Tropisetron

General characteristics. Structure:

Active ingredient : 1 mg of a tropisetron (in the form of a hydrochloride).

Pharmacological properties:

Pharmacodynamics. Selectively blocks presynaptic 5-HT3-retseptory of peripheral neurons and TsNS owing to what the emetic reflex is oppressed. Blocks the emetic reflex (and the feeling of nausea accompanying it) caused by the chemotherapeutic antineoplastic drugs stimulating serotonin emission (5-NTZ) from enterokhromaffinopodobny cells in a mucous membrane of digestive tract and also a syndrome of postoperative nausea and vomiting (POTR). Duration of effect makes 24 h that allows to use drug of 1 times a day. Keeps efficiency when using during repeated courses of chemotherapy. Unlike some other the drugs used for prevention of nausea and vomiting трописетрон does not cause extrapyramidal side effects (a lack of coordination of movements with reduction of their volume and trembling). Makes additional direct impact on 5-HT3-serotoninovye receptors in TsNS which mediate momentum transfer on n.vagus on a target cell.

Pharmacokinetics. Tropisetron is soaked up from digestive tract almost completely (more, than for 95%). The period of semi-absorption averages about 20 min.

Nonspecific binding of a tropisetron with proteins of plasma (it is preferential with alfa1-glycoproteins) makes 71%. Distribution volume at adults makes from 400 to 600 l; at children aged from 3 up to 6 years — about 145 l, at children aged from 7 up to 15 years — about 265 l.

The maximum concentration in plasma is reached within 3 hours. Bioavailability depends on dose size: after administration of drug in a dose of 5 mg it reaches about 60% and raises (up to 100%) after administration of drug in a dose of 45 mg. Values of bioavailability and a final elimination half-life at children are similar to the corresponding indicators observed at healthy volunteers. Metabolism of a tropisetron is carried out by a hydroxylation in 5, 6 or 7 provisions of an indole ring, from the subsequent conjugation test with formation of a glucuronide or sulfate and removal with urine or with bile (the ratio of content of metabolites in urine and Calais makes 5:1). Activity of metabolites of a tropisetron concerning 5-HT3-receptors is considerably reduced, and they do not participate in implementation of pharmacological effect of drug. Metabolism of a tropisetron has communication with genetically determined polymorphism of sparteine/debrisoquine. It is known that about 8% of persons of Caucasian race have low metabolism of sparteine/debrisoquine.

At repeated purposes of a tropisetron in the doses exceeding 10 mg twice a day there can be a saturation of fermental system of the liver participating in metabolism of a tropisetron that can lead to dozozavisimy increase in levels of a tropisetron in plasma. However, at persons, badly metabolizing трописетрон, use of such doses of drug does not lead to increase in concentration of drug in plasma above transferable values. In case of use of a tropisetron for the purpose of the prevention of nausea and vomiting during antineoplastic chemotherapy for 6 days and more in a dose of 5 mg once a day, accumulation of a tropisetron has no clinical value.

At persons, quickly metabolizing трописетрон, the elimination half-life (beta phase) makes about 8 hours; at patients, badly metabolizing трописетрон, the size of this indicator can be extended to 45 h.

The general clearance of a tropisetron makes about 1 l/min, at the same time the renal clearance makes about 10% of this size. At patients, badly metabolizing трописетрон, the general clearance decreases to 0.1–0.2 l/min, at the same time the size of renal clearance does not change. Decrease in extrarenal clearance is led approximately to 4-5-fold lengthening of an elimination half-life and to 5-7-fold increase in values of the area under a curve by "concentration time" (AUC). The size of the maximum concentration and volume of distribution at such patients do not differ from the corresponding indicators at patients, quickly metabolizing трописетрон. Patients with a low metabolic rate have a tropisetrona a share of the not changed drug which is removed with urine, above than at patients, quickly metabolizing трописетрон.

Indications to use:

The prevention of nausea and vomiting, arising owing to antineoplastic chemotherapy

Elimination of nausea and vomiting, arising in the postoperative period

The prevention of nausea and vomiting, the gynecologic intraabdominal surgical interventions arising later. For the purpose of achievement of optimum size of a ratio "effect/risk" use of drug has to be limited to patients in whose anamnesis there are data on development of postoperative nausea and vomiting.

Route of administration and doses:

The prevention of nausea and vomiting, arising owing to antineoplastic chemotherapy.

