항불안약물과 항우울약물의 허가사항 내임신부 안전성정보에 대한 일치도 분석:한국, 미국, 영국, 일본 허가사항을 중심으로 = Agreement of Label Information on Anxiolytics and Antidepressants for Pregnant Women: Comparison among Korea,the USA, the UK and Japan

다국어 초록 (Multilingual Abstract)

Objective Anxiolytics and antidepressants are commonly used to treat depressive disorders in pregnant women. Specific and clear evidence is required when managing pregnant patients with such medications to ensure safety. However, information provided by approval label information is insufficient and often different among many countries. By analyzing label information of approval label and other references, this study aims to show the limitations and suggest appropriate directions for retrieving safety information.
Methods We selected five anxiolytics and eleven antidepressants, which belongs to Korea drug classification codes 117 (psychotropic agents). We chose four countries, Korea, the United States of America (USA), the United Kingdom, Japan and collected safety information for pregnant women in label information. We evaluated the safety information based on recommendation level and evidence level. Then, kappa value and overall agreement were calculated using SAS 9.3. to assess data homogeneity. We further searched Reprotox and a textbook about contraindicated drugs in label information.
Results Recommendation level and evidence level was different in each country. The number of commonly contraindicated drug in label information of four countries was none, and contraindicated drugs in labels were different respectively. Kappa value of evidence level between label information of Korea and Japan, the USA and Japan was 0.61, 0.43 respectively, corresponding to ‘substantial agreement’ and ‘moderate agreement’. The overall agreement was 75%, 62.5% respectively. The information of label was different from that of other references, Reprotox and a textbook in terms of the clinical evidences and recommendation levels.
Conclusion Safety information of anxiolytics and antidepressants in label information needs to be updated on a regular basis both for health professionals and patients. With the implication of the inconsistent guidance for the safety information in pregnant women, reliable safety information in pregnant women would be needed.

국문 초록 (Abstract)

임신부에서 우울증 등을 치료하기 위해서는 항우울약물 및 항불안약물의 적절한 사용이 필요하며, 이에 약물치료 전 임신부에 대한 상대적인 안전성정보를 반드시 고려해야 한다. 이처럼 임신부에서 신뢰할만한 안전성정보의 제공이 요구되어 본 연구에서는 한국, 미국, 영국, 일본에 공통으로 허가되어 있는 약물을 대상으로 허가사항 내 안전성정보의 일치도를 분석하였다. 안전성정보를 금기/주의 등 권고수준과 허가사항에 기재된 근거의 수준에 따라서 등급을 분류하여, 국가별로 각 등급에 해당하는 일치도 수준을 kappa 값과 전체 일치도를 이용하여 제시하였다. 국가별로 금기/주의 등 권고수준의 편차가 매우 심하여, 4개국에서 권고수준이 일치하는 성분이 없는 것으로 나타나서, 국가 간 허가사항 내 임신부 안전성정보 기준을 통일하여 표준화할 필요성이 있는 것으로 나타났다. 근거수준의 경우 한국과 일본 간 근거수준에 대한 kappa값이 0.61로 상당히 일치하는 편이였으며, 미국과 일본이 0.43의 kappa값을 보여 중등도로 일치하는 것으로 나타났다. 항불안약물과 항우울약물의 경우 허가사항 내 임신부 안전성정보가 산부인과학 교과서와 의약정보원에 비하여 충실하지 않은 것으로 나타났는데, 특히 메타분석, 코호트연구, 환자-대조군연구 등 임신부에서 최신의 연구결과와 전문가 의견을 반영한 최신의 안전성정보 제공이 필요한 것으로 나타났다.

참고문헌 (Reference)

1 이소영, "임신과 수유기 우울증의 치료 전략" 대한생물정신의학회 14 (14): 91-98, 2007

2 식품의약품안전처, "의약품전자민원창구"

3 "의약품의 품목허가신고심사 규정"

4 "Weblio"

5 "Warnings and Precautions Contraindications and Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products - Content and Format"

6 "Truvan Health Analytics"

7 Landis JR, "The measurement of observer agreement for categorical data" 33 : 159-174, 1977

8 Shimazawa R, "Safety information in drug labeling: a comparison of the USA, the UK, and Japan" 22 : 306-318, 2013

9 Kim CH, "Practical issues in the psychopharmacotherapy during pregnancy and lactation" 11 : 22-34, 2000

10 "Pharmaceuticals and Medical Devices Agency"

11 Rougemont M, "French summaries of product characteristics: content in relation to therapeutic monitoring of psychotropic drugs" 24 : 377-384, 2010

12 Sackett DL, "Evidence-based Medicine" Churchill Livingstone 2000

13 "Electronic Medicines Compendium"

14 "Drugs@FDA FDA Approved Drug Products"

15 Briggs GG, "Drugs in Pregnancy and Lactation" Wolters Kluwer Health 44-727, 2011

16 Kim HJ., "Drugs for common illnesses during pregnancy" 50 : 440-446, 2007

17 Pfistermeister B, "Different indications, warnings and precautions, and contraindications for the same drug--an international comparison of prescribing information for commonly used psychiatric drugs" 22 : 329-333, 2013

18 "Dailymed"

19 Ward RK, "Benefits and risks of psychiatric medications during pregnancy" 66 : 629-636, 2002

20 National Collaborating Centre for Mental Health (UK), "Antenatal and Postnatal Mental Health: The NICE Guideline on Clinical Management and Service Guidance" UK: British Psychological Society 10-17, 2007

21 Kim SJ, "A comparative evaluation of drug information databases in Korea" 11 : 30-41, 2001