Toviaz

Toviaz (Fesoterodine) is a medication used to treat symptoms of overactive bladder (OAB). OAB is characterized by frequent, strong and sudden urges to urinate, 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 the urge to urinate.

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 due to an urgent need to urinate.

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

Release form

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

Pharmacodynamics

1. Muscarinic receptor antagonism: Fesoterodine is a muscarinic receptor antagonist. The drug blocks muscarinic receptors (M3 receptors) in the smooth muscles of the bladder. These receptors are responsible for muscle contraction when stimulated by acetylcholine.
2. Decreased bladder contractions: By blocking M3 receptors, fesoterodine reduces spontaneous and involuntary contractions of the bladder. This results in a decrease in the frequency and strength of the urge to urinate.
3. Increased bladder capacity: The drug helps increase bladder capacity, allowing you to hold more urine before you need to urinate. This reduces the frequency of urination and improves control over urination.
4. Reducing Urgency: Fesoterodine helps reduce the urge to urinate, 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 muscarinic receptor antagonist activity.
6. Peripheral action: Fesoterodine acts primarily on 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 non-specific esterases to its active metabolite 5-hydroxymethyl-tolterodine (5-HMT).
   • The maximum concentration of the active metabolite in 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 is 50% bound to plasma proteins.

3. Metabolism:

   • After hydrolysis to the active metabolite 5-HMT, it is further metabolized in the liver by the enzymes CYP2D6 and CYP3A4.
   • In individuals who are poor metabolizers via CYP2D6, the concentration of the active metabolite may be higher.

4. Excretion:

   • The main route of excretion 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 the feces.
   • The half-life of the active metabolite is approximately 7-8 hours.

5. Special populations:

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

Dosing and administration

Recommended dosage:

For adults:

• Initial dose: It is usually 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.

Directions for use:

• Taking tablets: Tablets should be taken orally with a sufficient amount of water.
• Time of administration: Tablets can be taken regardless of food intake.
• Frequency: The drug is taken once a day, preferably at the same time each 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 almost 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 immediate medical attention. Symptoms of overdose may include dry mouth, rapid heartbeat, dizziness, and blurred vision.

Special categories of patients:

• Patients with renal impairment: Dose adjustment may be required for patients with mild or moderate renal impairment. In patients with severe renal impairment, it is not recommended to exceed a dose of 4 mg daily.
• Patients with liver impairment: For patients with moderate liver impairment, it is also recommended not to exceed 4 mg per day. The drug is not recommended for patients with severe liver impairment.
• Elderly patients: For elderly patients, the dosage is usually no different from the standard, but their general health condition and the possibility of side effects should be taken into account.

Use Toviaza during pregnancy

1. Consultation with a doctor: Before starting to take fesoterodine during pregnancy, you should consult with your doctor. The doctor will assess the need for using the drug, taking into account the health of the mother and possible risks to the fetus.
2. Benefit vs. Risk: Use of fesoterodine during pregnancy can be justified only in cases where the potential benefit to the mother outweighs the possible risks to the fetus.
3. First trimester: Particular attention should be paid to the use of drugs 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 drugs.
4. Alternatives: If possible, consider alternative treatments or medications with more established safety in pregnant women.

Contraindications

1. Hypersensitivity: The drug is contraindicated in people with known hypersensitivity or allergic reaction to fesoterodine, its active metabolite (5-hydroxymethyltolterodine), or any other components of the drug.
2. Closed-angle glaucoma: Toviaz may increase intraocular pressure and is therefore contraindicated in patients with uncontrolled closed-angle glaucoma.
3. Tachyarrhythmias: Fesoterodine may worsen tachyarrhythmias and should be avoided in patients with this condition.
4. Myasthenia: 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 <30 ml/min), as the drug may accumulate in the body and cause toxic effects.
6. Severe liver failure: The drug is contraindicated in patients with severe liver dysfunction (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 stenosis and urinary retention: Toviaz is contraindicated in patients with urinary retention or significant urethral stenosis 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 (indigestion).
   • Dry skin.
   • Rapid heartbeat (tachycardia).
   • Blurred vision.

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

   • Urinary tract infections.
   • Difficulty urinating (urinary retention).
   • Abdominal 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 of consciousness.
   • Hallucinations.
   • Heart rhythm disturbances (eg, prolongation of the QT interval, arrhythmia).

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

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

Overdose

1. Severe dry mouth
2. Difficulty urinating (acute urinary retention)
3. Dilation of the pupils (mydriasis)
4. Tachycardia (rapid heartbeat)
5. Arrhythmias
6. Severe dizziness
7. Excitement and anxiety
8. Cramps
9. Redness of the skin
10. Hyperthermia (increased body temperature)
11. Severe visual impairment
12. Confusion, hallucinations and delirium

Treatment of overdose

Treatment for fesoterodine overdose is aimed at relieving symptoms and supporting 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 helpful if large amounts of the drug have been taken recently.
3. Activated charcoal: Using activated charcoal may help reduce the absorption of the drug from the gastrointestinal tract if a short period of time has passed since administration.
4. Symptomatic therapy: Treatment of symptoms such as tachycardia and seizures as needed. This may include 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 should be carefully monitored because of possible side effects.

Interactions with other drugs

1. CYP3A4 inhibitors:

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

2. CYP3A4 inducers:

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

3. Drugs metabolized by CYP2D6:

   • Patients taking drugs metabolized by CYP2D6 may experience changes in the concentration of fesoterodine and its metabolites. This is especially true for patients with poor metabolism through 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. Drugs that prolong the QT interval:

   • Concomitant use with drugs that prolong the QT interval (eg, 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.