医薬品安全性情報 Vol.6 No.11 2008/05/29

1 1 MHRA Medicines and Healthcare products Regulatory Agency Drug Safety Update 2008 OTC ..2 FDA U. S. Food and Drug Administration Drug Safety Newsletter Vol. 1 No. 2 Winter 2008 - TNF- infliximab Remicade etanercept Enbrel adalimumab humira ..3 Mycophenolate mofetil CellCept mycophenolic acid Myfortic PML ..9 Aprotinin Trasylol Bayer ..11 Health Canada Canadian Adverse Reaction Newsletter Varenicline Champix ..13 Aprotinin Trasylol BART Health Canada ..15 EU EMEA European Medicines Agency Bortezomib Velcade Q&A ..16 1 2 MedDRA-J 2008/05/29 2008/05/29 2 2008 05/29 R01 MHRA OTC Updated advice.

2 Over-the-counter cough and cold medicines for children Drug Safety Update 2008 2008/04/07 Paediatric Medicines Expert Advisory Group CHM Commission on Human Medicines OTC FDA *1 CHM Yellow Card 2 5 1981 CHM OTC 2 CHM 2 / CHM 2 6 - Paracetamol ibuprofen - - vapour rub - 2008/05/29 3 OTC 2 - brompheniramine chlorphenamine diphenhydramine - dextromethorphan pholcodine - guaifenesin ipecacuanha - phenylephrine pseudoephedrine ephedrine oxymetazoline xylometazoline 2 6 1 2 2 1 2008/02/21 FDA 2008/05/14 TGA 2008 05/29 R02 FDA - TNF- infliximab Remicade

3 Etanercept Enbrel adalimumab humira Tumor necrosis factor alpha TNF- antagonists; infliximab marketed as Remicade , etanercept marketed as Enbrel , and adalimumab marketed as humira : Serious Skin Reactions Drug Safety Newsletter Vol. 1 No. 2 Winter 2008 2008/03/18 FDA - tumor necrosis factor alpha TNF- infliximab 2008/05/29 4 Remicade etanercept Enbrel adalimumab humira EM Erythema Multiforme SJS Stevens-Johnson syndrome TEN Toxic Epidermal Necrolysis Infliximab 1 FDA etanercept adalimumab infliximab etanercept adalimumab FDA MedWatch Infliximab etanercept adalimumab TNF- Infliximab adalimumab TNF- etanercept TNF IgG1 Fc TNF- Remicade Enbrel humira Remicade Enbrel humira Remicade Enbrel humira

4 Enbrel humira Remicade humira Remicade Enbrel Remicade humira 1,2,3 Infliximab etanercept adalimumab infliximab etanercept adalimumab FDA Adverse Event Reporting System AERS 1 1 Infliximab etanercept adalimumab infliximab 1998/08 2006/08 *n = 21 etanercept 1998/11 2006/11 * n = 22 adalimumab 2002/12 2006/11 *n = 7 5 7 1 16 14 6 - 1 1

5 54 53 51 27 70 20 1 16 84 23 61 RA-13 RA-15 RA- 5 CD- 4 PA- 3 CD- 1 UC- 3 AS- 1 - 1 - 1 - 2 -1 2008/05/29 5 EM 15 13 4 SJS 5 4 2 TEN 1 4 - SJS/TEN - 1 - EM/SJS - - 1

6 EM SJS / TEN 1 15 71% carbamazepine celecoxib diltiazem furosemide/ hydrochlorothiazide leflunomide methotrexate mercaptopurine meloxicam naproxen rofecoxib sulfasalazine sertraline 15 68% aspirin amoxicillin celecoxib ciprofloxacin diclofenac etoricoxib ethinyl estradiol/ levonorgestrel flurbiprofen hydroxychloroquine indapamide isoniazid lamotrigine methotrexate meloxicam naproxen rofecoxib sulfasalazine terbinafine venlafaxine warfarin 2 29% methotrexate 28 50 60 4 18 11 5 52 6 3 - 2 1 -2 1 -1 -1 6 17 2 -1 2 -1 - 4 4 - 3 - 5 17 -1 - 15 1 1 1 1 0 12 9 1 1 1 - - - 1 8.

7 5 - 11 1 15 11 4 2 3 - 1 3 - RA CD UC PA AS EM SJS TEN * AERS Etanercept 2 GVHD infliximab 1 AERS FDA AERS / AERS Etoricoxib 2008/05/29 6 SJS 1 TEN Infliximab Remicade FDA 1998 8 2006 8 infliximab 21 7 14 EM 15 SJS 5 TEN 1 21 16 5 / study/registry cases SJS 2 EM 3 4,5.

8 6 76% 62% infliximab 28 1 6 2 1 2 3 SJS SJS 15 71% EM SJS TEN 1 5 sulfasalazine mercaptopurine leflunomide 12 TEN 1 20 15 2 infliximab 1 5 infliximab AERS infliximab Etanercept Enbrel FDA 1998 11 2006 11 etanercept 22 10 12 EM SJS TEN 17 5 / 22 EM 13 TEN 4 SJS 4 SJS/TEN 1 EM 13 2 EM EM 1 SJS/TEN 1 7 14 64% 2008/05/29 7 etanercept Etanercept 2 5 9 Etanercept 6 1 4 1 etanercept 17 4 etanercept 15 68% EM SJS TEN 5 etanercept isoniazid indapamide ciprofloxacin terbinafine ethinyl estradiol/levonorgestrel etanercept 11 11 3 3 6 etanercept 1 4 etanercept 1 EM EM 1 Adalimumab humira FDA 2002 12 2006 11 7 4 3 7 EM

9 4 SJS 2 EM SJS 1 adalimumab EM 1 7 85% 5 71% adalimumab Adalimumab 60 3 2 adalimumab 1 2 1 EM 2 adalimumab 2 EM SJS TEN methotrexate AERS 7 adalimumab 1 7 4 adalimumab adalimumab 3 TNF- EM SJS TEN 6,7,8 EM SJS TEN 1 TNF- 2008/05/29 8 TNF- infliximab etanercept adalimumab FDA TNF- TNF- TNF- 1 Infliximab Remicade product labeling.

10 2 Etanercept Enbrel product labeling. 3 Adalimumab humira product labeling 4 Kiely PDW, Johnson DM. Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open-label study. Rheumatology Oxford 2002;41 6 :631-637. 5 Bingham SJ, Buch MH, Kerr MA, et al.