「藥物安全簡訊」出刊計畫

Drug Safety Newsletter 2003. Mar. Vol.1...2...2 1. Premarin...2 2. Serevent...2 3. Serzone...3 4. Deep Brain Stimulators...3 --- Arava...4...8 ADR --- Ketorolac...12 --- Phenytoin...16 Taiwan Drug Relief Foundation National Reporting Center of Adverse Drug Reactions in Taiwan

~~~~~~~~~~~~~~~~~~~~~~~~~~ by http://adr.doh.gov.tw ADR ADR ADR ADR by 1. Premarin WHI a HRT HRT 1.26 1.29 37 24 FDA Wyeth Premarin http://adr.doh.gov.tw/main09.asp http://www.doh.gov.tw/newverprog/proclaim/content.asp?class_no=25&now_fod_list_ no=25&array_fod_list_no=&level_no=1&doc_no=21101 http://www.fda.gov/medwatch/safety/2003/safety03.htm#prempr a : Writing Group for the Women s Health Initiative Investigators. Risk and benefits of estrogen plus progestin in healthy postmenopausal women---principal results from the women s health initiative randomized controlled trial. JAMA 2002;288:321-33. 2. Serevent GSK Drug Safety Newsletter 2003.Mar. Vol. 1 2

~~~~~~~~~~~~~~~~~~~~~~~~~~ Serevent Serevent Serevent http://adr.doh.gov.tw/main09.asp http://www.fda.gov/medwatch/safety/2003/safety03.htm#sereve 3. Serzone Serzone Serzone Seroquel Quetiapine fumarate, http://adr.doh.gov.tw/main09.asp http://www.fda.gov/medwatch/safety/2003/safety03.htm#serzon 4. Deep Brain Stimulators FDA deep brain stimulators DBS http://adr.doh.gov.tw/main09.asp http://www.fda.gov/medwatch/safety/2002/safety02.htm#diathe 100 19-1 1 02 2358-7343 E-mail adr@tdrf.org.tw Drug Safety Newsletter 2003.Mar. Vol. 1 3

~~~~~~~~~~~~~~~~~~~~~~~~~~ --- Arava Leflunomide Arava 2 leflunomide Disease modifying anti-rheumatic drug; DMARD 1 A771726; M1 or leflunomide RS-61980 European Medicine Evaluation dihydroorotate dehydrogenase DHODH Agency s scientific committee T pyrimidine leflunomide 1998 9 77,200 17,200 EMEA 300 9,600 296 2002 12 129 10, 20, 100 2 15 Leflunomide 9 3 100 20 leflunomide 10 6 25 Drug Safety Newsletter 2003.Mar. Vol. 1 4

~~~~~~~~~~~~~~~~~~~~~~~~~~ 2 leflunomide 26 64 5 99 78 leflunomide Methotrexate 20 20 NSAIDs 27 6 4 2000 A77 191 32 5 A771726 2000 5 7,8 2002/5/31 99 leflunomide leflunomide 11 79 4 6 3,4 1. Leflunomide 2. Methotrexate 16 3. pancytopenia 9 - leflunomide leflunomide 7,8 191 Drug Safety Newsletter 2003.Mar. Vol. 1 5

~~~~~~~~~~~~~~~~~~~~~~~~~~ leflunomide A771726; M1 RS-61980 leflunomide 11 4 28 2 leflunomide washout period 3 cholestyramine leflunomide 8 DMARD : 50 11 methotrexate leflunomide leflunomide 4. 9,10 B C 7 leflunomide Drug Safety Newsletter 2003.Mar. Vol. 1 6

