Fractal

General characteristics. Structure:

Active ingredients: 6 mg of a tegaserod (in the form of a tegaserod of a hydromaleate).

Excipients: silicon dioxide colloid, the talc purified magnesium stearate, sodium of a kroskarmelloz, starch corn, cellulose microcrystallic, dye quinolinic yellow (E-104).

Purgative.

Pharmacological properties:

Pharmacodynamics. Tegaserod has high affinity to 5-HT4-receptors of the person, but has no essential affinity to 5-HT3 - and dopamine receptors. Has moderate affinity to 5-HT1-retseptorami. At the expense of an agonizm on 5-HT4-retseptorov of neurons initiates release from nerve terminations of afferent neurons of the peptide connected with a calcitonin gene that is the neurotransmitter. Activation of 5-HT4-retseptorov of digestive tract stimulates a peristaltic reflex and intestinal secretion, at the same time suppressing visceral sensitivity. The researches in vivo showed what тегасерод increases basal motility and normalizes the weakened motility of all digestive tract. Researches also showed what тегасерод reduces visceral sensitivity of a large intestine to stretching at animals.

Pharmacokinetics. The maximum concentration in blood is reached in 1 hour after oral administration. Absolute bioavailability of a tegaserod at appointment on an empty stomach makes about 10%. In the range of doses from 2 to 12 mg at reception two times a day within 5 days pharmacokinetic parameters are proportional to a dose. Clinically significant cumulation of a tegaserod in plasma at appointment in a dose of 6 mg was not noted 2 times a day within 5 days.

At appointment with food bioavailability of a tegaserod decreases by 40-65%, and the maximum concentration - approximately for 20-40%. Decrease in concentration in a blood plasma at purpose of a tegaserod in a period of 30 min. is possible, to food and 2,5 hours after food. The maximum time lasts from 1 to 2 o'clock at reception a tegaseroda after food, but decreases till 0,7 o'clock at reception in 30 min. prior to food.

Tegaserod for 98% contacts proteins of plasma, is preferential with acid 1 - an alpha glycoprotein. It is metabolized in two ways. The first - presistemny hydrolysis in a stomach (it is catalyzed by acid) with the subsequent oxidation and conjugation with formation of the main metabolite of a tegaserod - a glucuronide of 5-metoksiindol-3-carboxylic acid. The main metabolite has low (it can not be considered) relationship with in vitro 5-HT4-retseptorami. At the person system influence of a tegaserod did not change at neutral indicators рН a stomach. The second way of metabolism of a tegaserod - a direct glyukuronidation with formation of three isomeric N-glucuronides. About 2/3 tegaserod are allocated in not changed look through a GIT, 1/3 - with urine, is preferential in the form of the main metabolite.

The pharmacokinetics of a tegaserod at patients with a syndrome of the angry intestines is comparable with pharmacokinetics at healthy volunteers.

Changes of pharmacokinetics of a tegaserod at patients with a renal failure who are treated by means of a hemodialysis were not observed (clearance of creatinine of 15 ml/min. / 1,73 sq.m). The maximum concentration and AUC (the area under a pharmacokinetic curve) the main pharmacological an inactive metabolite to a tegaserod - a glucuronide of 5-metoksiindol-3-carboxylic acid, increase in 2 and 10 times respectively at patients with a heavy renal failure in comparison with healthy volunteers. Patients with a slight and moderate renal failure do not need dosing change to a tegaserod.

Abnormal liver function. At patients with an easy form of a liver failure average AUC was 31% higher and the maximum concentration is 16% higher in comparison with the same parameters of healthy volunteers.

At an easy form of a liver failure of change of a dosage are necessary, however it is necessary to appoint with care тегасерод to patients of this group. In the presence of a moderate and heavy hepatic unsufficiency it is not recommended to apply тегасерод due to the lack of these clinical trials.

To elderly patients to change a dosage to a tegaserod it is unnecessary.

Indications to use:

• a syndrome of the angry intestines which main manifestation are locks,

• chronic locks.

Route of administration and doses:

Adults accept on 1 tablet (6 mg) inside, just before reception of food, 2 times a day within 4-6 weeks. Wash down with water.

Patients who had an effective treatment within 4-6 weeks can recommend an additional 4-6 weeks course.

Features of use:

Safety and efficiency of use are not established to a maleate tegaserod at children.

It is not recommended to appoint тегасерод to patients with a heavy renal failure.

Pregnancy and feeding by a breast. Safety of use during pregnancy is not established. Pregnant women should appoint drug only in case the expected advantage for treatment of mother exceeds possible risk for a fruit. Feeding period breast. There are no data on excretion of a tegaserod in women's milk therefore it is recommended to a tegaserod to stop for reception feeding by a breast.

