Fesoterodine (Toviaz) is a prodrug that is activated to the active metabolite 5 HMT (5-hydroxymethyl tolterodine). It acts as an anticholinergic drug that inhibits muscarinic receptors. The drug is commonly used to treat patients with symptoms of urinary urgency and frequency.
Fesoterodine (Toviaz) Uses:
-
Overactive bladder:
- It is indicated for the treatment of patients with 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:
- 4 mg orally once a day.
- The dose may be increased to 8 mg once a day based on the patients' clinical response and tolerability.
-
Dosing adjustment for concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin):
- The maximum recommended dose is 4 mg once a day.
Use in Children:
Not indicated.
Fesoterodine (Toviaz) Pregnancy Risk Category: N
- Animal reproduction studies have shown adverse pregnancy outcomes.
Fesoterodine use during breastfeeding:
- It is unknown if the drug will be excreted into breastmilk.
- Manufacturers recommend weighing the risks to the infant and the benefits for the mother during lactation.
Fesoterodine (Toviaz) Dose in Kidney Disease:
-
CrCl ≥30 mL/minute:
- Adjustment in the dose is not necessary.
-
CrCl <30 mL/minute:
- The maximum recommended dose is 4 mg once a day.
Fesoterodine (Toviaz) Dose in Liver disease:
-
Mild to moderate impairment (Child-Pugh class A or B):
- Adjustment in the dose is not necessary.
-
Severe impairment (Child-Pugh class C):
- It has not been studied in these patients. Avoid using the drug in patients with severe hepatic impairment.
Common Side Effects of Fesoterodine (Toviaz):
-
Gastrointestinal:
- Xerostomia
Less Common Side Effects of Fesoterodine (Toviaz):
-
Cardiovascular:
- Peripheral edema
-
Central nervous system:
- Insomnia
-
Dermatological:
- Skin rash
-
Endocrine & Metabolic:
- Increased Gamma-Glutamyl Transferase
-
Gastrointestinal:
- Constipation
- Dyspepsia
- Nausea
- Abdominal Pain
-
Genitourinary:
- Urinary Tract Infection
- Dysuria
- Urinary Retention
-
Hepatic:
- Increased Serum ALT
-
Neuromuscular & Skeletal:
- Back Pain
-
Ophthalmic:
- Dry Eye Syndrome
-
Respiratory:
- Upper Respiratory Tract Infection
- Cough
- Dry Throat
Contraindications to Fesoterodine (Toviaz):
- Allergic reactions to fesoterodine, tolterodine, or any component of the formulation;
- Urinary retention
- gastric retention
- Uncontrolled narrow-angle glaucoma
Warnings and precautions
-
Angioedema
- Reports of hypersensitivity reactions, including angioedema, have been made.
- If angioedema is detected in the tongue, hypopharynx or larynx, it must be treated immediately.
-
CNS effects
- Anticholinergic drugs can cause blurred vision, headaches, dizziness, drowsiness, and/or blurred eyes, which may lead to impairment of mental or physical abilities.
- Patients should be cautious about driving or operating heavy machinery.
- If the patient experiences neurological side effects, treatment may be stopped or reduced.
-
Heat prostration:
- Patients with heat-related conditions and people who engage in extreme outdoor activities should avoid using it.
- It may lead to elevated body temperatures, which can cause heat stroke or exhaustion.
-
Bladder flow obstruction
- Patients with symptoms of bladder obstruction or urinary retention should not take the drug.
-
Gastrointestinal obstructive disorders:
- Patients with gastrointestinal motility disorders should not take the drug.
- Patients with constipation, intestinal obstruction and pyloric dysfunction should avoid it.
-
Glaucoma:
- Patients with narrow-angle glaucoma, whether confirmed or suspected, should be cautious about using the drug.
-
Hepatic impairment
- Patients with severe hepatic impairment have not had it studied and should be cautious.
-
Myasthenia gravis:
- Patients suffering from myasthenia gravis should be careful when taking the drug.
-
Renal impairment
- Patients with impaired renal function may be advised to take the drug with caution.
- People with a CrCl lower than 30 ml/minute might need to adjust their dose.