~~~~~~~~~~~~~~~~~~~~~~~~~~ leflunomide B C leflunomide leflunomide 2000/3/29 2002/5/31 MTX 20 8 11 1 11 6 MTX: methotrexate leflunomide London (UK): European Agency for the Evaluation of Medicinal Products. 10 8. 1999/10/25. Available: www.emea.eu.int/ htms/human/drugalert/drugalert.htm. Leflunomide: reports of pancytopenia and serious skin reactions. Who Health Alert #91 1999/11/11. 9. Http://www.eudra.org/humandocs/Huma cholestyramine ns/epar/arava/arava.htm 10. Http://www.fda.gov/cder/approval/index. 1. Kremer J. Rational use of new and existing desease-modifying agents in rheumatoid arthritis. Ann Intern Med 2001;134(8):695-706. 2. DrugDex under the title of leflunomide. Micromedex Inc. 2003, Vol. 115. 3. EMEA public statement on leflunomide (Arava): severe and serious hepatic reactions [doc ref EMEA/5611/01/en]. London (UK): European Agency for the Evaluation of Medicinal Products. 2001/03/12. Available: www.emea.eu.int/ htms/human/drugalert/drugalert.htm. 4. Leflunomide: severe and serious hepatic reactions. Who Health Alert #101 2001/03. 5. Adverse Drug Reactions Advisory Committee (ADRAC). Leflunomide: serious hepatic, blood, skin and respiratory reactions. Aust Adverse Drug Reactions Bull 2001;20(2):7. 6. Candian Adverse Reaction Newsletter. 2002;12:Issue 4. 7. EMEA public statement on leflunomide (Arava): pancytopenia and serious skin reactions [doc ref EMEA/31637/99]. htm Drug Safety Newsletter 2003.Mar. Vol. 1 7

~~~~~~~~~~~~~~~~~~~~~~~~~~ 1 2 1 2 ; 87 5 19 87 10 12 88 1 12 11 17 Drug Safety Newsletter 2003.Mar. Vol. 1 8

~~~~~~~~~~~~~~~~~~~~~~~~~~ 3. 爲 89 5 19 89 5 31 6 2 1. 2. 爲 11 17 Drug Safety Newsletter 2003.Mar. Vol. 1 9

~~~~~~~~~~~~~~~~~~~~~~~~~~ 90 9 24 3. 4. 1. 88 1 91 12 2. 278 265 244 223 Drug Safety Newsletter 2003.Mar. Vol. 1 10

~~~~~~~~~~~~~~~~~~~~~~~~~~ 89 25 4 60 130 4 65 - carbamazepine 29 (n=130) 19 13 17 Off label use 24 18 38 1 Carbamazepine 29 Phenytoin 10 Allopurinol 9 Rifampicin 4 Cefazolin 3 Lamotrigine 3 Skin and subcutaneous disorders 65 Immune system disorder 11 Hepato-biliary disorders 4 Blood and lymphatic system disorders 4 Nervous system disorders 2 General disorders and administratin site conditions 2 Respiratory, thoracic and mediastinal disorders 1 19 1 1 02 2358-4097 http://www.tdrf.org.tw Drug Safety Newsletter 2003.Mar. Vol. 1 11

~~~~~~~~~~~~~~~~~~~~~~~~~~ ADR Ketorolac 1,2 2 1,2 1 2 1 2 1 2 0.12 0.09 Ketorolac 0.04 trometamol ASA ketorolac score 15 1-4 Ketorolac 5,6 NSAIDs 16 ketorolac 7 ketorolac ketorolac 53 30 56.6 aspirin NSAIDs 22 41.5 8 9-14 39.5 15 ketorolac ketoprofen diclofenac 37 1.38 Ketorolac 0.17 1.04 2 Drug Safety Newsletter 2003.Mar. Vol. 1 12

~~~~~~~~~~~~~~~~~~~~~~~~~~ (%) 15 28.3 20 37.7 18 34.0 5 9.4 37 69.8 5 9.4 6 11.3 89 7 13.2 90 15 28.3 91 31 58.5 30 56.6 22 41.5 1 1.9 <19 1 1.9 20-29 15 28.3 30-39 5 9.4 40-49 10 18.9 50-59 3 5.7 60-69 2 3.8 >70 3 5.7 14 26.4 ( ) 39.5(9-88) 47 88.7 1 1 1.9 2 1 1.9 3 2 3.8 6 1 1.9 10 1 1.9 (%) ADR 2 3.8 2 3.8 5 9.4 6 11.3 38 71.7 7 13.2 40 75.5 5 9.4 1 1.9 23 43.4 26 49.1 1 1.9 3 5.7 43.4% 26 49.1% 53 26.8 22.5 14.1-3.8 2 3.8 5 9.4 ketorolac ADR 89 1,524 90 1,831 91 6 11 2,027 11.3 37 ketorolac 7 53 70 40 75.5 5 23 51 Drug Safety Newsletter 2003.Mar. Vol. 1 13

~~~~~~~~~~~~~~~~~~~~~~~~~~ 1992 Goetz ketorolac 17 18 ketorolac ketorolac Ketorolac 7 ketorolac 100 ketorolac 5,600 NSAIDs 2 19 ketorolac ketorolac NSAIDs relative risk, 4.4 RR ketorolac RR 24.7 diclofenac sodium naproxen tenoxicam (%) 20 mg/day ketorolac 10 19(26.8) 16(22.5) 10(14.1) 3(4.2) 2(2.8) 2(2.8) 2(2.8) 2(2.8) 2(2.8) 1(1.4) 1(1.4) 1(1.4) 1(1.4) 1(1.4) 1(1.4) 1(1.4) 1(1.4) 1(1.4) 1(1.4) - 1(1.4) 1(1.4) 5 47 10 ketorolac 7 Drug Safety Newsletter 2003.Mar. Vol. 1 14

