Fesoterodine

Oral
Overactive bladder

Patient taking moderate CYP3A4 inhibitors (e.g. erythromycin, fluconazole, diltiazem, verapamil, grapefruit juice):
Renal Impairment: Mild (GFR 50-80 mL/min) to moderate (GFR 30-50 mL/min): 4 mg daily.
Hepatic Impairment: Mild: 4 mg daily.

CrCl (mL/min)	Dosage
<30	Max: 4 mg daily.

Severe (Child Pugh C): Contraindicated.

May be taken with or without food. Swallow whole, do not chew/divide/crush.

Urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, myasthenia gravis, severe ulcerative colitis, toxic megacolon. Severe hepatic impairment (Child Pugh C). Concomitant use of potent CYP3A4 inhibitors in patients with renal or hepatic impairment.

Patient with bladder flow obstruction (e.g. benign prostatic hyperplasia), decreased gastrointestinal motility (e.g. severe constipation), gastrointestinal obstructive disorders (e.g. pyloric stenosis), GERD, controlled or treated narrow-angle glaucoma, risk for QT prolongation (e.g. hypokalaemia, bradycardia), pre-existing cardiac diseases (e.g. MI, arrhythmia, CHF), autonomic neuropathy. Renal and mild to moderate hepatic impairment. Pregnancy and lactation.

Significant: Angioedema, CNS effects (e.g. drowsiness, dizziness, headache, blurred vision), heat prostration.
Eye disorders: Dry eye syndrome.
Gastrointestinal disorders: Dry mouth, constipation.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection.

PO: C

This drug may cause dizziness, somnolence and blurred vision, if affected, do not drive or operate machinery.

Monitor for anticholinergic effects (e.g. dry mouth, constipation, dizziness), renal function, LFT, postvoid residual (PVR) urine volume and UTI prior to treatment initiation.

Symptoms: Severe anticholinergic effects. Management: Symptomatic and supportive treatment. Monitor ECG. Perform gastric lavage and administer activated charcoal. Hallucinations and severe excitation may be treated with physostigmine; benzodiazepines for convulsions and pronounced excitation; betablockers for tachycardia; pilocarpine eye drops for mydriasis.

Increased therapeutic and side effects (e.g. constipation, dry mouth, drowsiness, urinary retention) with other antimuscarinics and anticholinergics (e.g. amantadine, TCAs, certain neuroleptics). May reduce efficacy of metoclopramide. Increased plasma concentration with moderate (e.g. fluconazole, erythromycin) to potent (e.g. ketoconazole, clarithromycin) CYP3A4 inhibitors. Decreased plasma concentration with CYP3A4 inducers (e.g. carbamazepine, rifampicin).

Decreased plasma concentration with St. John’s Wort. Increased plasma concentration with grapefruit juice.

Description:
Mechanism of Action: Fesoterodine acts as a prodrug and is converted to its active metabolite, 5-hydroxymethyl tolterodine (5-HMT), which is responsible for its antimuscarinic activity and acts as a competitive antagonist of muscarinic receptors. It blocks the receptors in the bladder thus preventing symptoms of urgency and frequency.
Pharmacokinetics:
Absorption: Well absorbed from gastrointestinal tract. Bioavailability: 52% (5-HMT). Time to peak plasma concentration: Approx 5 hours (5-HMT).
Distribution: Volume of distribution: 169 L (5-HMT). Plasma protein binding: Approx 50%, mainly to albumin and alpha₁-acid glycoprotein (5-HMT).
Metabolism: Rapidly and extensively hydrolysed to active metabolite, 5-HMT by non-specific esterases; further metabolised in the liver by CYP2D6 and CYP3A4 to inactive metabolites, carboxy-N-desisopropyl and N-desisopropyl.
Excretion: Via urine (approx 70%; 16% as 5-HMT, approx 53% as inactive metabolites); faeces (7%). Elimination half-life: Approx 7 hours.

Source: National Center for Biotechnology Information. PubChem Database. Fesoterodine, CID=6918558, https://pubchem.ncbi.nlm.nih.gov/compound/6918558#section=Structures (accessed on June 26, 2020)

Store between 20-25°C. Protect from moisture.

Drugs for Bladder & Prostate Disorders

G04BD11 - fesoterodine ; Belongs to the class of urinary antispasmodics.

Anon. Fesoterodine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 18/06/2020.

Anon. Fesoterodine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/06/2020.

Buckingham R (ed). Fesoterodine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/06/2020.

Fesoterodine Fumarate Tablet, Film Coated, Extended Release (Cadila Healthcare Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/06/2020.

Joint Formulary Committee. Fesoterodine fumarate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/06/2020.

Toviaz (Aesica Pharmaceuticals GmbH). MIMS Malaysia. http://www.mims.com/malaysia. Accessed 09/06/2020.