Dolasetron (
dolasetron mesilate) is a
pseudopelletierine-derived
5-HT3 antagonist which has recently become available for clinical use. It is rapidly converted in vivo to its active major metabolite,
hydrodolasetron, which appears to be largely responsible for its pharmacological activity. In clinical trials, single intravenous or oral doses of
dolasetron were effective in preventing acute
chemotherapy-induced
nausea and
vomiting (CINV). Intravenous doses of 1.8 mg/kg achieved complete suppression of
vomiting in approximately 50% of patients receiving highly emetogenic
cisplatin-containing
chemotherapy and in approximately 60 to 80% of patients receiving moderately emetogenic
chemotherapy. In the latter setting, oral doses of 200 mg achieved similar response rates. In comparative studies, intravenous
dolasetron 1.8 mg/kg was as effective as intravenous
granisetron 3 mg or
ondansetron 32 mg after highly emetogenic
chemotherapy, and oral
dolasetron 200 mg was equivalent to multiple oral doses of
ondansetron (3 or 4 doses of 8 mg) after moderately emetogenic
chemotherapy.
Dolasetron 1.8 mg/kg was superior to
metoclopramide in preventing
emesis induced by high dose
cisplatin or by moderately emetogenic
chemotherapy in high risk subgroups.
Dolasetron has also shown efficacy in preventing
radiotherapy-induced
nausea and
vomiting (RINV) in preliminary studies. Single intravenous or oral
dolasetron doses ranging from 12.5 to 100 mg and 25 to 200 mg, respectively, were significantly more effective than placebo in preventing
postoperative nausea and vomiting (
PONV) in female surgical patients. A 50 mg intravenous dose was as effective in preventing
PONV as
ondansetron 4 mg in a mixed-gender group. Intravenously administered
dolasetron was also effective in treating established
PONV, although complete suppression of
vomiting was achieved in < 40% of patients.
Dolasetron has a tolerability profile characteristic of this class of compounds, with
headache,
dizziness and diarrhoea being the most commonly occurring adverse events in clinical trials. Diarrhoea is not thought to be related to
dolasetron administration, being experienced mostly by patients receiving
chemotherapy.
Dolasetron and other
5-HT3 receptor antagonists have been associated with minor changes in ECG intervals, but these generally do not appear to be clinically important. Thus, available evidence suggests that
dolasetron will provide an alternative to other
5-HT3 receptor antagonists for the management of CINV and
PONV. Further studies are required to determine whether it offers any advantages over other agents in these settings and to determine the optimum dosage for preventing RINV.