Tropisetron

International not patented name

Tropisetron

Pharmacologic action

Pharmacodynamics

It blocks the peripheral neurons presynaptic 5-HT3 receptors and the CNS thus the vomiting reflex is blocked. It blocks the vomiting reflex (and the nausea feeling accompanying the same) provoked by chemotherapeutic anti-tumor preparations stimulating the serotonin (5-HT₃) throw from the enterochromaffine-like cells in the gastro-intestinal tract mucous membrane as well as the postoperative nausea and vomiting syndrome (PONV). The effect duration is 24 hours allowing the preparation to be taken once a day. It is efficient when used again during the repeated courses of chemotherapy. Unlike a number of other preparations applied for preventing nausea and vomiting tropisetron does not provoke extrapyramidal effects (movements coordination changing manifesting by their volume reduction and tremor). It has an additional direct effect on the CNS 5-HT3 serotonin receptors transmitting impulses to the target cell by n. vagus.

Side effects

When the preparation is applied in the recommended doses the undesirable side effect are transitory. When tropisetron is received headache, constipation, dizziness, tiredness, abdominal pain, diarrhea are possible.

As in cases of appliance of other 5-HT3-receptors antagonists hypersensitivity reactions (“reactions of I type”) characterized by one or several of the following symptoms: feeling of blood rash to face and/or a generalized urticaria, feeling of heaviness behind the breast bone, dyspnea, bronchospasm developing acutely, arterial hypertension are rare.

There are publications about very rare cases of collapse, syncope or heart arrest but the causal relation with tropisetron is not determined. Some of those side effects may be provoked by the accompanying therapy or by the basal disease.

Contraindications

Hypersensitivity, pregnancy and lactation (breast feeding should be stopped for the period of treatment), childish age younger 2 years.

Appliance during pregnancy and lactation

Tropisetron is contraindicated during pregnancy. Breast feeding should be stopped for the period of treatment.

Caution measures

Care should be taken when the preparation is prescribed on the background of a not controlled hypertension, the reactions reduction possibility should be considered too.

Interaction with other medicinal preparations

The liver microsomal enzymes inductors (rifampycin, phenobarbital) reduce the blood tropisetron concentration. That is why patients metabolizing tropisetron quickly should receive the preparation larger doses (it is not necessary for patients metabolizing tropisetron slowly). Cytochrome P450 enzymic system inhibitors such as cimetidine influence on the tropisetron plasma levels are insignificant; no need to change the preparation dose in such cases. Studies of tropisetron interaction with preparations for anesthesia were not performed.

The QT interval lengthening was observed in several patients receiving tropisetron in combination with preparations provoking this interval lengthening. At the same time in the same studies it was determined that when tropisetron alone was applied in the therapeutic doses no QT interval lengthening was observed. Nevertheless when prescribing tropisetron and preparations provoking QT interval lengthening care should be taken.

Overdosing

Symptoms: In case tropisetron very high doses are prescribed repeatedly visual hallucinations may occur; in patients with preceding arterial hypertension – the arterial pressure may increase.

Treatment: A symptomatic therapy under a permanent control of vital functions and of the patient state is indicated.