Drug Safety Newsletter 2006.Mar. Vol.13... 2... 2... 4...6... 6... 6 ADR...9.13...22 Taiwan Drug Relief Foundation National Reporting Center of Adverse Drug Reactions in Taiwan
by 1. 2005 10 05 ADR 2005 9 Eli Lily Strattera atomoxetine atomoxetine FDA Eli Lily a Patient Medication Guide MedGuide atomoxetine Strattera atomoxetine Attention Deficit Hyperactivity Disorder, ADHD 12 6-18 11 ADHD 1 enuresis 12 1357 atomoxetine 851 atomoxetine 2200 atomoxetine FDA atomoxetine 1 Strattera atomoxetine ADHD 2 ADHD 3 4 2 Drug Safety Newsletter 2006 Mar. Vol.13
2. Cymbalta duloxetine hydrochloride 2005 10 27 ADR Eli Lily Cymbalta duloxetine HCl 2005 10 05 Cymbalta duloxetine HClFDA major depression disorder diabetic peripheral neuropathic pain Eli Lily Cymbalta Cymbalta transaminase level 20 cholestatic jaundice transaminase level Cymbalta transaminase bilirubin alkaline phosphate Cymbalta Cymbalta duloxetine HCl http://www.fda.gov/medwatch/safety/2005/safety05.htm#cymbalta 3. Evra 2005 11 18 ADR FDA 2005 11 10 Evra Evra ethinyl estradiol norelgestromin FDA Evra FDA Evra Evra Evra Evra 35 mcg estrogen 60 Evra 25 http://www.fda.gov/medwatch/safety/2005/safety05.htm#evra Drug Safety Newsletter 2006 Mar. Vol.13 3
4. 2005 11 22 ADR FDA salmeterol xinafoate fluticasone propionate salmeterol formeterol 2 long-acting β 2 -adrenergic agonist, LABA LABAs FDA LABA LABA LABAs LABA LABA LABA LABAs LABAs COPD LABAs http://www.fda.gov/medwatch/safety/2005/safety05.htm#laba 1. 2006 02 20 ADR (Cochlear implants, ) ( ) CDC/FDA ( positioner) (Bacterial meningitis) (Streptococcus pneumoniae) 24! (positioner) 4 Drug Safety Newsletter 2006 Mar. Vol.13
Advanced Bionics Corporation 2002 06 CDC : Positioner 8 http://www.fda.gov/cdrh/safety/020606-cochlear.html 2006 02 21 ADR 94 5 22 21 4 010114 " " 500 ml Drug Safety Newsletter 2006 Mar. Vol.13 5
1. Sanofi-Aventis 30 Clexane Injection ( enoxaparin) 2006 02 10 ADR 2006 2 10 Sanofi-Aventis enoxaparin Clexane Injection Clexane Injection 2006 2 22 0950313629 http://en.sanofi-aventis.com/images/060210_enox_tcm24-12080.pdf 2006 03 02 ADR 2006 2 21 Haldol Drops / LDPE haloperidol haloperidol 2002 30 30 Haldol Drops 1. The First Years (Liquid-Filled Teethers) 2006 02 01 ADR The First Years Pseudomonas aeruginosa Pseudomonas putida 6 Drug Safety Newsletter 2006 Mar. Vol.13
2 21 http://www.fda.gov/cdrh/recalls/recall-012506.html 2006 02 10 ADR Balance Salt BSS FDA endotoxin FDA Toxic Anterior Segment Syndrome, TASS FDA 300 Cytosol BSS 1 2006 2 15 2 http://www.fda.gov/bbs/topics/news/2006/new01315.html 2.Baxter COLLEAGUE and COLLEAGUE CX 2006 02 16 ADR Baxter COLLEAGUE and COLLEAGUE CX 1 12 2 3 Drug Safety Newsletter 2006 Mar. Vol.13 7
4 : 5 : 2 6 2 8 a. FDA Colleague b. 2005 FDA 510K 2006 Colleague 2005 Colleague FCA http://www.fda.gov/cdrh/recalls/recall-121305.html 02-2396-0100 www.adr.doh.gov.tw email ADR ADR E-mail E-mail adr@tdrf.org.tw 8 Drug Safety Newsletter 2006 Mar. Vol.13
ADR 1 1 2 1 2 0.1 % 77.5 % 50.8 % 49.2 % 10 3.5 % 50 57.1 % 2.7 14,477 316 425 11.42 2600 69.86 1,524 207 5.56 1,831 2,325 123 3.30 2,252 2,505 362 9.73 5 0.13 3,722 1831 49.19 1891 50.81 ADR ( ) <10 130 3.49 10~20 135 3.63 20~30 375 10.08 30~40 377 10.13 40~50 482 12.95 50~60 564 15.15 60~70 604 16.23 70~80 657 17.65 80~90 262 7.04 >90 37 0.99 99 2.66 ADR 3,722 2,505 48.4 % ADR 90.1 % 9.7 % 5 Drug Safety Newsletter 2006 Mar. Vol.13 9
