[논문]Warfarin과 Simvastatin/Gemfibrozil의 약물 상호 작용 : 높은 수치의 ALT/AST, 횡문근 융해와 급성 신장 장애

윤현옥

Warfarin과 Simvastatin/Gemfibrozil의 약물 상호 작용 : 높은 수치의 ALT/AST, 횡문근 융해와 급성 신장 장애
Drug Interaction of Warfarin with Simvastatin / Gemfibrozil : high levels of ALT/AST, rhabdomyolysis and acute renal failure 원문보기

한국임상약학회지 = Korean journal of clinical pharmacy, v.21 no.3, 2011년, pp.270 - 275

윤현옥 (미국 하워드 대학교 약학대학)

초록
AI-Helper

이 증례는 드물게 보는 경우로 simvastatin과 gemfibrozil을 오랫동안 함께 복용했음에도, 특이한 문제가 발현되지 않았지만, 이들을 warfarin와 함께 치료하는 경우, 아주 높은 alanine aminotransferase (ALT), aspartate aminotransferase(AST) 혈중 농도, rhabdomyolysis, 급성 신장 장애가 발생하였다. 그 후, Simvastatin와 gemfibrozil을 복용 중단시켰더니, ALT/AST는 빠르게 정상수치로 돌아온 경우이다. 이 증례 보고서는 의료인들에게 simvastatin과 gemfibrozil을 함께 혹은 따로 warfarin과 함께 복용시켜 치료할 경우, creatine phosphokinase (CPK) 와 creatinine 혈중 수치들을 포함하여 ALT/AST 농도들을 주의 깊게 모니터하도록 경각심을 주고자 한다.

주제어

AI 본문요약
AI-Helper

* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.

문제 정의

It was the assessment of suspected concurrent use of simvastatin and gemfibrozil together with warfarin to induce rhabdomyolysis, transaminitis and acute renal failure.
This report presents a case of rhabdomyolysis that is complicated with acute renal failure and significantly high levels of AST/ALT being associated with the concomitant use of simvastatin, gemfibrozil and warfarin.

제안 방법

9C, respiratory rate 18, SpO2 97% and his chest was clear. He was afebrile, had mild leg muscle tenderness, and labs were Scr 3.41, AST 1277, ALT 626, normal T bill, CPK 453, white blood count (WBC) 3, red blood count(RBC) 6. In addition, his lab data were Scr 1.
He was taking several medications prior to admission such as aspirin 81 mg tablet orally once daily, nortriptyline 10 mg capsule orally once daily but occasionally at bedtime, acetaminophen-codeine 300-30 mg orally every 4 hours as needed for pain, while not exceeding 6 tablets in 24 hours, warfarin 2.5 mg orally as directed by anticoagulation service, simvastatin 80mg orally every evening, lisinopril 10mg orally once daily, gemfibrozil 600 mg orally twice daily.
This case study demonstrated to report abnormal skyrocketing levels of transaminases, including rhabdomyolysis to an interaction between simvastatin, gemfibrozil and warfarin as the history of his drug regimen. It has given health providers a valuable lesson of monitoring clinical and laboratory data more carefully as well as to hold or reduce the dose of simvastatin and/or gemfibrozil when patient begins to take warfarin.

대상 데이터

An 81year–old–Asian male who was 179cm height, 75.7 kg weight with permanent pacemaker, chronic kidney disease {Serum creatinine (Scr) 1.73 in 2010}, anemia, hypertension, embolism of artery, prostate cancer, hyperlipidemia, arterial fibrillation and chronic pain was admitted to the emergency department (ED) of a hospital.
41, AST 1277, ALT 626, normal T bill, CPK 453, white blood count (WBC) 3, red blood count(RBC) 6. In addition, his lab data were Scr 1.96, AST 1045, ALT 490, normal T bill, CPK 356 at outpatient setting one day before his admission of hospital. He was anuric.

성능/효과

35 mmol/L) than the case of low dose. The reported cases of myopathy, including rhabdomyolysis, were significantly increased in the high-dose group (0.9% versus 0.03%; CI 6.5-109). The research showed that 7 confirmed cases were rhabdomyolysis (defined as CPK > 40 times the upper limit of normal (ULN)with the evidence of end-organ damage (eg, doubling of plasma creatinine)) and another 7 cases were with CPK levels higher than than 40 times ULN in the high-dose group.

참고문헌 (35)

Mol MJ, Stuyt PM, Stalenhoef AF, van 't Laar A. Cholesterol synthesis inhibitors in hyperlipidaemia. Lancet 1988; 1: 597.
Schulzeck P, Bojanovski M, Jochim A, Canzler H, Bojanovski D. Comparison between simvastatin and bezafibrate in effect on plasma lipoproteins and apolipoproteins in primary hypercholesterolaemia. Lancet 1988; 1: 611-3.
Bard JM, Luc G, Douste-Blazy P, et al., Effect of simvastatin on plasma lipids, apolipoproteins and lipoprotein particles in patients with primary hypercholesterolaemia. Eur J Clin Pharmacol 1989; 37: 545-50.

