Drug Saf

A risk-benefit assessment of serotonin 5-HT3 receptor antagonists in antineoplastic therapy-induced emesis.

Perez EA.
Mayo Foundation, Jacksonville, Florida, USA.
Insight into the pathophysiology of antineoplastic therapy-induced nausea and vomiting led to the development of the serotonin 5-HT3 receptor antagonists as the most potent class of antiemetic agents. Among those which have been investigated are ondansetron, granisetron, tropisetron and dolasetron. A risk-benefit analysis of these drugs must not only account for the modest clinical differences in efficacy and tolerability, but also should include such issues as ease of use, route of administration, dosage considerations and patient preference. Pharmacokinetic and preclinical studies reveal distinctions among these antiemetics, but, overall, these distinctions do not translate in to clinically significant differences. In clinical trials, the most widely studied members of the 5-HT3 receptor antagonists are granisetron and ondansetron, which have been found to possess equivalent antiemetic efficacy. Dolasetron and tropisetron are also available, and some randomised trials have also documented their similar antiemetic activity, depending on the doses and schedules used. The equivalent efficacy of oral granisetron 2 mg versus intravenous ondansetron 32 mg has recently been demonstrated in prospective randomised clinical trials in patients receiving either highly emetogenic or moderately emetogenic antineoplastic therapy. The utilisation and efficacy of oral ondansetron and dolasetron in patients receiving moderately emetogenic antineoplastic therapy has also been documented. This review offers a brief overview of the pharmacokinetic and preclinical research on the 5-HT3 antagonists, a review of the comparative clinical trials of the major members of this class and a summary risk-benefit assessment that considers clinical applicability and cost, as well as efficacy and safety.

A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch.

Year 1998
Greenland S. Satterfield MH. Lanes SF.
Department of Epidemiology, University of California, Los Angeles, USA.
To estimate the frequency of adverse effects associated with the use of the transdermal nicotine patch, we abstracted and analysed data from 47 reports of 35 clinical trials. The meta-analysis presented here represents a synthesis of data from 41 groups of nicotine patch recipients totalling 5501 patients, and 33 groups of placebo recipients totalling 3752 patients. Smoking abstinence was the primary outcome in 32 of the trials, and relief of colitis symptoms was the primary outcome in 2 of the trials; 1 study of contact sensitisation was included in the skin irritation analysis. The patch was clearly effective as an aid to smoking abstinence. Despite the large number of patients in the analysis, few adverse cardiovascular outcomes (myocardial infarction, stroke, tachycardia, arrhythmia, angina) were reported, and no excess of these outcomes was detected among patients assigned to nicotine-patch use. The incidences of several minor adverse effects were clearly elevated among the nicotine-patch groups, especially sleep disturbances, nausea or vomiting, localised skin irritation and respiratory symptoms, but the background rates and risk ratios varied considerably across studies. The incidence of nausea or vomiting appeared to be lowest when the patch dose was tapered. The results of this meta-analysis indicate that very large studies would be needed to assess the effect of the patch, if any, on serious, rare outcomes. These results also suggest that the rate of minor adverse effects might be lowered by modifying patch-use protocols.