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w wz 21«1y Kor. J. Clin. Pharm., Vol. 21, No. 1. 2011 m w : w w B Á ³ C B û w w w C û w w w (2010 12 3 Á2011 3 21 Á2011 3 22 ) A Descriptive Research on Drug Use Pattern of Narcotic Analgesics: a Case of University Hospital in Korea Mi-Sook Rah a and Bong-Kyu Yoo b * a Graduate School of Clinical Pharmacy, Yeungnam University, 317-1 Daemyung-dong, Nam-gu, Daegu, 705-802, Korea b College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Kyungsan, 712-749, Korea (Received December 3, 2010ÁRevised March 21, 2011ÁAccepted March 22, 2011) The objective of this study was to find out drug use pattern of narcotic analgesics in university hospitals in Korea. A university hospital located in Kyungbuk province was chosen for this study. The drug use pattern was analyzed in terms of ingredient, administration route, patient type, and attending department. Amount of drug usage was counted by unit dose defined by the number of ampule or vial for injectable, tablet or capsule for oral, and each for patch preparations. Result showed that 11 narcotic analgesic ingredients were used during 2007-2009, and the drug usage was increased by about 20% annually during the period. Proportion of oral preparations used for pain management was about two third of all narcotic analgesics usage and kept increasing during the period. Proportion of the drug usage for outpatients was also steadily increased. Notably, the usage of oral preparations of oxycodone, morphine, and hydromorphone was rapidly increased for the management of cancer pain while the usage of codeine and codeine-containing composite preparations for cancer pain were minimal (<10%). About 90% of all narcotic analgesics were used by physicians in Internal Department, especially in Oncology Division of the Department. These findings suggest that pain management is becoming more aggressive and in agreement with WHO's guidelines regarding selection of administration route. However, in terms of 3-step ladder for cancer pain management, the drug use pattern was not congruent to WHO's guidelines. Therefore, in conclusion, it appears that physicians need to try to be congruent to the guidelines when using narcotic analgesics for cancer pain. Key words - narcotic analgesics, drug use pattern, morphine, oxycodone, cancer pain m ùkù hw ø e w m m w. m w 1) e» sww w w w. p» y ù kù m ƒ w» y ƒw w k.» (WHO) ù w ƒ m w e «š w w š, m w Correspondence to : ³ û w w w (712-749) 214-1 Tel: +82-53-810-2822, Fax: +82-53-810-4654 E-mail: byoo@ynu.ac.kr v. 2,3) m m v ³, m w zm, w w. ù 2001 w y v y wz 4) ww z m e m ƒ ƒ y m e»ƒ. w 2004 m 5) e «š w s m. 2010 x «6) š 4 ù y m sƒ m w w e œwš. m w 2009 w w 70,779 w y w 5 ƒ w 35 w šm 30

m w : w w 31 š. w y xw š 7) m ƒ ùkù m» y 70-80%ƒ xw š š, w m ƒwš y w. ù m š 8,9) m š» y w m e wš, ¾ w ù xk e ƒ w 3» p y w x š š. 10) ew w w 3 m w m n mw w m ƒ w š š w. w y, xy wì w m ƒ w w e ƒ š w. 2010 3 1 l 8 31 ¾ w, A w 2007 l 2009 ¾ 3 m y y w. m, n,,, w w. w m ü ü w w. m ampule vial, tablet capsule, v patch unit dose( w dose ) w w. A w 2007 l 2009 ¾ 3 w m» 2007 2008 10, 2009 11 ùkû (Table 1). m 2007 259,011 dose, 2008 314,600 dose, 2009 381,866 dose 21% ƒw. p morphine oxycodone 2009 2007 w ƒƒ 632%, 450% w ƒ ùkþ. Oxycodone x x 2009 w w x 33,024 dose, x 34,912 doseƒ. v 2009 2007 w 256% ƒw. wr, pethidine j yƒ. n m A w 2007 l 2009 ¾ 3 m n Fig. 1 ùkü. 2008 w w 2009 ƒw m 32% w. 2007 148,548, 2008 Table 1. Amount of all narcotic analgesics used during 2007-2008 (unit: unit dose*) Administration route Ingredient 2007 2008 2009 Morphine HCl 83,817 68,927 93,282 Morphine sulfate 1,910 1,993 4,130 Injectable Pethidine HCl 11,863 10,248 10,893 Fentanyl citrate 5,088 5,898 6,352 Remifentanil HCl 120 46 42 Codeine phosphate (IR) 60,197 73,959 76,384 Oxycodone HCl (IR) 0 0 33,024 Oral Oxycodone HCl (SR) 15,103 22,040 34,912 Morphine sulfate (IR) 2,131 2,385 13,466 Hydromorphone HCl (SR) 0 0 4,004 CIA (IR) 71,117 114,443 85,718 Patch Fentanyl 7,665 14,661 19,659 Total 259,011 314,600 381,866 *unit dose: ampule or vial for injectable, tablet or capsule for oral, and each for patch preparations. CIA: combination product containing codeine phosphate 10 mg, ibuprofen 200 mg, and acetaminophen 250 mg in a capsule; IR: immediaterelease formulation; SR: sustained-release formulation.

