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1 한국임상약학회지제 24 권제 3 호 Korean J Clin Pharm, Vol. 24, No. 3, 2014 Korean Journal of Clinical Pharmacy Official Journal of Korean College of Clinical Pharmacy Available online at pissn: 파스제의점착력관리기준및피부부작용조사연구 김지연 1 김광준 2 박상욱 1 방준석 3 이원재 1,2 * 1 조선대학교대학원식품의약학과, 2 조선대학교약학대학약학과, 3 숙명여자대학교임상약학대학원 (2014 년 7 월 2 일접수 2014 년 8 월 18 일수정 2014 년 8 월 21 일승인 ) Investigation on Adhesion Control Standards and Skin Adverse Effects of Skin Attached Formulations Ji Yeon Kim 1, Kwang Joon Kim 2, Sang-Wook Park 1, Joon Seok Bang 3, and Wonjae Lee 1,2 * 1 Department of Food and Drug, Chosun University Graduate School, Gwangju , South Korea 2 College of Pharmacy, Chosun University, Gwangju , South Korea 3 Graduate School of Clinical Pharmacy, Sookmyung Women's University, Seoul , South Korea (Received July 2, 2014 Revised August 18, 2014 Accepted August 21, 2014) Objectives: This paper was aimed to investigate the adhesion control standards of pain relieving patch (PRP) drugs and to survey it s adverse effects on the skin of patients for safe use of PRP drugs. Methods: In this study, the related documents of PRP drugs of Korea pharmacopoeia (KP), United States pharmacopoeia (USP), Japanese Pharmacopoeia (JP), European pharmacopoeia (EP), and information web sites of the Ministry of Food and Drug Safety (MFDS) were surveyed. Also, the past and current labeling of PRP drugs marketed in the pharmacy was investigated and compared. Results: In KP and JP, the lower limit standard for PRP's adhesion control is established, but the upper limit standard is not designated. In USP and EP, neither the lower nor upper limit standard is established. The main reasons of skin adverse effects are considered as inherent adverse reactions of the applied drugs for PRP. Another reason is involved in patient's medication mistakes related to PRP's adhesion control, respiratory depression of skin according to physical skin closure, and microbial growth, etc. Conclusion: For safe use of PRP drugs, we proposed ensured guidelines like additional instructions of pharmacist's prescription and detailed labeling systems for usage of PRP drugs applied on skin. Key words - pain relieving patch, adhesion control standards, skin adverse effect 통상적으로 파스 라칭하는의약품류는환자의피부를통하여국소또는전신적으로약물을전달하여효과를기대하는외용제로서우리나라에서는작용기전및제조방법등에따라첩부제, 카타플라스마제, 경피흡수제로구분하고있다. 1) 이들파스형제제는간초회통과 (first-pass metabolism) 효과를겪지않으므로간에서의약물대사를피할수있고, 위장장애와같은동일효과경구용제제로흔히발생되는부작용도회피할수있으며, 필요시약물투여의중단이용이한등경구제나주사제에비해많은장점이부각된다. 2) 이같은이유때문에일반의약품인진통소염제 ( 케토프로펜, 플루르비프로펜등 ) 및금연보조제패취 ( 니코틴 ) 외에도전문의약품인마약성진통제패취 ( 펜타닐 ), 마취제패취 ( 리도카인 ), 알츠하이 Correspondence to : Wonjae Lee College of Pharmacy, Chosun University 309 Pilmundaero, Dong-gu, Gwangju , Tel: , Fax: wlee@chosun.ac.kr 머패취 ( 리바스티그민 ) 등점차다양한제품군으로용도가확산중이다. 한편, 한국소비자원에서는파스류의사용시피부의표피박탈등심각한부작용이발생한사례를지난 2012년 11월에사회적으로부각시켰는데, 부작용발생의주된원인으로써파스류의약품이지닌높은점착력을지적하면서점착력의상한기준을시급히마련해야한다고주장하였다. 3) 인체는외부환경으로부터자신을보호하는기능을담당하는피부기관이발달했으므로약물이피부를손쉽게통과하여일정한혈중농도에도달하는것이쉽지않다. 이때문에파스가지닌고유하고적정한수준의약효를나타내기위해서는약물투과의장벽으로작용하는피부고유의기능을감소시키거나, 이를극복할수있는별도의기술이필요하다. 이러한용도로프로드럭 (prodrug) 또는투과촉진제의사용등약물의생체내경피흡수를용이하게할목적으로다양한제제연구와기술이개발중이나 2), 한편으로파스류의약품의사용으로인해발생가능한피부부작용을최소화시키기위한연구는 219