Influence on ability to manage vehicles or to work with difficult mechanisms. Due to an opportunity dizziness, it is necessary to drive the car and to work with mechanical devices with care.

The fractal is not appointed to patients with the available or frequent diarrhea. At patients with available the abdominal pain amplifying administration of drug it is necessary to stop immediately. Also patients have to be informed on possibility of diarrhea during treatment. Most of the patients receiving тегасерод had single episodes of diarrhea. In most cases diarrhea took place in the first week of treatment and of course stopped at therapy continuation. If the patient has a diarrhea at present or he is inclined to its emergence, then it is not necessary to begin treatment tegaserody. It is necessary to consult with the doctor in case of emergence or strengthening of abdominal pains, heavy diarrhea or diarrhea which is followed by strong spasms, an abdominal pain, dizziness.

Side effects:

From system of digestion: diarrhea, an abdominal cavity pain, nausea, a meteorism, a syndrome of the angry intestines about ponosam, tenesmus, increase in appetite, an eructation, increase in ASAT and ALAT, KFK, a bilirubinemia, an exacerbation of cholecystitis, appendicitis, partial intestinal obstruction.

From a nervous system: headache, dizziness, migraine, sleep disorder, depression.

From cardiovascular system: arterial hypotension, stenocardia, arrhythmia, blockade of legs of a ventriculonector, tachycardia supraventrikulyarniya.

From respiratory system: asthmatic attacks.

From urinogenital system: an albuminuria, the speeded-up urination, a polyuria, pain in kidneys, an oothecoma, threat of abortion, a menorah ґі I.

From integuments: an itch, the increased sweating, a dermahemia, face edemas.

Others: an onychalgia, to back, spasms in muscles of legs, an arthropathy, increase in risk of development of neoplastic processes of a mammary gland.

Interaction with other medicines:

in vitro given researches of medicinal interaction showed absence in a tegaseroda of the oppressing influence on isoenzymes of CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 of system of P450 cytochrome, but is not excluded oppressing effect on CYP1A2 and CYP2D6. However in vivo was not observed clinically significant medicinal interaction to a tegaserod with dextromethorphan (model CYP2D6 substrate) and theophylline (model CYP1A2 substrate).

Influence on pharmacokinetics of digoxin, oral contraceptives and warfarin was not noted. The main metabolite to a maleate tegaserod in an organism - a glucuronide of 5-metoksiindol-3-carboxylic acid - does not influence activity of isoenzymes of system of P450 cytochrome in the researches in vitro.

Co-administration of a tegaserod and dextromethorphan does not change pharmacokinetics of any of these substances in clinically significant degree.

At purpose of a tegaserod along with dextromethorphan it is necessary to change a dose of these substances.

It is probable what тегасерод will not change pharmacokinetics of the medicinal substances which are metabolized by means of CYP2D6 (for example, fluoxetine, омепразол, captopril).

Co-administration of a tegaserod and theophylline does not influence theophylline pharmacokinetics therefore correction of a dose of theophylline unnecessary. Thus, it is not expected, тегасерод changes pharmacokinetics of medicinal substances which are metabolized through CYP1A2 (for example, oestradiol, омепразол).

Purpose of a tegaserod lowers Cmax and exposure of digoxin approximately by 15%. This decrease in bioavailability is not considered as clinically significant.

It is improbable that at co-administration of a tegaserod and digoxin it will be required to adjust a digoxin dose.

Researches of pharmacokinetic and pharmakodinamichesky interaction with warfarin showed lack of influence of a tegaserod on warfarin parameters at co-administration. It is not necessary to adjust a warfarin dose at co-administration with tegaserody.

Co-administration of a tegaserod does not influence ethinylestradiol pharmacokinetics at its equilibrium concentration and lowers the peak of concentration and exposure of levonorgestrel by 8%. Tegaserod does not increase risk of an ovulation at the women accepting oral contraceptives. At co-administration of a tegaserod there is no need to change the scheme of reception of oral contraceptives.

Contraindications:

Children's age up to 18 years. Tegaserod a maleate is contraindicated to patients with a heavy renal failure, with a moderate or heavy liver failure, intestinal impassability in the anamnesis, with clinically expressed diseases of a gall bladder, at suspicion on dysfunction of a sphincter of Oddi, with an adhesive desease, with the established or probable hypersensitivity to active ingredient or excipients of drug.

Overdose:

Overdose symptoms: diarrhea, headache, abdominal pain, abdominal distention, nausea and vomiting. In case of overdose it is recommended to wash out a stomach, to carry out a symptomatic treatment and the corresponding maintenance therapy.

Storage conditions:

To store in original packaging at a temperature not above 25 °C in the place, dry and unavailable to children. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister, on 1 blister in a cardboard pack.