32 Kor. J. Clin. Pharm., Vol. 21, No. 1, 2011 Fig. 3. Drug use pattern of oral narcotic analgesics. Percent of hydromorphone HCl does not show up in 2007 and 2008 because it was landed in 2009. Fig. 1. Drug use pattern of all narcotic analgesics by administration route. * unit dose: ampule or vial for injectable, tablet or capsule for oral, each for patch. Fig. 2. Drug use pattern of injectable narcotic analgesics. Percent of remifentanil HCl does not show up in the graph due to small value (<0.1%). 212,827, 2009 247,508 doseƒ w ƒw. m w 2007 57.4% 2008 67.7%, 2009 64.8% ƒw. v w 2009 19,659 doseƒ, 2007 157% ƒ ùkù m 5.1% w. m Fig. 2 ùkü. Morphine HCl w 3 j y 80%. Pethidine HCl fentanyl citrate ƒƒ 10% 5% j yƒ. morphine sulfate 2007 1.9% 2008 2009 ƒƒ 2.3%, 3.6% ƒw. Remifentanil HCl 0.1% w û. m Fig. 3 ùkü. Codeine w w w 3 ƒ š codeine, oxycodone HCl, morphine sulfate, hydromorphone HCl ùkû. Codeine 2007 40.5% 2008 2009 ƒƒ 34.8%, 30.9% w w. oxycodone HCl 2007 10.2% 2009 27.4% ƒw. y m 3 m, y w w Fig. 4 Fig. 5 ùkü. y m 2007 2008 û 2009 û ùk û. ù û 5% s p j. y y m 3 yƒ. 2007 y 60.1% y 39.9% w 20% s p ƒ 2008 12.6% s p, 2009 9% s p ƒ š ùkû (Fig. 5). m m Fig. 6 ùkü. A w m 3 2 ü š,, x, ƒ w ùkû.

마약성 진통제의 사용양상에 관한 서술적 조사연구: 한 대학병원의 경우 Fig. 4. Drug use pattern of all narcotic analgesics by gender. Fig. 6. Drug use pattern of all narcotic analgesics by attending departments. 2.4%에 불과하였다. Fig. 5. Drug use pattern of all narcotic analgesics by admission status. 최근 3년 동안 내과에서 사용된 마약성 진통제의 양은 모두 667,911 dose로서 병원 전체 사용량 955,477 dose의 69.9% 를 차지했다. 특히 morphine HCl, morphine sulfate, codeine phosphate, oxycodone, fentanyl patch 등은 90% 이상이 내과 에서 사용되었다. Pethidine은 정형외과(28.6%), 일반외과 (28.0%), 내과(14.7%), 신경외과(8.9%), 산부인과(6.0%) 등 거의 모든 진료과에서 사용되었다. Fentanyl citrate 주사용 제제는 신경외과(34.0)%, 일반외과(25.9%), 정형외과(14.3%), 산부인과(9.6%)의 순으로 사용되었으며 내과에서의 사용량은 33 내과를 전문내과별로 세분하여 연도별 사용양상을 살펴보 면 혈액종양내과에서 내과 전체 사용량의 절반 이상을 차지 하여 가장 많이 사용하였으며 이어서 감염내과, 호흡기내과, 소화기내과의 순서로 나타났다(Fig. 7). 특히 2009년도에는 혈액종양내과가 내과 전체 사용량의 70%를 차지하였는데 이 는 2009년도 암센타 개원이 원인인 것으로 여겨진다. 최근에 는 알레르기내과에서 사용량이 증가하여 2009년의 경우 소 화기내과에 이어서 내과 중에서는 다섯 번째로 마약성 진통 제를 많이 사용하는 것으로 나타났다. 암성 통증의 치료에 사용된 마약성 진통제의 양과 백분율 은 Table 2에 요약되어 있다. 주사용 제제 중에서 암성 통증 에 주로 사용되는 것은 morphine 뿐이며 pethidine, fentanyl, remifentanil 등 그 밖의 약물은 95% 이상이 암성 통증과 관 계없는 다른 목적으로 사용되고 있는 것으로 나타났다. 반면 에 경구용 제제와 경피용 제제의 경우는 codeine 단일제제 및 codeine 함유 복합제제(codeine phosphate 10 mg, ibuprofen 200 mg, acetaminophen 250 mg)를 제외한 모든 약물이 암성 통증에 주로 사용되었음을 알 수 있다. Codeine 단일제제는 기관지확장증과 천식 등 호흡기질환에 약 20%가 사용되었으 며, codeine 함유 복합제제는 각종 진단시 통증 및 기타 통증 Fig. 7. Drug use pattern of narcotic analgesics by divisions in the department of internal medicine

