224 医 療 薬 学 Vol.30, No.3 (2004) Jpn. J. Pharm. Health Care Sci. ノ ー ト30(3)224-230 (2004) Study on Use of Non-steroidal Anti-inflammatory Drugs (NSAIDs) in Chikugo City Hospital with a View to Promoting Rational Drug Use (1) Hideaki Kido1, Yen Sun1, Kumiko Takaba1, Mihoko Nakashima1, Mitsuhiro Wada1, Takashi Kawada2, Hiizu Hara2 and Kenichiro Nakashima*1 Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University1 Chikugo City Hospital2 Received June 9, 2003 〔Accepted December 20, 2003 〕 During the period March 2000-February 2001, we conducted a study on prescriptions to determine how non-steroidal anti-inflammatory drugs (NSAIDs) were being used in Chikugo City Hospital, a medium-sized hospital, in order to promote rational drug use. The use of NSAIDs was evaluated for 10 clinical departments, together and individually. We found that Diclofenac (DIC) and sodium loxoprofen were used to about the same extent in almost all departments and that Aceta- minophen (ACE) was also prescribed as frequently as DIC. Except for ACE, no NSAIDs were used for children, particu- larly in the case of those under 9 years in age. We also evaluated the co-prescription of NSAIDs with H2-receptor antago- nists because NSAIDs are known to cause gastric adverse reactions. The number of patients who had been prescribed H2- receptor antagonists increased with patient age, especially for those over fifty years old. Zaltprofen was more frequently co- prescribed with H2-receptor antagonists than other NSAIDs. The prescription of etodolac was also found to increase with patient age, particularly so for those over fifty. Thus, we consider that information obtained by studying prescriptions can be used to evaluate the intentions of those prescribing drugs and clarify problems in the use of NSAIDs. Key words- non-steroidal anti-inflammatory drugs (NSAIDs), prescription research, rational use of drugs, drug-drug interaction PGs 8). Although COX-2 inhibitors that can inhibit only the formation of PGs being responsible for pain and inflamma- Introduction tion are required, there is no drug that can completely in- Non-steroidal anti-inflammatory drugs (NSAIDs), which hibit only COX-2. have several effects as analgesic, anti-inflammatory and anti- Recently, it has become very important to consider "ra- pyretic, are frequently and widely used clinically1). They are tional use of drug" due to the increase in interests of people actually prescribed for rheumatoid arthritis, osteoarthritis and in medical and health cares. The appropriate use of NSAIDs ankylosing spondylitis, moderate to heavy pains such as for controlling pain may be very difficult, since medical shoulder pain, menstrual pain and cramps. These pharma- providers have trouble in understanding pain rating scale for cological actions can be demonstrated by inhibiting cycloo- patients. The rating scales have been utilized to assess the xygenase (COX) activity and the following decrease of pros- pain levels of patients by many practitioners9). Other factors taglandins (PGs) biosynthesis at the site of inflammation2). for choice of NSAIDs are as follows : safety, gastrointestinal Recent studies have shown that COX has two isoenzyme pathology of the patients, whether the sickness is acute or forms, i.e. COX-1 and COX-23,4). The former protects the chronic process, and according to the type of inflammatory stomach lining and intestine, and the latter is related to the process of patients10). It is known that gastric disorder is the PGs formation in the inflammation process5-7). The main most frequent side effect of the NSAIDs. Thus, the appear- NSAID's side effect is recognized to be gastric disorders ance of a side effect is one of the most important factors to such as gastric ulcer and duodenal ulcer, which are caused evaluate the use of NSAIDs. Moreover, we have to consider by inhibiting COX-1 with a loss of local protective effects drug-drug interactions when NSAIDs are prescribed together of gastric mucosal cells and decreasing biosynthesis of with other drugs. As there are several types of pain, pre- 1 長 崎 市 文 教 町1-14; 1-14, Bunkyo-machi, Nagasaki-shi, 852-8521 Japan 2 福 岡 県 筑 後 市 大 字 和 泉917-1; 917-1, Izumi, Chikugo-shi, Fukuoka, 833-0041 Japan 医 療 薬 学 Vol.30, No.3 (2004) 225 scriptions of analgesic drugs with NSAIDs are frequently Table 1. Standard Dosage of NSAIDs. performed. Therefore, to know these interactions, monitoring of NSAIDs concentrations in blood is required. For this pur- pose, a high-performance liquid chromatography (HPLC) method is recommended. In our previous study, the simulta- neous determination ofarylpropionic acid derivatives, a group of NSAIDs, in human plasma was developed11). On the other hands, it is considered that a prescription re- search can give a significant information to a rational use of drugs. Recently, Butatsu et al. have been reported the analy- sis using prescription database for urate-lowering drugs and