Bach P H, Berndt W O, Delzell E, Dubach U, Finn W F, Fox J M, Hess R, Michielsen P, Sandler D P, Trump B, Williams G
Biomedical Research Centre, Sheffield Hallam University, Omaha, NE, USA.
Ren Fail. 1998 Nov;20(6):749-62. doi: 10.3109/08860229809045173.
Overuse and abuse of phenacetin-containing mixed analgesics has contributed to end-stage renal disease. Combination analgesics, especially those coformulated with caffeine, have been implicated as imparting a greater risk of analgesic-associated nephropathy (AAN) than single or coformulated analgesics without caffeine. This has led to a recommendation that the sale of "two plus caffeine" analgesic mixtures be reclassified from over-the-counter to prescription only availability. There is a rational basis for coformulating acetylsalicylic acid (ASA) and acetaminophen (paracetamol) as this reduces the dose of each, without altering efficacy. The coformulation of caffeine with these analgesics has a significant adjuvant effect and increases analgesic efficacy 1.4-1.6-fold. Currently available animal and human data do not support the notion that the nephrotoxic risk from coformulated ASA and acetaminophen is higher than the risk from either ASA or acetaminophen alone, in equivalent analgesic doses. There are no epidemiological data that implicate caffeine in AAN, and only limited evidence that links excessive acetaminophen usage to renal disease. There is no evidence that caffeine increases analgesics papillotoxicity directly. The presence of caffeine in mixtures of analgesics are no more addictive than other sources of caffeine. There is no evidence to suggest that adding caffeine to analgesic mixtures enhances the potential for promoting analgesic misuse in the general population. Thus distinct therapeutic benefits of ASA, acetaminophen and caffeine appear to outweigh any known risk. It is doubtful if preventing the availability of these products will significantly affect the role of analgesic abuse/overuse in end-stage renal disease. Better risk management would come from a focused educational program, developed in a close collaboration between industry, healthcare professionals and consumer organizations, such a program must warn against the potential dangers of analgesic and non-steroidal anti-inflammatory drug misuse.
含非那西丁的复方镇痛药的过度使用和滥用已导致终末期肾病。复方镇痛药，尤其是与咖啡因共同配制的那些，被认为比不含咖啡因的单一或复方镇痛药具有更高的镇痛相关性肾病（AAN）风险。这导致了一项建议，即“两种加咖啡因”的镇痛混合物的销售应从非处方药重新分类为仅凭处方可用。将乙酰水杨酸（ASA）和对乙酰氨基酚（扑热息痛）共同配制有合理依据，因为这会降低每种药物的剂量，而不改变疗效。咖啡因与这些镇痛药共同配制具有显著的辅助作用，可使镇痛效果提高1.4至1.6倍。目前可得的动物和人体数据不支持这样的观点，即在等效镇痛剂量下，共同配制的ASA和对乙酰氨基酚的肾毒性风险高于单独使用ASA或对乙酰氨基酚的风险。没有流行病学数据表明咖啡因与AAN有关，仅有有限证据将过量使用对乙酰氨基酚与肾脏疾病联系起来。没有证据表明咖啡因会直接增加镇痛药的乳头毒性。镇痛药混合物中咖啡因的存在并不比其他咖啡因来源更具成瘾性。没有证据表明在镇痛药混合物中添加咖啡因会增加普通人群中促进镇痛药滥用的可能性。因此，ASA、对乙酰氨基酚和咖啡因明显的治疗益处似乎超过了任何已知风险。禁止这些产品的供应是否会显著影响镇痛药滥用/过度使用在终末期肾病中的作用，这值得怀疑。更好的风险管理将来自于由行业、医疗保健专业人员和消费者组织密切合作制定的重点教育计划，这样的计划必须警告镇痛药和非甾体抗炎药滥用的潜在危险。
