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The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis

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The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis ORIGINAL ARTICLE Gastroenterology & Hepatology http://dx.doi.org/10.3346/jkms.2016.31.10.1604 • J Korean Med Sci 2016; 31: 1604-1610 The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis Young Mi Hong,1 Ki Tae Yoon,1 Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver Jeong Heo,2 Hyun Young Woo,2 cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding Won Lim,2 Dae Seong An,3 the prescription of analgesics in these patients. Therefore, we aimed to evaluate the Jun Hee Han,3 and Mong Cho1 prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory 1Department of Internal Medicine, College of Medicine Pusan National University, Liver Center, drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Research Institute of Convergence for Biomedical Assessment Service database between January 1, 2012 and December 31, 2012. A total of Science and Technology, Pusan National University 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 2 Yangsan Hospital, Yangsan, Korea; Digestive 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one Disease Center, Pusan National University Hospital, Busan, Korea; 3Research and Statistical Support, prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, Research Institute of Convergence for Biomedical NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more Science and Technology, Pusan National University prescribed than acetaminophen even in decompensated cirrhosis compared with Yangsan Hospital, Yangsan, Korea compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference Received: 30 March 2016 in prescription preference between acetaminophen and NSAIDs among physicians. Accepted: 10 July 2016 Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed Address for Correspondence: acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Mong Cho, MD Department of Internal Medicine, College of Medicine Pusan Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more National University and Liver Center, Pusan National University frequently prescribed although they should be avoided. The prescription pattern of Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea analgesics were different significantly among physicians in patients with liver cirrhosis. The E-mail: [email protected] harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians Funding: This study was supported by year 2015 research grant prescribing analgesics. of Pusan National University. Keywords: Acetaminophen; Non-Steroid Anti-Inflammatory Drugs (NSAIDs); Pattern of Prescription; Liver Cirrhosis INTRODUCTION 3 grams per day or up to 4 grams per day in the short term in most patients with cirrhosis, including those who regularly con- Acute or chronic pain is one of the most common symptoms sume alcohol (1). NSAIDs can cause gastrointestinal bleeding, suffered by patients with cirrhosis secondary to various comor- hepatic injury, and acute kidney injury more frequently in pa- bidities. Pain relief is essential to improve quality of life for these tients with cirrhosis. NSAIDs can also cause new-onset ascites patients. The management of pain in these patients, however, is in patients with compensated cirrhosis or makes it difficult to a clinical challenge to physicians and a source of considerable control existing ascites. As a rule, NSAIDs should be used cau- misconception and concern among physicians. Various types tiously in patients with cirrhosis (2). of analgesics can be used in the treatment of pain. The prescrip- Although analgesic are commonly used and can affect the tion of the proper type of analgesics is important to relieve pain natural course of disease in patients cirrhosis, there are few rec- more effectively and avoid unnecessary adverse events. ommendations regarding the proper use of analgesics in this Analgesics including non-steroidal anti-inflammatory drugs population (2-4). To our knowledge, there are only a few reports (NSAIDs) and acetaminophen, are some of the most frequently such as physician opinions or prescription patterns related to prescribed drugs in patients with cirrhosis. Cirrhotic liver is vul- analgesics and these reports were based on the survey of a small nerable to cellular injury by many drugs. Many drugs increase number of patients (5,6). Therefore, this study assesses the pre- the risk of hepatic injury and exacerbation of clinical sequelae scription pattern of analgesics in patients with liver cirrhosis in patients with cirrhosis. and examines the differences in prescription patterns among Although acetaminophen is known as a hepatotoxic drug at physician types. higher dose, it can be used safely in maximum daily dose of 2 to © 2016 The Korean Academy of Medical Sciences. pISSN 1011-8934 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. eISSN 1598-6357 Hong YM, et al. • Prescription Pattern of Analgesics in Patients with Liver Cirrhosis MATERIALS AND METHODS with cirrhosis. We then evaluated the prescription pattern of acetamino- Data source phen and NSAIDs. Given the large variety of NSAIDs used, we This study was a retrospective review of nationwide claims for were unable to analyze all those prescribed. However, the three analgesics prescribed to patients with cirrhosis, which includes most commonly prescribed NSAIDs accounted for the majority adjusted medical and pharmacy claims taken from the HIRA (70%), and we therefore analyzed the top three drugs. The du- database. Korea has a health care system that is managed and ration of prescription was based on the sum of the total number supervised by the government organization. Ninety-seven per- of days each drug was prescribed during the one year follow-up cent of the population is legally obliged to register in the Korea period. Long-term prescriptions was defined as drugs prescrib- National Health Insurance Program. All medical institutions ed for 15 days or longer. Mean daily dose was calculated by di- must submit data of inpatients and outpatients care to HIRA viding the total dose administered by the total number of pa- database to obtain reimbursement of the medical costs. Patient tients and days used. Defined daily dose (DDD) is the typical information, including diagnoses (coded according to the In- maintenance dose required per day for a drug prescribed for its ternational Classification of Disease, Tenth Revision [ICD-10]), main indication in adults (7). We evaluated the frequency of procedures, prescription records, demographic information, drug use by dividing prescriptions into regular use (≥ 0.5 DDD/ and direct medical costs, is available from HIRA database. day) and intermittent use (< 0.5 DDD/day). Subgroup analysis was performed for compensated cirrhosis Patients selection and decompensated cirrhosis as well as physician practice type, First, we identified all patients greater than 20 years of age diag- divided into gastroenterologists, internists, and other physicians. nosed with liver cirrhosis using ICD-10 code K746 between Internists was defined as specialists for internal medicine in- January 2012 and December 2012 from HIRA data. Those who cluding gastroenterologists and other physicians was defined had at least one prescription for acetaminophen or NSAIDs as specialists other than internists. When analyzing the prescrip- with a diagnostic code of cirrhosis (ICD-10 code K746) were in- tion pattern between internists and other physicians and be- cluded in this study cohort. Patients with concomitant diagno- tween gastroenterologists and other internists, we compared ses of cancer (ICD 10 code C) were excluded. The reimburse- the total number of prescriptions written by each group rather ment claims for analgesics in patients with cirrhosis were re- than the total number of prescribing doctors. viewed for one year period following enrollment in this study. Statistical analysis Data collection The distribution of sex, age, medication use and comorbidities Information was collected about the following patient charac- was expressed as a frequency (with %). The distribution of sex, teristics: age, gender and cause of cirrhosis (e.g., viral hepatitis age, medication use and comorbidities was expressed as a fre- B and C, as well as other causes). Cause of cirrhosis was defined quency (with %). To determine the prescription rate of acetami- as cirrhosis with diagnostic code such as viral hepatitis B and C. nophen and NSAIDs, the prescriptions were categorized by chief Compensated cirrhosis was defined as being free from sequel- ingredient code. To determine the day used of analgesics, the ae associated with cirrhosis. Decompensated cirrhosis was de- prescriptions were categorized by the duration of days in each fined as cirrhosis with sequelae
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