2 220 Kor. J. Clin. Pharm., Vol. 24, No. 3, 2014 상대적으로많지않은실정이다. 2012년한국소비자원이보도한사항에대하여우리나라식품의약품안전평가원이시행한연구에서새로운첩부제를개발시고려해야하는시험항목인신축성시험, 방출시험, 안정성시험등과더불어박리력, 점착력, 응집력에대한시험항목도추가설정되어야할필요성을제시한바있으나, 점착력의구체적기준이나피부부작용과점착력의상관관계에대한어떠한내용도제시하지못하였으므로그연구결과만으로는파스류의피부부작용이나점착력을이해하는데한계가있었다. 3,4) 따라서, 본연구에서는국내 외파스류의약품의허가현황과점착력시험기준을중심으로본의약품류의관리현황, 부작용발생의원인고찰및제품의안전사용수칙의표시기재여부를분석하고, 이와함께파스류의약품의안전한임상사용을위한제도적개선사항을제안하고자한다. 연구방법 국내 외파스류의약품과관련된본연구를위하여한국 ( 대한약전 ) 1,9), 일본 ( 日本藥局方 ) 5), 미국 (USP) 6), 유럽 7) 등각국의의약품공정서인약전을포함하여취득가능한다양한자료원을취득, 검토, 분석을진행하였다. 또한, 우리나라에서시판중인피부부착형의약품및의약외품류의허가현황은식품의약품안전처의이지드럭사이트 8) 를검색하였고, 우리나라약국에서판매중인 20여개제품을직접구매하여이들제품의포장면과첨부문서에기재된표시사항을분석하였다. 연구결과 국내 외피부부착용제제의분류와정의우리나라에서는피부에부착하여치료효과를기대하는의 Table 1. Legal status of the skin attached formulations for PRP drugs in domestically available items. 8) Category No.* Class Formulation Ingredients Product name P Ketoprofen, Flurbiprofen, Diclofenac, Felbinac, Indomethacin, Loxoprofen, Buprenorpine, Methyl salicylic acidcontaining complexes 케토톱플라스타 Ketotop Plaster 신신파스아렉스 SinSin PAS-RX 264 Analgesic, Anti-itching, Astringent, Anti-inflammatory C Ketoprofen, Felbinac, Indomethacin, Methyl salicylic acid-containing complexes 제일쿨파프 Cool Pap Jeil 제놀쿨카타플라스마 Zenol Cool Cataplasma TA Ketoprofen Piroxicam 케펜텍플라스타 Kefentech Plaster 트라스트패취 Trast Patch Drugs 121 Local anesthetics P Lidocaine 266 Emollients P** Salicylic acid 유패치플라스타 Youpatch Plaster 대일살리실산반창고 Aminosalicylic CA 신신티눈고 SinSin Corn Plaster 119 CNS drugs TA Rotigotin Rivastigmine 뉴프로패취 Neupro Patch 디누보패취 Dinuvo Patch 217 Vasodilator TA Nitroglycerine 앤지덤패취 Angiderm Patch 235 Emetic, Antiemetic TA Scopolamine Granisetron 키미테패취 Kimite Patch 산쿠소패취 Sancuso Patch 799 Others TA Nicotine 니코스탑패취 Nicostop Patch 821 Synthetic narcotics TA Fentanyl 펜타스패취 Fentas Patch Quasi-drugs 791 Adhesive plaster P Adhesive plaster - * Drug classification number according to regulation on drug classification number (Standard Operating Procedure of Korea Ministry of Food and Drug Safety); ** Anti-wart & anti-corn plaster; CNS (central nervous system); P (plaster); C (cataplasma); TA (transdermal absorbent)

3 파스제의점착력관리기준및피부부작용조사연구 221 약품을첩부제, 카타플라스마제, 경피흡수제등 3종으로분류하고있다. 1) 첩부제 (plaster) 란보통포 ( 布 ) 또는플라스틱제필름등에주성분과기제또는첨가제로된혼합물을전연또는봉입한다음피부표면의환부또는피부를통해국소환부에주성분이도달할수있도록점착시켜쓰는국소작용외용제 ( 예 : 케토톱플라스타, 신신파스아렉스등 ) 이다. 카타플라스마제 (cataplasma) 란보통주성분과물을함유하는혼합물을이상 ( 泥狀 ) 으로만들거나포상 ( 布上 ) 에전연성형하여국소부위의습포에사용되는외용제 ( 예 : 제일쿨파프, 제놀쿨카타플라스마등 ) 이다. 경피흡수제 (transdermal system) 란피부면에적용하여주성분이피부를통하여전신순환혈류에송달될수있도록설계된제제 ( 예 : 케펜텍플라스타, 트라스트패취, 키미테패취등 ) 이다. 아울러상처보호를위해피부에부착하는반창고류는 의약외품 으로분류되어있다. Table 1은현재피부에부착하는제제로써우리나라식품의약품안전처에서허가된의약품및의약외품의전체현황을보여주고있다. 주요외국의피부부착형제제의경우는 Table 2에나타내었는데, 일본에서는주성분을함유한국소적용제를 테이프제 (tapes, plaster) 로, 주성분과물을함유한국소적용제를 파프제 (cataplasma, gel patch) 로분류하고있다. 5) 한편, 미국에서는보호 밀봉을위한반고형외용제를 플라스타 (plaster) 로, 주성분을함유한국소적용제를 테이프 (tape) 로, 주성분을함유한전신순환제를 경피흡수제 (transdermal system) 로분류하고있다. 6) 유럽에서는피부의보호나각질용해등을위한반고형외용제를 플라스타 (medicated plaster) 로, 주성분을함유한국소외용제를 패취제 (cutaneous patch) 로, 주성분을함유한전신순환제를 경피흡수제 (patches, transdermal) 로분류하고있다. 7) 국내 외피부부착용제제에대한점착력관리기준국내 외피부부착용제제개별제품에대해점착력기준이설정되어있는지를조사한결과를 Table 2에제시하였다. 먼저우리나라에서설정되어있는기준으로는 Peel Adhesion Test시에케토프로펜함유첩부제는제품폭 12 mm 당 150 g 이상의점착력이 10), 이외의첩부제및카타플라스마제는제품폭 12 mm 당 42 g 이상의점착력을유지하여야한다. 11) 아울러의약외품인반창고는제품폭 12 mm 당 150 g 이상의점착력기준이설정되어있다. 9,12) 일본약전에는 Salicylic Acid Adhesive Plaster 제제가수재되어있는데별도의점착력기준은제시되어있지않았으며 6), 대신일본의약품제조판매지침에는패취제시험법으로 Steel Ball Test를이용한점착력시험법이기술되어있고, 2 g 볼이상의점착력을가지도록권장기준이제시되어있었다. 13) 미국약전에는클로니딘 니코틴경피흡수제가수재되어있는데일본약전과마찬가지로별도의점착력기준은설정되어있지않았고, General Requirement Part에경피흡수제 (transdermal system) 의점착력시험법으로 Peel Adhesion Test, Release Liner Peel Test, Tack Test 등을소개하고있다. 5) 유럽약전에서는첩부제등파스류제제자체가수재되어있지않았고따라서점착력의시험법도수재되어있지않았다. 