p. 300 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| moderate | yes (co-administration study) Comment: Cmax and AUC of metoprolol increased by 90% and 229% and of desipramine by 79% and 241%, respectively; The Cmax and AUC of tamsulosin was increased by 60% when co-administered with mirabegron Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202611Orig1s000ClinPharmR.pdf#page=27 Page: 27.0 |
|||
| no | ||||
| no | ||||
| unlikely | ||||
| unlikely | ||||
| unlikely | ||||
| unlikely | ||||
| unlikely | ||||
| unlikely | ||||
| weak | ||||
| weak | ||||
| weak | ||||
| weak | yes (co-administration study) Comment: The Cmax and AUC of tamsulosin (a CYP2D6 and CYP3A4 substrate) was increased by 60% when co-administered with mirabegron Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202611Orig1s000ClinPharmR.pdf#page=30 Page: 30.0 |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | yes (co-administration study) Comment: Ketoconazole (inhibitor) increased the Cmax and AUC of mirabegron by 45% and 81%; rifampin (inducer) reduced the Cmax and AUC by 35% and 44%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202611Orig1s000ClinPharmR.pdf#page=27 Page: 27.0 |
|||
| minor | ||||
| minor | ||||
| minor | ||||
| no | ||||
| no | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | yes (co-administration study) Comment: Ketoconazole (inhibitor) increased the Cmax and AUC of mirabegron by 45% and 81%; rifampin (inducer) reduced the Cmax and AUC by 35% and 44%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202611Orig1s000ClinPharmR.pdf#page=27 Page: 27.0 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Effect of pre-contraction on β-adrenoceptor-mediated relaxation of rat urinary bladder. | 2009 Dec |
|
| Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder. | 2010 Dec |
|
| Mirabegron, a β₃-adrenoceptor agonist for the potential treatment of urinary frequency, urinary incontinence or urgency associated with overactive bladder. | 2010 Oct |
|
| The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. | 2013 May |
|
| Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
Patents
Sample Use Guides
25 mg once daily, with or without food. 25 mg is effective within 8 weeks. Based on individual efficacy and
tolerability, may increase dose to 50 mg once daily.
Route of Administration:
Oral
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| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
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NCI_THESAURUS |
C48149
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LIVERTOX |
NBK547887
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NDF-RT |
N0000185008
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WHO-VATC |
QG04BD12
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WHO-ATC |
G04BD12
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EMA ASSESSMENT REPORTS |
BETMIGA (AUTHORIZED: URINARY BLADDER, OVERACTIVE)
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| Code System | Code | Type | Description | ||
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DB08893
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8907
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9865528
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Mirabegron
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Mirabegron
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CHEMBL2095212
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100000126336
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N0000185007
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PRIMARY | Adrenergic beta3-Agonists [MoA] | ||
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m11690
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MVR3JL3B2V
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BETANIS
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PRIMARY | APPROVED JUNE 2011 | ||
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223673-61-8
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WW-31
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MVR3JL3B2V
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7445
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N0000182137
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PRIMARY | Cytochrome P450 2D6 Inhibitors [MoA] | ||
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SUB32690
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65349
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C90633
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1300786
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4382
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
