Cardiovascular safety of the 5-HT3-receptor antagonists readdressed.
Talbot DC., Harris AL.
8209 Background: Of the available 5-HT3-receptor antagonists (RAs), dolasetron, tropisetron and palonosetron include cardiovascular (CV) warnings/precautions in their labelling that should be considered when using these products in patients with existing or possible cardiac impairment. A recent report reviewed CV safety among 5-HT3-RAs and suggested that ECG alteration is a class effect.(1) In contrast, other recently published reports demonstrate important differences regarding CV safety. METHODS: This review will readdress issues regarding CV safety among 5-HT3-RAs. RESULTS: Clinical trials demonstrate that dolasetron is associated with increases in PR, QRS and QTc intervals and increased heart rate, whereas granisetron and ondansetron lack proarrhythmic activity.(2) Recently, a 'signal' for ventricular arrhythmia and cardiac arrest was found for dolasetron but not granisetron in the FDA combined SRS/AERS database (adverse events 1966-present).(3) Granisetron is not associated with significant CV changes, even at doses as high as 160 μg/kg.(4) Ondansetron does not have a CV precaution, but a significant increase in QTc interval has been reported with higher doses.(5) Contrary to the idea that all 5-HT3-RAs carry a similar CV risk, evidence in patients and healthy volunteers suggests otherwise.(3) However, whether trials have reported asymptomatic or clinically relevant 5-HT3-RA-evoked CV changes may be of little relevance, as the issue of CV safety should be considered in context: elderly patients represent the majority of cancer patients and CV comorbidity is common in this population. CONCLUSIONS: QT interval changes have been linked with sudden cardiac death. Thus the CV safety of cancer and supportive therapies, and their additive complications, should be a consideration when choosing therapy. Therefore, it seems prudent to use a 5-HT3-RA that has no warning/precaution concerning CV safety. 1 Navari, Koeller. Ann Pharmacother 2003;37:1276-86 2 Keefe. Oncologist 2002;7:65-72 3 Schnell, Coop. SIOG 2003;37 4 Carmichael, Harris. Anti-Cancer Drugs 2003;14:739-44 5 Boike et al. Am J Health-Syst Pharm 1997;54:1172-6 # [Table: see text].