Drug Safety Newsletter 2003. Sept. Vol.3...2 1. Permax...2 2. Repaglinide Gemfibrozil...2 3. Lindane...2 4. Rapamune...2...3 Repaglinide Gemfibrozil...9 ADR NSAID Acetaminophen...11 Carbamazepine...16 Taiwan Drug Relief Foundation National Reporting Center of Adverse Drug Reactions in Taiwan
~~~~~~~~~~~~~~~~~~~~~~~~~~ by 1. Permax Eli Lilly Permax (Pergolide mesylate) Permax (cardiac valvulopathy) Permax http://www.fda.gov/medwatch/safety/2003/permax.htm 2. Repaglinide Gemfibrozil EMEA The European Agency for the Evaluation of Medicinal Products repaglinide gemfibrozil gemfibrozil repaglinide repaglinide gemfibrozil http://www.emea.eu.int/humandocs/humans/epar/novonorm/novonorm.htm http://www.emea.eu.int/humandocs/humans/epar/prandin/prandin.htm 3. Lindane FDA 92 3 Lindane (Lindane ) Lindane 110 (50 ) Lindane 110 Lindane Lindane Lindane 1 (Sucabis Cream 1 ) Lindane Lindane http://www.fda.gov/medwatch/safety/2003/safety03.htm 4. Rapamune Wyeth FDA Rapamune tacrolimus bronchial anastomotic dehiscence Rapamune http://www.fda.gov/medwatch/safety/2003/safety03.htm#rapamu 2 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ 1, 2 3 1 2 3 (Harvard School of Public Health) 1986 CIOMS I (CIOMS I) (expedited reporting) 1990 CIOMS II~VI (World Health Organisation; (pharmacovigilance) WHO) (United CIOMS I~VI Nations Educational, Scientific and (proposal)( ) Cultural Organisation; UNESCO) 1949 CIOMS I (The (Expedited reporting of Council for International Organisations individual ADRS) of Medical Sciences; CIOMS) CIOMS I : ( WHO UNESCO) (compliance) (scientific interests) (suspected) CIOMS ( ) CIOMS I 1990 (human values) (international dialogue) (causality assessment) 15 (international nomenclature of diseases) CIOMS I 1977 ICH CIOMS International Conference on Harmonisation ICH E2A Drug Safety Newsletter 2003.Sept. Vol. 3 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug ( CIOMS 1992 CIOMS II ) CIOMS IA (international birth date; IBD) (data lock poin (Harmonisation of data elements and DLP) 45 fields for electronic reporting of individual ADRS) CIOMS IA CIOMS I 1. 2. (core data sheet) (expectedness) 3. 1995 4. (actions) CIOMS 5. (p CIOMS II exposure) (Periodic safety updates) 6. (CIOMS line listing) CIOMS 1989 ( --- ) ( ) CIOMS CIOMS II 7. CIOMS (proposal) * CIOMS I 1990 CIOMS IA 1995 CIOMS II 1992 CIOMS III 1995; 1999 CIOMS IV - 1998 CIOMS V 2001 CIOMS VI * Sue Roden. CIOMS Working Groups and their Contribution to Pharmacovigilance, Table 25.1. In: Ron Mann and Elizabeth Andrews. Pharmacovigilance. 2002 ed 1995 CIOMS IA 4 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug (targeted new (principles) safety studies) (guidelines) CIOMS III 8. 