Fesoterodine

Uses

Fesoterodine is an antimuscarinic agent used in the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

For the treatment of overactive bladder (with symptoms of urinary frequency, urgency, or urge incontinence).

Fesoterodine is also used to associated treatment for these conditions: Urinary Bladder, Overactive

How Fesoterodine works

Fesoterodine, once converted to its active metabolite, 5-hydroxymethyltolterodine, acts as a competitive antagonists at muscarinic receptors. This results in the inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder.

Toxicity

Rat, Oral, LD50: ~ 681 mg/kg Mouse, Oral, LD50: ~ 316 mg/kg Rat, Intravenous, NOAEL: 10 mg/kg Mouse, Intravenous, NOAEL: 10 mg/kg

Food Interaction

• Take with or without food.

[Moderate] MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 such as grapefruit juice may increase the plasma concentrations of fesoterodine's active metabolite, 5-hydroxymethyl tolterodine, which is partially metabolized by the isoenzyme.

The possibility of prolonged and

Because 5-hydroxymethyl tolterodine is also metabolized by CYP450 2D6, the clinical significance of the interaction may be greater in patients who are CYP450 2D6-deficient, or so-called poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent) who may rely more on the 3A4 metabolic pathway for clearance of the drug.

MANAGEMENT: Caution is advised if fesoterodine is administered with grapefruit or grapefruit juice.

Patients should be advised to notify their physician if they experience potential adverse effects of fesoterodine such as irregular heartbeat, blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, gastrointestinal upset, or constipation.

Fesoterodine Drug Interaction

Moderate: tolterodine, fentanylMinor: modafinilUnknown: calcium / vitamin d, multivitamin with minerals, heparin, potassium chloride, lithium, loteprednol ophthalmic, pregabalin, metoprolol, metoprolol, pramipexole, acetaminophen, vitamin a topical, bioflavonoids, sotalol, cyanocobalamin, ascorbic acid, cholecalciferol

Fesoterodine Disease Interaction

Major: GI retention, narrow-angle glaucoma, urinary retentionModerate: hepatic dysfunction, myasthenia gravis, renal dysfunction

Volume of Distribution

IV, 5-HMT: 169 L

Elimination Route

Tmax (5-HMT): 5 hours post-adminitration of fesoterodine. AUC (0,∞)= 49.5 ng·h/ ml
Bioavailability, 5-HMT = 52%

Half Life

7-8 hours for the active metabolite 5-hydroxymethyl tolterodine

Clearance

5-HMT, healthy subjects: 14.4 L/h 5-HMT is also secreted into the nephron.

Elimination Route

Renal: 70% of fesoterodine was recovered in urine as 5-HMT; 35% carboxy metabolite; 18% carboxy-N-desisopropylmetabolite, and 1% N-desisopropyl metabolite Fecal: 7% Hepatic: fesoterodine elimination via CYP2D6 and CYP3A4

Innovators Monograph

You find simplified version here Fesoterodine