Rolitan® (Roliten®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceTolterodinTolterodin
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    • Dosage form: & nbsp
    Film-coated tablets.
    Composition:

    Each film-coated tablet contains:

    Active substance: Tolterodine Tartrate 2 mg

    Excipients:

    Microcrystalline cellulose, calcium hydrophosphate, sodium carboxymethyl starch

    (TypeA), silicon dioxide colloidal, magnesium stearate.

    Sheath:

    Colorant opedraj white (OY-S-58910)* (* - hypromellose, titanium dioxide, macrogol 400,

    talc), purified water **.

    (** - evaporates during production)

    Description:Round, biconcave tablets white to almost white Colors covered with a film sheath.
    Pharmacotherapeutic group:M-holinoblokator.
    ATX: & nbsp

    G.04.B.D   Spasmolytics

    G.04.B.D.07   Tolterodin

    Pharmacodynamics:Antagonist of m-holinoretseptorov, localized in the bladder and salivary glands. Reduces the contractile function of the bladder and reduces salivation. It causes incomplete emptying of the bladder, increases the amount of residual urine and reduces detrusor pressure.The persistent therapeutic effect of tolterodine is achieved after 4 weeks. Tolterodin and its active metabolite, 5-hydroxymethyl are highly specific for muscarinic receptors, have selectivity for the receptors of the bladder (in comparison with the salivary gland receptors).
    Pharmacokinetics:

    Suction:

    After taking the drug inside tolterodine quickly absorbed from the gastrointestinal tract. The maximum concentration (CmOh) in the serum is achieved in 1-3 hours. The value of CmOh increases in proportion to the dose of tolterodine in the range from 1 to 4 mg. Absolute bioavailability of tolterodine is 65% in individuals with reduced metabolism (deprived CYP2D6) and 17% in individuals with elevated metabolism (most patients).

    Food does not affect the exposure of unbound tolterodine and the active 5-hydroxymethyl metabolite in people with increased metabolism, although the level of tolterodine rises when it is taken with food.


    Distribution:

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


    Metabolism:

    Tolterodin is mainly metabolized in the liver with a polymorphic enzyme CYP2D6 with the formation of a pharmacologically active 5-hydroxymethyl metabolite. Further metabolism leads to the formation of 5-carboxylic acid and its N- dealkylated metabolites.

    In persons with a decreased metabolism (lacking SRS2D6), tolterodine It is not metabolized to the active 5-hydroxymethyl metabolite, but is dealkylated with isoenzymes CYP3A4 with education N-dealkylated tolterodine, which does not possess pharmacological activity.

    Tolterodin and the 5-hydroxymethyl metabolite bind mainly to the orosomucoid; unrelated fractions are 3.7% and 36%, respectively.


    Excretion:

    Systemic clearance of tolterodine in persons with increased metabolism is about 30 liters / hour, and the half-life (T1/2) - 2-3 hours. T1/2 5-hydroxymethyl metabolite

    is 3-4 hours. After the introduction 14 C-tolterodine approximately 77% of the radioactive label is excreted in the urine and 17% - with feces, while less than 1% - unchanged and about 4% in the form of an active metabolite. Carboxylated metabolite and its corresponding dealkylated metabolite account for about 51% and 29% of the amount that is excreted in the urine.


    Pharmacokinetics in special clinical cases:

    Reduced clearance and lengthening T1/2 (up to 10 hours) tolterodine in people with a decreased metabolism leads to an increase in its concentration (about 7 times) against the background of not detectable concentrations of the 5-hydroxymethyl metabolite. As a result, the area under the "concentration / time" curve (AUC) Tolterodin in persons with a decreased metabolism is close to the sum of the values AUC tolterodine and its active 5-hydroxymethyl metabolite in patients with increased metabolism under the same dosage regimen. Consequently, the safety, tolerability and clinical effect of the drug are the same regardless of the phenotype. Value AUC tolterodine and its active 5-hydroxymethyl metabolite is approximately 2-fold increased in patients with cirrhosis of the liver.