1995 ( ) CIOMS III 1999 ( ) (Development Core Safety 9. DLP Information; DCSI) (investigator brochure) ( ) CIOMS III 65 (good safety information) CIOMS II CIOMS III ( ) CIOMS III (standards) CIOMS CIOMS II 1996 ICH (guidelines) ICH E2C ( (regulations) CIOMS III )(European Labelling Guidelines) CIOMS III (Core clinical-safety information) () CIOMS - IV (Benefit-Risk evaluation) CIOMS CIOMS III CIOMS IV CIOMS I II (Core Safety Information; CSI) CIOMS III (standard frequencies) * (Incidence) (Standard frequencies) (Very common) 1/10 (10%) (Common; frequent) 1/100 and 1/10 (1%-10%) (Uncommon; infrequent) 1/1000 and 1/100 (0.1%-1%) (Rare) 1/10000 and 1/1000 (0.01%-0.1%) (Very rare) 1/10000 ( 0.01%) * Sue Roden. CIOMS Working Groups and their Contribution to Pharmacovigilance, Table 25.3. In: Ron Mann and Elizabeth Andrews. Pharmacovigilance. 2002 ed. Drug Safety Newsletter 2003.Sept. Vol. 3 5
~~~~~~~~~~~~~~~~~~~~~~~~~~ - h. (benefit-risk i. relationship) (excess incidence) j. (significant) CIOMS 4. - (net benefit) ( (benefit-risk evaluation) ) CIOMS IV 1998 a. - 1. b. ( a. ) b. ( ) c. - c. d. 2. * a. d. 5. b. ( ) (options analysis) c. a. ( ) b. (impact analysis) 3. (risk evaluation) a. c. b. d. c. - d. (probable) (possible) e. e. CIOMS V f. (Good case management and reporting practices) g. CIOMS V 2001 * (benefit) (compliance) 6 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug 1. ICH E2A (c). a. (Consumer reports) (reference safety CIOMS V information) (d). (e). b. 3. (Good summary reporting practices) c. CIOMS II ICH E2C 6 6 d. (Solicited reports) 4. (Population exposure data) CIOMS 5. (World-wide clinical safety reporting regulations) e. (Disease-specific registries CIOMS and other database) V CIOMS VI (Surveillance and assessment of drug safety data from clinical trials) 2. CIOMS I~V (Good case management practices) CIO (a). 2001 CIOMS VI (coding) (b). CIOMS V Drug Safety Newsletter 2003.Sept. Vol. 3 7
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug CIOMS VI CIOMS 1. Sue Roden. Chapter 25: CIOMS Working Groups and their Contribution to (www.cioms.ch) Pharmacovigilance. pp. 317-331. In: Ron CIOMS ICH Mann and Elizabeth Andrews. Pharmacovigilance. 2002 ed. John Wiley & Sons. West Sussex, England. ICH 2. CIOMS (1990) International Reporting of WHO Adverse Drug Reactions: Final Report of CIOMS Working Group. Geneva: Council for International Organisations of Medical CIOMS Sciences. 3. CIOMS (1992) Internatonal Reporting of WHO Periodic Drug-Safety Update Summaries: ( ) Final Report of CIOMS Working Group II. CIOMS Geneva: Council for International Organisations of Medical Sciences. ICH 4. CIOMS (1995) Guidelines for Preparing Core Clinical-Safety Information on Drugs: Report of CIOMS Working Group III. Geneva: Council for International CIOMS Organisations of Medical Sciences. 5. CIOMS (1998) Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals: Report of CIOMS Working Group IV. Geneva: Council for International Organisations of Medical Sciences. 6. CIOMS (1999) Guidelines for Preparing Core Clinical-Safety Information on Drugs, 2 nd edn. Report of CIOMS Working Group III and V. Geneva: Council for International Organisations of Medical Sciences. 