Urotol pills 2mg, 56pcs

Composition

Active ingredient:  

tolterodine * hydrotartrate 2 mg.

Auxiliary substances:  

microcrystalline cellulose,

sodium carboxymethyl starch (type A),

colloidal silicon dioxide,

sodium stearyl fumarate.

Shell composition:  

hypromellose 2910/5, macrogol 6000, titanium dioxide, talc.

* – nonproprietary international name recommended by WHO – tolterodine.

Pharmacological action

Both tolterodine and its 5-hydroxymethyl derivative are highly specific for muscarinic receptors, competitively blocking m-holinoreceptors with the greatest selectivity for bladder receptors (in comparison with salivary gland receptors).

The drug reduces the tone of the smooth muscles of the urinary tract, the contractile activity of the detrusor, and also reduces salivation.

In doses higher than therapeutic, it causes incomplete emptying of the bladder and increases the amount of residual urine. The therapeutic effect of tolterodine is achieved after 4 weeks. Tolterodine does not inhibit CYP2D6,2 WITH 19, FOR 4 or 1 A 2.

Pharmacokinetics

Suction

After oral use, tolterodine is rapidly absorbed from the gastrointestinal tract (GIT). The maximum concentration (Cmax) in serum is reached after 1-2 hours. In the range of therapeutic doses (1-4 mg), there is a linear relationship between the value of Cmax in blood serum and the dose of the drug.

The absolute bioavailability of tolterodine is 65% in individuals with CYP2D6 deficiency and 17% in most patients.

Food does not affect the bioavailability of the drug, although the concentration of tolterodine increases when it is taken with a meal.

Distribution

Tolterodine and the 5-hydroxymethyl metabolite bind predominantly to orosomucoid. The unbound fractions are 3.7% and 36%, respectively.

The volume of distribution of tolterodine is 113 liters. Due to the difference in protein binding of tolterodine and the 5-hydroxymethyl metabolite, the area under the concentration-time curve (AUC) of tolterodine in individuals with CYP2D6 deficiency is close to the sum of the AUC values of tolterodine and the 5-hydroxymethyl metabolite in most patients with the same dosage regimen. Therefore, the safety, tolerability and clinical effect of the drug do not depend on the activity of CYP2D6.

Metabolism

Tolterodine is mainly metabolized in the liver by the polymorphic enzyme CYP2D6 to form a pharmacologically active 5-hydroxymethyl metabolite, which is then metabolized to 5-carboxylic acid and N-dealkylated 5-carboxylic acid.

The 5-hydroxymethyl metabolite has pharmacological properties similar to tolterodine and significantly enhances the effect of the drug in most patients. In individuals with reduced metabolism (with a lack of CYP2D6), tolterodine undergoes dealkylation by CYP3A4 isoenzymes to form N-dszalkylated tolterodine, which has no pharmacological activity.

Deduction

The systemic clearance of tolterodine in serum in most patients is about 30 l/h. After taking the drug, the half-life (T 1/2) of tolterodine is 2-3 hours, and T 1/2 of the 5-hydroxymethyl metabolite is 3-4 hours. In individuals with reduced metabolism, T 1/2 is about 10 hours.

A decrease in the clearance of the parent compound in individuals with CYP2D6 deficiency leads to an increase in the concentration of tolterodine (approximately 7 times) against the background of undetectable concentrations of the 5-hydroxymethyl metabolite.

Approximately 77% of tolterodine is excreted in the urine and 17% in the faeces. Less than 1% of the dose is excreted unchanged and about 4% – in the form of a 5-hydroxymethyl metabolite. 5-carboxylic acid and N-dealkylated 5-carboxylic acid make up, respectively, about 51% and 29% of the amount that is excreted in the urine.

Pharmacokinetics in special clinical cases

The AUC of tolterodine and its active 5-hydroxymethyl metabolite increases approximately 2-fold in patients with cirrhosis of the liver.

The mean AUC of tolterodine and the 5-hydroxymethyl metabolite is 2 times higher in patients with severe renal impairment (glomerular filtration rate <30 ml / min). The plasma content of other metabolites in these patients is significantly higher (12 times). The clinical significance of increasing the AUC of these metabolites is unknown.

Indications

Hyperreflexia (hyperactivity, instability) of the bladder, manifested by frequent, imperative urge to urinate, increased urination and / or urinary incontinence.

Use during pregnancy and lactation

The use of Urotol during pregnancy is possible only if the intended benefit of therapy for the mother outweighs the potential risk to the fetus.