34 Kor. J. Clin. Pharm., Vol. 21, No. 1, 2011 Table 2. Amount and percentage of narcotic analgesics used for the management of cancer pain during 2007-2008 (unit: unit dose * ) Administration route Ingredient 2007 2008 2009 2007-2009 Injectable Morphine HCl 44,140 (52.7) 18,038 (26.2) 36,082 (38.7) 98,260 (39.9) Morphine sulfate 696 (36.4) 431 (21.6) 1193 (28.9) 2,320 (28.9) Pethidine HCl 117 (1.0) 227 (2.2) 197 (1.8) 541 (1.6) Fentanyl citrate 121 (2.4) 83 (1.4) 76 (1.2) 280 (1.6) Remifentanil HCl 7 (5.8) 0 (0) 2 (4.8) 9 (4.3) Codeine phosphate 2,657 (4.4) 1,938 (2.6) 8,864 (11.6) 13,459 (6.4) Oxycodone HCl 3,923 (26.0) 7,400 (33.6) 37,313 (54.9) 48,636 (46.3) Oral Morphine sulfate 511 (24.0) 1,094 (45.9) 6,262 (46.5) 7,867 (43.7) Hydromorphone HCl 0 (0) 0 (0) 1,265 (31.6) 1,265 (31.6) CIA 899 (1.3) 2,681 (2.3) 2,509 (2.9) 6,089 (2.2) Patch Fentanyl 3,009 (39.3) 4,117 (28.1) 5,934 (30.2) 13,060 (31.1) * unit dose: ampule or vial for injectable, tablet or capsule for oral, and each for patch preparations. Numbers in parentheses represent percentage of usage for cancer pain. CIA: combination product containing codeine phosphate 10 mg, ibuprofen 200 mg, and acetaminophen 250 mg in a capsule. y 90%. š ƒwš ¾ œs. p ù» p» ù» m w f» ù m j» w. m j ƒ š w. 11,12)» m w 3 m (3-step ladder for cancer pain relief) w y ƒ m y w wš. m ƒ 3 2) w 1 (mild pain) acetaminophen ù l m, 2 (moderate pain) codeine, dihydrocodeine, hydrocodone ƒ w m, 3 (severe pain) morphin, hydromorphone, oxycodone, fentanyl w m w «wš. ù m e «š e» 3 m «wš. 3) «š x w w m m w (sustained-release formulation) «wš x (immediate-release formulation) w m w «wš. n k n š wš mƒ n ƒ š w v w wš. w mz w ù ¼ w v w ww w wš. A w m, 2009 2007 w 9.7% s p w v 2007 w ƒƒ 7.4% s p 2.1% s p ƒw (Table 1). A w m «š e w w y š ùkü. w m 2007 w 2009 11.6% ƒ e 66.6% ƒ, v 156.5% ƒ w y š w. w m y ƒwš m w wš w (Fig. 5). w y ƒ y m ƒ. Oxycodone HCl 2007 2008 š x x. ù x oxycodone HCl 2009 landing w» oxycodone HCl (34,912 dose) w 33,024 dose

m w : w w 35 ù. x m ƒ z promotion w. «š e w m ƒ w x w w w x ƒ «š e w. w» ù 3 w 2 m ƒ w m wš 3 m w m w «wš. A w m w m codeine y» y e š m e 6.4% w (Table 2). Codeine w w m 2.2%., A w, y ƒ w m m w w ù y w w m yw w. m y w w «w w m ùkù w m w w. w w m w ƒ ù w w t w. w y m ƒ m w w w z d mw w v ƒ. m» w w w w, 3 j yƒ v ƒwš w y m ƒw., w m» «š e w w y š. ù m x š w w m ƒ š» «š 3 m w wz w v w. š x 1. Baumann TJ. Pain management. In: Dipiro JT, ed. Pharmacotherapy: a pathophysiologic approach. 6th ed. New York: McGraw-Hill, 2005: 1089-104 2. http://www.who.int/cancer/palliative/painladder/en/(accessed on November 30, 2010). 3. Jost L, Roila F, ESMO Guidelines Working Group. Management of cancer pain: ESMO clinical recommendations. Ann Oncol 2008; Suppl 2: ii119-21. 4.,,, et al. m. w y v y wz 2007; 10: 184-9. 5. w y v y wz, ww z. m e. q (2001). 6.. m e «š 4. available at http://www.cancer.go.kr/cms/data/edudata/ icsfiles/ afieldfile/2010/05/27/cancer_pain_management_guideline (Dr).PDF (accessed on November 30, 2010). 7. http://kostat.go.kr/wnsearchnew/search.jsp (accessed on November 30, 2010). 8. z,, ƒ, et al., y m e w Ultracet z. w y v y wz 2006; 9: 101-5. 9., ½x, ½, et al., m. w y v y wz 2003; 6: 22-33. 10.,, ½ z, et al., w y v y» xy. w y v y wz 2008; 11: 196-205. 11. Lema MJ, Foley KM, Hausheer FH. Types and epidemiology of cancer-related neuropathic pain: the intersection of cancer pain and neuropathic pain. Oncologist 2010; 15 Suppl 2: 3-8. 12. Reville B, Axelrod D, Maury R. Palliative care for the cancer patient. Prim Care 2009; 36: 781-810.