7. CIOMS (2001) Current Challenges in Pharmacovigilance: Pragmatic Approaches: Report of CIOMS Working Group V. Geneva: Council for International Organisations of Medical Sciences. ADR CIOMS 8 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ Repaglinide Gemfibrozil Fibrates CYP 2C8 (The European Agency for the Niemi Repaglinide Evaluation of Medicinal Products, Gemfibrozil EMEA) Niemi Repaglinide pharmacokinetics 5 22 (pharmacodynamics) 4 Repaglinide Gemfibrozil Repaglinide Niemi Gemfibrozil Repaglinide 1 Repaglinide Megnitinide Concentration time curve, AUC 8.1 5.5~15.0 Sulfonylurea β, p<0.001 1999 2.4 1.7~6.1, 0.5 1 p<0.001 1.3 cytochromes P-450 CYP 3.7 p<0.001 Repaglinide 2C8 3A4 15 30 Repaglinide 15 40 80 ml/min 2 2 4 3 Drug Safety Newsletter 2003.Sept. Vol. 3 9
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug Regulatory Action 5 24 5 28 5 7 8 0920303264 EMEA/11700/03 Public Statement on Replaglinide (Novonorm and Prandin) Repaglinide Contraindication of Concomitant use of Gemfibrozil Replaglinide and Gemfibrozil 6 Available from URL: http://www.emea.eu.int/index/indexh1.htm 2. DrugDex under the title of Repaglinide. Micromedex Inc. 2003, Vol. 115. 3. Chang C, Lu F, Yang YC, Wu JS, Wu TJ, et al. Epidemiologic study of type 2 diabetes in Taiwan. Diabetes Res Clin Pract. 2000 Oct; 50 Suppl 2:S49-59. 4. Niemi M, Backman JT, Neuvonen M, Neuvonen PJ. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia. 2003; 46(3): 347-51. 5. Available from URL: http://adr.doh.gov.tw/ 6. 92 7 8 0920303264 ( ) 7. Nelson RC, Palsulich B, Gogolak V.Good pharmacovigilance practices: technology enabled.drug Saf. 2002; 25(6): 407-14. 7 Risk Benefit assessment 10 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ ADR NSAID Acetaminophen 1,2 1,2 1,2 1 2 1 2 1 2 1-4 5-8 150 9 NSAID 1,2 524 448 NSAID 87 91... 3,4,5 (97.1 %) (1.6%) (1.3%) NSAID acetaminophen 31.5% B ( 79.7%) (55.0%) 87 91 29.7% NSAID acetaminophen 524 (59.6%) (36.8%) [ ] (56.5%) (34.6%) [ ] (6.9%) 2.0% Naranjo NSAID ( 0 ) [ ] A B [ ] Drug Safety Newsletter 2003.Sept. Vol. 3 11
~~~~~~~~~~~~~~~~~~~~~~~~~~ acetaminophen (n= 448 ) 288 (%) 4 87 1 0.2 diclofenac 88 17 3.8 89 96 21.4 90 156 34.8 diclofenac 96 ketoprofen 91 178 39.7 90 aspirin 50 ketorolac 20 57 12.7 51 acetaminophen 23 21-40 123 27.4 41-60 102 22.8 61-80 85 19.0 81 19 4.2 288 62 13.8 22 9 231 51.6 13 168 212 47.3 5 1.1 93 8 435 97.1 6 1.3 7 1.6 A a 91 20.3 (6 B b 357 79.7 ) 6 64 14.3 Stevens-Johnson 69 15.4 246 55.0 69 15.4 ketoprofen (65 ) diclofenac 62 ketorolac 33 406 90.6 42 9.4 aspirin 24 ibuprofen 23 acetaminophen 16 7 1.6 165 36.8 268 59.8 8 1.8 43 a b: (42 ) 14 22 12 1 1 tiaprofenic acid aspirin 12 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ ketoprofen diclofenac (%) aspirin 5 31 6.9 acetaminophen diclofenac aspirin 253 56.5 acetaminophen 155 34.6 9 2.0 288 64.3 3 aspirin 43 9.6 naproxen 1 42 9.4 diclofenac naproxen 22 4.9 14 3.1 acetaminophen 12 2.7 aspirin 10 2.2 3 0.7 5 1.1 4 0.9 NSAID 1 0.2 4 0.9 / 4 NSAID tiaprofenic acid NSAID (2 naproxen meloxicam) (1 acetaminophen aspirin) 2 NSAID (7 aspirin) 10 cyclooxygenase 4 (1) E F2α (2) leukotriene Drug Safety Newsletter 2003.Sept. Vol. 3 13