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
Risk Factor C (Monitor therapy) |
|
| Acetylcholinesterase Inhibitors | May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. |
| Alcohol (Ethyl) | May enhance the CNS depressant effect of Fesoterodine. |
| Amantadine | May enhance the anticholinergic effect of Anticholinergic Agents. |
| Anticholinergic Agents | May enhance the adverse/toxic effect of other Anticholinergic Agents. |
| Aprepitant | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Bosentan | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Botulinum Toxin-Containing Products | May enhance the anticholinergic effect of Anticholinergic Agents. |
| Cannabinoid-Containing Products | Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. |
| Chloral Betaine | May enhance the adverse/toxic effect of Anticholinergic Agents. |
| Clofazimine | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| CYP2D6 Inhibitors | May increase serum concentrations of the active metabolite(s) of Fesoterodine. |
| CYP3A4 Inducers (Moderate) | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| CYP3A4 Inhibitors (Moderate) | May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
| Deferasirox | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Duvelisib | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Erdafitinib | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Erdafitinib | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Fosaprepitant | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Fosnetupitant | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Gastrointestinal Agents (Prokinetic) | Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). |
| Glucagon | Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. |
| Itopride | Anticholinergic Agents may diminish the therapeutic effect of Itopride. |
| Ivosidenib | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Larotrectinib | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Mianserin | May enhance the anticholinergic effect of Anticholinergic Agents. |
| Mirabegron | Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. |
| Netupitant | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Nitroglycerin | Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. |
| Opioid Agonists | Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. |
| Palbociclib | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Ramosetron | Anticholinergic Agents may enhance the constipating effect of Ramosetron. |
| Sarilumab | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Siltuximab | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Simeprevir | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Thiazide and Thiazide-Like Diuretics | Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. |
| Tocilizumab | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
| Topiramate | Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. |
Risk Factor D (Consider therapy modification) |
|
| CYP3A4 Inducers (Strong) | May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
| CYP3A4 Inhibitors (Strong) | May increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. |
| Dabrafenib | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
| Enzalutamide | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
| Lorlatinib | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
| MiFEPRIStone | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
| Mitotane | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
| Pitolisant | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. |
| Pramlintide | May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. |
| Secretin | Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. |
| St John's Wort | May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
| Stiripentol | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
Risk Factor X (Avoid combination) |
|
| Aclidinium | May enhance the anticholinergic effect of Anticholinergic Agents. |
| Cimetropium | Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. |
| Conivaptan | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Eluxadoline | Anticholinergic Agents may enhance the constipating effect of Eluxadoline. |
| Fusidic Acid (Systemic) | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Glycopyrrolate (Oral Inhalation) | Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). |
| Glycopyrronium (Topical) | May enhance the anticholinergic effect of Anticholinergic Agents. |
| Idelalisib | May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
| Ipratropium (Oral Inhalation) | May enhance the anticholinergic effect of Anticholinergic Agents. |
| Levosulpiride | Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. |
| Oxatomide | May enhance the anticholinergic effect of Anticholinergic Agents. |
| Potassium Chloride | Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. |
| Potassium Citrate | Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. |
| Revefenacin | Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. |
| Tiotropium | Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. |
| Umeclidinium | May enhance the anticholinergic effect of Anticholinergic Agents. |
Monitoring parameters:
- Monitor for anticholinergic effects such as dry mouth, dizziness, and constipation);
- Monitor renal functions;
- Liver function;
- Postvoid residual (PVR) urine volume and
- Urinary tract infection before treatment initiation.
How to administer Fesoterodine (Toviaz)?
- It may be administered without regard to meals.
- The tablets may be swallowed whole without breaking, crushing, or chewing the tablets.
Mechanism of action of Fesoterodine (Toviaz):
- Fesoterodine acts as a competitive inhibitor on muscarinic receptors.
- It is converted first to 5-hydroxymethyltolterodine (5HMT), which has antimuscarinic properties.
- It acts on the muscarinic receptors of the smooth muscles of your urinary bladder to relieve symptoms of urgency and frequency and inhibits them.
Absorption:
- Very well absorbed
Protein binding:
- Around 50% of 5-HMT (primarily albumin and alpha-acid glycoproteins) is bound to plasma proteins.
Metabolism:
- It is rapidly and extensively metabolized by nonspecific esterases to its active metabolite 5hydroxymethyl tolterodine (5-HMT);
- 5-HMT is further metabolized via CYP2D6 and CYP3A4 to inactive metabolites.
Bioavailability:
- 5-HMT: 52%
Half-life elimination:
- ~7 hours
Time to peak plasma:
- 5-HMT: about 5 hours;
- C higher in poor CYP2D6 metabolizers
Excretion:
- About 70% of the drug is excreted in urine (16% as 5-HMT, ~53% as inactive metabolites);
- feces (7%)
International Brand Names of Fesoterodine:
- Toviaz
- Avionol
- Grandocain
- Toviaz PR
Fesoterodine Brands Names in Pakistan:
No Brands Available in Pakistan.
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