Reset Askild, Skurtveit Svetlana, Furu Kari, Skovlund Eva
Medical Studies, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
Scand J Pain. 2018 Oct 25;18(4):667-674. doi: 10.1515/sjpain-2018-0103.
Background and aims Dextropropoxyphene (DXP) is a synthetic opioid that was prescribed worldwide for mild to moderate pain. It was withdrawn from the European market in 2009. In this study we aim to investigate the effect of the market withdrawal of dextropropoxyphene in Norway on overall use of opioids and other analgesics at an individual level. Methods Data were collected from the nationwide Norwegian Prescription Database (NorPD). It covers all prescription of drugs from 01 January 2004 from Norwegian pharmacies dispensed to individuals outside institutions. The study period was divided in two 2-year periods from 01 September 2008 to 31 August 2010, and from the market withdrawal of DXP on 01 September 2010 to 31 August 2012. We included every individual that filled at least one prescription of dextropropoxyphene in the first 2-year period in our study population. In this study dextropropoxyphene, codeine and tramadol are defined as "weak opioids", and all other opioids are termed "strong opioids". Results Nine thousand one hundred and seventy-one individuals were included in our study population. Four thousand two hundred and ninety filled a prescription of DXP only once and were classified as "single users", 2,990 were users with prescriptions of up to 200 defined daily doses (DDD) over the first 2-year period, or "sporadic users", and 1,886 were classified high users with over 200 DDDs over a 2-year period. After the market withdrawal 8,392 continued to be prescribed analgesics or benzodiazepines. In the single user group, the proportion of users of weak opioids decreased from 69.5% to 57.6%, whereas the proportion of users of strong opioids was unchanged. Among the sporadic user group, the proportion of users of weak opioids went from 69.7% to 71.0%, the proportion using tramadol from 39.1% to 43.9%, and the users of strong opioids from 25.8% to 31.3%. In the high user group, there was an increase in the number of users of strong opioids from 37.8% to 51.4%. The amount of strong opioids prescribed in the high user group increased from a mean of 262.5 DDD to a mean of 398.3 DDD in the following 2 years. The amount of tramadol increased in all groups and was 3 times as high in the high user group after market withdrawal of DXP. Conclusions Our study showed that the withdrawal of DXP lead to an increase in prescription of other analgesics. The proportion of users increased in all three groups and so did the prescribed amount of other analgesics. Both the proportion of users of other opioids and the amount prescribed increased considerably. However, 1 in 10 earlier users of DXP stopped using prescribed analgesics altogether in the following 2 years. The increase in use among earlier high users of DXP was most striking. Implications This study documents markedly increased prescriptions of other opioids after withdrawal of dextropropoxyphene due to its high risk of serious complications. However, consequences of the increased use of opioids among earlier high users of DXP such as changes in risk of poisonings, accidental deaths and suicides remain to be investigated.
背景与目的 右丙氧芬(DXP)是一种合成阿片类药物,曾在全球范围内用于治疗轻至中度疼痛。它于2009年退出欧洲市场。在本研究中,我们旨在调查挪威右丙氧芬退市对个体层面阿片类药物和其他镇痛药总体使用情况的影响。方法 数据收集自挪威全国处方数据库(NorPD)。该数据库涵盖了2004年1月1日起挪威药店向机构外个人发放的所有药品处方。研究期分为两个2年时间段,从2008年9月1日至2010年8月31日,以及从2010年9月1日右丙氧芬退市至2012年8月31日。我们将在第一个2年时间段内至少开具过一张右丙氧芬处方的每个人纳入研究人群。在本研究中,右丙氧芬、可待因和曲马多被定义为“弱阿片类药物”,所有其他阿片类药物被称为“强阿片类药物”。结果 我们的研究人群包括9171人。4290人仅开具过一次右丙氧芬处方,被归类为“单次使用者”;2990人在第一个2年时间段内开具的处方剂量高达200限定日剂量(DDD),被归类为“偶尔使用者”;1886人在2年时间段内开具的剂量超过200 DDD,被归类为高剂量使用者。退市后,8392人继续被开具镇痛药或苯二氮䓬类药物。在单次使用者组中,弱阿片类药物使用者的比例从69.5%降至57.6%,而强阿片类药物使用者的比例未变。在偶尔使用者组中,弱阿片类药物使用者的比例从69.7%升至71.0%,使用曲马多的比例从39.1%升至43.9%,强阿片类药物使用者的比例从25.8%升至31.3%。在高剂量使用者组中,强阿片类药物使用者的数量从37.8%增至51.4%。高剂量使用者组中开具的强阿片类药物剂量在接下来的2年里从平均262.5 DDD增至平均398.3 DDD。所有组中曲马多的使用量均增加,在右丙氧芬退市后,高剂量使用者组中的使用量是原来的3倍。结论 我们的研究表明,右丙氧芬退市导致其他镇痛药的处方量增加。所有三组中使用者的比例均增加,其他镇痛药的处方量也增加。其他阿片类药物使用者的比例和处方量均大幅增加。然而,10%的右丙氧芬早期使用者在接下来的2年里完全停止使用处方镇痛药。右丙氧芬早期高剂量使用者中使用量的增加最为显著。意义 本研究记录了由于右丙氧芬存在严重并发症的高风险,其退市后其他阿片类药物的处方量显著增加。然而,右丙氧芬早期高剂量使用者中阿片类药物使用量增加的后果,如中毒风险、意外死亡和自杀风险的变化,仍有待研究。