Tropisetron Other names: Tropisetron hydrochloride

As a prolongation of the QTc interval has been observed in patients administered tropisetron, care should be taken when other drugs that are likely to prolong the QT interval are taken concomitantly with tropisetron.

Concomitant administration of tropisetron with rifampicin or with other liver enzyme-inducing drugs (e.g. phenobarbital) results in lower plasma concentrations of tropisetron and, therefore, requires an increase in dosage in extensive metabolisers (but not in poor metabolisers).

Category B3.

Reproductive studies have been performed in rats, rabbits and monkeys at oral doses up to 60, 120 and 180 mg/kg/day, respectively, and have revealed no evidence of a drug related teratogenic effect. In rats and rabbits there were increased incidences of post implantation loss and delayed development of pups at doses greater than 20 and 60 mg/kg/day, respectively. Studies in rats also showed an increased incidence of post-natal loss at doses of 15 mg/kg/day and above.

Tropisetron is excreted in the breast milk of rats. It is not known whether tropisetron is excreted into human milk and therefore patients on tropisetron should not breast-feed.

Carcinogenicity studies showed no evidence of a drug related carcinogenic response at doses up to 45 mg/kg/day in the rat and 90 mg/kg/day in the female mouse. In the male mouse there was a statistically significant increase in the incidence of benign hepatocellular neoplasia at doses of 30 mg/kg/day and above. Tropisetron was not mutagenic in standard tests for mutagenicity.

No data exist on the effect of tropisetron on the ability to drive or operate machinery. The occurrence of dizziness and fatigue as side effects should be taken into account.

In general, tropisetron is well tolerated and the side-effects are transient at the recommended dose. The most frequently reported adverse reaction at the 2 mg dose was headache. At the 5 mg dose, constipation and, less frequently, dizziness, fatigue, somnolence, and gastrointestinal disorders, such as abdominal pain, diarrhoea and anorexia were observed as well.

As with other 5-HT₃ receptor antagonists, hypersensitivity reactions (“type 1-reactions”) with one or more of the following symptoms have been observed: flushing and/or generalised urticaria, chest discomfort, dyspnoea, acute bronchospasm, hypotension.

Tropisetron was found to cause prolongation of the QT interval although this was not of clinical significance.

Listed in the following table are the frequencies of adverse events observed in more than 1% of patients exposed to each treatment in the clinical trials discussed under Clinical trials on use in post-operative nausea and vomiting.

With the exception of headache, the frequency, severity and relationship to the study drug of these events was similar for tropisetron and placebo. Therefore it is likely that these events can be attributed to the anaesthesia or the surgical procedures.

The following adverse reactions have been observed in less than 1% of patients exposed to each treatment in the clinical trials: syncope, urticaria generalized.

Post-marketing experience

The following adverse reactions have been reported during post approval use of tropisetron. Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following hypersensitivity reactions have been rarely observed: rash, erythema and anaphylactic reactions/shock. In very rare instances, collapse and cardiovascular arrest have been reported. Some may have been caused by the concomitant chemotherapy or the underlying disease.