35.2 % A 64.8 % B ( 55.2 %) ( 32.6 %) 61.7 % 24.8 % Fair data 74.8 % Good data 10.0 % Poor (FDA) data 15.2 % (AERs) 2004 422,889 1 2.91 30.6 % ADR 0.15 27.4 % % 12.2 % ADR 0.016 % 70.2 % ADR ADR phenytoin ketorolac rifampicin diclofenac carbamazepine ADR ADR 93 9.73 % ADR 38.3 % 594 871 10 Drug Safety Newsletter 2006 Mar. Vol.13
(%) 78 2.10 97 2.61 538 14.45 7 0.19 168 4.49 667 17.92 1 0.03 2167 58.22 A 1309 35.17 B 2413 64.83 1213 32.59 2054 55.19 252 6.77 203 5.45 316 8.49 2296 61.69 924 24.83 86 2.31 48 1.29 52 1.40 Good 373 10.02 Fair 2784 74.80 Poor 564 15.15 1 0.03 1451 30.59 1301 27.42 577 12.16 416 8.77 207 4.36 185 3.90 141 2.97 113 2.38 97 2.04 Drug Safety Newsletter 2006 Mar. Vol.13 11
Phenytoin 129 Skin rash, Stevens Johnson syndrome, erythema multiforme, fever, leukopenia, etc. Ketorolac 125 Allergy, urticaria, face edema, eyelid edema, diarrhea, rash, dyspnea, etc. Rifampicin 121 Skin rash, jaundice, abnormal liver function, hepatitis, nausea, vomiting, etc. Diclofenac 104 Skin rash, edema, urticaria, allergy, etc. Carbamazepine 78 Stevens Johnson syndrome, skin rash, etc. Iopromide 76 Vomiting, skin rash, dizziness, nausea, skin itching, etc. Vancomycin 75 Skin rash, itching, allergy, erythema multiforme, red man syndrome, nephrotoxicity, renal dysfunction, fever, etc. Cefazolin 64 Skin rash, diarrhea, etc. Ketoprofen 56 Face edema, eye edema, skin rash, urticaria, allergy, etc. Oxacillin 56 Skin rash, liver function abnormal, leukopenia, etc. (02)2396-0100 1. US FDA. Center for Drug Evaluation and Research 2004 Report to The Nation- URL http://adr.doh.gov.tw Improving Public Health through Human Drugs. Available at: [Aug 22, 2005]. 2. 12 Drug Safety Newsletter 2006 Mar. Vol.13
1 1 2 1 2 1 2 1 2 9 5-8 1-4 0 87 isoflurane sevoflurane 12 11 methoxyflurane, enflurane, isoflurane, 3 desflurane, sevoflurane ADR 21 6 55 16 10 91 Malignant hyperthermia, MHT1 9 10 87 94 19 8/10 80 83 5/6 8 80 5 Naranjo Drug Safety Newsletter 2006 Mar. Vol.13 13
dantrolene 2/7, 28.6 70 24 Dantrolene 1 Isoflurane 41 C ( ) 2 Isoflurane 42 C ( ) 3 Isoflurane 4 Isoflurane 40 C ( 21 ) 5 Isoflurane 6 Isoflurane ( ) 7 Isoflurane 8 Isoflurane Succinylcholine 9 Sevoflurane Succinylcholine 10 Sevoflurane Succinylcholine 41 C ( ) ( ) 14 Drug Safety Newsletter 2006 Mar. Vol.13
(hypermetabolism) (myoglobinuria) 1,2,8 ryanodine RYR1 (halothane, isoflurane, desflurane, sevoflurane, etc.) (suspected susceptible, MHS) (succinylcholine) ( ) (hypermetabolic) 2,6 2,7,8,9,12 halothane 6,12 1-2 100 44 propofol, ketamine, benzodiazepines (disseminated intravascular caffeine - dantrolene coagulation, DIC) sodium Drug Safety Newsletter 2006 Mar. Vol.13 15
Creatinine kinase CK 20 mg/kg CK 14 6 1 mg/kg CK 2,5 ) 36 0.1-0.3mg/kg/hr (dantrolene infusion) dantrolene sodium 20mg dantrolene sodium 3 gm mannitol 70 36 dantrolene 2,5 6 dantrolene Dantrolene sodium 1979 Dantrolene sodium dantrolene Dantrolene RYR1 ph 1,8 dantrolene 1979 80 1985 MHS 10 (pedigree analysis) MHS 5 ( dantrolene 1/200 Dantrolene sodium 1/2000 2.5 mg/kg (hypercarbia) (hypermetabolism) 1/15,000 1/40,000 12,19 16 Drug Safety Newsletter 2006 Mar. Vol.13
