Roliten, 2 mg 30 pcs.

Roliten has a cholinolytic and antispasmodic effect.

Pharmacodynamics

An antagonist of m-cholinoreceptors localized in the bladder and 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 reduces detrusor pressure. Permanent therapeutic effect of Tolterodin is achieved after 4 weeks. Tolterodine and its active metabolite 5-hydroxymethyl are highly specific for muscarinic receptors and are selective for bladder receptors (compared to salivary gland receptors).

Pharmacokinetics

Intake. After oral administration of the drug, tolterodine is rapidly absorbed from the gastrointestinal tract. C_max in serum is reached after 1-3 hours. The C_max value increases in proportion to the tolterodine dose between 1 and 4 mg. Absolute bioavailability of tolterodine is 65% in persons with decreased metabolism (deprived of CYP2D6) and 17% in persons with increased metabolism (most patients).

Food has no effect on the exposure of unbound tolterodine and the active 5-hydroxymethyl metabolite in those with increased metabolism, although levels of tolterodine are increased when taken with meals.

Distribution. Equilibrium concentration is reached within 2 days. The volume of distribution of tolterodine is 113 liters.

Metabolism. Tolterodine is mainly metabolized in the liver by the polymorphic enzyme CYP2D6 to form the pharmacologically active 5-hydroxymethyl metabolite. In persons with reduced metabolism (with CYP2D6 deficiency) tolterodine undergoes dealkylation by CYP3A4 isoenzymes to form N-dealkylated tolterodine which has no pharmacological activity.

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

Elimation. Systemic clearance of tolterodine in persons with increased metabolism is about 30 L/h, and T_1/2 is 2-3 h. The T_1/2 of the 5-hydroxymethyl metabolite is 3-4 h. After administration of 14C-tolterodine, approximately 77% of the radioactive label is excreted in the urine and 17% in the feces, with less than 1% unchanged and about 4% as an active metabolite. The carboxylated metabolite and its corresponding dealkylated metabolite account for about 51% and 29% of what is excreted with the urine.

Pharmacokinetics in special clinical cases. Decreased clearance and prolongation of T_1/2 (up to 10 h) of tolterodine in persons with decreased metabolism leads to an increase in its concentration (approximately 7-fold) against undetectable concentrations of the 5-hydroxymethyl metabolite. As a consequence, the AUC value of tolterodine in patients with reduced metabolism is close to the sum of the AUC values of tolterodine and its active 5-hydroxymethyl metabolite in patients with increased metabolism with the same dosing regimen. Consequently, the safety, tolerability and clinical effect of the drug are the same regardless of the phenotype.

The AUC value of tolterodine and its active 5-hydroxymethyl metabolite is increased approximately 2-fold in patients with cirrhosis.

Indications

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

Active ingredient

Composition

Active ingredient:

tolterodine tartrate 2 mg;

Associates:

MCC;

calcium hydrophosphate;

sodium carboxymethyl starch (type A);

colloidal silicon dioxide;

magnesium stearate;

Film coating:

Opadry white dye (OY-S-58910) (contains: hypromellose, titanium dioxide, macrogol 400, talc); purified water

How to take, the dosage

Overly, 2 mg 2 times a day. In case of hepatic and/or renal insufficiency and in case of side effects the dose is reduced to 1 mg 2 times a day.

In 6 months the need for further treatment should be evaluated.

Interaction

When using Roliten in combination with other drugs with anticholinergic properties, the therapeutic effect and adverse effects may increase.

In concomitant use of Roliten with m-cholinomimetics the therapeutic effect of the drug may decrease.

When Roliten is used concomitantly with metoclopramide and cisapride the effects of the latter may be diminished.

Possible pharmacokinetic interaction with other drugs that are metabolized by cytochrome P450 system (CYP2D6 or CYP3A4) or inhibit them. However, co-administration of Roliten with fluoxetine (a strong CYP2D6 inhibitor that is metabolized to norfluoxetine, which is a CYP3A4 inhibitor) results only in a slight increase in the total AUC of tolterodine and its active 5-hydroxymethyl metabolite, which causes no clinically significant interaction.

Concomitant treatment with strong CYP3A4 inhibitors, such as antibiotics of macrolide group (erythromycin and clarithromycin) or antifungal agents (ketoconazole, itraconazole and miconazole) should be avoided.

In clinical trials, there have been no interactions of Roliten with warfarin or combined oral contraceptives (containing ethinylestradiol/levonorgestrel).

The clinical trial with metabolic probes gave no indication that Tolterodine can inhibit CYP2D6, CYP2C19, CYP3A4 or CYP1A2 activity.

Special Instructions

Before starting treatment, organic causes of frequent and imperative urge to urinate should be excluded.

Roliten is not recommended for use in children because the safety and effectiveness in this patient population has not been studied.

Women of childbearing age should use reliable contraception during therapy with Roliten.

Impact on the ability to drive and operate machinery. Because Roliten may cause accommodation disturbances and decrease the speed of psychomotor reactions, the question about the possibility of engaging in potentially dangerous activities should be decided only after assessing the patient’s individual reaction to the drug.

Contraindications

Side effects

The digestive system: not frequent – dyspepsia, constipation, abdominal pain, flatulence, vomiting; rarely – gastroesophageal reflux.

CNS and peripheral nervous system: not common – headache, dizziness, somnolence, nervousness, paresthesia; rarely – disorders of consciousness.

Others: not frequent – weakness, fatigue, weight gain; rarely – chest pain; allergic reactions, flushes to the skin of the face.

Overdose

Symptoms: impaired accommodation and painful urge to urinate. Hallucinations, severe agitation, seizures, respiratory failure, tachycardia, urinary retention, dilated pupils are possible.

The treatment: gastric lavage, prescription of activated charcoal, symptomatic therapy: with marked central anticholinergic effects (including In hallucinations) – physostigmine; in convulsions or marked agitation – benzodiazepines; in tachycardia – beta-adrenoblockers; in respiratory failure – artificial respiration; in urinary retention – catheterization; in dilated pupils – pilocarpine in the form of eye drops and/or transfer of patient to a dark room.