~~~~~~~~~~~~~~~~~~~~~~~~~~ 90 mg 60 Micromedex. Ketorolac Aust 1993; 159(7):488. Med 1992; 92(4):450-452. NSAIDs 1):294-296. Wis Med J 1995; 94(8):445-447. DeAndrade JR, Maslanka M, Maneatis T, Bynum L, Burchmore M. The use of ketorolac in the management of postoperative pain. Orthopedics 1994; 17(2):157-166. DiPalma JR. Ketorolac: an injectable NSAID. Am Fam Physician 1991; 43(1):207-210. Mofenson HC, Caraccio TR. Safety of intravenous ketorolac therapy. J Pediatr 1997; 130(5):846-84V. Resman-Targoff BH. Ketorolac: a parenteral nonsteroidal antiinflammatory drug. DICP 1990; 24(11):1098-1104. Rooks WH, Maloney PJ, Shott LD, Schuler ME, Sevelius H, Strosberg AM et al. The analgesic and anti-inflammatory profile of ketorolac and its tromethamine salt. Drugs Exp Clin Res 1985; 11(8):479-492. Rooks WH, Tomolonis AJ, Maloney PJ, Wallach MB, Schuler ME. The analgesic and anti-inflammatory profile of (+/-)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2a]p yrrole-1-carboxylic acid (RS-37619). Agents Actions 1982; 12(5-6):684-690. Bucaneve G, Hill EM, Hord AH. Ketorolac (Monograph). Hutchison TA, Shapiro N, editors. Drugdex system[115 (Edition expires 3/2003)]. 2002. Greenwood Village, Colorado, Bizzarri C. Anti-inflammatory analgesics and drugs used in gout. In: Dukes MNG, editor. Meyler's Side Effects of Drugs. Amsterdam, Netherlands: Elsevier Science B.V., 1996: 204. Anon. Ketorolac and renal failure. Adverse Drug Reactions Advisory Committee. Med J Boras-Uber LA, Brackett N-CJ. Ketorolac-induced acute renal failure. Am J Buck ML, Norwood VF. Ketorolac-induced acute renal failure in a previously healthy adolescent. Pediatrics 1996; 98(2 Pt Patel NY, Landercasper J. Ketorolac-induced postoperative acute renal failure: a case report. Pearce CJ, Gonzalez FM, Wallin JD. Renal failure and hyperkalemia associated with ketorolac tromethamine. Arch Intern Med 1993; 153(8):1000-1002. Quan DJ, Kayser SR. Ketorolac induced acute renal failure following a single dose. J Toxicol Clin Toxicol 1994; 32(3):305-309. Forrest JB, Camu F, Greer IA, Kehlet H, Abdalla M, Bonnet F et al. Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery. Br J Anaesth 2002; 88(2):227-233. Schoch PH, Ranno A, North DS. Acute renal failure in an elderly woman following intramuscular ketorolac administration. Ann Pharmacother 1992; 26(10):1233-1236. Goetz CM, Sterchele JA, Harchelroad FP. Anaphylatoid reaction following ketorolac tromehtamine administration. Ann Pharmacother 1992;26(10):1237-8. Anon. Pharmacovigilance case report. No. 098, 113, 199, 236. Taipei, Taiwan, Taiwan Drug Relief Foundation. Garcia-Rodriguez LA, Cattaruzzi C, Troncon MG, Agostinis L. Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. Arch Intern Med 1998; 158(1):33-39. Drug Safety Newsletter 2003.Mar. Vol. 1 15

~~~~~~~~~~~~~~~~~~~~~~~~~~ Phenytoin I-wen Yu 1 2 1 2 SJS, Stevens Johnson syndrome TEN, Toxic epidermal necrosis Acute hepatitis 1938 phenytoin 54.7 21.4 8-85 - generalized tonic-clonic status epilepticus phenytoin n=7 FDA n=4 1 off label phenytoin 6.7 phenytoin 300 mg 200-500 mg 20.7 11 7-51 carbamazepine, 223 phenobarbital, valproic acid 14 phenytoin 15 Drug Safety Newsletter 2003.Mar. Vol. 1 16