200,000 dantrolene dantrolene 1/5000 20 1/60,000 15,20 52.1 < 15 65.8 succinylcholine succinylcholine 3.3 22 1,3,4 0.002 0.006 succinylcholine 19 1,12 2003 6 70 dantrolene 2/7, 28.6 66 66 100 dantrolene (pulse oximeter) 51 77.3 dantrolene ETCO 2 13 19.7 dantrolene - dantrolene 23 dantrolene 34.9 6 dantrolene Drug Safety Newsletter 2006 Mar. Vol.13 17
43 65.1 dantrolene dantrolene 70.7 ± 34.7 21 17 dantrolene 15 6 (MHT cart or kit) 28.6 dantolene dantrolene 50% dextrose mannitol calcium -dantrolene chloride sodium bicarbonate furosemide ABGs CK myoglobin dantrolene 13,14 15 dantrolene 12 10 dantrolene dantrolene 15 36 dantrolene ECG pulse 21 oximeter capnography (end-expiratory CO 2 ) 10 18 Drug Safety Newsletter 2006 Mar. Vol.13
36 dantrolene 6 dantrolene dantrolene dantrolene 90 22,23 dantrolene 1-18 (induction 89 1 14 and maintenance) N 2 O minimum dantrolene alveolar concentration, MAC) 89 halothane 92 desflurane sevoflurane 9 74 dantrolene sevoflurane Drug Safety Newsletter 2006 Mar. Vol.13 19
dantrolene 16 6 dantrolene 11,12 dantrolene 1. Strazis KP, Fox AW: Malignant hyperthermia: a review of published cases. (routine parameters) Anesth Analg. 1993 Aug; 77(2):297-304 ETCO 2 2. Malignant Hyperthermia; http://www.medscape.com/viewarticle/491 434 3. Moore JL, Rice EL: Malignant isoflurane sevoflurane hyperthermia. Am Fam Physician. 1992 May;45(5):2245-51 4. Popp M, Seeling W: Malignant hyperthermia in a 41-year-old woman. MHS Anaesthesist. 1986 Mar;35(3):203-5 5. Halliday NJ: Malignant hyperthermia. J dantrolene Craniofac Surg. 2003 Sep;14(5):800-2 6. Depret T, Krivosic-Horber R: Malignant dantrolene hyperthermia: 1 new developments in 10,12 diagnosis and clinical management. Ann Fr Anesth Reanim. 2001 Dec;29(10):838-52 7. Heggie JE: Malignant hyperthermia: 20 Drug Safety Newsletter 2006 Mar. Vol.13
considerations for the general surgeon. Can J surg. 2002 Oct;45(5):369-72 8. Krause T, Gerbershagen MU, Fiege M, Weisshorn R, Wappler F: Dantrolene a review of its pharmacology, therapeutic use and new developments. Anaesthesia. 2004 Apr;59(4):364-73 9. Halloran LL, Bernard DW: Management of drug-induced hyperthermia. Curr Opin Pediatr. 2004 Apr;16(2):211-5 10. Jacquot C, Stieglitz P: Management of a patient with malignant hyperthermia susceptibility during anesthesia and daily living. Ann Fr Anesth Reanim. 1989;8(5):417-26 11. Malignant hyperthermia: an OR emergency! Plast Surg Nurs. 2000 Winter;20(4):222-6 12. Johnson C, Edleman KJ: Malignant hyperthermia: a review. J Perinatol. 1992 Mar;12(1):61-71 13. Haslego H: Malignant hyperthermia: How to spot it early. RN. 2002 Jul;65(7):31-5; quiz 36 14. Suyama H, Kawamoto M, Yugo O: Prevention and treatment of malignant hyperthermia in certified training hospitals in Japan: a questionnaire. J Anesth. 2002;16(3):207-10 15. Yip WH, Mingi CL, Ooi SJ, Chen SC, Chiang YY: A survey for prevention and treatment of malignant hyperthermia in Taiwan. Acta Anaesthesiol Taiwan. 2004 Sep;42(3)147-51 16. Golembiewski J: Considerations in selecting an inhaled anesthetic agent: case studies. Am J Health Syst Pharm. 2004 Oct 15;61 Suppl 4:S10-7 17. Micromedex Healthcare Series, http://drugmdx.csis.com.tw 18. Schatke H, Schneider J, Abbushi W, Schneck HJ.: The early diagnosis of malignant hyperthermia--the place of end-expiratory CO2 monitoring. Anasthesiol Intensivmed Notfallmed Schmerzther. 