Urotol (Urotol)

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: & nbspFilm coated tablets.
    Composition:

    Each film-coated tablet contains:

    Active substance:

    Tablets 1 mg: tolterodine hydrotartrate -1 mg.

    Tablets 2 mg: tolterodine hydrotartrate - 2 mg.

    Excipients:

    Core:

    Tablets 1 mg: cellulose microcrystalline - 73.0 mg, sodium carboxymethyl starch (Type A) 3.5 mg, silicon dioxide colloid 1.0 mg, sodium stearyl fumarate 1.5 mg.

    Tablets 2 mg: cellulose microcrystalline - 146.0 mg, sodium carboxymethyl starch (Type A) - 7.0 mg, silicon dioxide colloid - 2.0 mg, sodium stearyl fumarate - 3.0 mg.

    Sheath:

    Tablets 1 mg: hypromellose 2910/5 - 1.75 mg, macrogol 6000 - 0.3 mg, titanium dioxide - 0.15 mg, talc - 0.25 mg, iron-oxide oxide yellow - 0.05 mg.

    Tablets 2 mg: hypromellose 2910/5 - 3,5 mg, macrogol 6000 - 0,6 mg, titanium dioxide - 0,4 mg, talc - 0,5 mg.

    Description:

    Tablets 1 mg: Round biconcave, film-coated tablets of yellow color.

    Tablets 2 mg: Round biconvex, film-coated tablets of white color.

    Pharmacotherapeutic group:M-holinoblokator.
    ATX: & nbsp

    G.04.B.D   Spasmolytics

    G.04.B.D.07   Tolterodin

    Pharmacodynamics:
    how tolterodine, and its 5-hydroxymethyl derivative are highly specific for muscarinic receptors, competitively block m-cholinergic receptors with the highest selectivity for the receptors of the bladder (in comparison with the salivary gland receptors). The drug reduces the tone of the smooth muscles of the urinary tract, detrusor contractile activity, and also reduces salivation.
    In doses exceeding therapeutic, causes incomplete emptying of the bladder and increases the amount of residual urine. The therapeutic effect of tolterodine is achieved after 4 weeks. Tolterodin does not inhibit CYP2D6, 2C19, 3A4, or 1A2.
    Pharmacokinetics:

    Suction

    After taking the drug inside tolterodine quickly absorbed from the gastrointestinal tract (GIT). The maximum concentration (CmOh) in the serum is achieved in 1-2 hours. In the range of therapeutic doses (1-4 mg) there is a linear relationship between the value of CmOh in the serum and dose of the drug.

    Absolute bioavailability of tolterodine is 65% in subjects with insufficiency CYP2D6 and 17% in the majority of patients.

    Food does not affect the bioavailability of the drug, although the concentration of tolterodine rises when it is taken with food.

    Distribution

    Tolterodin and 5-hydroxymethyl metabolite bind mainly with orosomucoid. Unrelated fractions are 3.7% and 36%, respectively. The volume distribution of tolterodine is 113 liters.

    Due to the difference in binding to the proteins of tolterodine and the 5-hydroxymethyl metabolite, the area under the "concentration-time" curve (AUC) tolterodine in persons with insufficiency CYP2D6 is close to the sum of the quantities AUC tolterodine and 5-hydroxymethyl metabolite in most patients with the same dosing regimen. Consequently, the safety, tolerability and clinical effect of the drug are independent of activity CYP2D6.

    Metabolism

    Tolterodin is mainly metabolized in the liver with a polymorphic enzyme CYP2D6 to form a pharmacologically active 5-hydroxymethyl metabolite, which is then metabolized to a 5-carboxylic acid and N-dealkylated 5-carboxylic acid. 5-hydroxymethyl metabolite has pharmacological properties close to the tolterodine and in the majority of patients it significantly enhances the effect of the drug.

    In individuals with reduced metabolism (with insufficiency CYP2D6) Tolterodine is dealkylated with isoenzymes CYP3A4 with education N-dealkylated tolterodine, which does not possess pharmacological activity.

    Excretion

    The systemic clearance of tolterodine in serum in most patients is about 30 l / h. After taking the drug, the elimination half-life (T1/2) Tolterodine is 2-3 hours, and T1/2 5-hydroxymethyl metabolite - 3-4 hours. In persons with a decreased metabolism T1/2 about 10 hours.

    Decrease in the clearance of the original compound in persons with insufficiency CYP2D6 leads to an increase in the concentration of tolterodine (about 7 times) against the background of not detectable concentrations of the 5-hydroxymethyl metabolite.

    Approximately 77% of tolterodine is excreted in the urine and 17% - with feces. Less than 1% of the dose is excreted unchanged and about 4% - in the form of a 5-hydroxymethyl metabolite. 5-carboxylic acid and N-dealkylated 5-carboxylic acid are, respectively, about 51% and 29% of the amount that is excreted in the urine.

    Pharmacokinetics in special clinical cases

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

    average value AUC tolterodine and 5-hydroxymethyl metabolite is 2 times higher in patients with marked renal dysfunction (glomerular filtration rate <30 ml / min). The plasma content of other metabolites in these patients is much higher (12 times). Clinical significance of enhancement AUC these metabolites are unknown.