    Indications:Hyperreflexia (hyperactivity, instability) of the bladder, manifested by frequent, mandatory urge to urinate and / or urinary incontinence.
    Contraindications:Hypersensitivity, urine retention, angle-closure glaucoma (not treatable), myasthenia gravis, ulcerative colitis, megacolon, pregnancy, lactation period, children's age.
    Carefully:Obstruction of the urinary tract, obstructive lesions of the gastrointestinal tract, neuropathy, unrecoverable hernia.
    Dosing and Administration:
    The drug is administered orally 2 mg twice a day. In case of hepatic and / or renal failure, and also in case of side effects, the dose is reduced to 1 mg twice a day.
    After 6 months, the need for further treatment should be assessed.
    Side effects:

    Side effects associated with anticholinergic action: often (more than 10%) - dry mouth; not often (1 - 10%) - disorders of accommodation, reduced tearing (xerophthalmia), dry skin; rarely (less than 1%) - delay urination.

    From the digestive system: not often (1-10%) - dyspepsia, constipation, abdominal pain, flatulence, vomiting; rarely (less than 1%) -gastroesophageal reflux.

    From the side of the central nervous system and the peripheral nervous system: not often (1-10%) - headache, dizziness, drowsiness, nervousness, paresthesia; rarely (less than 1%) - impaired consciousness.

    Other: not often (1-10%) - weakness, fatigue, weight gain, rarely (less than 1%) - chest pains, allergic reactions, flushes of blood to the skin of the face.

    Overdose:
    The highest dose received by volunteers was 12.8 mg tolterodine

    L-tartrate for 1 dose.

    The most important symptoms noted in this case were disorders of accommodation and painful urge to urinate. Possible hallucinations, severe agitation, convulsions, respiratory failure, tachycardia, urinary retention, dilated pupils.

    Treatment: gastric lavage, the appointment of activated charcoal, symptomatic therapy: with pronounced central anticholinergic effects (including hallucinations) - physostigmine; with convulsions or pronounced excitation - benzodiazepines; with tachycardia - beta-blockers; with respiratory failure - artificial respiration; with a delay in urination - catheterization; with the dilatation of the pupils - pilocarpine in the form of eye drops and / or transfer the patient to a dark room.
    Interaction:

    When combined with other products with anticholinergic properties, it is possible to increase the therapeutic effect and undesirable effects.

    With the simultaneous use of Roliten with m-cholinomimetics, the therapeutic effect of the drug may decrease.

    With the combined use of Roliten with metoclopramide and cisapride, the effects of the latter may be weakened.

    Possible pharmacokinetic interaction with other drugs that are metabolized by the cytochrome P system450 (CYP2D6 or CYP3A4) or inhibit them. However, the combined use of Roliten with fluoxetine (a strong inhibitor CYP2D6, which is metabolized to norfluoxetine, which is an inhibitor CYP3A4) leads only to a slight increase in the total AUC tolterodine and its active 5-hydroxymethyl metabolite, which does not cause a clinically significant interaction.

    It is necessary to avoid simultaneous treatment with strong inhibitors CYP3A4, such as macrolide antibiotics (erythromycin and clarithromycin) or antifungal agents (ketoconazole, itraconazole and miconazole).

    When carrying out clinical trials, there was no evidence of interaction between Roliten and warfarin or combined oral contraceptives (containing ethinylestradiol / levonorgestrel).

    A clinical study using metabolic probes did not give any indication that, tolterodine is able to inhibit activity CYP2D6, CYP2c19, CYP3a4 or CYP1a2.

    Special instructions:
    Before starting treatment, the organic causes of frequent and imperative urination should be ruled out.
    Raliten is not recommended for prescribing to 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 with Rolitan.
    Effect on the ability to drive transp. cf. and fur:Since Roliten can cause accommodation disorders and reduce the speed of psychomotor reactions, the question of the possibility of practicing potentially dangerous activities should be addressed only after assessing the patient's individual response to the drug.
    Form release / dosage:Film-coated tablets.
    Packaging:For 10 tablets in a blister of aluminum foil / PVC / PVDNH. 3 or 6 blisters with instructions for use in a cardboard pack.
    Storage conditions:Store in a dry place at a temperature of no higher than 25 ° C. Keep out of the reach of children.
    Shelf life:4 years. Do not use after the date shown on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-001584/08
    Date of registration:14.03.2008
    The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India
    Manufacturer: & nbsp
    Information update date: & nbsp09.09.2015
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