7) 즉, 우리나라및일본을제외하고는피부부착용제제의점착력기준을의약품공정서에제시하는등국가가주도하여일괄적으로관리하지않고있으며, 일본의경우도우리나라와마찬가지로하한선만제시할뿐어느나라도점착력의상한선기준을제시하고있지는않았다. 피부부착용제제사용에따른피부부작용의원인파스사용에따른피부부작용의원인이될수있는아래와같은다양한개연성이대두되었다. (1) 전술된한국소비자원의보도내용에따르면, 파스사용에따른피부부작용이주로점착력에기인한다고주장하였으나 3), 이외에도파스에도포된약리작용성분자체의부작용에기인한것은아닌지를고려할필요가있다. 약리성분자체의피부부작용유발영향을알아보기위해파스의주요한약리성분으로사용되는케토프로펜, 디클로페낙등 13 Table 2. Lower and upper limits of the adhesive strength for the skin attached formulations for PRP drugs. 5,7,9-13) Country Formulation Test methods Lower limit Upper limit Plasters 11) (exclude ketoprofen plaster) Peel adhesion test 42 g/12 mm Ketoprofen plaster 10) Peel adhesion test 150 g/12 mm Korea Cataplasma 11) Peel adhesion test 42 g/12 mm Transdermal systems 9) Adhesive plaster 9,12) Peel adhesion test 150 g/12 mm Japan 13) Tapes, Plasters Steel ball test 2 g balls USA 5) EU 7) Plasters, Tapes, Transdermal systems Plasters, Patches, Transdermal systems Peel adhesion test, Release liner peel test, Tack test

4 222 Kor. J. Clin. Pharm., Vol. 24, No. 3, 2014 Table 3. Comparison of the side effects and precautions for external and oral formulations. 8) Ingredients External-use* Oral-use** Ketoprofen Diclofenac Indomethacin Piroxicam Roxoprofen Felbinac Flurbiprofen Methyl salicylic acid (combo-preparation) Indomethacin (combo-preparation) [Contraindication] History of hypersensitivity and photosensitivity RS Stop applying when these symptoms are Sometimes shows redness, itching, edema, erosion, irritation and present: swelling, contact dermatitis, dry skin, pigmentation photosensitivity, hair loss, herpetic lesions Photosensitivity, skin rash including SJS and RS [Notes] When under using or until 2 weeks after starting the drug, regardless of the weather, avoid outdoor activities, and whenever in outdoor, do not expose to the UV light on the application sites and protect by clothing, sunglasses, hat, sunscreen, etc. Colored cloths are recommended because white or light-colored clothes can transmit UV light (photosensitivity is possible after or under using the preparations) (1) Sometimes these may be present: itching, redness, sores, dermatitis (rashes, eczema, papules, contact dermatitis, edema), skin stripped and rough, irritation, blister-forming, rarely pigmentation. (2) If under long-term or broad-area using, may occur disseminated skin rash, photosensitivity (by cream, gel). Sometimes cause itching, redness, rash, contact dermatitis, eczema (when administering stopped the symptoms are simply disappeared) can occur, and rarely shows warmth, swelling, redness, anaphylactic, photosensitivity, burning, irritation, dryness, tingling feeling, gastrointestinal discomfort, headache, dizziness. Stop applying the medication when the above symptoms are severly present. Skin: Sometimes present local itching, redness, rash, scales, eczema, dermatitis, contact dermatitis, erythema Rarely present photosensitivity Stop applying the above symptoms are severly present. Itching, erythema, contact dermatitis, rash ( 1~3%) (1) Sometimes cause itching, rash, redness, dermatitis (rash, eczema), contact dermatitis, and rarely cause irritation or blisters. If symptoms occurred heavily, stop applying (Cataplasmas only). (2) Sometimes cause itching, rash, redness, irritation, dermatitis, and rarely cause blisters and abnormal sensation. If symptoms occurred heavily, stop applying (Ointments only). Occasionally flare (the congestion redness), rash, drug rash, itching and burning (burning