FESOTERODINE FUMARATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Competitive antagonist of muscarinic acetylcholine receptors (M1, M2, M3, M4, M5), with highest affinity for M3 receptors; reduces detrusor muscle contractions and bladder overactivity.
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4; also hydrolyzed by esterases to active metabolite 5-hydroxymethyl tolterodine (5-HMT). Major metabolite is 5-HMT, which also contributes to therapeutic effect. |
| Excretion | Primary route is renal (70% of administered dose as metabolites, 7% as unchanged drug). Hepatic metabolism with biliary/fecal elimination accounts for ~23% (primarily via CYP2D6 and CYP3A4).<|im_end|> |
| Half-life | Terminal elimination half-life is approximately 7 hours (range 5–10 hours) for the active metabolite (5-hydroxymethyl tolterodine, 5-HMT). The parent drug fesoterodine has a very short half-life (<1 hour) and is rapidly hydrolyzed to 5-HMT. Clinical context: steady-state achieved within 2–4 days of b.i.d. dosing. |
| Protein binding | Fesoterodine: ~89% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). Active metabolite 5-HMT: ~50% bound to plasma proteins. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) for active metabolite 5-HMT is approximately 169 L (2.2 L/kg for a 70 kg adult). Clinical meaning: extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability of fesoterodine is approximately 52% (range 40–60%) for the extended-release formulation. Absolute bioavailability is not determined due to rapid presystemic hydrolysis; reported as that of the active metabolite. No other routes are indicated. |
| Onset of Action | Oral immediate-release formulation: 30–60 minutes for detectable effect; 1–2 weeks for maximal therapeutic benefit. No other routes are clinically approved. |
| Duration of Action | Dosing interval is every 12 hours (b.i.d.) for extended-release (ER) formulation. Duration of action per dose is approximately 12 hours, with sustained antimuscarinic effects throughout the dosing interval. Clinical note: peak effect on bladder capacity occurs at 4–6 hours post-dose. |
4 mg orally once daily; may be increased to 8 mg once daily based on tolerability.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | eGFR 30-89 mL/min: no adjustment; eGFR 15-29 mL/min: maximum dose 4 mg daily; eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: maximum dose 4 mg daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric patients under 18 years of age; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor renal function and anticholinergic side effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause urinary retention and blurred vision.
| Breastfeeding | It is not known if fesoterodine or its active metabolite (5-hydroxymethyl tolterodine) is excreted in human milk. In lactating rats, radiolabeled drug was detected in milk. The M/P ratio is unknown. Caution should be exercised when administered to a nursing woman; consider the developmental and health benefits of breastfeeding and the mother's clinical need. |
| Teratogenic Risk | Fesoterodine fumarate is classified as FDA Pregnancy Category C. Animal studies have shown fetal toxicity (reduced fetal weight, skeletal anomalies) at doses 2-5 times the maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women. First trimester: Potential risk based on animal data; avoid unless clearly needed. Second and third trimesters: Limited data; may cause fetal anticholinergic effects (e.g., tachycardia, urinary retention). Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Common Effects | Dry mouth |
| Serious Effects |
["Urinary retention","Gastric retention","Uncontrolled narrow-angle glaucoma","Hypersensitivity to fesoterodine fumarate or any component"]
| Precautions | ["Use with caution in patients with clinically significant bladder outlet obstruction due to risk of urinary retention.","Use with caution in patients with gastrointestinal obstructive disorders (e.g., pyloric stenosis) due to risk of gastric retention.","Use with caution in patients with decreased gastrointestinal motility (e.g., severe constipation, ulcerative colitis, myasthenia gravis).","Use with caution in patients with narrow-angle glaucoma (controlled); contraindicated in uncontrolled narrow-angle glaucoma.","May cause angioedema requiring immediate treatment.","May cause drowsiness and blurred vision; avoid driving or hazardous activities.","Adjust dose in patients with severe renal impairment (CrCl <30 mL/min) or moderate hepatic impairment (Child-Pugh B); not recommended in severe hepatic impairment.","CYP2D6 poor metabolizers or patients on potent CYP3A4 inhibitors may require dose reduction."] |
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| Fetal Monitoring | Monitor maternal heart rate and blood pressure for anticholinergic effects (tachycardia, hypertension). Assess for signs of urinary retention or gastrointestinal obstruction. Fetal monitoring: Standard prenatal care; consider fetal growth ultrasound if used for prolonged periods due to potential for reduced placental perfusion. |
| Fertility Effects | Animal studies have shown no significant effects on fertility or reproductive performance in male or female rats at doses up to 10 mg/kg/day. However, anticholinergic effects may theoretically impair sexual function (erectile dysfunction, decreased libido) which could affect fertility indirectly. |