Kotlinska-Lemieszek Aleksandra, Paulsen Ornulf, Kaasa Stein, Klepstad Pål
Department of Palliative Medicine Karol Marcinkowski University of Medical Sciences, Poznan, Poland; Hospice Palium, University Hospital of the Lord's Transfiguration, Poznan, Poland.
Palliative Care Unit, Department of Medicine, Telemark Hospital Trust, Skien, Norway; European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
J Pain Symptom Manage. 2014 Dec;48(6):1145-59. doi: 10.1016/j.jpainsymman.2014.03.008. Epub 2014 Apr 26.
Patients with advanced cancer need multiple drugs to control symptoms and to treat cancer and concomitant diseases. At the same time, the goal of treatment changes as life expectancy becomes limited. This results in a risk for polypharmacy, maintained use of unneeded drugs, and drug-drug interactions (DDIs).
The aim of the study was to analyze the use of medications and to identify unneeded drugs, and drugs and drug combinations with a risk for DDIs in a cohort of advanced cancer pain patients, defined by a need for a World Health Organization analgesic ladder Step III opioid.
All drugs taken within a study day by cancer patients receiving opioids for moderate or severe pain (Step III opioids) were analyzed. Nonopioids and adjuvants were analyzed for their use across countries. Unneeded medications and drugs and drug combinations with a risk for pharmacodynamic and pharmacokinetic DDIs were identified on the basis of published literature and electronic resources.
In total, 2282 patients from 17 centers in 11 European countries were included. They received a mean of 7.8 drugs (range 1-20). Over one-quarter used 10 or more medications. The drugs and drug classes most frequently coadministered with opioids were proton pump inhibitors, laxatives, corticosteroids, paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs, metoclopramide, benzodiazepines, anticoagulants, antibiotics, anticonvulsants, diuretics, and antidepressants. The use of nonopioids and essential adjuvants varied across countries. Approximately 45% of patients received unnecessary or potentially unnecessary drugs, and about 7% were given duplicate or antagonizing agents. Exposures to DDIs were frequent and increased the risk of sedation, gastric ulcerations, bleedings, and neuropsychiatric and cardiac complications. Many patients were exposed to pharmacokinetic DDIs involving cytochrome P450, including about 58% who used a Step III opioid CYP3A4 (izoenzyme of cytochrome P450) substrate, and more than 10% who were given major CYP3A4 inhibitors or inducers.
Patients with cancer treated with a World Health Organization Step III opioid use a high number of drugs. Nonopioid analgesics and corticosteroids are frequently used, but different patterns of use between countries were found. Many patients receive unneeded drugs and are at risk of serious DDIs. These findings demonstrate that drug therapy in these patients needs to be evaluated continuously.
晚期癌症患者需要多种药物来控制症状、治疗癌症及并发疾病。同时，随着预期寿命缩短，治疗目标也会改变。这导致了多重用药、持续使用不必要药物以及药物相互作用（DDIs）的风险。
本研究旨在分析一组晚期癌症疼痛患者的用药情况，确定不必要的药物以及存在药物相互作用风险的药物和药物组合，该组患者定义为需要世界卫生组织镇痛阶梯Ⅲ级阿片类药物。
分析了接受中度或重度疼痛阿片类药物（Ⅲ级阿片类药物）治疗的癌症患者在研究日内服用的所有药物。对非阿片类药物和辅助药物在不同国家的使用情况进行了分析。根据已发表的文献和电子资源，确定了不必要的药物以及存在药效学和药代动力学药物相互作用风险的药物和药物组合。
总共纳入了来自11个欧洲国家17个中心的2282名患者。他们平均服用7.8种药物（范围为1 - 20种）。超过四分之一的患者使用10种或更多药物。与阿片类药物最常联合使用的药物和药物类别有质子泵抑制剂、泻药、皮质类固醇、对乙酰氨基酚、非甾体抗炎药、甲氧氯普胺、苯二氮䓬类、抗凝剂、抗生素、抗惊厥药、利尿剂和抗抑郁药。非阿片类药物和必需辅助药物的使用在不同国家有所不同。约45%的患者接受了不必要或可能不必要的药物，约7%的患者服用了重复或拮抗药物。药物相互作用的情况很常见，增加了镇静、胃溃疡、出血以及神经精神和心脏并发症风险。许多患者存在涉及细胞色素P450的药代动力学药物相互作用，其中约58%使用Ⅲ级阿片类细胞色素P450 3A4（细胞色素P450同工酶）底物，超过10%的患者使用主要的细胞色素P450 3A4抑制剂或诱导剂。
接受世界卫生组织Ⅲ级阿片类药物治疗的癌症患者使用大量药物。非阿片类镇痛药和皮质类固醇经常使用，但发现不同国家的使用模式不同。许多患者接受了不必要的药物，且存在严重药物相互作用的风险。这些发现表明，这些患者的药物治疗需要持续评估。