feeling), contact dermatitis Rash, redness, itching, edema Rash, redness, itching, skin lacquer, burning, edema, pain, heat, dryness, etc. Rarely possible symptoms are skin rash, hives, vesicular herpes, stripped dermatitis, purpura, allergic purpura, SJS, RS, photosensitivity, redness, itching, eczema, dermatitis, vasculitis, erythema multiforme, flush, exudative dermatitis Stop using the medication and take proper treatments. Rarely expressed with SJS, RS, hair loss, nodular erythema Stop applying when the above symptoms are present. Rarely SJS, RS, photosensitivity, etc. Stop applying when the above symptoms are present. You can also receive a nail dissection, abnormal growth of the nail, hair loss, bullous reaction rarely be present. May causing SJS, RS. Therefore, observation should be thoroughly. If each ADR is present, stop immediately administering and take proper treatments.

5 파스제의점착력관리기준및피부부작용조사연구 223 Table 3. Comparison of the side effects and precautions for external and oral formulations. 8) (continued) L-menthol (combo-preparation) Vanillyl nonylamide (combo-preparation) Formulations containing capsicum tincture Herbal-containing (combo-preparation) Rash, redness, itching, edema (1) Rash, redness, itching, dermatitis, pigmentation, peeling skin, etc. (2) Severe itching and pain (1) Rash, redness, itching, dermatitis, pigmentation, peeling skin, etc. (2) Severe itching and pain Rash, redness, itching, etc. NSAIDs - [Precautions] Skin reactions: May cause serious ADRs such as deciduous dermatitis, SJS, RS, which cause fatal results. These serious ADRs can occur without any alarming symptoms. In most cases, these ADRs occur within 1 month after initiating. Patients should be aware of the signs and symptoms of the serious skin reactions and must stop the medication when find the first signs and symptoms such as skin rash or other hypersensitive reactions. *Preparations for the external-use only such as creams, gels, cataplasmas, plasters, lotions, ointments, etc. **Preparations for the oral-use only such as tablets, capsules, etc.; RS (Riel's syndrome or toxic epidermal necrosis); SJS (Stevens-Johnson syndrome); ADR (adverse drug reaction); UV (ultraviolet); NSAIDs (non-steroidal anti-inflammatory drugs) 개성분의외용제및경구제의약품의허가사항을비교, 검토하였다. 8) 성분별외용제와경구제부작용및주의사항을비교, 정리한 Table 3에서는비스테로이드성소염진통제의경우외용제뿐만아니라경구용제제도탈락성피부염, 스티븐스 -존슨증후군및독성표피괴사등과같은중대한이상반응을일으킬수있음을경고하고있다. 그러므로 Table 3의결과를볼때파스형제제를피부에부착했을때뿐만아니라동일성분을함유한내복약을복용시에도피부이상반응이발현될수있는가능성은매우높다. 또한, 약리성분자체의피부이상반응유발영향을보다분명히보여주는사례가있는데, 니트로글리세린경피흡수제에피부부작용을나타낸환자에게니트로글리세린연고제를사용한경우에도유사한피부반응이나타났으며, 타사연고제품으로바꾸어도피부반응이달라지지않았다. 14) 또한, ethinylestradiol과 norelgestromin이함유된경피흡수제를사용한환자에서는피부반응이나타났으나, 약물이함유되지않은경피흡수제위약대조군연구에서는피부반응이나타나지않았다. 15) 이와같은임상사례들을분석해볼때, 파스류의약품사용시발현가능한피부부작용이단지점착력때문이라기보다는약리성분자체의특성에서도기인했을가능성이매우높다는것을시사한다. (2) 파스류개별제품에따라부착시간이상이하다는사실 도주의깊게살펴볼필요가있다. 이를위해시중에서유통중인파스류주요제품인 A( 케토프로펜 ), B( 피록시캄 ), C( 플루르비프로펜 ), D( 살리실산메칠등복합제 ) 제품각각의효능 효과와용법 용량을비교해보았다 (Table 4). 위제품들은모두관절염, 근육통등에선택되는속칭유사제품인데, A, C, D 제품의용법은 1일 2회부착인반면, B 제품의용법은 2일동안 1매를부착하도록지시하고있다. 만약 B 제품을주로사용하던환자가 A 제품으로바꾸어사용하였을때환자의실수로부주의하게 A 제품의용법 용량을지키지못하고, 이제품을전에사용하던 B 제품과같이 2일동안환부에부착했다면피부조직의손상이더욱심하게나타날수도있을것이다. 이와관련해서미국식품의약국 (FDA) 에서는투약시간을준수하지않거나, 패취제가피부에서탈락하지않도록고정시키기위해덧붙이는밀착포를제대로사용하지못하는등사용법의오류사례를 FDA 인터넷홈페이지의 Safety Page 란에게시하고있다. 16) (3) 파스류표면에도포되어있는접착제및지지체는피부표면을적극적으로폐쇄시킴으로써피부의호흡작용을방해하며, 땀이나피지등과같은피부분비물을각질층아래에축적시켜미생물의번식또는피부자극반응을유발할수있다. 또한, 장기간동일한병소부위에반복적으로파스를부착하는경우에도물리적자극에의한피부부작용의발현가능성이증가할수있다.

