Björkman A, Phillips-Howard P A
Department of Infectious Diseases, Roslagstull Hospital, Stockholm, Sweden.
Bull World Health Organ. 1991;69(3):297-304.
National adverse drug reaction registers in Sweden and the United Kingdom provided data on the type, severity and frequency of reported adverse reactions attributed to sulfa drugs. Reactions to the ten principal drugs were examined in terms of their half-lives and usual indications for use. Of 8339 reactions reported between 1968 and 1988, 1272 (15%) were blood dyscrasias, 3737 (45%) were skin disorders, and 578 (7%) involved the liver. These side-effects occurred with all types of sulfa drugs investigated, although at different relative rates, and 3525 (42%) of them were classified as serious. The overall case fatality rate (CFR) was 1:15 serious reactions, and was highest in patients with white blood cell dyscrasias (1:7). Drugs with longer elimination half-lives had higher CFRs, particularly for fatalities after skin reactions. In Sweden, the estimated incidences of serious reactions were between 9 and 33 per 100,000 short-term users of sulfa drugs (two weeks), between 53 and 111 among those on malaria prophylaxis, and between 1744 and 2031 in patients on continuous therapy. For dapsone, the incidence appeared to increase with higher doses. Our results indicate that sulfa drugs with short elimination half-lives deserve to be considered for use in combination with proguanil or chlorproguanil for malaria chemotherapy and possibly prophylaxis. The smaller risk of adverse reactions associated with lower-dose dapsone suggests that it should also be evaluated as a potentially safe alternative.
瑞典和英国的国家药物不良反应登记处提供了有关磺胺类药物所致不良反应的类型、严重程度和发生频率的数据。对十种主要药物的反应，根据其半衰期和常用适应证进行了研究。在1968年至1988年期间报告的8339例反应中，1272例（15%）为血液系统疾病，3737例（45%）为皮肤疾病，578例（7%）涉及肝脏。尽管相对发生率不同，但所有研究的磺胺类药物都出现了这些副作用，其中3525例（42%）被归类为严重不良反应。总体病死率（CFR）为1:15严重反应，在白细胞发育异常患者中最高（1:7）。消除半衰期较长的药物CFR较高，尤其是皮肤反应后的死亡情况。在瑞典，磺胺类药物短期使用者（两周）每10万人中严重反应的估计发生率在9至33例之间，疟疾预防用药者中为53至111例，持续治疗患者中为1744至2031例。对于氨苯砜，发生率似乎随剂量增加而升高。我们的结果表明，消除半衰期短的磺胺类药物值得考虑与氯胍或氯丙胍联合用于疟疾化疗以及可能的预防。低剂量氨苯砜相关不良反应风险较小，表明它也应作为一种潜在安全的替代药物进行评估。
