Fesoterodine is a medication used primarily to treat overactive bladder (OAB) symptoms such as urgency, frequency, and urinary incontinence. It belongs to a class of drugs called antimuscarinics or anticholinergics, which work by blocking the action of a neurotransmitter called acetylcholine in the bladder muscles, helping to relax these muscles and reduce bladder contractions.

A prodrug called fesoterodine (Toviaz) is activated to produce the active metabolite 5 HMT. (5-hydroxymethyl tolterodine). It blocks muscarinic receptors by acting as an anticholinergic medication. The medication is frequently prescribed to people who have frequent and urgent urination.

Fesoterodine (Toviaz) Uses:

• Overactive bladder:
  • It is indicated for the treatment of patients with an overactive bladder that may manifest as increased urinary urgency, frequency, or urge incontinence.

Fesoterodine (Toviaz) Dose in Adults

Fesoterodine (Toviaz) Dose in the treatment of Overactive bladder:

• When treating overactive bladder with fesoterodine, the usual dose is 4 milligrams once a day by mouth.
• If needed and tolerated, your doctor may increase the dose to 8 milligrams once daily.

Dosing modification for concurrent use of powerful CYP3A4 inhibitors (such as clarithromycin, itraconazole, and ketoconazole):

• If you're taking strong CYP3A4 inhibitors (like ketoconazole, itraconazole, or clarithromycin) alongside fesoterodine, the maximum dose is 4 milligrams once a day.
• This adjustment is made to avoid potential interactions between the medications.

Use in Children

Not indicated.

Fesoterodine (Toviaz) Pregnancy Risk Category: N

• Some animal reproduction studies have shown adverse effects associated with fesoterodine.
• This means that when the medication was tested on animals during pregnancy, there were negative outcomes observed.
• However, it's essential to understand that animal studies may not always accurately predict how a medication will affect human pregnancies.

Fesoterodine use during breastfeeding:

• The presence of fesoterodine in breast milk is not confirmed.
• According to the manufacturer, if you're considering breastfeeding while taking fesoterodine, you should weigh the potential risk of the infant being exposed to the medication against the benefits of breastfeeding for the infant and the benefits of the treatment for you, the mother.

Fesoterodine (Toviaz) Dose in Kidney Disease:

• If your creatinine clearance (CrCl) is equal to or greater than 30 milliliters per minute, there's no need to adjust the dosage of fesoterodine.
• If your creatinine clearance (CrCl) is less than 30 milliliters per minute, the maximum recommended dose of fesoterodine is 4 milligrams once daily. This adjustment is made because individuals with decreased kidney function may process the medication differently, so a lower dose is prescribed to minimize any potential risks.

Fesoterodine (Toviaz) Dose in Liver disease:

• For individuals with mild to moderate impairment, which corresponds to Child-Pugh class A or B liver impairment, no dosage adjustment is typically necessary when taking fesoterodine.
• In cases of severe impairment, corresponding to Child-Pugh class C, the use of fesoterodine is generally not recommended. This is because there hasn't been enough study to determine its safety and effectiveness in this population.

Common Side Effects of Fesoterodine (Toviaz):

• Gastrointestinal:
  • Xerostomia

Less Common Side Effects of Fesoterodine (Toviaz):

• Central nervous system:
  • Insomnia
• Cardiovascular:
  • Peripheral edema
• Dermatological:
  • Skin rash
• Gastrointestinal:
  • Constipation
  • Dyspepsia
  • Nausea
  • Abdominal Pain
• Endocrine & Metabolic:
  • Increased Gamma-Glutamyl Transferase
•  
• Genitourinary:
  • Urinary Tract Infection
  • Dysuria
  • Urinary Retention
• Hepatic:
  • Increased Serum ALT
• Ophthalmic:
  • Dry Eye Syndrome
• Neuromuscular & Skeletal:
  • Back Pain
• Respiratory:
  • Upper Respiratory Tract Infection
  • Cough
  • Dry Throat

Contraindications to Fesoterodine (Toviaz):

• If you're allergic to fesoterodine, tolterodine, or any part of the medicine, or if you've had problems like not being able to pee, issues with your stomach emptying, or uncontrolled narrow-angle glaucoma, you shouldn't take fesoterodine.
• These conditions could be made worse by the medication.

Warnings and precautions

Angioedema

• Angioedema, which involves swelling of the face, lips, tongue, or throat, has been reported in some people taking fesoterodine, even after their first dose.
• If you experience swelling of your tongue, throat, or voice box, you should stop taking fesoterodine right away and seek medical help.
• This swelling can be serious and needs immediate attention to prevent further complications.

CNS effects

• Anticholinergic medications like fesoterodine can sometimes lead to side effects in the central nervous system (CNS), such as feeling drowsy, dizzy, experiencing headaches, or having blurred vision.
• These effects may affect your ability to stay alert and perform tasks that require mental focus, such as driving or operating machinery.
• If you experience any of these symptoms, it's important to be cautious and consider reducing your dosage or stopping the medication altogether.

Heat prostration:

• Heat prostration, a condition where the body overheats due to high temperatures, can be a risk while taking fesoterodine, especially in hot weather or during exercise.
• It's essential to be cautious in these situations to avoid overheating and related complications.
• Stay hydrated, avoid excessive heat exposure, and be mindful of any signs of heat-related illness, such as dizziness, weakness, or excessive sweating.
• If you experience any of these symptoms, seek shade, rest, and drink fluids to cool down.

