Toviaz, 8 mg 28 pcs.

Competitive inhibitor of m-cholinoreceptors.

Fesoterodine is rapidly and intensively hydrolyzed after oral administration with the participation of nonspecific esterases to form the active metabolite 5-hydroxymethyl tolterodine, which determines the m-cholinolytic activity of fesoterodine.

The activation of postganglionic parasympathetic m-cholinoreceptors of bladder smooth muscles induces detrusor contraction. Fezoterodine inhibits these receptors in the bladder, which is thought to produce the corresponding pharmacological effects.

The clinical use of fezoterodin has been shown to increase bladder volume by the time of the first detrusor contraction and to increase bladder capacity.

These effects increase in proportion to increasing dose.

Indications

Active ingredient

Composition

How to take, the dosage

It is taken orally.

The recommended starting dose is 4 mg once daily. Depending on effectiveness and tolerability, the dose may be increased to 8 mg once daily.

The dose of 4u mg/day should not be exceeded in patients with impaired renal function at CK < 30 ml/min; in patients receiving strong CYP3A4 isoenzyme inhibitors such as ketoconazole, itraconazole and clarithromycin.

Physoterodine is not recommended for use in patients with impaired liver function (Child-Pugh class C).

Interaction

When concomitant use of Fezoterodin with other m-cholinoblockers that cause dry mouth, constipation, urinary retention and other anticholinergic effects, the frequency and/or severity of such effects may increase. Anticholinergic agents may impair absorption in concomitant use with some drugs due to their anticholinergic effect on the motility of the gastrointestinal tract.

Fezoterodin in doses greater than 4 mg is not recommended in patients receiving strong CYP3A4 isoenzyme inhibitors such as ketoconazole, itraconazole and clarithromycin. Co-administration of ketoconazole and fesoterodine leads to an increase in Cmax and AUC of 5-hydroxymethyl tolterodine, the active metabolite of fesoterodine, by almost 2 times.

Moderate CYP3A4 inhibitors have no clinically significant effect on the pharmacokinetics of fesoterodine. When concomitant use with moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole, diltiazem, verapamil and grapefruit juice) no dose adjustment is required.

When concomitant use of fesoterodine at a dose of 8 mg and the CYP3A4 inducer rifampin at a dose of 600 mg once daily the Cmax and AUC of the active metabolite of fesoterodine are decreased by approximately 70% and 75%, respectively, while the T1/2 of the active metabolite is unchanged.

In persons with decreased CYP2D6 metabolism, Cmax and AUC of active fesoterodine metabolite are increased 1.7 and 2-fold, respectively, when CYP2D6 is maximally inhibited. No dose adjustment is required when concomitant use with CYP2D6 inhibitors.

Special Instructions

If angioedema develops, fesoterodine should be withdrawn and appropriate therapy started immediately. In some cases, angioedema develops after the first dose.

Phesoterodine should be used with caution in patients with clinically significant bladder outlet constriction because of the risk of urinary retention; in patients with decreased GI motility (e.g., severe constipation); in patients treated for closed-angle glaucoma and only when the expected benefit of therapy exceeds the possible risk; in patients with myasthenia.

The condition of patients should be monitored for symptoms of CNS anticholinergic effects, especially at the beginning of treatment and after increasing the dose. If such effects develop, the dose may be reduced or fesoterodine may be discontinued.

Phesoterodine is not recommended for use in patients with severe hepatic dysfunction, since fezoterodine has not been studied in this category of patients.

The use of fesoterodine in a dose greater than 4 mg is not recommended in patients receiving strong CYP3A4 inhibitors (including ketoconazole, itraconazole, clarithromycin).

In concomitant use with moderate CYP3A4 isoenzyme inhibitors (e.g. erythromycin, fluconazole, diltiazem, verapamil and grapefruit juice) no dose adjustment is required for fezoterodine.

The effect of weak CYP3A4 isoenzyme inhibitors (e.g., cimetidine) has not been studied in clinical trials, but some pharmacokinetic interaction should be expected, although less pronounced than with moderate CYP3A4 inhibitors.

Impact on driving and operating machinery

Patients who experience headache, dizziness or drowsiness after taking fesoterodine should refrain from driving vehicles and other potentially dangerous activities.

Contraindications

Side effects

Digestive system disorders: dry mouth, constipation, dyspepsia, nausea, vomiting, abdominal pain, increased ALT and AST activity; in single cases – irritable bowel syndrome.

Urinary system disorders: urinary tract infections, dysuria, urinary retention.

Respiratory system disorders: cough, dry throat.

Visually: dry eyes, blurred vision.

Muscular system: back pain.

Skin and subcutaneous fatty tissue: skin rash, itching.

Allergic reactions: angioedema with airway obstruction, facial edema, urticaria.

CNS disorders: dizziness, headache, drowsiness.

Cardiovascular system disorders: palpitation; in single cases – prolongation of QTc interval on ECG.

General reactions: peripheral edema.