Tolterodine
When ATH:
G04BD07
Characteristic.
Толтеродина тартрат — белый кристаллический порошок. Value pKa - 9,87; растворимость в воде — 12 mg / ml; Soluble in methanol, slightly soluble in ethanol, practically nerastvorim in toluene. Octanol / water at pH 7,3 is equal to 1,83.
Pharmacological action.
Holinoliticheskoe, antispasmodic.
Application.
Overactive Bladder, manifested by frequent mandatory impulses to urinate or urinary incontinence.
Contraindications.
Hypersensitivity, urinary retention, intention to treat myasthenia gravis, zakrыtougolynaya glaucoma, severe ulcerative colitis, megacolon.
Restrictions apply.
A large ventricle outflow of urine with the risk of delay of urination, obstructive lesion of STOMACH (for example, pyloric stenosis), kidney or liver failure, neuropathy, nevpravimaja hernia, childhood (the safety and efficacy of the children are not identified).
Pregnancy and breast-feeding.
Studies in mice have shown, that when a pregnant females oral doses of tolterodine 20 mg / kg / day, anomalies or malformations were observed. High doses of (30-40 mg/kg/day is approximately 20-25 times higher dose for a person, in terms of the AUC) cause jembrioletal'nost', decrease in body weight of embryos, increase the frequency of fetal deformities (cleft palate, finger anomalies, abdominal hemorrhage, abnormalities of the skeleton, primary reduction ossification).
In pregnant rabbits, treated with p/to tolterodine in dose 0,8 mg / kg / day, There were no embryotoxicity and teratogenicity.
When pregnancy is possible, if the potential benefit to the mother outweighs the potential risk to the fetus (adequate and well-controlled studies in pregnant women were not conducted).
Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)
Tolterodine is excreted in the milk of mice. Introduction to the dose of tolterodine 20 mg/kg/day in mice during lactation resulted in a slight decrease in body weight gain in offspring, but the weight of the maturation phase, restored.
At the time of treatment should stop breastfeeding (data on excretion of tolterodine in breast milk of women are missing).
Side effects.
From the nervous system and sensory organs: blurred vision (incl. ccomodation) - 4,7%, dizziness - 8,6%, headache - 11%, xerophthalmia — 3,8%, drowsiness - 3%, fatigue is 6,8%.
Cardio-vascular system: arterial hypertension (dizziness) - 1,5%.
From the digestive tract: dry mouth - 39,5%, dyspepsia - 5,9%, nausea - 4,2%, constipation - 6,5% or diarrhea — 4%, abdominal pain- 7,6%, flatulence is 1,3%.
With the genitourinary system: urinary tract infection (shortness of, urodynia, urgency, leucocyturia, hematuria) - 5,5%, dysuria is 2,5%.
Other: flu-like symptoms (incl. joint pain) - 4,4%; allergic reactions - <1%. When taken in pill form: xerosis, bronchitis, increased body weight is 1-10%, chest pain - 3,4%. When administered in capsules prolonged action: sinusitis is 1-10%.
Cooperation.
When coupled with the use of anticholinergic therapeutic effect is amplified by means of tolterodine and increases the risk of side effects. Agonists muskarinovykh holinergicakih receptors reduces the effect of tolterodine. Tolterodine impact prokinetics (metoclopramide, cisapride). Possible pharmacokinetic interaction with HP, those izofermentami cytochrome P450 — CYP2D6 or CYP3A4 (inducers/inhibitors). Joint application with fluoxetine (a potent inhibitor of CYP2D6, which is metabolised to norfluoxetine, is an inhibitor of CYP3A4) leads to a significant inhibition of metabolism of tolterodine have extensive metabolizantov (increase tolterodine AUC at 4,8 times, decrease in Cmax and AUC of the active-metabolita gidroksimetil'nogo 5 on 52 and 20% respectively, When the total concentration of unrelated factions tolterodine and 5-hydroxy-metabolite is increased by 25%), However, changes dosage not required. Avoid the simultaneous appointment of tolterodine with strong CYP3A4 inhibitors, like macrolide antibiotics (Erythromycin, clarithromycin) or antifungals (ketoconazole, itraconazole, mikonazol). There is no interaction with warfarin and combined oral contraceptives, containing ethinyl estradiol / levonorgestrel.
Overdose.
Symptoms: hallucinations, rampage, convulsions, respiratory insufficiency, tachycardia, midriaz, Parez akkomodacii, urinary retention, tenesmus.
Treatment: gastric lavage, administration of activated charcoal, simptomaticheskaya therapy. When delay urination-urinary bladder catheterization. Strong central anticholinergic effects — Physostigmine, cramps or expressed excited showing benzodiazepines (diazepam, Lorazepam); When advanced respiratory failure-IVL. ECG monitoring is needed in connection with the possible elongation QT interval. If tachycardia is beta-adrenoblokatora. When midriaze-eye drops with pilokarpinom and/or transfer of the patient in the dark room.
Dosing and Administration.
Inside, 2 mg 2 once a day. When kidney and/or liver failure, as well as in the case of side effects reduce the dose to 1 mg 2 once a day. Duration of course of treatment is 3-6 months, then it is necessary to assess the need for further treatment.
Precautions.
Before treatment to rule out organic causes frequent and mandatory sneeze on urination.
Women of reproductive age should be appointed only if the use of reliable contraception. Need to consult a dentist in case, If dry mouth persists for more than two weeks.
Should not be used during the drivers of vehicles and people, skills relate to the high concentration of attention.