상세보기
Boccuzzi SJ, Bocanegra TS, Walker JF, Shapiro DR, Keegan ME. Long-term safety and efficacy profile of simvastatin. Am J Cardiol 1991; 68: 1127-31.

상세보기
Ayanian JZ, Fuchs CS, Stone RM. Lovastatin and rhabdomyolysis. Ann Intern Med 1988; 109 :682-3.

상세보기
Corpier CL, Jones PH, Suki WN, et al., Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients. Jama 1988; 260: 239-41.

상세보기
Jacobson RH, Wang P, Glueck CJ. Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone. Jama 1997; 277: 296-7.

상세보기
Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med 1995; 333: 664-5.

상세보기
Schmassmann-Suhijar D, Bullingham R, Gasser R, Schmutz J, Haefeli WE. Rhabdomyolysis due to interaction of simvastatin with mibefradil. Lancet 1998; 351: 1929-30.
Becquemont L. [Drug interactions with antilipemics]. Therapie 2003; 58: 85-90.

상세보기
Capone D, Stanziale P, Gentile A, Imperatore P, Pellegrino T, Basile V. Effects of simvastatin and pravastatin on hyperlipidemia and cyclosporin blood levels in renal transplant recipients. Am J Nephrol 1999; 19: 411-5.

상세보기
Ohno Y, Hisaka A, Suzuki H. General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs. Clin Pharmacokinet 2007; 46: 681-96.

상세보기
Fenneteau F, Poulin P, Nekka F. Physiologically based predictions of the impact of inhibition of intestinal and hepatic metabolism on human pharmacokinetics of CYP3A substrates. J Pharm Sci; 99: 486-514.
Yeo KR, Yeo WW. Inhibitory effects of verapamil and diltiazem on simvastatin metabolism in human liver microsomes. Br J Clin Pharmacol 2001; 51: 461-70.

상세보기
Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs 2003;63: 769-802.
Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol; 32: 675-703.

상세보기
Olsson AG, Rossner S, Walldius G, Carlson LA. Effect of gemfibrozil on lipoprotein concentrations in different types of hyperlipoproteinaemia. Proc R Soc Med 1976; 69 Suppl 2: 28-31.
Betteridge DJ, Higgins MJ, Galton DJ. Properties of sterol biosynthesis in human leukocytes: effects of gemfibrozil. Proc R Soc Med 1976; 69 Suppl 2: 104-6.
Knoll RW, Ciafone R, Galen M. Rhabdomyolysis and renal failure secondary to combination therapy of hyperlipidemia with lovastatin and gemfibozil. Conn Med 1993; 57: 593-4.

상세보기
Armitage J, Bowman L, Wallendszus K, et al., Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet; 376: 1658-69.
Chang JT, Staffa JA, Parks M, Green L. Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiol Drug Saf 2004; 13: 417-26.

상세보기
Backman JT, Kyrklund C, Kivisto KT, Wang JS, Neuvonen PJ. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 2000; 68: 122-9.

상세보기
Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006; 80: 565-81.

상세보기
Prueksaritanont T, Ma B, Yu N. The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. Br J Clin Pharmacol 2003; 56: 120-4.

상세보기
Franson JC. Enzyme activities in plasma, liver and kidney of black ducks and mallards. J Wildl Dis 1982;18: 481-5.

상세보기
Dianzani MU. [Distribution of lactic acid oxidase in liver and kidney cells of normal rats and rats with fatty degeneration of the liver]. Arch Fisiol 1951 ;50 :181-6.

상세보기
Barchetta I, Angelico F, Del Ben M, et al., Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med; 9: 85.
Figueroa RB, Klotz AP. The Effect of Whiskey and Low-Protein Diets on Hepatic Enzymes in Rats. Am J Dig Dis 1964; 9 :121-7.
Hofmann AF, Korman MG, Krugman S. Sensitivity of serum bile acid assay for detection of liver damage in viral hepatitis type B. Prospective study in five patients. Am J Dig Dis 1974; 19 :908-10.
Hickmott H, Wynne H, Kamali F. The effect of simvastatin co-medication on warfarin anticoagulation response and dose requirements. Thromb Haemost 2003; 89: 949-50.
Keech A, Collins R, MacMahon S, et al., Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study. Eur Heart J 1994; 15: 255-69.

상세보기
Gaw A, Wosornu D. Simvastatin during warfarin therapy in hyperlipoproteinaemia. Lancet 1992; 340: 979-80.
Ahmad S. Gemfibrozil interaction with warfarin sodium (coumadin). Chest 1990; 98: 1041-2.
Dixon DL, Williams VG. Interaction between gemfibrozil and warfarin: case report and review of the literature. Pharmacotherapy 2009; 29: 744-8.

상세보기
Mogyorosi A, Bradley B, Showalter A, Schubert ML. Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. J Intern Med 1999; 246: 599-602.

상세보기

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증