6 224 Kor. J. Clin. Pharm., Vol. 24, No. 3, 2014 Table 4. Comparison of the major retailing products. 8) Product A B C D Ingredient Ketoprofen Piroxicam Flubiprofen Methyl salicylate Efficacy & Effects Usage & Volume *OA (osteoarthritis) Analgesic, anti-inflammatory for the following diseases and conditions: OA, shoulder periarthritis, tenosynovitis, peri-, lateral-epicondylitis (tennis elbow, etc.), myalgia, swelling and pain after trauma After removing the cover, then attach the product on lesions as twice a day Degenerative arthritis (OA)*, tenosynovitis (tendon synovitis), muscle pain, bone joint pain, post-traumatic pain, pain after fracture healing Apply 1 piece of product every other day on lesions. After a bath or shower, or if the surface is sweaty, 1 piece can be attached in each day. Let clean and dry the affected area. After removing the cover from the patch, then applying on lesions and get the good press with the palm of the hand. In particular, make sure the edges of the patch stuck well. Analgesic, anti-inflammatory for the following diseases and conditions: OA, shoulder periarthritis, tenosynovitis, peri-, lateral-epicondylitis (tennis elbow, etc.), myalgia, swelling and pain after trauma After removing the cover from the drug, attaching on lesions as twice a day Analgesic, anti-inflammatory for the following diseases and conditions: Stiff neck, back pain, neuralgia, rheumatism, bruises, sprains, muscle pain, joint pain Attaching on the painful part as once or twice a day (4) 파스에사용되는것은주로감압접착제인데일반적으로약한압력이가해졌을때기질에달라붙고제거될때부착면에아무런잔류물도남기지않은물질로써주로 polyisobutylene류, acrylics, silicone류가쓰이고있다. 이들접착제는자체로서피부자극성질을지니지않았다고알려져있다. 2) 그러나앞서보도된한국소비자원의자료에의하면, 이들이가지는점착력때문에파스를떼어낼때피부의각질층일부가함께제거될수있으며, 이때피부부작용이발생한다고주장하고있으나, 어느정도의점착력이피부부작용을유발하는지구체적인증거는제시되지않았다. 3) 한편, 일부연구에따르면피부의움직임에따라부착된경피흡수제가유연성을가지고함께움직이는경우에는피부부작용이최소화됨을보여주고있다. 17) 이는경피흡수제의중앙부위보다는피부에더많은점착력이작용되는가장자리부위에서피부부작용이더많이발생할수있음을보여주고있다. 점착력과피부부작용의상관관계파스는사용기간동안기대에부응하는치료효과가발현하도록피부에잘밀착되어있어야하고, 탈착시에는통증이최소화되어야한다. 또한제품의사용기간동안에는점착제의노화로인한점착성능의저하없이적절한물리적성질이유지되어야한다. 이런점에서파스는개별품목마다최적의점착성을지녀야하고, 이를확증하기위해점착력시험이필수적이다. 점착력과피부부작용의상관관계를이해하기위해서는우선점착력시험법에대한이해가필요하다. 점착력시험법은 제품의품질을보증할수있어야하고, 시험자체가안정적으로실시될수있어야하며, 제품성능에영향을미치는어떠한변화도감지할수있어야한다. 또한재현성이있어야한다. 18) 현재가장많이채택되는점착력시험법은 Peel Adhesion Test 로서피착제에점착시킨점착제를벗겨낼때기록되는힘의세기를측정한다. 점착력값은단위폭당작용하는힘 ( 예 : g/cm) 으로표시된다. 주로 stainless steel 판을피착제로사용하여일정한속도로점착제를 90 o 또는 180 o 로벗겨낼때작용하는힘을계산한다. 이시험법은피착제의종류, 피착각도, 피착속도뿐만아니라약물지지체및점착제의두께에도영향을받는다. 5,18) 이외에도경사진점착면에강철구를굴려서멈췄을때강철구직경과대비되는힘의세기를측정하는 Steel Ball Test, 프로브를점착제에점착시킨후 probe가떨어지는초기접착력을측정하는 Probe Tack Test 등이있다. 2,18) 이들시험은모두실험실적으로실시하는시험법으로서주로 stainless steel 재질의피착제를사용한다. 이렇게 stainless steel판을이용하여측정한점착력과실제피부에서의측정한점착력간에는특별한상관관계를찾을수없었다. 17,19) 이는피부표면에는땀, 피지, 털이나고굴곡이있어테스트에사용되는 stainless steel판의기질과는매우다르기때문이다. Stainless steel판은이러한피부의물리 화학적특성을대표할수없으며이는파스대피부, 파스대 stainless steel 판간에존재하는표면에너지의차이로이해할수있다. 2,18) 깨끗한피부의표면에너지 (27 dyn/cm) 는주로피착제로사용되는 stainless steel (500 dyn/cm), polyethylene (31 dyn/

