Usage
Fesoterodine fumarate is prescribed for the treatment of overactive bladder (OAB) in adults and neurogenic detrusor overactivity (NDO) in children 6 years and older. OAB is characterized by symptoms of urinary urgency, frequency, and urge incontinence. NDO refers to increased bladder contractions due to neurological conditions like spinal cord injury or multiple sclerosis.
It is pharmacologically classified as a competitive muscarinic receptor antagonist, specifically targeting M3 receptors in the bladder.
Fesoterodine’s mechanism of action involves blocking the binding of acetylcholine to M3 receptors in the bladder’s smooth muscle. This inhibits detrusor muscle contractions, reducing urinary urgency, frequency, and incontinence episodes.
Alternate Names
The active metabolite of fesoterodine is 5-hydroxymethyltolterodine (5-HMT). The drug is commonly marketed under the brand name Toviaz.
How It Works
Pharmacodynamics: Fesoterodine is a prodrug metabolized primarily by CYP3A4 to its active metabolite, 5-HMT. 5-HMT competitively binds to muscarinic M3 receptors in the detrusor muscle of the bladder, reducing its contractility and decreasing OAB symptoms.
Pharmacokinetics: Fesoterodine is rapidly absorbed after oral administration, reaching peak plasma concentrations within 1 to 6 hours for fesoterodine and 3 to 8 hours for 5-HMT. It has good oral bioavailability. 5-HMT is primarily eliminated through hepatic metabolism, with a small amount excreted renally. The elimination half-life of 5-HMT is about 7 hours.
Mode of Action: 5-HMT acts as a competitive inhibitor at muscarinic M3 receptors, preventing acetylcholine from binding and stimulating detrusor muscle contraction. This decreases bladder pressure and the sensation of urgency.
Receptor Binding/Enzyme Inhibition: Fesoterodine itself has little to no affinity for muscarinic receptors. Its active metabolite, 5-HMT, selectively binds to M3 receptors in the bladder.
Elimination Pathways: Fesoterodine is primarily metabolized in the liver by CYP3A4 enzymes, and 5-HMT is further metabolized by other enzymes. A small portion of the drug is eliminated unchanged via renal excretion.
Dosage
Standard Dosage
Adults:
The recommended initial dose is 4 mg orally once daily. The dose may be increased to 8 mg orally once daily based on individual response and tolerability.
Children (6 years and older):
- Weighing 25 kg up to 35 kg: 4 mg orally once daily. The dose may be increased to 8 mg orally once daily.
- Weighing more than 35 kg: 4 mg orally once daily initially. After one week, the dose may be increased to 8 mg orally once daily.
Special Cases:
- Elderly Patients: No dosage adjustment is generally recommended.
- Patients with Renal Impairment:
- Mild to moderate (CrCl ≥ 30 mL/min): No dosage adjustment necessary.
- Severe (CrCl < 30 mL/min): Maximum dose of 4 mg once daily.
- Patients with Hepatic Dysfunction: Use with caution. Dose adjustment may be necessary. Patients with severe hepatic impairment should avoid Fesoterodine.
- Patients with Comorbid Conditions: Use with caution in patients with gastrointestinal disorders or bladder outlet obstruction.
Clinical Use Cases
Fesoterodine is not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is limited to OAB and NDO management.
Dosage Adjustments
Dosage adjustments may be required in patients with renal impairment, hepatic impairment, or those taking potent CYP3A4 inhibitors (e.g., ketoconazole). Concomitant use with potent CYP3A4 inducers is not recommended.
Side Effects
Common Side Effects:
Dry mouth, constipation, blurred vision, dizziness, drowsiness, dyspepsia, urinary tract infection, abdominal pain, nausea, headache.
Rare but Serious Side Effects:
Angioedema (including swelling of face, lips, tongue, and/or larynx), anaphylaxis, urinary retention, severe allergic reactions, QT prolongation.
Long-Term Effects:
Limited data are available on long-term effects. Chronic complications are usually related to continued side effects like dry mouth or constipation.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include angioedema, urinary retention, and severe allergic reactions requiring immediate medical attention.
Contraindications
- Urinary retention
- Gastric retention
- Uncontrolled narrow-angle glaucoma
- Hypersensitivity to fesoterodine, its ingredients, or tolterodine
- Myasthenia Gravis
Drug Interactions
- Potent CYP3A4 Inhibitors: Reduce Fesoterodine dose.
- Potent CYP3A4 Inducers: Co-administration not recommended.
- Anticholinergic Drugs: May enhance anticholinergic effects.
- Drugs that prolong the QT interval: Use with caution.
- Potassium-lowering diuretics: May enhance hypokalemia.
Pregnancy and Breastfeeding
- Pregnancy: Fesoterodine should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: It is unknown if fesoterodine is excreted in human milk. Breastfeeding is not recommended during treatment.
Drug Profile Summary
- Mechanism of Action: Competitive muscarinic M3 receptor antagonist in the bladder.
- Side Effects: Dry mouth, constipation, blurred vision, dizziness, angioedema (rare).
- Contraindications: Urinary retention, gastric retention, narrow-angle glaucoma.
- Drug Interactions: CYP3A4 inhibitors/inducers, anticholinergics, QT prolonging drugs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 4-8 mg once daily; Children (6+ years, >25 kg): 4-8 mg once daily.
- Monitoring Parameters: Monitor for urinary retention, side effects, and response to therapy.
Popular Combinations
Fesoterodine is typically used as monotherapy. Combinations with other OAB drugs are not routinely recommended.
Precautions
- Assess for pre-existing medical conditions like urinary retention, gastric retention, and glaucoma.
- Monitor renal and hepatic function.
- Caution patients about potential side effects and impact on driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fesoterodine Fumarate?
A: Adults: Initial dose is 4 mg orally once daily, may be increased to 8 mg daily. Children (6+ years, >25 kg): 4-8 mg orally once daily depending on weight. Dose adjustments are necessary in patients with renal impairment and concomitant use of certain medications.
Q2: What is the mechanism of action of Fesoterodine?
A: Fesoterodine is a prodrug converted to 5-HMT, which acts as a competitive antagonist of M3 muscarinic receptors in the bladder, relaxing the detrusor muscle and decreasing bladder contractions.
Q3: What are the common side effects of Fesoterodine?
A: Common side effects include dry mouth, constipation, blurred vision, dizziness, and drowsiness.
Q4: What are the contraindications to using Fesoterodine?
A: Contraindications include urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and hypersensitivity to fesoterodine or tolterodine.
Q5: How should Fesoterodine be administered?
A: Administer orally once daily, with or without food. Swallow the tablet whole; do not crush or chew.
Q6: What are the significant drug interactions with Fesoterodine?
A: Potent CYP3A4 inhibitors (e.g., ketoconazole) require dosage reductions. Potent CYP3A4 inducers (e.g., rifampin) are not recommended for co-administration. Concomitant use with other anticholinergic medications can exacerbate anticholinergic effects.
Q7: Can Fesoterodine be used during pregnancy or breastfeeding?
A: Fesoterodine is generally not recommended during pregnancy or breastfeeding due to limited safety data.
Q8: How should I monitor patients on Fesoterodine?
A: Monitor patients for side effects, including dry mouth, constipation, blurred vision, and urinary retention. Periodically assess OAB symptoms and renal function.
Q9: What should patients know about taking Fesoterodine?
A: Patients should be advised to drink plenty of fluids to avoid dehydration, be aware of potential side effects like dry mouth and constipation, and avoid driving or operating machinery if they experience dizziness or blurred vision. They should also inform their doctor about all medications they are taking.