    Indications:Hyperreflexia (hyperactivity, instability) of the bladder, manifested by frequent, imperative urges to urinate, increased frequency of urination and / or urinary incontinence.
    Contraindications:
    Hypersensitivity to the components of the drug;
    Delayed urination;
    Unprotected closed angle glaucoma;
    Myasthenia gravis;
    Severe ulcerative colitis;
    Megacolon;
    Age to 18 years.
    Carefully:With caution appoint the drug with severe obstruction of the lower urinary tract due to the risk of delay in urination, with an increased risk of reducing gastrointestinal motility, with obstructive diseases of the digestive tract (for example, stenosis of the doorkeeper), with renal or hepatic insufficiency (daily dose should not exceed 2 mg) neuropathy, hernia of the esophageal opening of the diaphragm.
    Pregnancy and lactation:
    The use of tolterodine during pregnancy is possible only if the intended benefit of therapy for the mother exceeds the potential risk to the fetus. Since data on the excretion of tolterodine with breast milk are not available, the use of the drug during lactation should be avoided.
    Women of childbearing age Use reliable methods of contraception during therapy with tolterodine.
    Dosing and Administration:
    The drug is administered orally 2 mg 2 times a day, regardless of food intake.
    The total dose of the drug can be reduced to 2 mg per day, based on the individual tolerability of the drug.

    When violations of the liver and / or kidney function, and also with simultaneous application with ketoconazole or other strong inhibitors of CYP3A4, it is recommended to reduce the dose of the drug to 1 mg 2 times a day.
    The effectiveness of therapy should be re-evaluated 2-3 months after the start of treatment.
    Side effects:

    From the immune system: allergic reactions, Quincke's edema (very rarely).

    From the nervous system: nervousness, impaired consciousness, hallucinations,

    dizziness, drowsiness, paresthesia, headache.

    On the part of the organs of vision: dry eyes, disruption of accommodation.

    From the side of the cardiovascular system: tachycardia, increased heart rate,

    arrhythmia (rarely).

    From the digestive tract: dry mouth, indigestion, constipation, abdominal pain, flatulence, vomiting, rarely - gastroesophageal reflux.

    From the skin: dry skin.

    From the urinary system: retention of urination.

    Other: increased fatigue, chest pain, peripheral edema, bronchitis,

    increase in body weight.

    Overdose:

    Symptoms: paresis of accommodation, mydriasis, painful urination, hallucinations, severe agitation, convulsions, respiratory failure, tachycardia, lengthening of the interval QT, retention of urine.

    Treatment: gastric lavage, Activated carbon. With the development of hallucinations, strong excitation - physostigmine, with convulsions or severe excitation - anxiolytics of benzodiazepine structure, with developed respiratory failure - IVL, with tachycardia - beta adrenoblockers, with urinary retention - catheterization of the bladder, with mydriasis - pilocarpine in eye drops and / or transfer of the patient to a dark room.

    Interaction:
    Simultaneous administration of tolterodine with strong inhibitors of CYP3A4, such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole, itraconazole and miconazole), Protease inhibitors, due to the possible increase in the serum concentrations of tolterodine, which increases the risk of overdose.
    Agonists muscarinic cholinergic receptors reduce the effectiveness of tolterodine.
    Medicines with anticholinergic properties increase the effect and increase the risk of side effects. The drug weakens the effect of prokinetics (metoclopramide, cisapride). Perhaps pharmacokinetic interactions with drugs metabolized by cytochrome P450 CYP2D6 or CYP3A4 (inducers and inhibitors). Joint application with fluoxetine (a potent inhibitor of CYP2D6, which is metabolized to norfluoxetine, an inhibitor of CYP3A4) results in only a slight increase in total AUC of tolterodine and its active 5-hydroxymethyl metabolite, which does not cause clinically significant interactions.
    There is no interaction with warfarin and combined oral contraceptives (containing ethinyl estradiol / levonorgestrel). Tolterodin is not an inhibitor of CYP2D6, 2C19, 4A4, 1A2, therefore, it is not expected to increase the level of drugs that are metabolized by these isoenzymes in blood plasma, when taken together with tolterodine.
    Special instructions:
    Before the beginning of treatment it is necessary to exclude organic causes of frequent and imperative urge to urinate.
    Women of reproductive age should be treated only if reliable contraception is used.
    At present, the safety and efficacy of the drug in children have not been studied.
    During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention, rapidity of psychomotor reactions and good vision (may cause accommodation disorders and a decrease in the rate of psychomotor reactions).
    Form release / dosage:Tablets coated with a film coat of 1 mg and 2 mg.
    Packaging:For 14 tablets in a blister of PVC / PVDC / A1.For 2 or 4 blisters together with instructions for use in a cardboard box.
    Storage conditions:
    List B. In a dry place.
    Keep out of the reach of children.
    Shelf life:
    2 years.
    Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-005815/09
    Date of registration:17.07.2009
    The owner of the registration certificate:Zentiva as.Zentiva as. Czech Republic
    Manufacturer: & nbsp
    ZENTIVA, a.s. Czech Republic
    Representation: & nbspZENTIVA PHARMA, LLCZENTIVA PHARMA, LLC
    Information update date: & nbsp09.09.2015
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