7 파스제의점착력관리기준및피부부작용조사연구 225 Table 5. Comparison of the labeled information in the 20 main products. No. Product name Manufacturer Whether safety rules for precautions are indicated or not * Reported information in November 2012 ** Reviewed results in July 케토톱플라스타 Ketotop Plaster 태평양제약 Pacific Pharm 2 케토톱엘플라스타 Ketotop-L Plaster 태평양제약 Pacific Pharm 3 케토크린플라스타 Ketoclin Plaster 신신제약 SinSin Pharm 4 케펜텍플라스타 Kefentech Plaster 제일약품 Jeil Pharmaceutical 5 제놀골드플라스타 Zenol Gold Plaster 녹십자 Green Cross Corp 6 케펨플라스타 Kephem Plaster 종근당 Chong Kun Dang Pharm 7 케논엘플라스타 Kenon-L Plaster 아이큐어 Icure Pharmaceutical 8 케바논첩부제 Kebanon Plaster 대화제약 Daehwa Pharmaceutical 9 케노펜플라스타 Kenofen Plaster 일동제약 Ildong Pharmaceutical 10 맨담케토플라스타 Menthom Keto Plaster 보령제약 Boryung Pharm 11 신신파스아렉스 SinSin PAS-RX 신신제약 SinSin Pharm *** 12 제일탑첩부제 Jeil Top Plaster 제일약품 Jeil Pharm 13 트라스트패취 Trast Patch 에스케이케미칼 SK Chemical 14 투어펜플라스타 Tourpen Plaster 신일제약 Sinil Pharm 15 플럭스플라스타 Flux Plaster 아이큐어 Icure Pharmaceutical 16 노펜첩부제 Nofen Plaster 중외제약 JW-Pharm 17 조인업첩부제 Joinup Plaster 일양약품 Ilyang Pharm 18 키페낙에스첩부제 Keyfenac S Plaster 유한메디카 Yuhan Medica 19 플로스탑플라스타 Flostop Plaster 현대약품 Hyundai Pharm 20 맨담플루비플라스타 Menthomfluvi Plaster 보령제약 Boryung Pharm * The additional safety information including the authorized indications and clinical symptoms is described; ** Reported information issued by Korea Customer Agency (KCA) 3) ; *** Safety information for precaution is already included in the authorized information for users in detail. cm), polymethacrylate (39 dyn/cm), polystyrene (33 dyn/cm) 의표면에너지보다작다. 20) 따라서현재주로채택되는점착력시험법으로측정된점착력과피부부작용간의상관관계를정확히규명할수없으며, 이에대하여심층적이고다각적인 연구가더필요하다고사료된다. 시중유통품목의안전사용표시실태조사현재약사법및의약품등의안전에관한규칙등관련

8 226 Kor. J. Clin. Pharm., Vol. 24, No. 3, 2014 법률에따르면, 허가사항이외파스안전사용에대한표시기재는의무사항이아니나, 제품의안전한사용을위해제조업체가파스탈부착시주의사항등을자율적으로표시하고있다. 2012년 11월한국소비자원에서는 20개제품중 12개제품이허가사항외안전사용법이표시되어있었다고발표하였다. 3) 현시점에서이들제품의표시기재사항이어떻게변화했는지알아보기위해한국소비자원이조사한 20품목으로 2013년이후제조되어시중에유통중인제품을대상으로허가사항이외안전사용표기실태현황을조사하였다. Table 5 에서조사결과를보여주고있는바와같이, 제품포장면또는첨부문서에안전사용수칙을표시한제품이 12개 (2012년기준, 60%) 에서 18개로 (2014년기준, 90%) 30% 증가했음을알수있었다. 안전사용수칙을표시하지않은 2개제품중 1개는이미허가사항에파스의안전한사용방법을상세히포함하고있기때문에실질적으로안전사용수칙을표시하지않은제품은 1개라고볼수있다. 그러나임상현장일선의약사들이의약품정보검색에많이활용하는인터넷사이트 드럭인포 21) 와 약학정보원홈페이지 22) 에안내된제품정보에는위 20개제품모두허가사항이외의안전사용에대한내용이전혀언급되지않았다. 