antiarteriosclerotic agents, and successfully evaluated the ra- tional use of drugs12'13). Thereupon, we attempted to survey how NSAIDs is actually used for considering the rational use of NSAIDs and drug-drug interaction of NSAIDs. Results and Discussions In this paper, a preliminary research to evaluate the use of NSAIDs in Chikugo City Hospital for a year (March 2000•` 1. NSAIDs used in each clinical section February 2001) is described by surveying the following ele- As shown in Fig. 1 A, DIC (30%) and LOX (29 %) were ments : 1) the practical use of NSAIDs at all or each of 10 used the most in the total amounts of NSAIDs that pre- clinical sections, 2) the practical use of NSAIDs on each scribed in all sections. The reason for this is that DIC has disorder in the special clinical section (orthopedics), 3) the many different product forms such as suppository, tablets prescription of NSAIDs with H2-receptor antagonists in or- and long-acting capsule. These product forms are adopted in thopedics. Chikugo City Hospital and the percentages for suppository, tablets and long-acting capsule were 42.7, 19.3 and 38.0%, respectively. LOX, a representative propionic acid derivative Method in NSAIDs is also prescribed very often, because it has mo- The use of NSAIDs prescribed in Chikugo City Hospital derate anti-inflammation, analgesic, and antipyretic effects from March 2000 to February 2001 is studied by using the and shows only few side effects14'15). On the other hand, data from computer for demanding clinical fees (about 2000 ACE (30%) and DIC (27%) were most frequently pre- prescriptions) to patients. This hospital has 220 beds and scribed (Fig. 1 B). Though, ACE was used most frequently consists of 10 clinical sections such as orthopedics, medi- in pediatrics, the quantity of the standard dosage adminis- cine, surgery, pediatrics, rhinolarygology, urinology, ophtha- tered to child per dose was small. lmology, brain surgery, gynecotokology and actinogenics. The total amounts of NSAIDs prescribed to outpatients Nine NSAIDs investigated in this study were sodium diclo- were largest in the orthopedics section (Fig. 2). In this sec- fenac (DIC), ampiroxicam (AMP), mefenamic acid (MEF) tion, the main symptom complained by outpatients was their etodolac (ETO), zaltprofen (ZAL), sodium loxoprofen (LOX), pain. LOX having few side effects and DIC in several pro- oxaprozin (OXA), tiaramide hydrochloride (TIA) and aceta- duct forms were prescribed in most in this hospital. The ad- minophen (ACE). vantage of the use of DIC is its strong and rapid analgesic Firstly, the use of NSAIDs prescribed for outpatients at all effect, and thus, this drug is suitable for acute pain16). Vari- and each individual clinical section was investigated. Subse- ous prescriptions can be designed on a case-by-case and se- quently, we focused on the use of NSAIDs prescribed in or- lected sustained-release form to avoid gastrointestinal disor- thopedics, especially rheumatoid arthritis, gout, herniated nu- der, and many other product forms have been released. cleus pulposis of the lumbar spine, osteoarthritis of the knee, ETO, a selective inhibitor of COX-2, has been prescribed to sciatic pain, lumbar spinal canal stenosis and osteoporosis. patients who need a long-term use due to a chronic pain. In Moreover, the use of NSAIDs prescribed with H2-receptor the medical section, ETO with few gastric side effects was antagonists in orthopedics was also examined. The particular prescribed to patients who have gastrointestinal disorder H2-receptor antagonists in this research were famotidine, risks caused by NSAIDs. The prescription frequencies of ranitidine and nizatidine. NSAIDs separated by age are shown in Fig. 3. In the under The data were presented as frequency of prescription and 19 years old groups, ACE was mostly prescribed for outpa- total amounts of the NSAIDs. NSAIDs have several dosage tients. No NSAIDs, except for ACE, were used for children and product forms, such as tablets, capsules and supposito- especially in the under 9 years old group. Though ACE is ries. The amounts of NSAIDs were summarized up in every not included in NSAIDs, it has the same effects with them. prescription, and then, divided by the standard dosage ad- Owing to the safety consideration, ACE was frequently used ministered to adult per dose. Table 1 shows the standard for children in pediatrics to reduce sudden fever17). These dosages of NSAIDs, which were used for the conversion in demonstrate that the prescription was planned to reduce the this study. side effect of NSAIDs in case of these drugs use. In this re- 226 医 療 薬 学 Vol.30, No.3 (2004) (A) (B) Fig. 1. Total Amounts (A) and Prescription Frequency (B) of NSAIDs for Chikugo City Hospital. NSAIDs, DIC : diclofenac sodium, LOX : loxoprofen sodium, MEF : mefenamic acid, ETO : etodolac, OXA : oxaprozin, AMP : ampiroxi- cam, ZAL : zaltprofen, ACE : acetaminophen, TIA : tiaramide hydro- chloride.