Expiration date: 02/2025

The composition and form of issue:

Tablets, film-coated. 1 tablet contains:

the tolterodine tartrate 2 mg

Excipients: microcrystalline cellulose calcium hydrogen phosphate carboximetilkrahmal sodium (type A) silica colloidal anhydrous magnesium stearate 

film cover: white colorant Opadry (OY-S-58910) (contains: hypromellose, titanium dioxide, macrogol 400, talc) purified water* 

*evaporates during the production process 

blistere in 10 PCs. in cardboard pack of 3 or 6 blisters.

Description pharmaceutical form:

Round, biconvex tablet white to almost white film-coated.

Pharmacokinetics:

Suction. After taking the drug inside tolterodine is rapidly absorbed from the gastrointestinal tract. Cmax in serum is reached after 1-3 h. the Value of Cmax increases proportionally to the dose of tolterodine in the range of from 1 to 4 mg. the Absolute bioavailability of tolterodine is 65% in individuals with reduced metabolizers (devoid of CYP2D6) and 17% among those with a high metabolism (most patients).

Food has no effect on the exposure of unbound tolterodine and the active 5-hydroxymethylene metabolite in individuals with increased metabolism, although the level of tolterodine is raised when it is taken during a meal.

Distribution. Equilibrium concentration achieved within 2 days. The volume of distribution of tolterodine is 113 L.

Metabolism. Tolterodine is mainly metabolised in the liver via the polymorphic enzyme CYP2D6 with formation of the pharmacologically active 5-hydroxymethylene metabolite. Individuals with reduced metabolism (deficiency of CYP2D6) tolterodine is subjected to dezalkilirovania isoenzymes CYP3A4 with the formation of N-desalkilirovannogo of tolterodine, non-pharmacological activity.

Tolterodine and 5-gidroksimetil metabolite are associated primarily with orosomucoid unbound fraction is 3.7% and 36%, respectively.

Excretion. Systemic clearance of tolterodine in individuals with increased metabolism is about 30 l/h and T1/2 is 2-3 h. T1/2 5-hydroxymethylene metabolite is 3-4 hours After administration 14C-tolterodine is approximately 77% of the tracer is excreted in the urine and 17% in the feces, with less than 1% in an unmodified form, and about 4% as active metabolite. Carboxylated metabolite and the corresponding dezalkilirovania metabolite account for about 51 and 29% of the amount that is excreted in the urine.

Pharmacokinetics in special clinical cases. The decrease in clearance and elongation of T1/2 (10 h) of tolterodine in individuals with reduced metabolism leads to the increase of its concentration (about 7 times) on the background of non-detectable concentrations of 5-hydroxymethylene metabolite. Consequently the value of AUC of tolterodine in individuals with reduced metabolic rate close to the sum of the AUC of tolterodine and its active 5-hydroxymethylene metabolite in patients with increased metabolism at the same dosing regime. Consequently, the safety, tolerability and clinical effect of the drug is the same regardless of phenotype.

The value of the AUC of tolterodine and its active 5-hydroxymethylene metabolite is increased about 2 times in patients with liver cirrhosis.

Description pharmacological action:

An antagonist of m-cholinergic receptors, localized in the bladder and salivary glands. Reduces contractile function of the bladder and reduces salivation. Causes incomplete emptying of the bladder, increases the amount of residual urine and reduces the pressure of the detrusor. Persistent therapeutic effect of tolterodine is achieved after 4 weeks. Tolterodine and its active metabolite 5-gidroksimetil highly specific with regard to muscarinic receptors have selectivity to receptors of the bladder (compared with the receptors of the salivary glands).

Indications:

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

Contraindications:

• hypersensitivity
  
• urinary retention
  
• angle-closure glaucoma (not treatable)
  
• myasthenia gravis
  
• ulcerative colitis
  
• megacolon
  
• pregnancy
  
• lactation
  
• the children's age.
  

Caution: obstruction of the urinary tract, obstructive lesions of the gastrointestinal tract, neuropathy, irreducible hernia.

Side effects:

The incidence of side effects was determined in the following manner: frequently — more than 10% — 1-10% seldom — less than 1%

Side effects associated with anticholinergic effects: often — dry mouth is not often, accommodation disturbances, reduced tearing (xerophthalmia), dryness of the skin rarely — urinary retention.

From the digestive system: — indigestion, constipation, abdominal pain, flatulence, vomiting rare — gastroesophageal reflux.

CNS and peripheral nervous system: not often — headache, dizziness, drowsiness, nervousness, paresthesia, rarely — violation of consciousness.

Other: — weakness, fatigue, weight gain, rarely — pain in the chest allergic reactions, a rush of blood to the skin.

Drug interactions:

In the combined use of Roliana with other drugs with anticholinergic properties may increase the therapeutic action and unwanted effects.

While the use of Roliana with m-holinomimetiki the therapeutic effect of the drug may be reduced.

In the combined use of Roliana with metoklopramidom and cizapridom possible weakening of the latter.

Possible pharmacokinetic interaction with other drugs that are metabolized by the cytochrome P450 system (CYP2D6, or CYP3A4) or inhibit them. However, the combined use of Roliana with fluoxetine (a strong inhibitor of CYP2D6, that is metabolized to norfluoksetina, which is an inhibitor of CYP3A4) leads only to a slight increase in the total AUC tolterodine and its active 5-hydroxymethylene metabolite that does not cause clinically significant interactions.

Avoid concurrent treatment with strong CYP3A4 inhibitors such as macrolide antibiotics (erythromycin and clarithromycin) or antifungal means (ketoconazole, Itraconazole and miconazole).

While clinical trials found no interaction Roliana with warfarin or combined oral contraceptives (containing ethinylestradiol/levonorgestrel).

Clinical study of the use of metabolic probes gave no indication that tolterodine is able to inhibit the activity of CYP2D6, ???2?19, CYP3A4, or CYP1A2.

Method of application and dose:

Inside, 2 mg, 2 times a day. In hepatic and/or renal failure, and in the case of developing side effects dose reduced to 1 mg 2 times a day.

After 6 months should evaluate the need for further treatment.

Overdose:

The highest dose received by volunteers was 12.8 mg of tolterodine tartrate for 1 admission.

Symptoms: disorders of accommodation and painful urge to urinate. Possible hallucinations, strong excitation, cramps, respiratory failure, tachycardia, urinary retention, dilated pupils.

Treatment: gastric lavage, the appointment activated carbon, symptomatic therapy: in severe Central anticholinergic effects (including hallucinations) — physostigmine in convulsions or pronounced excitation — benzodiazepines with tachycardia — beta-adrenoblokatora with respiratory failure — artificial respiration in urinary retention — catheterization of the enlargement of the pupil — pilocarpine in the form of eye drops and/or transfer the patient to a dark room.

Special instructions:

Before treatment should rule out organic causes frequent and mandatory sneeze on urination.

Rolite not recommended to assign children, because at present the safety and efficacy of the drug in this category of patients has not been studied.

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

Effects on ability to drive a car or operate machinery. Because Rolite may cause accommodation disturbances and reduce the speed psychomotor reactions, the possibility of engaging in potentially hazardous activities should be addressed only after the evaluation of individual patient response to the drug.