파스안전사용에대한표시내용은제품에따라크게차이가없었으며, 그주요내용은다음과같다. - 질환부위를깨끗이하고건조한상태에서부착하십시오. - 같은질환부위에반복부착시부착위치를약간씩바꾸어도약효는동일하게지속됩니다. - 무릎등굽혀지는관절부위에부착하실때에는약 45도로관절을굽힌상태에서부착하십시오. - 손목또는손가락관절부위에는적당한크기로잘라서사용하십시오. - 가려움증이발생하는경우는즉시떼어내고, 질환부위를흐르는찬물에담가두거나, 얼음으로차게하여주십시오. - 피부이상이있는경우즉시사용을중지하고이상부위를차거나서늘하게한뒤, 의사또는약사와상의하십시오. - 본제품은관절부위에도적용이가능한강한접착력을지녔으므로, 건조한상태의피부나목과같이연약한부위에사용한경우에는미지근한물을가해적당히불려서떼어내면만약에발생할수도있는통증을경감시킬수있습니다. - 사우나, 온찜질후에는피부의각질층이약해지고내피층도손상되기쉬우므로본제품의부착시주의하십시오. 또한, 일부제품에서는허가사항에없는효능 효과에대해직접적으로언급하고있으며 ( 예 : OOO은통증에대하여압박지지효과가있음 ), 케토프로펜제제와달리광과민증부작용이알려지지않은플루르비프로펜제제의경우에는허가사항에없는광과민증예방법을소개하고있는경우도확인되었다. 고찰 파스형의약품은경구용제품이가지는위장장애, 간초회통과효과등과같은단점이없어주로근육통, 관절통등에소염 진통효과를기대하며널리사용되는제품이다. 특히, 경구투여가곤란한환자의경우피부를통해손쉽게투약할수있기에편리성이우수한제제이다. 그러나파스가약효를나타내기위해서는약물성분이피부의보호장벽층을물리 화학적으로뚫고체내로이행되어야하므로일정시간이상의부착이필요하며, 이과정에서피부접촉부위에홍반, 피부탈락등의부작용이나타날수있다. 따라서장시간부착에따른피부부작용의정도와유형을인식하고이를최소화할수있는방안이필요하다. 본연구에서조사한바에따르면, 파스의피부부작용을나타내는대표적인원인은주성분자체의특성때문이라할수있다. 특히케토프로펜제제는광과민증, 발진등을일으킬수있으므로파스사용중에는옥외활동을피하고, 일상외출시에는도포부위를옷, 자외선차단제등으로써자외선에노출을피해야한다. 또다른원인으로는환자의투약과오를들수있다. 경구제나주사제등다른제제에비해취급이편리한점이파스제품의가장큰장점이나취급이손쉬운만큼투약과오도많다는점을주의해야한다. 환자는반드시정해진투약시간이나투약부위, 투약방법등을잘숙지해야하며이를위해서약사의복약지도에대한준수가필요하다. 이외피부부작용을나타내는원인으로는물리적인피부폐쇄에따른피부호흡저하, 미생물번식등이있다. 이를최소화하기위해서파스를같은부위에반복적으로부착하여장시간사용해야하는경우에는부착부위를변화시키거나어느정도의휴식기를두고사용할수있도록해야한다. 참고로한국소비자원에서는파스부작용의주요원인으로점착력을꼽으며, 부작용을줄이기위해파스의점착력상한선이있어야한다고주장하였으나 3) 국외사례, 점착력과피부부작용과의상관관계등을종합해보면현시점에서점착력상한선을정하는것은어려움이있다고판단된다. 또한 2012년한국소비자원에서조사했던시중유통중인파스 20개제품의표기실태를현시점에서재조사하여비교해본결과, 90% 에해당되는 18개제품이자율적으로허가사항이외의안전사용수칙을표기하고있었다. 이는 2012년한국소비자원의조사결과때보다안전사용수칙표기가 30% 가증가한것으로업계스스로파스사용에따른피부부작용을최소화하기위해노력하고있음을알수있었다. 다만일부제품은허가사항에도없는효과를직접적으로언급하는등부적절한내용을담고있었고, 또한의약품정보사이트인드럭인포와약학정보원홈페이지에서는안전사용수칙이전혀언급되고있지않아환자가직접접하는파스제품에표시된안전사항정보와의약품사이트를통한온라인정보간에는상

9 파스제의점착력관리기준및피부부작용조사연구 227 당한차이가있음이조사되었다. 21,22) 따라서, 파스로인한피부부작용을최소화하면서안전하게사용할수있도록다음의개선이필요하다고사료된다. (1) 소비자가파스의허가된용법 용량을준수하고, 파스사용시주의할사항을충분히인식할수있도록약사의복약지도와소비자교육및홍보를강화시킨다. 복약지도시소비자가꼭알아야하는핵심사항을간추려제품표면에스티커를부착하는방법, 또는복약안내서를추가로제공하면서설명하는방법등을활용하여파스탈 부착교환시기, 특정약물에대한알레르기발현가능성등복약지도를충실히행할수있도록한다. 또한유 소아부터노년층까지전세대가손쉽게사용할수있는의약품임을감안하여학교보건교육, 공익광고, 약국내팜플릿등을활용하여파스의올바른사용법에대한교육및홍보가필요하다. (2) 약물부작용정보뿐만아니라피부에안전하게붙이거나떼어내는방법, 부착한후햇볕, 물등의자극이있는옥외활동시주의할사항등안전사용에관한내용을의약품허가사항으로관리한다. 식품의약품안전처고시 의약품의품 목허가 신고 심사규정 제 17조에따르면, 허가항목중사용상주의사항에는그의약품이안전하고합리적으로사용되는데필요한최신의안전성관련사항을모두기재하여야하고, 특히투여경로, 부위등투여에필요한주의사항을기재하도록하고있다. 11) 따라서현재제조사가자율적으로표기하는안전사용수칙내용을객관적검증후허가함으로서유사제품군에는통일된내용이표시되고, 제품포장면의표시내용과온라인제품정보내용이동일하게관리될수있어야한다. 감사의말씀 본연구는 2014년도조선대학교학술연구비지원에의해수행되었음. 참고문헌 1. Notice # , KMFDS Korean Pharmacopoeia: General Formulation mfds.go.kr/index.do?x=0&searchkey =title:contents&mid=1013&searchword= 대한민국약전 &y= 0&division=&pageNo=1&seq=6313&cmd=v (Accessed on February 12, 2014). 2. Transdermal formulation, Choi HK, Shinil Books, Seoul, Korea, Report information by Korea Customer Agency (Accessed on November 9, 2012). 