Bladder flow obstruction

• If you have bladder flow obstruction, it's important to use fesoterodine with caution.
• This medication could potentially increase the risk of urinary retention in such cases.
• Urinary retention is when you have trouble emptying your bladder completely.
• If you experience any symptoms like difficulty urinating or a weak urine stream while taking fesoterodine.

Gastrointestinal obstructive disorders:

• If you have conditions that affect the movement of your gastrointestinal tract or gastrointestinal obstructive disorders such as pyloric stenosis, it's important to use fesoterodine with caution.
• This medication may increase the risk of gastric retention, which is when food or liquid stays in your stomach longer than usual.
• If you experience symptoms like bloating, nausea, vomiting, or discomfort in your stomach while taking fesoterodine.

Glaucoma:

• If you have narrow-angle glaucoma that is under control with treatment, you should use fesoterodine with caution.
• While this medication can help with overactive bladder symptoms, it's essential to be aware that anticholinergic drugs like fesoterodine can potentially worsen narrow-angle glaucoma by increasing the pressure inside the eye.

Hepatic impairment

• Fesoterodine use is not recommended for individuals with severe hepatic impairment.
• This means that if your liver is severely impaired, it's best to avoid using fesoterodine because its safety and effectiveness haven't been studied in this specific group of people.

Myasthenia gravis:

• If you have myasthenia gravis, it's important to use fesoterodine with caution.
• Myasthenia gravis is a condition that causes muscle weakness, and medications like fesoterodine, which have anticholinergic effects, can potentially worsen muscle weakness in people with this condition.

Renal impairment

• If you have renal impairment (kidney problems), it's important to use fesoterodine with caution.
• Recommendation is adjusting the dosage if you have severe renal impairment, defined as having a creatinine clearance (CrCl) less than 30 milliliters per minute.
• This adjustment helps to ensure that the medication is safely metabolized and eliminated from your body.

Fesoterodine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Anticholinergic Effects:

• Fesoterodine can cause side effects like dry mouth, constipation, and dizziness.
• These effects happen because fesoterodine blocks certain signals in your body.

Renal Function:

• If you have kidney problems, your doctor will be cautious when prescribing fesoterodine.
• They may adjust your dosage, especially if your kidney function is severely impaired.

Hepatic Function:

• If your liver is not working well, it's best to avoid using fesoterodine.
• The safety and effectiveness of fesoterodine haven't been studied enough in people with severe liver problems.

Postvoid Residual (PVR) Urine Volume and Urinary Tract Infection (UTI) Prior to Therapy:

• Before starting fesoterodine, your doctor may check how much urine is left in your bladder after you pee (PVR).
• They may also check for urinary tract infections (UTIs).
• These checks help your doctor understand your bladder health before starting the medication.

How to administer Fesoterodine (Toviaz)?

• You can take fesoterodine with or without food.
• Just swallow the tablet whole; don't chew, crush, or break it into pieces.
• This helps the medication work properly and be absorbed by your body the right way.

Mechanism of action of Fesoterodine (Toviaz):

• Fesoterodine works as a prodrug, which means it changes into an active form in the body.
• Once absorbed, it transforms into a substance called 5-hydroxymethyl tolterodine (5-HMT).
• This active metabolite is responsible for fesoterodine's main action—it blocks certain receptors in the bladder known as muscarinic receptors.
• By acting as a competitive antagonist, 5-HMT inhibits these receptors, which are involved in controlling bladder contractions.
• This inhibition helps reduce symptoms like urgency and frequency by preventing the bladder from contracting too often or too strongly.
• In simple terms, fesoterodine helps calm down an overactive bladder by blocking the signals that tell it to contract excessively.

Absorption:

• Fesoterodine is well absorbed in the body.

Distribution:

• When given intravenously, the active metabolite 5-hydroxymethyl tolterodine (5-HMT) has a large volume of distribution (V) of 169 liters, indicating widespread distribution in the body.

Protein Binding:

• Approximately 50% of 5-HMT binds to proteins in the blood, primarily to albumin and alpha-acid glycoprotein.

Metabolism:

• Fesoterodine is quickly and extensively broken down into its active form, 5-hydroxymethyl tolterodine (5-HMT), by enzymes called esterases.
• 5-HMT undergoes further metabolism through the enzymes CYP2D6 and CYP3A4 to form inactive metabolites.

Bioavailability:

• The bioavailability of 5-HMT, the active metabolite, is around 52%.

Half-life Elimination:

• The elimination half-life of fesoterodine is approximately 7 hours.

Time to Peak, Plasma:

• The time taken to reach peak plasma levels of 5-HMT is approximately 5 hours. In individuals with poor CYP2D6 metabolism, the concentration of 5-HMT in the blood may be higher.

Excretion:

• Fesoterodine and its metabolites are primarily excreted in the urine, with about 70% eliminated this way (16% as 5-HMT and approximately 53% as inactive metabolites).
• A smaller portion is excreted in the feces (about 7%).

International Brand Names of Fesoterodine:

• Toviaz
• Avionol
• Grandocain
• Toviaz PR

Fesoterodine Brands Names in Pakistan:

Not available.