Drug Class Description
5HT3 -antagonists (anti-emetics).

Generic Name
Tropisetron

Drug Description
2mg/2ml ampoules. Uncoloured glass ampoules containing clear, colourless or very faintly brown-yellow solution. Each ampoule contains 2.26mg of tropisetron hydrochloride (corresponding to 2mg of tropisetron base) in 2ml.

Presentation
Glass ampoules containing an aqueous solution for intravenous administration.

Indications
AdultsTreatment of post-operative nausea and vomiting.Prevention of post-operative nausea and vomiting in patients at high risk of developing post-operative nausea and vomiting.ChildrenPrevention of cancer chemotherapy-induced nausea and vomiting.

Adult Dosage
Post-operative nausea and vomiting in adultsnavoban is recommended as a single 2mg dose given intravenously either as an infusion (diluted in a common infusion fluid such as normal saline, Ringer's solution, glucose 5% or fructose 5%) administered over 15 minutes, or as a slow injection (not less than 30 seconds).In the case of treatment of post-operative nausea and vomiting, NAVOBAN has been shown to be effective when given within two hours of the end of anaesthesia prior to patients being moved from the operating theatre recovery area.In the case of prevention of post-operative nausea and vomiting, NAVOBAN should be administered shortly before the induction of anaesthesia.Cancer chemotherapy-induced nausea and vomiting in childrenIn children, the efficacy and safety of tropisetron 0.2mg/kg/day (maximum 5mg/day) has only been investigated in open label, non-comparative studies which have included 164 children aged 2 years and over.The recommended dose for NAVOBAN in children over two years of age is 0.2mg/kg, up to a maximum dose of 5mg per day. On day one, shortly before chemotherapy commences, NAVOBAN should be given by intravenous administration as a slow injection (not less than 1 minute) or as an injection into a running infusion. For intravenous infusion, NAVOBAN should be diluted (1mg tropisetron per 20ml diluent) in sodium chloride 0.9% w/v (physiological saline). Alternative diluents are Ringer's solution, glucose 5% and fructose 5%; diluents other than those recommended should not be used.For children weighing less than 25kg, NAVOBAN should be given once daily by intravenous administration on days 2 up to 5 dependent upon the chemotherapy regimen. For children weighing 25kg and above, NAVOBAN (5mg) should be given once daily by oral administration on days 2 up to 6. If oral administration is problematic NAVOBAN (5mg) can be given by intravenous administration.

Child Dosage
Chemotherapy: under 2 years, not recommended; over 2 years, 0.2 mg/kg by slow intravenous injection or infusion shortly before chemotherapy, maximum 5 mg daily. In children under 25kg, repeat intravenous administration on day 2 up to day 5 depending on chemotherapy regimen; in children over 25 kg, give 5 mg orally on day 2 up to day 6.

Contra Indications
Hypersensitivity to tropisetron, or other 5-HT3 receptor antagonists. NAVOBAN must not be given to pregnant women, unless termination of early pregnancy is part of the surgical procedure.

Special Precautions
Use in poor metabolisers of sparteine/debrisoquineIn patients belonging to this group (about 8% of the Caucasian population) the elimination half-life of tropisetron is prolonged (4 to 5 times longer than in extensive metabolisers), however, studies indicate that for 7 day courses in patients with poor metabolism, the usual dose of 2mg does not need to be reduced.ElderlyThere is no evidence that elderly patients require different dosages or experience side effects different from those in younger patients.Use in patients with impaired hepatic or renal functionNo change in the pharmacokinetics of tropisetron occurs in patients with acute hepatitis or fatty liver disease. In contrast, patients with liver cirrhosis or impaired kidney function may have plasma concentrations up to 50% higher than those found in healthy volunteers belonging to the group of extensive metabolisers of sparteine/debrisoquine. Nevertheless, no dosage reduction is necessary in such patients when the recommended 2mg dose is given.Use in childrenNAVOBAN is not recommended for the treatment or prevention of post-operative nausea and vomiting in children.Use in adultsWhen used for the prevention of cancer chemotherapy-induced nausea and vomiting in adults, NAVOBAN capsules 5mg and NAVOBAN ampoules 5mg/5ml should be used. Use of NAVOBAN ampoules 2mg/2ml for this indication is reserved for children.Use in cardiac patientsProlongation of the QTc interval, which was not clinically significant, has been observed after high (up to 80mg) doses of IV tropisetron. Therefore caution should be exercised in patients with cardiac rhythm or conduction disturbances, or in patients treated with anti-arrhythmic agents or beta-adrenergic blocking agents.Preclinical safety studiesIn several in vitro and in vivo tests, NAVOBAN has been shown to have no mutagenic potential. In 2-year carcinogenicity studies in rats and mice, the incidence of liver adenomas was increased only in male mice receiving 30 and 90mg/kg/day, with no effects seen at 10mg/kg/day Additional in vitro and in vivo investigative studies suggested that the observed effects in the livers of male mice were probably both species- and sex-specific.

Interactions
Concomitant administration of NAVOBAN with therapeutic agents known to induce hepatic metabolic enzymes (e.g. rifampicin, phenobarbital) results in lower plasma concentrations of tropisetron and therefore requires an increase in dosage in extensive metabolisers (but not in poor metabolisers). The effects of cytochrome P450 enzyme inhibitors such as cimetidine on tropisetron plasma levels are negligible and do not require dose adjustment.Care should be taken when other drugs that are likely to prolong QT interval are used concomitantly with tropisetron.

Adverse Reactions
The undesirable effects are transient at the recommended dose. Most frequently reported at the recommended 2mg dose was headache, whereas at higher doses constipation and, less frequently, dizziness, fatigue and gastrointestinal disorders such as abdominal pain and diarrhoea were observed as well.As with other 5-HT3 receptor antagonists, hypersensitivity reactions ('type I-reactions') with one or more of the following symptoms have rarely been observed: facial flushing and/or generalised urticaria, chest tightness, dyspnoea, acute bronchospasm, hypotension. In very rare instances when NAVOBAN has been used to prevent chemotherapy-induced nausea and vomiting, collapse, syncope or cardiovascular arrest have been reported. The relationship to NAVOBAN has not been established and these effects may have been caused by the concomitant therapy or the underlying disease.

Manufacturer
Novartis Pharmaceuticals UK Ltd

Drug Availability
(POM)

Updated
01 June 2009