4. Korea National Institute of Food and Drug Safety Evaluation, Research on establishing of guidelines for evaluating the effectiveness of drug safety, Japanese Pharmacopoeia 15 th edition, Ministry of Health, United States Pharmacopoeia 34 th edition, USP Convention, European Pharmacopoeia 7.0, European Directorate for the Quality of Medicines & Health Care, EZdrug, Korea Ministry of Food and Drug Safety. ezdrug.mfds.go.kr (Accessed on June, 2014) 9. Notice # , KMFDS Korean Pharmacopoeia: Individual Monograph. Internet site: index.do?x=0&searchkey=title:contents&mid=1013&searchwo rd= 대한민국약전 &y=0&division=&pageno=1&seq=6313 &cmd=v (Accessed on February 12, 2014). 10. Notice # , KMFD Criteria for non-formulary drugs excluding Korean Pharmacopoeia. Internet site: mfds.go.kr/index.do?x=0&searchkey= title:contents&mid =1013&searchword= 대한민국약전외 &y= 0&division=&page No=1&seq=6312&cmd=v (Accessed on November 21, 2013). 11. Notice # , KMFD Regulations for marketing and sales, report, review of authorized medications. Internet site: contents&mid=1013&searchword= 의약품의품목 &y=0& division=&pageno=1&seq=7773&cmd=v (Accessed on February 12, 2014). 12. Notice # , KMFD Standards and test methods on the quasi-drugs. Internet site: index.do?x=0&searchkey=title:contents&mid=1013&search word= 의약외품 &y=0&division=&pageno=1&seq=7737 &cmd=v (Accessed on February 12, 2014). 13. Drug approval and licensing procedures in Japan Prez-Caldern R, Gonzalo-Garijo MA, Rodrguez-Nevado I. Generalized allergic contact dermatitis from nitroglycerin in transdermal therapeutic system. Contact Dermatitis 2002;46(5): Alfaya T, Mur Gimeno P, Iglesias AM, et al. Allergic contact dermatitis caused by an ethinylestradiol norelgestromin transdermal therapeutic system. Contact Dermatitis 2011;64(4): FDA safety page, drug topics. April 1, Lee M and Phillips J. 17. Tokumura F, Ohyama K, Fujisawa H, et al. Conformability and irritancy of adhesive tapes on the skin. Contact Dermatitis 1997;37(4): Wokovich AM, Prodduturi S, Doub WH, et al. Transdermal drug delivery system (TDDS) adhesion as a critical safety,

10 228 Kor. J. Clin. Pharm., Vol. 24, No. 3, 2014 efficacy and quality attribute. Eur J Pharm Biopharm 2006;64(1): Cilurzo F, Gennari CG, Minghetti P. Adhesive properties: a critical issue in trans- dermal patch development. Expert opin drug deliv 2012;9(1): Satas D. Handbook of Pressure Sensitive Adhesive Technology, 3rd ed. Rhode Island: Satas & Associates, 1999; Korea Pharmaceutical Information Center (Accessible at Druginfo, Drug Information Organization in Korea (Accessible at