Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
National Poisons Information Centre, Tox Info Suisse, Associated Institute of the University of Zurich, Zurich, Switzerland.
JAMA Netw Open. 2020 Oct 1;3(10):e2022897. doi: 10.1001/jamanetworkopen.2020.22897.
Acetaminophen (paracetamol) is among the most widely used pain medications worldwide; while safe within the therapeutic range, intake exceeding 4000 mg/d can lead to hepatotoxicity. Prior evidence suggests that limiting the availability of large quantities of acetaminophen is associated with decreased acetaminophen-related poisonings and mortality; in Switzerland, 500-mg tablets are available over-the-counter (OTC) and, as of October 2003, 1000-mg tablets are available with prescription.
To evaluate the association of adding 1000-mg acetaminophen tablets to the Swiss market with utilization and poisonings.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a quasi-experimental interrupted time series analysis to evaluate 15 790 acetaminophen poison records from January 1, 2000, to December 31, 2018. All calls for acetaminophen-related poisonings identified from the National Swiss Poisons Centre and all sales for oral acetaminophen tablets (prescription and OTC) dispensed between January 2000 and December 2018 were included.
October 3, 2003 (Q4 2003), was defined as the intervention date, corresponding to the date of market entry for 1000-mg acetaminophen tablets in Switzerland.
The primary outcome was the number of quarterly acetaminophen-related poison calls to the National Poison Centre. Additional outcomes included quarterly sales for acetaminophen and change in poisoning circumstances, stratified by preintervention and postintervention periods and by formulation (ie, 500-mg and 1000-mg tablets).
Between 2000 and 2018, 15 790 acetaminophen-related poisoning calls were identified, of which 10 628 (67.3%) were regarding women, and the mean (SD) age of patients was 25.2 (18.2) years. The interrupted time series analysis identified a significant increase in the slope for the number of reported poisonings following the intervention point, particularly for accidental circumstances (z score, -3.62; P < .001). In the preintervention period, 120 of 961 poisonings (15.3%) involved a dose greater than 10 000 mg, while for the postintervention period, 1140 of 5696 (30.6%) had a dose larger than 10 000 mg (P < .001). There was a rapid uptake in 1000-mg acetaminophen sales, while sales of the 500-mg tablet decreased slightly. Since 2012, a mean (SD) of 20.7 million (1.4 million) 1000-mg tablets were dispensed quarterly compared with 2.7 million (0.5 million) 500-mg tablets.
This study found a significant increase in acetaminophen dispensing and acetaminophen-related poisonings in Switzerland following the approval of 1000-mg tablets in 2003. The availability of 1000-mg acetaminophen should be re-evaluated to minimize the potential for accidental poisonings.
对乙酰氨基酚（扑热息痛）是世界上使用最广泛的止痛药物之一；在治疗范围内使用是安全的，但摄入量超过 4000 毫克/天可能会导致肝毒性。先前的证据表明，限制大剂量扑热息痛的供应与减少与扑热息痛相关的中毒和死亡率有关；在瑞士，500 毫克片剂可在柜台（OTC）购买，自 2003 年 10 月起，1000 毫克片剂可凭处方购买。
评估在瑞士市场添加 1000 毫克对乙酰氨基酚片剂与利用率和中毒之间的关联。
设计、设置和参与者：本横断面研究使用准实验中断时间序列分析评估了 2000 年 1 月 1 日至 2018 年 12 月 31 日期间的 15790 例扑热息痛中毒记录。所有从国家瑞士中毒中心识别的与扑热息痛相关的中毒电话以及 2000 年 1 月至 2018 年 12 月期间分发的口服对乙酰氨基酚片剂（处方和 OTC）的所有销售均包括在内。
2003 年 10 月 3 日（2003 年第四季度）被定义为干预日期，对应于瑞士 1000 毫克对乙酰氨基酚片剂上市的日期。
主要结果是国家中毒中心接到的与扑热息痛相关的中毒电话数量的季度数。其他结果包括对乙酰氨基酚的季度销售情况以及中毒情况的变化，按干预前和干预后期间以及制剂（即 500 毫克和 1000 毫克片剂）进行分层。
在 2000 年至 2018 年期间，共确定了 15790 例扑热息痛相关中毒电话，其中 10628 例（67.3%）涉及女性，患者的平均（SD）年龄为 25.2（18.2）岁。中断时间序列分析确定，在干预点后，报告的中毒数量的斜率显著增加，特别是在意外情况下（z 分数，-3.62；P <.001）。在干预前期间，961 例中毒中有 120 例（15.3%）剂量大于 10000 毫克，而在后干预期间，5696 例中毒中有 1140 例（30.6%）剂量大于 10000 毫克（P <.001）。1000 毫克对乙酰氨基酚的销售量迅速增加，而 500 毫克片剂的销售量略有下降。自 2012 年以来，每季度平均（SD）分发 2070 万（140 万）粒 1000 毫克片剂，而分发 270 万（50 万）粒 500 毫克片剂。
本研究发现，自 2003 年批准 1000 毫克片剂以来，瑞士的对乙酰氨基酚配药和与对乙酰氨基酚相关的中毒显著增加。应重新评估 1000 毫克对乙酰氨基酚的供应情况，以尽量减少意外中毒的可能性。