~~~~~~~~~~~~~~~~~~~~~~~~~~ angiotensin II catecholamine (%) (n= 448 ) Diclofenac 96 21.4 Ketoprofen 90 20.1 7 Aspirin 50 11.2 Ketorolac 51 11.4 Acetaminophen 23 5.1 cyclooxygenase ( Ibuprofen 26 5.8 Naproxen 21 4.7 ) NSAID Sulindac 17 3.8 Indomethacin 15 3.3 Celecoxib 12 2.7 Nabumetone 11 2.5 Meloxicam 10 2.2 NSAID Etodolac 8 1.8 Piroxicam 8 1.8 cyclooxygenase Mefenamic acid 6 1.3 endoperoxide thromboxane A2 Tiaprofenic acid 2 0.4 Tenoxicam 2 0.4 7 aspirin NSAID acetaminophen Langerhan (3) NSAID 4 T NSAID ketoprofen ketorolac I ( II IV ) 4 cyclooxygenase Stevens-Johnson (Toxic epidermal necrolysis) 14 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ aminotransferase diclofenac ibuprofen fenclofenac sulindac pirprofen 7 Fries JF, Millet SR, Spitz PW, Williams CA, Hubert HB, et al. Toward an epidemiology of gastropathy associated with non-steroidal anti-inflammatory drug use. Gastroenterology 1989; 96: 647-55. acetaminophen Roth SH. NSAID and gastropathy: a rheumatologist s review. Journal of NSAID Rheumatology 1988; 15: 912-19. J.L. Carson and L. Rees Willett. Toxicity of NSAID nonsteroidal anti-inflammatory drugs. Drug 1993; 46 (suppl. 1): 243-48. G. P. Velo and R. Milanino. Nongastrointestinal adverse reaction to NSAID. Journal of Rheumatology 1990; 17 (suppl 20): 42-5. Clive DM, Stoff JS. Renal syndrome associated with nonsteroidal anti-inflammatory drugs. New England Journal of Medicine 1984; NSAID acetaminophen 310: 563-572. Facts and Comparisons, 2003; 420-29. NSAID acetaminophen NSAID New York: Macmillan, 1985: 674-715. acetaminophen Drug Facts and Comparisons 57th ed. Missouri: Flower RJ, Moncada S, Vane JR. Analgesic-antipyretics and anti-inflammatory agents: drugs employed for the treatment of gout. In: Goodman and Gilman s The Pharmacological Basis of Therapeutics, 7 th ed. 100 19-1 1 02 2358-7343 E-mail adr@tdrf.org.tw Drug Safety Newsletter 2003.Sept. Vol. 3 15
~~~~~~~~~~~~~~~~~~~~~~~~~~ Carbamazepine 1,2,3 2 1 2 3 1 2 1 2 (agranulocytosis) - (Stevens-Johnson syndrome, SJS) (toxic epidermal necrolysis, TEN) (erythema multiforme, EM) CBZ Carbamazepine (CBZ) 44 (partial seizure) [1] (absence seizures) - CBZ (Stevens-Johnson syndrome, SJS) (toxic epidermal CBZ necrolysis, TEN) CBZ CBZ Tegretol Tegretol Carmapine Tegol Carpine Noderin Neurotol (mg/tablet) 200 100, 400 100, 400 200 200 200 20 mg/ml ( ) * * 16 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug (43.2%) 25 (56.8%) CBZ 13 88 1 91 12 8 15 CBZ 6 44 (myalgia and myositis) 1 EM/SJS/TEN 43 (myoclonus) 1 (97.7%) 44 21 (47.7%) 23 (erythema multiforme, EM) (52.3%) 1 SJS TEN 40 2 39 (88.6%) 5 1 (2.3%) (11.4%) CBZ 44 28 ( ) (%) 16 44 100 63.6 28 26 14 31.8% 2 87.5% (14/16) 16 36.4 14 CBZ ( ) (%) 43 (97.7) 1 1 (erythema multiforme) 1 44 40 CBZ - (Stevens-Johnson syndrome) (toxic epidermal necrolysis) 2 44 1 (2.3) CBZ 283.8 (agranulocytosis) 1 / 1200 / 15.3 2 44 40 10 38.7 2 CBZ 75 19 4.4 mcg/ml Drug Safety Newsletter 2003.Sept. Vol. 3 17
