Toviaz

Toviaz (Fesoterodine) is a medicine used to treat symptoms of overactive bladder (OAB). OAB is characterized by frequent urination, strong and sudden urges, and possible urinary incontinence.

Fesoterodine is an antimuscarinic (anticholinergic) agent. It blocks muscarinic receptors in the bladder, which causes the detrusor muscle of the bladder to relax. This reduces the frequency and force of bladder contractions, improving urinary control and reducing the frequency and intensity of urge.

Indications Toviaza

1. Frequent urination: Increased frequency of urination during the day and at night (pollakiuria).
2. Urgency: A strong and sudden urge to urinate that is difficult to control.
3. Urge urinary incontinence: Involuntary loss of urine resulting from an urgent urge to urinate.

Fesoterodine helps reduce the frequency and intensity of the urge to urinate, improving urinary control and quality of life for patients with overactive bladder symptoms.

Release form

1. 4 mg tablets: extended-release, film-coated tablets.
2. 8 mg tablets: extended-release, film-coated tablets.

Pharmacodynamics

1. Muscarinic receptor antagonism: Fesoterodine is a muscarinic receptor antagonist. The drug blocks muscarinic receptors (M3 receptors) in the smooth muscle of the bladder. These receptors are responsible for muscle contraction when stimulated by acetylcholine.
2. Reducing bladder contractions: By blocking M3 receptors, fesoterodine reduces spontaneous and involuntary bladder contractions. This leads to a decrease in the frequency and strength of the urge to urinate.
3. Increasing bladder capacity: The drug helps increase bladder capacity, which allows you to hold more urine before you need to urinate. This reduces the frequency of urination and improves urinary control.
4. Reduced urgency: Fesoterodine helps reduce urinary urgency, which improves the quality of life of patients with overactive bladder.
5. Conversion to active metabolite: Fesoterodine is a prodrug that is converted in the body to the active metabolite 5-hydroxymethyltolterodine (5-HMT). This active metabolite has an antagonistic effect on muscarinic receptors.
6. Peripheral action: Fesoterodine acts primarily at peripheral muscarinic receptors in the bladder, which minimizes central side effects such as confusion and hallucinations.

Pharmacokinetics

1. Absorption:

   • After oral administration, fesoterodine is rapidly hydrolyzed by nonspecific esterases to its active metabolite 5-hydroxymethyltolterodine (5-HMT).
   • The maximum concentration of the active metabolite in the blood plasma is reached approximately 2 hours after administration.

2. Distribution:

   • The volume of distribution of the active metabolite (5-HMT) is approximately 169 liters.
   • 5-HMT binds to plasma proteins by 50%.

3. Metabolism:

   • After hydrolysis to the active metabolite 5-HMT, it is further metabolized in the liver with the participation of the enzymes CYP2D6 and CYP3A4.
   • People who are slow metabolizers via CYP2D6 may have higher concentrations of the active metabolite.

4. Excretion:

   • The main route of elimination of the active metabolite and its metabolites is through the kidneys.
   • Approximately 70% of the dose is excreted in the urine, of which about 16% is as unchanged 5-HMT.
   • Approximately 7% is excreted in feces.
   • The half-life of the active metabolite is about 7-8 hours.

5. Special populations:

   • In patients with renal failure, the concentration of the active metabolite may increase.
   • Patients with liver failure may experience changes in metabolism, which also requires dosage adjustment.

Dosing and administration

Recommended dosage:

For adults:

• Starting dose: It is generally recommended to start with 4 mg once daily.
• Maintenance dose: Depending on the response to treatment and tolerability of the drug, the doctor may increase the dose to 8 mg once a day.

Method of application:

• Taking tablets: Tablets should be taken orally with plenty of water.
• Time of administration: Tablets can be taken regardless of meals.
• Regularity: The drug is taken once a day, preferably at the same time every day to maintain a stable level of the drug in the body.

Special instructions:

• Missed dose: If you miss a dose, take it as soon as possible. If it is already time for your next dose, do not take a double dose to make up for the missed dose. Just continue taking it as usual.
• Overdose: In case of overdose, seek medical attention immediately. Symptoms of overdose may include dry mouth, rapid heartbeat, dizziness, and blurred vision.

Special categories of patients:

• Patients with Renal Impairment: For patients with mild or moderate renal impairment, dosage adjustment may be required. In patients with severe renal impairment, it is not recommended to exceed a dose of 4 mg per day.
• Patients with Hepatic Impairment: For patients with moderate hepatic impairment, it is also recommended not to exceed a dose of 4 mg per day. The drug is not recommended for patients with severe liver failure.
• Elderly patients: For elderly patients, the dosage is usually the same as the standard dosage, but their general health and the possibility of side effects should be taken into account.

Use Toviaza during pregnancy

1. Consultation with your doctor: You should consult your doctor before taking fesoterodine during pregnancy. The doctor will assess the need to use the drug, taking into account the mother’s health and possible risks to the fetus.
2. Benefit vs. Risk: The use of fesoterodine during pregnancy can only be justified in cases where the potential benefits to the mother outweigh the possible risks to the fetus.
3. First trimester: Particular attention should be paid to the use of medications in the first trimester of pregnancy, when the formation of the main organs and systems of the fetus occurs. During this period, it is especially important to avoid unnecessary use of medications.
4. Alternatives: If possible, consider alternative treatments or drugs with better established safety for pregnant women.

