Brabin Bernard J, Eggelte Teunis A, Parise Monica, Verhoeff Francine
Liverpool School of Tropical Medicine, Child and Reproductive Health Group, UK.
Drug Saf. 2004;27(9):633-48. doi: 10.2165/00002018-200427090-00002.
The need to consider using dapsone in pregnant women for its antimalarial activity is becoming greater in areas where Plasmodium falciparum resistance to chloroquine and pyrimethamine-sulfadoxine is rapidly increasing. Dapsone in combination with other antimalarials might provide a valuable alternative for both treatment and prophylaxis. This review assesses the clinical pharmacology of dapsone and its adverse drug reactions in relation to haemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, blood dyscrasias and methaemoglobinaemia. Studies are summarised reporting its use in leprosy, dermatological and other conditions, and malaria, in relation to maternal and infant outcomes. A total of 924 pregnancies were identified during which dapsone therapy was taken. Only limited data are available and this precludes a meaningful quantitative benefit-risk analysis. Mild degrees of haemolysis consistently occur with continued therapy, although adverse effects may be less likely with intermittent treatment, as most reported adverse effects have occurred with long-term use of dapsone. There are a number of gaps in knowledge where more data are needed. These include no data on pharmacokinetics in pregnancy and whether these are altered with co-administration of chlorproguanil. Potential complications in women with severe anaemia are unknown and there is no information on haemolytic effects in women or the fetus with G6PD deficiency. The use of dapsone in HIV-infected women in malarious areas could carry increased risks because of the immunosuppressive actions of the drug. Trials of dapsone therapy in pregnancy should be considered in malarious areas where there is good reason for its deployment. Controlled trials have provided data on maternal tolerance, and dapsone in combination with other antimalarial drugs can offer clear benefit in terms of improved birthweight. The use of dapsone combinations should be considered when no good alternative is available and the threat of malaria is the greater risk.
在恶性疟原虫对氯喹和乙胺嘧啶-磺胺多辛耐药性迅速增加的地区,考虑在孕妇中使用氨苯砜进行抗疟治疗的需求日益增大。氨苯砜与其他抗疟药联合使用可能为治疗和预防提供一种有价值的替代方案。本综述评估了氨苯砜的临床药理学及其与溶血、葡萄糖-6-磷酸脱氢酶(G6PD)缺乏、血液系统疾病和高铁血红蛋白血症相关的药物不良反应。总结了关于其在麻风病、皮肤病及其他疾病以及疟疾中的应用与母婴结局相关的研究。共确定了924例在孕期接受氨苯砜治疗的病例。现有数据有限,无法进行有意义的定量效益-风险分析。持续治疗时会持续出现轻度溶血,不过间歇治疗时不良反应可能较少,因为多数报告的不良反应都发生在长期使用氨苯砜的情况下。在许多知识领域存在空白,需要更多数据。这些空白包括孕期氨苯砜的药代动力学数据,以及与氯胍合用时其药代动力学是否改变。重度贫血女性的潜在并发症尚不清楚,也没有关于G6PD缺乏女性或胎儿溶血效应的信息。在疟疾流行地区,由于氨苯砜的免疫抑制作用,HIV感染女性使用氨苯砜可能会带来更高风险。在有充分理由使用氨苯砜的疟疾流行地区,应考虑进行孕期氨苯砜治疗试验。对照试验提供了关于母体耐受性的数据,氨苯砜与其他抗疟药联合使用在改善出生体重方面可带来明显益处。当没有其他良好替代方案且疟疾威胁风险更大时,应考虑使用氨苯砜联合用药。