Index of drugs

Symptomatic treatment of urinary incontinence with urgency and / or frequency of urination and urgency that may occur in people with overactive bladder syndrome.

1 tabl powl. contains 1 mg or 2 mg tolterodine tartrate. 1 capsule about release contains 4 mg of tolterodine tartrate; capsules contain lactose.

Urological spasmologist. Tolterodine is a specific, competitive antagonist of muscarinic receptors, selectively affectingin vivo on receptors located in the urinary gland and salivary glands. It is rapidly absorbed from the gastrointestinal tract and undergoes first pass metabolism in the liver, which is catalyzed by the CYP2D6 enzyme. The result is a 5-hydroxymethyl derivative, the main metabolite of tolterodine with equivalent pharmacological activity. The absolute bioavailability of tolterodine is 17% in people with good metabolism (most patients) and 65% in people with poor metabolism (no CYP2D6). Tolterodine, as well as its metabolite, reach C_max during 1-3 h. Tolterodyna in the form of a capsule about release is characterized by slower absorption, and as a result, C_max is observed during 4 (2-6) hours after administration of capsules. Tolterodine and its 5-hydroxymethyl metabolite bind mainly to orosomucoid. The unbound fractions are 3.7% and 36%, respectively. Tolterodine is extensively metabolised by the liver. The main metabolic pathway mediated by the polymorphic CYP2D6 enzyme leads to the formation of a 5-hydroxymethyl metabolite. Further metabolism leads to 5-carboxylic acid and N-dealkylated 5-carboxylic acid metabolites, which are 51% and 29% of metabolites recovered in urine, respectively. There is a subgroup of the general population (about 7%) without CYP2D6 enzyme activity. For these people (with a poor metabolism profile), the metabolic pathway identified is dealkylation with the participation of CYP3A4 to N-dealkylated tolterodine, which does not contribute to the clinical effect. The rest of the population is defined as persons with a good metabolic profile. In patients with poor metabolism, reduced clearance results in significantly higher levels of tolterodine in the blood (about seven times) and minimal concentrations of 5-hydroxymethyl metabolite. Due to differences in protein binding properties between tolterodine and its 5-hydroxymethyl metabolite, the exposure (AUC) of unbound tolterodine in poor metabolisers is similar to the combined exposure of unbound tolterodine and the 5-hydroxymethyl metabolite in patients with active CYP2D6 with the same dosing schedule. Safety, tolerability and clinical response are similar regardless of the phenotype. 77% of the dose is excreted in the urine and 17% in the faeces. Less than 1% of the dose is excreted unchanged, and about 4% as a 5-hydroxymethyl metabolite. The carboxylated metabolite and the corresponding dealkylated metabolite are respectively 51% and 29% of the dose recovered in the urine. T_0,5 tolterodine given in the form of powl. is 2-3 hours in people with a good metabolic profile and about 10 hours in people with poor metabolism (no CYP2D6); Steady-state concentrations are reached within 2 days of tablet administration. T_0,5 tolterodine given in the form of a capsule about the release is about 6 hours in people with good metabolism and about 10 hours in people with poor metabolism (no CYP2D6); steady state is achieved within 4 days after administration of the capsules.

Hypersensitivity to tolterodine or any of the excipients. Urinary retention. Uncontrolled narrow-angle glaucoma. Myasthenia gravis. A severe form of ulcerative colitis. Toxic dilation of the colon.

Before starting treatment, consideration should be given to the underlying causes of urgency and frequency of urination. Use with caution in patients with severe urinary tract obstruction and urinary retention, with disorders that reduce gastrointestinal patency (eg pyloric stenosis), with renal dysfunction, with liver disease, with autonomic neuropathy, with hiatal hernia, with the risk of reduced motility of the digestive system.Caution should be exercised when using tolterodine in patients with risk factors for QT prolongation, including: congenital or documented acquired QT prolongation, electrolyte disturbances (hypokalemia, hypomagnesaemia and hypocalcemia), bradycardia, with significant previously diagnosed cardiac diseases (cardiomyopathy) , myocardial ischemia, arrhythmias, congestive heart failure), in patients using concomitant medications that prolong the QT interval (including class IA antiarrhythmics - e.g. quinidine, procainamide and class III - e.g. Amiodarone, sotalol). The use of tolterodine in children and adolescents is not recommended. Due to the lactose content, the capsules on the front release should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose.

Pregnancy is not recommended and tolterodine should not be used during breast-feeding.

Table. powl. Very common: headache, dry mouth. Common: bronchitis, dizziness, drowsiness, paraesthesia, dry eyes, visual disturbances (including accommodation disorders), dizziness, palpitations, indigestion, constipation, abdominal pain, flatulence, vomiting, diarrhea, dry skin, anuria, urinary retention, fatigue, chest pain, peripheral edema, increased body weight. Uncommon: hypersensitivity, nervousness, memory disorders, tachycardia, heart failure, arrhythmia, gastro-oesophageal reflux. Not known: anaphylactoid reactions, confusion, hallucinations, confusion, redness of the skin, angioneurotic edema.Kaps. about release. Very common: dry mouth. Common: sinusitis, dizziness, drowsiness, headache, dry eyes, visual disturbances (including accommodation disorders), indigestion, constipation, abdominal pain, bloating, diarrhea, painful or difficult urination, fatigue, peripheral edema. Uncommon: hypersensitivity, nervousness, paresthesia, memory problems, labyrinthine dizziness, palpitations, heart failure, arrhythmias, urinary retention, chest pain. Not known: anaphylactoid reactions, confusion, hallucinations, confusion, tachycardia, flushing, gastro-intestinal reflux, vomiting, angioneurotic edema, dry skin. Dementia symptoms (eg confusion, confusion, hallucinations) have been reported in patients with dementia receiving cholinesterase inhibitors after initiation of tolterodine therapy.

Orally. Adults (including elderly patients).Table. powl.: 2 mg twice daily. In case of nuisance side effects, the dose may be reduced to 1 mg 2 times a day. Patients with impaired hepatic function or severe renal impairment (GFR ≤ 30 ml / min): 1 mg 2 times daily.Kaps. about release: 4 mg once a day. In the event of nuisance side effects, the dose can be reduced to 2 mg once a day. Patients with impaired hepatic function or severe renal impairment (GFR ≤ 30 ml / min): 2 mg once daily. Kaps. about release can be taken irrespective of meals; they should be swallowed whole. The results of treatment should be evaluated once every 2-3 months.