Contraindications

1. Hypersensitivity: The drug is contraindicated in people with a known hypersensitivity or allergic reaction to fesoterodine, its active metabolite (5-hydroxymethyltolterodine), or any other components of the drug.
2. Angle-closure glaucoma: Toviaz may increase intraocular pressure and is therefore contraindicated in patients with uncontrolled angle-closure glaucoma.
3. Tachyarrhythmias: Fesoterodine may worsen tachyarrhythmias and should be avoided in patients with this condition.
4. Myasthenia gravis: The drug is contraindicated in patients with myasthenia gravis, as it may worsen their condition.
5. Severe renal failure: Toviaz is contraindicated in severe renal failure (creatinine clearance
6. Severe hepatic impairment: The drug is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) due to the risk of accumulation and toxicity.
7. Gastrointestinal obstruction: Toviaz is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus, due to the risk of worsening the condition.
8. Severe ulcerative colitis and toxic megacolon: The drug is contraindicated in severe ulcerative colitis and toxic megacolon, as anticholinergic effects may aggravate these conditions.
9. Urethral constriction and urinary retention: Toviaz is contraindicated in patients with urinary retention or significant urethral constriction as it may aggravate these conditions.

Side effects Toviaza

1. Very common side effects (more than 10%):

   • Dry mouth.

2. Common side effects (1-10%):

   • Constipation.
   • Dry eyes.
   • Headache.
   • Fatigue.
   • Dyspepsia (digestive disorder).
   • Dry skin.
   • Rapid heartbeat (tachycardia).
   • Blurred vision.

3. Infrequent side effects (0.1-1%):

   • Urinary tract infections.
   • Difficulty urinating (urinary retention).
   • Stomach pain.
   • Dizziness.
   • Drowsiness.
   • Nausea.
   • Sinusitis.
   • Flu-like symptoms.

4. Rare side effects (0.01-0.1%):

   • Allergic reactions such as skin rash or itching.
   • Anaphylactic reactions.
   • Angioedema.
   • Confusion.
   • Hallucinations.
   • Heart rhythm disturbances (eg, QT prolongation, arrhythmias).

5. Very rare side effects (less than 0.01%):

   • Psychiatric disorders (eg, anxiety, depression).
   • Convulsions.
   • Worsening of glaucoma symptoms.
   • Difficulty breathing.

Overdose

1. Severe dry mouth
2. Difficulty urinating (acute urinary retention)
3. Dilated pupils (mydriasis)
4. Tachycardia (rapid heartbeat)
5. Arrhythmias
6. Severe dizziness
7. Excitement and restlessness
8. Convulsions
9. Skin redness
10. Hyperthermia (increased body temperature)
11. Severe visual impairment
12. Confusion, hallucinations and delirium

Treatment of overdose

Treatment of fesoterodine overdose is aimed at eliminating symptoms and maintaining vital functions. Measures may include:

1. Respiratory and cardiovascular support: Administer oxygen, maintain blood pressure, monitor cardiac activity, and ensure adequate breathing.
2. Gastric lavage: May be useful if you have recently taken a large amount of the drug.
3. Activated charcoal: Use of activated charcoal may help reduce the absorption of the drug in the gastrointestinal tract if some time has passed after administration.
4. Symptomatic therapy: Treat symptoms such as tachycardia and seizures as needed. This may include the use of beta blockers to control tachycardia or anticonvulsants for seizures.
5. Antidotes: In some cases, physostigmine may be used to counteract the anticholinergic effects, but its use must be carefully monitored due to possible side effects.

Interactions with other drugs

1. CYP3A4 inhibitors:

   • Drugs that inhibit the CYP3A4 enzyme (eg, ketoconazole, itraconazole, ritonavir, clarithromycin) may increase the blood concentration of fesoterodine, which may increase its side effects. In such cases, a reduction in the dosage of fesoterodine may be necessary.

2. CYP3A4 inducers:

   • Drugs that induce the enzyme CYP3A4 (eg, rifampicin, phenytoin, carbamazepine) may decrease the blood concentration of fesoterodine, which may reduce its effectiveness. Dosage adjustment may be required.

3. Drugs metabolized by CYP2D6:

   • Patients taking drugs metabolized by the CYP2D6 enzyme may experience changes in the concentrations of fesoterodine and its metabolites. This is especially true for patients with slow metabolism via CYP2D6.

4. Anticholinergic drugs:

   • Concomitant use with other anticholinergic drugs (eg, atropine, scopolamine, some antidepressants and antipsychotics) may increase anticholinergic side effects such as dry mouth, constipation, blurred vision, and difficulty urinating.

5. Medicines that prolong the QT interval:

   • Concomitant use with drugs that prolong the QT interval (for example, class IA and III antiarrhythmic drugs, some antidepressants and antipsychotics) may increase the risk of cardiac arrhythmias.

6. Drugs that change gastrointestinal motility:

   • Drugs that alter gastrointestinal motility (eg, metoclopramide) may affect the absorption of fesoterodine.