DIQTA 1.0: Drug-Induced QT Prolongation Atlas

FESOTERODINE FUMARATE

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

ADVERSE REACTIONS
Clinical Trials Experience
In Phase 2 and 3 placebo-controlled trials combined, the incidences of serious adverse events in patients receiving placebo, Toviaz 4 mg, and Toviaz 8 mg were 1.9%, 3.5%, and 2.9%, respectively. All serious adverse events were judged to be not related or unlikely to be related to study medication by the investigator, except for four patients receiving Toviaz who reported one serious adverse event each: angina, chest pain, gastroenteritis, and QT prolongation on ECG.
Patients also received Toviaz for up to three years in open-label extension phases of one Phase 2 and two Phase 3 controlled trials. In all open-label trials combined, 857, 701, 529, and 105 patients received Toviaz for at least 6 months, 1 year, 2 years, and 3 years, respectively. The adverse events observed during long-term, open-label studies were similar to those observed in the 12-week, placebo-controlled studies, and included dry mouth, constipation, dry eyes, dyspepsia, and abdominal pain. Similar to the controlled studies, most adverse events of dry mouth and constipation were mild to moderate in intensity. Serious adverse events, judged to be at least possibly related to study medication by the investigator and reported more than once during the open-label treatment period of up to 3 years, included urinary retention (3 cases), diverticulitis (3 cases), constipation (2 cases), irritable bowel syndrome (2 cases), and electrocardiogram QT corrected interval prolongation (2 cases).
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology: The effect of fesoterodine 4 mg and 28 mg on the QT interval was evaluated in a double-blind, randomized, placebo- and positive-controlled (moxifloxacin 400 mg once a day) parallel trial with once-daily treatment over a period of 3 days in 261 male and female subjects aged 44 to 65 years. Electrocardiographic parameters were measured over a 24-hour period at pre-dose, after the first administration, and after the third administration of study medication. Fesoterodine 28 mg was chosen because this dose, when administered to CYP2D6 extensive metabolizers, results in an exposure to the active metabolite that is similar to the exposure in a CYP2D6 poor metabolizer receiving fesoterodine 8 mg together with CYP3A4 blockade. Corrected QT intervals (QTc) were calculated using Fridericia's correction and a linear individual correction method. Analyses of 24-hour average QTc, time-matched baseline-corrected QTc, and time-matched placebo-subtracted QTc intervals indicate that fesoterodine at doses of 4 and 28 mg/day did not prolong the QT interval. The sensitivity of the study was confirmed by positive QTc prolongation by moxifloxacin.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24086

Other ADRs

11944

38369643

Odds Ratio = 0.801

Drug Property Information

ATC Code(s):

G04BD11 - fesoterodine fumarate

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

Active Ingredient:FESOTERODINE FUMARATE

Active Ingredient UNII:EOS72165S7

Drugbank ID:DB06702

PubChem Compound:6918558

CTD ID:C526675

PharmGKB:PA165958376

CAS Number:286930-02-7

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

Route(s) Of Administrator:oral

Daily Dose:

4.0 mg/day G04BD11

Chemical Structure:

SMILE Code:
CC(C)N(CC[C@H](C1=CC=CC=C1)C1=C(OC(=O)C(C)C)C=CC(CO)=C1)C(C)C

Reference

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