Since there are no data on the elimination of tolterodine in breast milk, the use of the drug during lactation should be avoided.

Women of childbearing age should use reliable methods of contraception during Urotol therapy.

Contraindications

• Urinary retention;
• untreatable angle-closure glaucoma;
• myasthenia gravis;
• severe ulcerative colitis;
• megacolon;
• age up to 18 years;
• hypersensitivity to the components of the drug.

With caution, the drug is prescribed for: severe obstruction of the lower urinary tract due to the risk of urinary retention; increased risk of decreased gastrointestinal motility; obstructive gastrointestinal diseases (for example, pyloric stenosis); renal or hepatic insufficiency (the daily dose should not exceed 2 mg); neuropathy; hiatal hernia.

Side effects

Immune system disorders: allergic reactions, angioedema (very rare).

Nervous system disorders: nervousness, impaired consciousness, hallucinations, dizziness, drowsiness, paresthesia, headache.

From the side of the visual organs: dry eyes, impaired accommodation.

From the cardiovascular system: tachycardia, increased heart rate, arrhythmia (rarely).

From the digestive system: dry mouth, dyspepsia, constipation, abdominal pain, flatulence, vomiting;  rarely-gastroesophageal reflux.

Dermatological reactions: dry skin.

Urinary system disorders: urinary retention.

Others: increased fatigue, chest pain, peripheral edema, bronchitis, weight gain.

Interaction

Concomitant use of tolterodine with strong CYP3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole, itraconazole and miconazole), protease inhibitors should be avoided, due to the possibility of increasing the concentration of tolterodine in the blood serum, which increases the risk of overdose of the drug. Muscarinic cholinergic receptor agonists reduce the effectiveness of tolterodine. Medications that have anticholinergic properties enhance the effect and increase the risk of side effects. The drug weakens the effect of prokinetics (metoclopramide, cisapride). Pharmacokinetic interaction with drugs metabolized by cytochrome P 450 isoenzymes CYP2D6 or CYP3A4 (inducers and inhibitors) is possible. Co-use with fluoxetine (a strong CYP2D6 inhibitor that is metabolized to norfluoxetine, which is a CYP3A4 inhibitor) results in only a slight increase in the total AUC of tolterodine and its active 5-hydroxymethyl metabolite, which does not cause a clinically significant interaction. There is no interaction with warfarin and combined oral contraceptives (containing ethinyl estradiol/levonorgestrel). Tolterodine is not an inhibitor of CYP2D6,2C19, FOR 4,1A2, as a result, it is not expected to increase the level of drugs that are metabolized by these isoenzymes in blood plasma, when co-administered with tolterodine.

How to take, course of use and dosage

The drug is prescribed orally at 2 mg 2 times / day, regardless of food intake. The total dose of the drug can be reduced to 2 mg/day, based on the individual tolerance of preprate.

In case of impaired liver and/or kidney function, as well as when used concomitantly with ketoconazole or other strong CYP3A4 inhibitors, it is recommended to reduce the dose of the drug to 1 mg 2 times / day.

The effectiveness of therapy should be re-evaluated 2-3 months after the start of treatment.

Overdose

Symptoms: paresis of accommodation, mydriasis, painful urination, hallucinations, severe agitation, convulsions, respiratory failure, tachycardia, prolongation of the QT interval, urinary retention.

Treatment: gastric lavage, activated charcoal. With the development of hallucinations, strong arousal-physostigmine, with convulsions or severe arousal-anxiolytics of the benzodiazepine structure, with respiratory failure-mechanical ventilation, with tachycardia-beta-blockers, with urinary retention-catheterization of the bladder, with mydriasis-pilocarpine in eye drops and/or transfer of the patient to a dark room.

Special instructions

Use in patients with liver function disorders

In case of impaired liver function, it is recommended to reduce the dose of the drug to 1 mg 2 times / day.

Use in patients with impaired renal function

In case of impaired renal function, it is recommended to reduce the dose of the drug to 1 mg 2 times / day.

Before starting treatment, organic causes of frequent and imperative urination should be excluded.

Use in pediatrics

Urotol should not be prescribed to children and adolescents under 18 years of age, as currently the safety and efficacy of the drug in this category of patients has not been studied.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Since Urotol can cause accommodation disorders and reduce the speed of psychomotor reactions, during treatment, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration, speed of psychomotor reactions and good eyesight.

Form of production

Coated tablets

Storage conditions

In a dry place

Shelf life

3 years

Active ingredient

Tolterodine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adult Doctor’s prescription