~~~~~~~~~~~~~~~~~~~~~~~~~~ Nikolsky - 14 13 phenytoin 1 1 phenytoin phenytoin 100 mg n 15 9 6 54.6 8-85 Phenytoin 300 200-500 mg ADR 20.7 7-51 Phenytoin 7 4 2 1 1-11 2 1 1 tid B urticarial HBSAg Anti-HCV - 1.5 4 GOT/GPT 6544/6544 Bilirubin T/D 1.5/1.4 Alk-P:251 GGT phenytoin phenytoin 1203 hypersensitivity syndrome lymphadenopathy thrombocytopenia Phenytoin 2-6 5,6 skin eruption 1/1,000-1/10,000 7 7-21 5-10 2,3 cranial radiation therapy morbiliform 8 scarlatiniform Drug Safety Newsletter 2003.Mar. Vol. 1 17

~~~~~~~~~~~~~~~~~~~~~~~~~~ phenytoin arene oxide 1-8 4 9 75 phenytoin 62.5 eosinophilia 89 10 40 leukocytosis 100 phenytoin phenytoin 38 phenytoin 1. phenytoin 300 mg 15 phenytoin 6 2. - 2 phenytoin phenytoin 1 3. 5 4. Drug Safety Newsletter 2003.Mar. Vol. 1 18

~~~~~~~~~~~~~~~~~~~~~~~~~~ right phenytoin thalamic hemorrhage phenytoin 300 mg QD phenytoin 27 phenytoin - Phenytoin 1. phenytoin 1. Phenytoin 300 2. phenytoin 2. - CNS depressants, phenytoin amiodarone, anticoagulants, 3. - acetazolamide, fluconazole, other anticonvulsants 4. phenytoin - 3. phenytoin 10-20µg/ml 4. Phenytoin 5. 1. 2. 3. - - phenytoin - 93-1 Drug Safety Newsletter 2003.Mar. Vol. 1 19

~~~~~~~~~~~~~~~~~~~~~~~~~~ 4. Roujeau JC, Kelly JP & Naldi L: Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333:1600-1607. 5. Flowers FP, Araujo OE & Hamm KA: Phenytoin hypersensitivity syndrome. J Emerg Med 1987; 5:103-108. 6. Tomsick RS: The phenytoin syndrome. Cutis 1983; 32:535-541. 7. Marik P: Anticonvulsant hypersensitivity syndrome occurring as sepsis with multiorgan dysfunction. Pharmacotherapy 1999; 19(3):346-348. 8. Delattre J, Safai B, Posner JB. Erythema phenytoin 1. DrugDex under the title of Phenytoin. multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology 1988; 38: 194-8. Micromedex Inc. 2003, Vol. 115 9. Mullick FG, Ishak KG. Hepatic injury 2. Silverman AK, Fairley J & Wong RC: Cutaneous and immunologic reactions to phenytoin. J Am Acad Dermatol 1988; associated with diphenylhydantoin therapy. A clinicopathologic study of 20 cases. Am J Clin Pathol 1980 74 442-452. 18:721-741. 10. Dreifuss FE, Langer DH. Hepatic 3. Ramsay RE: Use of phenytoin and carbamazepine in treatment of epilepsy. Neurol Clin 1986; 4:585-600. considerations in the use of antiepileptic drugs. Epilepsia 1987 28 Suppl 2 S23. 2002 Dec. Vol. 1 P5 13 P9 ADR http://adr.doh.gov.tw 湶 19-1 1 02 2358-7343 02 2396-0100 02 2358-4100 http://www.tdrf.org.tw http://adr.doh.gov.tw 7813 Drug Safety Newsletter 2003.Mar. Vol. 1 20