1991 Dec;26(8):468-70. 19. Kaus SJ, Rockoff MA: Malignant hyperthermia. 1994 Feb;41(1):221-37 20. Ording H: Incidence of malignant hyperthermia in Denmark: Anesth Analg. 1985 Jul;64(7):700-4 21. Sun WZ, Yeh HM: When economy meets medicine malignant hyperthermia in Taiwan. Acta Anaesthesiol Taiwan. 2004;42(3):125-6 22. http://www.tfrd.org.tw/intro/ 23. http://dohlaw.doh.gov.tw/chi/flaw/fla WDAT01.asp?lsid=FL013785 24. Drug Safety Newsletter 2006 Mar. Vol.13 21
1 2 6 94 94 14 106 1 94 53 22 29 2 33 12 61 61 45 22 Drug Safety Newsletter 2006 Mar. Vol.13
94 50.9±20.6 10 5.7 n 106 70 17.2 53 50.0 44 22 20.8 15 29 27.3 2 2 1.9 27 42.3 33 31.1 12 11.3 61 57.6 45 42.5 61 57.5 10 6 5.7 10~19 1 1.1 20~29 10 9.6 30~39 10 9.6 40~49 14 13.4 50~59 21 19.8 60~69 25 23.6 70~79 13 12.3 80 5 4.9 Mean±SD 50.9±20.6 15 5-4 3 2 1 2 1 phenytoin 1 diclofenac 27 74% 20 Drug Safety Newsletter 2006 Mar. Vol.13 23
94 n 106 n 44 17,919,715 15 34.1 14,550,000 81.1 2 4.5 2,500,000 14.0 27 61.4 869,715 4.9 n 60 17 28.3 9 15.0 34 56.7 n 2 1 50 1 50 0 3 2 12 1 1 13 60 21 35% 10 3 1 24 Drug Safety Newsletter 2006 Mar. Vol.13
94 n 60 21 35.0 13 21.7 12 20.0 10 16.7 3 5.0 1 1.6 13 94 88 93 phenytoin carbamazepine 94 lamotrigine 12 allopurinol allopurinol 7 phenytoin carbamazepine - rifampin isoniazid pyrazinamide 22 20 42.3 88 93 101 58.7 94 60 2,3 92 93 38 63.3 52.6 Drug Safety Newsletter 2006 Mar. Vol.13 25
88 93 n=171 94 n=52 Carbamazepine 42 24.6 Allopurinol 7 13.5 Phenytoin 26 15.2 Carbamazepine 6 11.5 Allopurinol 22 12.9 Anti-TB drugs 5 9.6 NSAIDs 17 9.9 Phenytoin 4 7.7 Anti-TB drugs 11 6.4 NSAIDs 4 7.7 others 53 31.0 others 26 50.0 NSAIDs Non-steroidal anti-inflammatory drugs 88 93 n 171 94 n 44 Skin and subcutaneous tissue disorders 127 Skin and subcutaneous tissue disorders 27 Immune system disorders 18 Hepato-biliary disorders 7 Hepato-biliary disorders 10 Immune system disorders 6 Blood and lymphatic system disorders 5 General disorders and administration site conditions 2 General disorders and administration site conditions 3 Nervous system disorders 1 Nervous system disorders 2 Renal and urinary disorders 1 Cardiac disorders 1 Ear and Labyrinth disorders 1 Metabolism and nutrition disorders 1 Musculoskeletal, connective tissue and bone disorders 1 Renal and urinary disorders 1 Respiratory, thoracic and mediastinal disorders 1 26 Drug Safety Newsletter 2006 Mar. Vol.13
94 n=52 n=46 Allopurinol 7 13.5 Carbamazepine 9 19.6 Carbamazepine 6 11.5 NSAIDs 8 17.4 Anti-TB drugs 5 9.6 Allopurinol 7 15.2 Phenytoin Anti-TB drugs 4 7.7 Ethambutol 3 6.5 NSAIDs 4 7.7 Phenytoin 2 4.3 others 26 50.0 others 17 37.0 NSAIDs Non-steroidal anti-inflammatory drugs 94 n=52 n=46 Antibiotics 16 30.8 Anticonvulsants 12 26.1 Anticonvulsants 15 28.8 NSAIDs 8 17.4 Allopurinol 7 13.5 Allopurinol 7 15.2 Anti-TB drugs Anti-TB drugs 5 9.6 Ethambutol 3 6.5 NSAIDs 4 7.7 Antibiotics 3 6.5 others 5 9.6 others 13 28.3 NSAIDs Non-steroidal anti-inflammatory drugs 94 47 57.3 82 78.8 Drug Safety Newsletter 2006 Mar. Vol.13 27
carbamazepine allopurinol misoprostol 1. 2003 1 8-11 2. 92 2004 6 16-19 3. 93 2005 9 20-24 19-1 1 02 2358-7343 02 2396-0100 02 2358-4100 http://www.tdrf.org.tw http://adr.doh.gov.tw 2281 28 Drug Safety Newsletter 2006 Mar. Vol.13