College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
Drug Saf. 2011 Nov 1;34(11):1079-88. doi: 10.2165/11593100-000000000-00000.
Paracetamol (acetaminophen) is the most common cause of acute liver failure (ALF). ALF attributed to paracetamol is most often associated with the following features: an unintentional overdose, a single product, an opioid-paracetamol combination, duration of <7 days, and a median dose of 7.5 g/day. Currently, the recommended maximum daily dose of paracetamol is 4 g.
The aims of the study were to determine opioid-paracetamol prescription patterns, including prescriptions exceeding the recommended dose of paracetamol (4 g/day) [prescriptions and beneficiaries]; examine factors associated with receiving opioid-paracetamol prescriptions in excess of paracetamol 4 g/day; and evaluate opioid-paracetamol prescription patterns for beneficiaries with liver dysfunction.
A retrospective cohort study examining prescription data of 4.8 million beneficiaries from a US health benefits organization from 1 January 2009 through 31 December 2009. The main outcomes examined were daily paracetamol dose and liver dysfunction.
A large proportion (8.1%) of the 5.3 million prescriptions for opioid-paracetamol exceeded the recommended maximum daily dose of paracetamol (4 g/day), putting over one-quarter of a million (255 123 [18.9%]) of the 1.35 million beneficiaries receiving an opioid-paracetamol prescription at risk of toxicity. The most frequently prescribed products that exceeded paracetamol dose guidelines contained dextropropoxyphene and hydrocodone. Multiple factors, including type of product (i.e. dextropropoxyphene or oxycodone-containing), geographical location (Midwest), strength of the paracetamol in the opioid-paracetamol product (>325 mg) and prescriber specialty (dentist, physician assistant), were associated with high-dose paracetamol prescriptions. Liver dysfunction was diagnosed in 3818 cases, and 23.4% of these beneficiaries received an opioid-paracetamol prescription in the 90 days prior to the liver dysfunction diagnosis.
Although most opioid-paracetamol prescriptions are written and dispensed for <4 g/day of paracetamol, a significant portion of beneficiaries are being prescribed and dispensed excessive doses of paracetamol. Efforts to curtail this practice may involve provision of prescriber and pharmacist education, utilization of benefit manager systems to flag excessive dosing or that require confirmation of dosing, and implementation of US FDA recommendations supported by these data.
对乙酰氨基酚（扑热息痛）是急性肝衰竭（ALF）最常见的原因。扑热息痛引起的 ALF 通常与以下特征有关：非故意过量、单一产品、阿片类药物与扑热息痛的组合、持续时间<7 天、中位数剂量为 7.5g/天。目前，扑热息痛的推荐最大日剂量为 4g。
本研究的目的是确定阿片类药物与扑热息痛的处方模式，包括超过推荐剂量的扑热息痛（4g/天）的处方和受益人群；检查与接受超过 4g/天扑热息痛处方相关的因素；并评估肝功能障碍受益人群的阿片类药物与扑热息痛处方模式。
这是一项回顾性队列研究，检查了一家美国健康福利组织在 2009 年 1 月 1 日至 2009 年 12 月 31 日期间 480 万受益人的处方数据。主要观察结果是每日扑热息痛剂量和肝功能障碍。
超过 530 万份阿片类药物与扑热息痛的处方中，有很大一部分（8.1%）超过了扑热息痛的推荐最大日剂量（4g/天），这使超过 25.5 万（18.9%）名接受阿片类药物与扑热息痛处方的受益人群面临毒性风险。最常开出的超过扑热息痛剂量指南的产品含有右丙氧芬和氢可酮。多种因素与高剂量扑热息痛处方有关，包括产品类型（即右丙氧芬或含羟考酮）、地理位置（中西部）、阿片类药物与扑热息痛产品中扑热息痛的强度（>325mg）和处方医生的专业（牙医、医师助理）。在 3818 例中诊断出肝功能障碍，其中 23.4%的患者在肝功能障碍诊断前的 90 天内接受了阿片类药物与扑热息痛的处方。
尽管大多数阿片类药物与扑热息痛的处方是为<4g/天的扑热息痛开具的，但仍有相当一部分受益人群被开具和配给过量的扑热息痛。减少这种做法的努力可能涉及提供处方医生和药剂师的教育、利用受益管理系统来标记过度剂量或需要确认剂量，并实施美国 FDA 的建议，这些建议得到了这些数据的支持。
