Urotol® [Tolterodyne]

Urotol is prescribed for the symptomatic treatment of increased activity of the bladder with frequent imperative urges to urinate and / or urinary incontinence.

Structure

active substance: tolterodine;

1 tablet contains 2 mg of hydrogen tartrate tolterodine, which is equivalent to 1.37 mg of tolterodine;

Excipients: microcrystalline cellulose, sodium starch (type A), colloidal silicon dioxide, sodium stearyl fumarate, hypromellose, macrogol 6000, titanium dioxide (E 171), talc.

Tolterodine is a specific competitive antagonist of muscarinic receptors with a selective effect (the effect on the bladder is more pronounced than on the salivary glands) in vivo. One of the metabolites of tolterodine (5-hydroxymethyl derivative of tolterodine) has a pharmacological profile similar to the parent compound. In patients with an accelerated (intensive) metabolism, this metabolite significantly enhances the therapeutic effect of tolterodine (see section "Pharmacokinetics").

Contraindications

The drug is contraindicated in patients with:

• hypersensitivity to tolterodine or to excipients of the drug
• urinary retention
• uncontrolled angle-closure glaucoma;
• myasthenia gravis;
• severe ulcerative colitis;
• toxic megacolon.

Dosage and administration

The recommended dose for adults and elderly patients is 2 mg 2 times a day.

In case of unwanted adverse reactions, the dose can be reduced to 2 mg / day (1 mg 2 times a day, it is possible to use tolterodine preparations in the appropriate dosage).

In patients with impaired liver and kidney function [glomerular filtration rate (inulin withdrawal) ≤ 30 ml / min], the recommended daily dose is 2 mg / day (1 mg 2 times a day, it is possible to use tolterodine preparations in the appropriate dosage).

Use along with CYP3A4 inhibitors, the recommended daily dose is 2 mg (1 mg 2 times a day) for patients who use ketoconazole or other powerful CYP3A4 inhibitors.

The effect of treatment should be evaluated after 2-3 months.

Application features

Use during pregnancy or lactation

Pregnancy.

Data on the use of tolterodine in pregnant women are not available. Animal studies have observed reproductive toxicity. The potential risk to humans is unknown, therefore it is not recommended to use during pregnancy.

Breastfeeding.

There is no data on the penetration of tolterodine into breast milk. The use of tolterodine during lactation should be avoided.

Children

The effectiveness of the drug in children has not been established, therefore it is not recommended for use by children.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Since the drug can lead to accommodation disorders and affect the reaction rate, the probable negative effect of the use of tolterodine on the ability to drive vehicles or work with other mechanisms.

Overdose

The highest dose used by healthy volunteers was 12.8 mg of tolterodine L-tartrate once. Adverse reactions were painful, recorded; there were disturbances in accommodation and difficulty urinating.

In case of an overdose of tolterodine, you should rinse your stomach and prescribe activated charcoal. In the treatment of overdose symptoms, the following measures should be taken:

• with the development of severe anticholinergic manifestations of central origin (hallucinations, significant arousal) - use physostigmine;
• with the development of severe court or severe excitement - use benzodiazepine drugs;
• with the development of respiratory failure - apply mechanical ventilation;
• with the development of tachycardia - use β-adrenergic receptor blockers;
• with the development of urinary retention - use catheterization of the bladder
• with the development of mydriasis - apply eye drops of pilocarpine and / or keep the patient in a dark room.

An increase in the duration of the QT interval was observed with a daily dose of 8 mg of immediate release tolterodine (which is twice the recommended daily dose of the immediate release drug and three times the maximum exposure of the drug in extended release capsule form), which were used for more than 4 days. In case of an overdose of tolterodine, standard supportive measures should be taken to regulate the prolongation of the QT interval.

Adverse reactions

The pharmacological effects of tolterodine may lead to the development of antimuscarinic effects, such as dry mucous membranes of the mouth, digestive disorders, and dry mucous membranes of the eye.

The following data were obtained during clinical trials and in the post-marketing period. Among the adverse reactions, dryness of the mucous membranes of the mouth was most often recorded - in 35% of patients who received tolterodyne in tablets, and in 10% of patients who received placebo. Headache was also very common - in 10.1% of patients receiving tolterodine tablets and in 7.4% of patients receiving placebo.

Infections and infestations: often - bronchitis.

On the part of the immune system - infrequently hypersensitivity reactions in the absence of other verification; unknown - anaphylactoid reactions.

Mental disorders: infrequently - nervousness; unknown - confusion, hallucinations, disorientation.

Neurological disorders: very often - headache; often - dizziness, drowsiness, paresthesia infrequently - memory impairment.

From the side of the organ of vision: often - dryness of the mucous membranes of the eye, impaired vision, including impaired accommodation.

On the part of the organs of hearing and the vestibular apparatus: often - vertigo.

From the side of the heart: often - palpitations; infrequently - tachycardia, heart failure, heart rhythm disturbances.

From the vessels: unknown - tides.

From the gastrointestinal tract: very often - dry mucous membranes of the mouth; often - digestive disorders, constipation, abdominal pain, bloating, nausea, diarrhea infrequently - gastroesophageal reflux.

On the part of the skin and subcutaneous tissue: often - dry skin; unknown - angioedema.

From the urinary system: often - dysuria, urinary retention.

General disorders: often - fatigue, chest pain, peripheral edema

Research: often - weight gain

When using tolterodine, cases of exacerbation of symptoms of dementia (confusion, disorientation, false beliefs) were recorded in patients taking cholinesterase inhibitors for the treatment of dementia.

Interaction with other drugs and other types of interactions

The simultaneous use of systemic drugs with potent inhibition of CYP3A4, such as macrolides (erythromycin, clarithromycin), antifungal agents (ketoconazole and itraconazole) and antiproteases, is not recommended, due to an increase in the concentration of tolterodine in the blood serum with a reduced level of CYP2D6 metabolism (and subsequent risk before the dose) see the section “Application Features”).

The simultaneous use of other drugs with antimuscarinic properties may lead to an increase in the therapeutic effect and manifestations of adverse reactions. Conversely, the therapeutic effect of tolterodine can be reduced with the simultaneous use of cholinergic muscarinic receptor agonists.

Tolterodine may reduce the therapeutic effects of prokinetics (metoclopramide and cisapride).

The simultaneous use of fluoxetine (a potent inhibitor of CYP2D6) does not lead to a clinically significant interaction, since tolterodine and its CYP2D6-dependent metabolite - 5-hydroxymethyl tolterodine - are equipotent.

Studies on the interaction of drugs have not established interactions with warfarin or combined oral contraceptives (ethinyl estradiol / levonorgestrel).

Clinical studies indicate that tolterodine is not a metabolic inhibitor of CYP2D6, 2C19, 2C9, 3A4 or 1A2. Thus, an increase in the plasma concentration of drugs metabolized by these isoenzymes is not expected if they are combined with tolterodine.

Storage conditions

It does not require special storage conditions. Keep out of the reach of children.

Shelf life is 2 years.