Pharmacogenomic in neurology ii

1. Pharmacogenomic in Neurology II: SJS/TEN caused by Carbamazepine , Phenobarbital and Phenytoin Lect. Nin Prapongsena , M.Ph . Huachiew Chalermpraiet University

2. Outline Introduction SJS/TEN Clinical presentation Management Pharmacogenomic related to cutaneous ADR in CBZ, Phenytoin , Phenobarbital usage. Introduction of HLA type Which HLA type related to cutaneous ADR in CBZ, Phenytoin , Phenobarbital usage???

3. Drugs induced SJS/TEN Antibiotics Sulphonamides , Vancomycin , Penicillins , Cephalosporins , Quinolones Anticonvulsants CBZ, Phenytoin , Phenobarbital , Valporate , Lamotrigine NSAIDs Piroxicam , Aspirin, Diclofenac ARV NVP, ABC, Protease inhibitors Anti-TB Isoniazid , Ethambutol Anti-Gout Allopurinol

4. Translational Research 2012 Volume 159 Number 5

5. SJS vs TEN Harr and French Orphanet Journal of Rare Diseases 2010, 5:39

6. SJS vs TEN SJS SJS/TEN TEN Occurred within 4 -28 days

7. SJS vs TEN (systemic sign)

8. Severity SJS/TEN Assessment

9. SJS/TEN Management (Supportive Care)

10. SJS/TEN Management (Supportive Care)

11. SJS/TEN Management (Drugs Therapy) Systemic steroids : “Pulse” High dose of dexamethasone Thalidomide : Anti-TNF α (No Benefit) Cyclosporine : 3-5 mg/kg oral/IV for 8-24 d or re- epithelialisation then taper off 2wk Cyclophosphamide : Should be benefit (small trials)

12. SJS/TEN Management (Continue) IVIG : High dose of IVIG (0.25-0.75 g/kg for 3-4 d)

13. Pharmacogenomic and Cutaneous ADR http://www.youtube.com/watch?v=VPvCekgPwRI

14. Polymorphism of HLA type on MHC I Related to Cutaneous ADR (SJS/TEN)

15. What’s polymorphism of HLA type that Related to SJS/TEN in Anticonvulsant HLA-A*3101 HLA-B*1502

16. HLA-A*3101

17. HLA-B*1502

18. HLA-B*1502

19. HLA-B*1502 Cross-reacted to Phenobarbital and Phenytoin (Case Report)

20. Case I (China) Feb 2005: Female 61 y (Complex partial seizure 2-4 times/month) On CBZ 200 mg 1*3: (10 th day: Erythematous rashes, Maculopapular rashes and leucocyte increased) Then off CBZ (1 week: rashes were clear) On Valproate Feb 2010: Tonic- clonic seizure: On Valproate 500 mg 1*2 + OXC 900 mg OD (2wk later: skin rxn ) Off OXC (5d: rashes were clear) Lab testing HLA-B*1502 (+) Nov 2010: Valproate 500 mg 1*2 + Levetiracetam 1000 mg OD (no symp )

21. Case II (China) March 2004: Female 20 y (Complex partial seizure q 2-3 month) EEG (+) On Phenytoin 100 mg 1*1 10d later: infected eyes, sore throat, erythematous rash (+), high fever (39.1), oral ulcer, maculopapule rashes >30% & leucocytosis Off Phenytoin but On steroid and antihistamine:(Rash cleared) Switched to Phenobarbital 90 mg OD 2wk later rashes were recurrence Switched to CBZ 100mg 1*3 and 300 mg 1*2, respectively 2wk later rashes were recurrence Now on topiramate 75 mg 1*2 (seizure free) Lab testing: HLA-B*1502 (+)

22. Conclusion HLA-A*3101 Related to SJS/TEN of CBZ (In Europe) HLA-B*1502 Related to SJS/TEN of CBZ (In Thailand) Note: HLA-B*1502 cross-reacted to phenobarbital , phenytoin (case report)

23. Pharmacist’s role Interpreted Laboratory data of pharmacogenomic that related to SJS/TEN Suggested doctor to avoid CBZ, Phenytoin and Phenobarbital If patients are HLA-B*1502 (+) Suggested doctor to switch medication to Topiramate / Valproate / Levetiracetam