Pharmacological action of the drug Detrol

Blocker of m-cholinergic receptors localized in the bladder and salivary glands. Tolterodine and its active 5-hydroxymethyl metabolite are highly specific for m-cholinergic receptors, and are selective for these receptors in the urinary bladder compared to the salivary glands.

Reduces the contractile function of the bladder and reduces salivation. Causes incomplete emptying of the bladder, increases the amount of residual urine and decreases detrusor pressure.

The time to achieve a therapeutic effect is 4 weeks.

Pharmacokinetics

Absorption is fast, high. Cmax in blood plasma increases in proportion to the dose in the range of 1-4 mg. It is metabolized 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. Bioavailability in persons with reduced metabolism (deprived of CYP2D6) is 65%, in persons with increased metabolism - 17%. Food does not affect the exposure of unbound tolterodine and the active 5-hydroxymethyl metabolite in persons with an increased metabolism, although its concentration increases when taken with food. Tolterodine and 5-hydroxymethyl metabolite bind predominantly to orosomucoid. Unbound fractions are 3.7 and 36%, respectively. Vd tolterodine - 113 liters. In persons with an increased metabolism, T1/2 and systemic clearance is higher than in persons with a reduced metabolism. It is excreted by the kidneys - 77% (51% in the form of 5-carboxylic acid, 29% - N-dealkylated 5-carboxylic acid), through the intestines - 17%, while less than 1% - unchanged and about 4% in the form of an active metabolite ...

Indication of the active substances of the drug Detrol

Overactive bladder, manifested by frequent urge to urinate or urinary incontinence.

Dosage regimen of the Detrol

Is taken orally at a dose of 4 mg / day. If necessary, incl. with renal and / or hepatic failure, concomitant therapy with ketoconazole or other potent inhibitors of CYP3A4, the daily dose is reduced to 2 mg.

Contraindications to use

Urinary retention, angle-closure glaucoma (not treatable), myasthenia gravis, severe ulcerative colitis, megacolon, pregnancy, lactation, hypersensitivity to tolterodine.

Application during pregnancy and lactation

Contraindicated during pregnancy and lactation.

Application for violations of liver function

Use with caution in liver failure.

Application for impaired renal function

Use with caution in renal failure.

Use in children

Currently, the safety and efficacy of the drug in children has not been studied.

Special instructions

Use with caution in severe obstruction of the lower urinary tract, obstructive lesions of the gastrointestinal tract (including pyloric stenosis), hepatic and / or renal failure, with neuropathy, hiatal hernia, in children and adolescents under the age of 18 years.

Before starting treatment, it is necessary to exclude the organic causes of frequent and urgent urge to urinate.

Currently, the safety and efficacy of the drug in children has not been studied.

Influence on the ability to drive vehicles and control mechanisms

During the period of treatment, patients should be careful when driving vehicles and other potentially hazardous activities that require increased concentration of attention, speed of psychomotor reactions and good vision (may cause disturbances in accommodation and a decrease in the speed of psychomotor reactions).

Drug interaction

When used simultaneously with drugs with anticholinergic properties, the effect of tolterodine is enhanced and the risk of side effects increases.

Agonists of m-cholinergic receptors reduce the effectiveness of tolterodine.

Tolterodine reduces the effect of prokinetics.

Possible pharmacokinetic interaction with drugs metabolized by isoenzymes CYP2D6 or CYP3A4, which are inducers or inhibitors of these isoenzymes. Simultaneous use with strong inhibitors of CYP3A4, such as macrolide antibiotics (erythromycin and clarithromycin), or azole antifungal agents (ketoconazole, itraconazole and miconazole) should be avoided.

Side effects

Get emergency medical help if you have any of these signs of an allergic reaction to Detrol: hives; labored breathing; Swelling of the face, lips, tongue, or throat. Stop using Detrol and call your doctor at once if you have any of these serious side effects:

• chest pain, fast or irregular heart rate;

• Confusion, hallucinations;

• Urination less than usual, or not at all; or

• painful or difficult urination.

Less serious side effects, such as:

• dry mouth, dry eyes;

• Blurred vision;

• Dizziness, drowsiness;

• Constipation or diarrhea;

• Stomach pain or upset;

• Joint pain; or

• Headache.