Eur J Clin Pharmacol. 2017 Apr;73(4):463-468. doi: 10.1007/s00228-016-2182-2. Epub 2016 Dec 27.
Zidovudine (ZDV) has been associated with risk of haematological toxicity. Safety data from clinical trials is generally limited to 48 weeks. We assessed the short- and mid-term toxicity of ZDV/lamivudine (3TC) fixed-dose combination scored tablets in HIV-infected children followed in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) network.
Fourteen cohorts provided data on patients <18 years of age taking ZDV/3TC scored tablets between 2008 and 2012. Rates of Division of AIDS (DAIDS) grade ≥3 laboratory adverse events (AEs) for hepatobiliary and haematological disorders were estimated by duration on drug (<12, 12-24, >24 months). Clinical adverse events and reasons for tablet discontinuation were described.
Of 541 patients on ZDV/3TC, 388 (72%) had weight and dose data available, of whom 350 (90%) weighed ≥14 kg and were eligible for tablet use; 161 (41%) were aged <10 years on an approved dose, 189 (49%) aged ≥10 years on an approved dose, and 30 (8%) were on an unapproved dose. Median age at ZDV/3TC start was 10 years, and 79% had taken ART previously (60% had prior exposure to ZDV/3TC). Overall rates of grade ≥3 AEs for absolute neutrophil counts, bilirubin, haemoglobin, platelet counts, white blood cell counts (WBC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were ≤2/100 person years (PY) for patients taking approved doses. Two hundred thirty-three (43%) patients were not on ZDV/3TC tablets at most recent follow-up; a small number (17 (7%)) discontinued due to AEs (17 (7%)), and the most common reason for discontinuation was treatment simplification (73 (31%)).
Scored ZDV/3TC tablets, both approved and taken off-label, appear to be well tolerated with few side effects. Few patients discontinued treatment due to toxicity. As ZDV/3TC tablets are taken with other antiretrovirals, it is difficult to infer association between toxicities and specific agents, highlighting the importance of widening long-term pharmacovigilance to a broader spectrum of drug combinations.
齐多夫定（ZDV）与血液学毒性风险相关。临床试验的安全性数据通常限于48周。我们在欧洲妊娠和儿科HIV队列协作组（EPPICC）网络中评估了HIV感染儿童服用齐多夫定/拉米夫定（3TC）固定剂量复方刻痕片的短期和中期毒性。
14个队列提供了2008年至2012年间年龄＜18岁服用齐多夫定/3TC刻痕片患者的数据。通过用药时间（＜12、12 - 24、＞24个月）估算艾滋病司（DAIDS）≥3级肝胆和血液系统疾病实验室不良事件（AE）的发生率。描述了临床不良事件和停用片剂的原因。
在541例服用齐多夫定/3TC的患者中，388例（72%）有体重和剂量数据，其中350例（90%）体重≥14 kg且符合片剂使用条件；161例（41%）年龄＜10岁且服用批准剂量，189例（49%）年龄≥10岁且服用批准剂量，30例（8%）服用未批准剂量。开始服用齐多夫定/3TC时的中位年龄为10岁，79%的患者此前接受过抗逆转录病毒治疗（60%曾接触过齐多夫定/3TC）。服用批准剂量的患者中，绝对中性粒细胞计数、胆红素、血红蛋白、血小板计数、白细胞计数（WBC）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）≥3级AE的总体发生率≤2/100人年（PY）。在最近一次随访时，233例（43%）患者未服用齐多夫定/3TC片剂；少数患者（17例（7%））因AE停药（17例（7%）），最常见的停药原因是治疗简化（73例（31%））。
已批准和超说明书使用的刻痕齐多夫定/3TC片剂似乎耐受性良好，副作用较少。很少有患者因毒性停药。由于齐多夫定/3TC片剂与其他抗逆转录病毒药物联用，难以推断毒性与特定药物之间的关联，这凸显了将长期药物警戒扩展到更广泛药物组合范围的重要性。
