DIQTA 1.0: Drug-Induced QT Prolongation Atlas

MIRABEGRON

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Ambiguous

Severity Score:1.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
The effect of multiple doses of MYRBETRIQ 50 mg, 100 mg and 200 mg once daily on QTc interval was evaluated in a randomized, placebo- and active-controlled (moxifloxacin 400 mg), four-treatment-arm, parallel crossover study in 352 healthy subjects. In a study with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on individual correction method (QTcI) was below 10 msec. For the 50 mg MYRBETRIQ dose group (the maximum approved dosage), the mean difference from placebo on QTcI interval at 4 to 5 hours post-dose was 3.7 msec (upper bound of the 95% CI 5.1 msec).
For the MYRBETRIQ 100 mg and 200 mg doses groups (dosages greater than the maximum approved dose and resulting in substantial multiples of the anticipated maximum blood levels at 50 mg), the mean differences from placebo in QTcI interval at 4 to 5 hours post-dose were 6.1 msec (upper bound of the 95% CI 7.6 msec) and 8.1 msec (upper bound of the 95% CI 9.8 msec), respectively. At the MYRBETRIQ 200 mg dose, in females, the mean effect was 10.4 msec (upper bound of the 95% CI 13.4 msec).
In this thorough QT study, MYRBETRIQ increased heart rate on ECG in a dose-dependent manner. Maximum mean increases from baseline in heart rate for the 50 mg, 100 mg, and 200 mg dose groups compared to placebo were 6.7 beats per minutes (bpm), 11 bpm, and 17 bpm, respectively. In the clinical efficacy and safety studies, the change from baseline in mean pulse rate for MYRBETRIQ 50 mg was approximately 1 bpm. In this thorough QT study, MYRBETRIQ also increased blood pressure in a dose-dependent manner (see Effects on Blood Pressure).
[Effects on Blood Pressure]
In a study of 352 healthy subjects assessing the effect of multiple daily doses of 50 mg, 100 mg, and 200 mg of MYRBETRIQ for 10 days on the QTc interval, the maximum mean increase in supine systolic blood pressure (SBP)/diastolic blood pressure (DBP) at the maximum recommended dose of 50 mg was approximately 4.0/1.6 mm Hg greater than placebo. The 24-hour average increases in SBP compared to placebo were 3.0, 5.5, and 9.7 mm Hg at MYRBETRIQ doses of 50 mg, 100 mg and 200 mg, respectively. Increases in DBP were also dose-dependent, but were smaller than SBP.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24058

Other ADRs

34758

38346829

Odds Ratio = 1.56

Drug Property Information

ATC Code(s):

G04BD12 - mirabegron

G04BD1 -
G04BD - Urinary antispasmodics
G04B - "OTHER UROLOGICALS, INCL. ANTISPASMODICS"
G04 - UROLOGICALS
G - GENITO URINARY SYSTEM AND SEX HORMONES

Active Ingredient:MIRABEGRON

Active Ingredient UNII:MVR3JL3B2V

Drugbank ID:DB08893

PubChem Compound:9865528

CTD ID:C520025

PharmGKB:

CAS Number:223673-61-8

Dosage Form(s):tablet, film coated, extended release

Route(s) Of Administrator:oral

Daily Dose:

50.0 mg/day G04BD12

Chemical Structure:

SMILE Code:
NC1=NC(CC(=O)NC2=CC=C(CCNC[C@H](O)C3=CC=CC=C3)C=C2)=CS1

Reference

1: Cardiovascular effects of antimuscarinic agents and beta3-adrenergic receptor agonist for the treatment of overactive bladder.

[Rosa Gian Marco,Baccino Danilo,Valbusa Alberto,Scala Carolina,Barra Fabio,Brunelli Claudio,Ferrero Simone]
Expert Opin Drug Saf,2018 May;17(5):487-497. PMID: 29542337

2: Cardiovascular safety in refractory incontinent patients with overactive bladder receiving add-on mirabegron therapy to solifenacin (BESIDE).

[Drake Marcus J,MacDiarmid Scott,Chapple Christopher R,Esen Adil,Athanasiou Stavros,Cambronero Santos Javier,Mitcheson David,Herschorn Sender,Siddiqui Emad,Huang Moses,Stoelzel Matthias]
Int J Clin Pract,2017 May;71(5):e12944. PMID: 28419650

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