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug 44 CBZ 18 (40.9 %) =44 CIOMS (The ± ()/ (%) Council for International Organizations (mg/day) 283.8±178.9 (100-1200) of Medical Sciences) [2] ADR (onset)( ) 15.3±11.3 (4-26) 7 ( ) 10 (22.7) CBZ (mcg/ml)* 4.4±2.8 (0.1-8.4) 2 42 (95.5%) (n=10) / 7/2 17 14 (n=18) ADR 17/14 (n=42) 18 (n=18) 1 (40.9%) ADR (n=42) 2 ) ( 1 14.9±8.1 (2-40) 6 (14.0) 42 (95.5%) * CBZ 1.1±0.3 2 1 2 (n=44 ) ± (%) 88 91 19 (43.2) 25 (56.8) ( ) 38.7±21.2 (2-75) CBZ EM/SJS/TEN 43 13 (29.6) 8 (18.2) a 15 (34.1) 28 16 b 6 (13.6) 14 2 (4.5) 39 (88.6) 5 (11.4) CBZ a 31.8% (carpal tunnel syndrome) CBZ (dorsopathies) b (organic psychotic conditions) (alcoholic psychoses) (schizophrenic disorders) (psychoses with origin specific to childhood) c (myalgia and myositis) (myoclonus) (myalgia/myos 18 Drug Safety Newsletter 2003.Sept. Vol. 3
~~~~~~~~~~~~~~~~~~~~~~~~~~ Safety Newsletter~~~~~~~~~~~~~~~~~~~~~~~~~ Drug CBZ ( 90 1 ) 8 CBZ ( 89 5 31 CBZ ) 1 SJS/TEN 2-3 2 1 89 11 [3] 8 [4] 15.3 26 off-label use 21 ( CBZ 90 ) CBZ 1200 / [5, 6] 1600 / 8 12 mcg/ml 44 50% (22/44) 1200 / 10 CBZ CBZ CBZ 4.4 mcg/ml Tegol CBZ CBZ Type B 44 3 (43 ) 1 Drug Safety Newsletter 2003.Sept. Vol. 3 19
~~~~~~~~~~~~~~~~~~~~~~~~~~ CBZ 1. Herman ST, Pedley TA. New options for the treatment of epilepsy. Journal of the CBZ American Medical Association 1998; 280: 693-4. 2. Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. Journal of Hepatology 1990; 11: 272-6. [7] CBZ 3. Fritsch PO, Sidoroff A. Drug-induced ( Stevens-Johnson syndrome/toxic epidermal necrolysis. American Journal of Clinical Dermatology 2000; 1: 349-60. ) 4. Rzany B, Correia O, Kelly JP, Naldi L, Auquier A, Stern R. Risk of CBZ Stevens-Johnson syndrome and toxic epidermal necrolysis during first weeks of antiepileptic therapy: a case-control study. Study Group of the International Case Control Study on Severe Cutaneous Adverse Reactions. Lancet 1999; 353: 2190-4. 5. Post RM, Uhde TW, Ballenger JC, Chatterji DC, Greene RF, Bunney WE, Jr. Carbamazepine and its -10,11-epoxide CBZ metabolite in plasma and CSF. Relationship to antidepressant response. Archives of General Psychiatry 1983; 40: 673-6. 6. Product Information: Tegretol(R), carbamazepine. Novartis Pharmaceuticals, East Hanover, NJ, 2002. 7. Lott RS, McAuley JW. Seizure disorders. In: Koda-Kimble MA YL, ed. Applied Therapeutics: The Clinical Use of Drugs. Baltimore: Lippincott Williams & Wilkins; 2002. p. 52.1-52.41. 湶 19-1 1 02 2358-7343 02 2396-0100 02 2358-4100 http://www.tdrf.org.tw http://adr.doh.gov.tw 7813 20 Drug Safety Newsletter 2003.Sept. Vol. 3