Adults. трописетрон it is recommended to adults in the form of 6-day courses on 5 mg/days. In the first day appoint in/in, for a short period before use of antineoplastic chemotherapy: in the form of infusion (after preliminary cultivation), or in the form of a slow injection (not less than 1 min.). For in/in in the form of infusions drug is dissolved with such common solutions for infusions as isotonic solution of sodium of chloride, Ringer's solution, 5% glucose solution. Then from the 2nd to the 6th day drug is appointed inside.

If use of one tropisetron has insufficient antiemetic effect, the medical effect of drug can be strengthened by purpose of dexamethasone. Inside drug should be accepted in the morning, washing down with water, at once after a rising, for 1 h before meal.

Children. At children the recommended dose of a tropisetron is more senior than 2 years makes 0,2 mg/kg; the maximum daily dose — to 5 mg. In the first day, for a short period before use of antineoplastic chemotherapy, it is recommended in/in introduction in the form of infusion (after preliminary cultivation). Then from the 2nd to the 6th day drug is appointed inside.

Tropisetron can be appointed in the form of solution for intake, at once after cultivation of the corresponding quantity of the tropisetron which is contained in an ampoule, orange juice or other drink and has to be accepted in the morning, to 1 h before meal.

Elimination and the prevention of nausea and vomiting, arising in the postoperative period.

Adults. It is recommended in/in introduction of a tropisetron in a dose of 2 mg in the form of infusion (after preliminary cultivation), or in the form of a slow injection (not less than 30 sec.). трописетрон it is necessary to apply to the prevention of nausea and vomiting arising in the postoperative period shortly before giving an anesthesia.

Features of use:

Glass ampoules contain on 5 mg of a tropisetron in 5 ml of aqueous solution. We will combine the solution which is contained in ampoules with the following solutions for injections (1 mg of a tropisetron gets divorced in 20 ml): glucose of 5%; Mannitolum of 10%; Ringer's solution; sodium chloride of 0,9%; potassium chloride of 0,3%. We will also combine the solution which is contained in ampoules with containers for infusions of usual type (made of glass, PVC), and sets for performing infusions.

To use only freshly cooked solutions.

Use during pregnancy and a lactation. Contraindicated during pregnancy. For the period of treatment it is necessary to stop breastfeeding.

It is necessary to be careful at appointment against the background of uncontrollable hypertensia and to consider a possibility of reduction in the rate of reaction.

Side effects:

At use of drug in the recommended doses undesirable effects have passing character. At use of a tropisetron the headache, a lock, dizziness, fatigue, abdominal pains, diarrhea are possible.

As well as in case of use of other antagonists of 5-HT3-receptors, hypersensitivity reactions ("reaction of the I type") which are characterized by one or several following symptoms are seldom observed: feeling of rush of blood to the person and/or a generalized small tortoiseshell, feeling of weight behind a breast, an asthma, sharply developing bronchospasm, arterial hypotension.

It was reported about very exceptional cases of a collapse, faint or cardiac standstill, but the causal relationship of these phenomena using a tropisetron was not established. Some of them could be caused by the accompanying therapy or a basic disease.

Interaction with other medicines:

Inductors of microsomal enzymes of a liver (rifampicin, phenobarbital) reduce concentration of a tropisetron in blood.

Therefore at patients who quickly metabolize трописетрон increase in doses (from patients who metabolize трописетрон slowly, it is not required) is necessary.

Influences of inhibitors of fermental system of P450 cytochrome, such as Cimetidinum, on levels of a tropisetron in plasma are insignificant; changes of a drug dosing in such cases are not required.

Researches of interaction of a tropisetron with anesthetics were not conducted.

Lengthening of an interval of QT was noted at several patients to whom трописетрон it was appointed in combination with the drugs causing lengthening of this interval.

At the same time, in those researches where only one was applied трописетрон in therapeutic doses, lengthening of an interval of QT was not noted. Nevertheless, it is necessary to be careful at the simultaneous use of a tropisetron and drugs causing lengthening of an interval of QT.

Contraindications:

Hypersensitivity, pregnancy and lactation (it is necessary to stop breastfeeding for the period of treatment), children's age up to 2 years.

Overdose:

Symptoms: In case of repeated use of very high doses of a tropisetron visual hallucinations are possible; patients with the previous arterial hypertension have an increase in arterial pressure.

Treatment: The symptomatic treatment under constant control of the vital functions of an organism and condition of the patient is shown

Issue conditions:

According to the recipe

Packaging:

Solution for injections of 0,1% in ampoules of 5 ml in a blister strip packaging No. 5х1, No. 5х2.