Adverse events ethnic differences

These differences may become particularly germane if co-prescribing with some antipsychotics is undertaken. For example, in certain individuals, combinations of clozapine with benzodiazepines may lead to unexpected adverse events, including delirium and augmented respiratory depression (Jackson, Markowitz Brewer-ton, 1995 Grohmann et al, 1989). Presumably if there are additive or synergistic effects of ethnicity on clearance of one or both substances, adverse events may be enhanced. Similar interactions are theoretically possible with olanzapine, as adverse interactions have been described between olanzapine and benzodiazepines, at least in the elderly (Kryzhanovskaya etal, 2006). 

Custom (continuing to do things as they have previously been done) also limits the power of trials to identify safety issues. While there are now regulatory inducements to include more women, the young, and ethnic minorities in trials, the first two groups still are not proportionately incorporated because of both the perceived risks of adverse events that they represent and because historically they have not been. Ethnic minorities, particularly African Americans, present a different problem in that there is a historically based resistance to participation in such trials. 

The end result of these differences, although apparent rather than real, may be why the recommended dose of captopril (an ACE Inhibitor, antihypertensive drug) is 75—450 mg per day in the United States and 37.5-122.5 mg per day in Japan (with overall adverse events of 39% and 3.8% respectively). With a nonsteroidal antiinflammatory agent, overall adverse events were 45-51 % in the United States and 24% in Japan at the same dosage however, efficacy was the same (Dziewanowska, 1992). In general, the British, Dutch and Scandinavian data are closer to those observed in the United States, with the German and Swiss data least reactive and French, Italian and Spanish in between. As mentioned previously, severe ADRs in clinical studies tend to be the same the major difference was in minor adverse events, such as nausea, headache and so on. Thus, national temperament also may play a part in the expectation of efficacy and ADR. This finding was reflected in a study of attitudes of 4000 nurses from 13 countries to ethnic tolerance of pain... 

Dr S. Walker of CMR approached European and US companies for information on 21 drugs available in the three regions. Within this narrow sample, only one drug had genetic polymorphism, but even this did not translate to ethnic variations. Three other drugs showed regional variability in PK, but these were attributable to different formulations, different sample times and reduction of the initial dose. The CMR survey confirmed that the reported levels of adverse events were lower in Japanese patients, even when adjusted for dose - a cultural variation. 

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