Khalid Hamid CHANGAL, Reyaz Ahmad PARRA, Fayaz Ahmad SOFİ

Lamotrigine induced Stevens-Johnson syndrome: A case report

Vaka sunumu, lamotrijin kullanımına bağlı nadiren oluştuğu bilinen Stevens Johsnon sendorumu gelişen bir kız çocuğunu bildirmektedir. Birkaç yıldır valproat tedavisi alan bu esnada herhangi bir deri döküntüsü olmayan hastaya lamotrijin tedavisi başlandı. Valproat kullanan hastaya lamotrijin verildiğinde, azalan glüküronizasyon nedeni ile lamotrijen düzeyini ve ciddi döküntü riskini artırdığı bilinmektedir. Stevens Johnson sendromu gelişimi, lamotrijin ve valproat arası bir ilaç etkileşimini düşündürmektedir. Bu vakada Stevens Johnson sendromu gelişimi, lamotrijin yüksek dozuna bağlı bir doza bağlı toksisiteye bağlanmıştır. Biz, lamotrijinin hızlı doz artırımın, hatta tek yüksek dozunun, özellikle valproat alan hastalarda kabul edilemez bir risk taşıdığını düşünmekteyiz.

Anahtar Kelimeler:

İlaç etkileşimi; ilaç reaksiyonu; lamotrijin; Stevens Johnson sendromu

Lamotrijin kullanımına bağlı Stevens-Johnson sendromu: Vaka sunumu

This case is about a young girl who had lamotrigine induced Stevens Johnson syndrome which is known to occur but is rare. Lamotrigine was started when the patient was also receiving valproate for several years; no adverse effects, including any minor skin rash, were recorded while on valproate monotherapy. Valproate is known to augment lamotrigine availability via reduced glucuronidation, which increases the risk of serious rash if patients are concomitantly given lamotrigine. This suggests that a drug-drug interaction between lamotrigine and valproate did contribute to the development of Stevens-Johnson syndrome. Stevens-Johnson syndrome was linked in this case with a higher dose of lamotrigine, suggesting a dose-dependent toxicity. We emphasize that a rapid dose escalation of lamotrigine, even a single higher dose, could expose to an unacceptable risk of Stevens-Johnson syndrome, particularly in patients taking valproate.

Keywords:

Drug interactions; drug reaction; lamotrigine; Stevens Johnson syndrome.,

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1. Cunnington MC. The International Lamotrigine pregnancy registry update for the epilepsy foundation. Epilepsia. 2004;45(11):1468.
2. Valencia I, Pinol-Ripoll G, Khurana DS, Hardison HH, Kothare SV, Melvin JJ, et al. Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy. Eur J Paediatr Neurol 2009;13(2):141-5.
3. Seo HJ, Chiesa A, Lee SJ, Patkar AA, Han C, Masand PS, et al. Safety and tolerability of lamotrigine: results from 12 placebocontrolled clinical trials and clinical implications. Clin Neuropharmacol 2011;34(1):39-47.
4. Sussman N. Anticonvulsants: other anticonvulsants. In: Sadock BJ, Sadock VA, eds. Kaplan&Sadock. comprehensive textbook of psychiatry. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2000, 2299-2304.
5. Chaffin JJ, Davis SM. Suspected lamotrigine-induced toxic epidermal necrolysis. Ann Pharmacother 1997;31(6):720-3.
6. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995;333(24):1600-7.
7. French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding. Allergol Int 2006;55(1):9- 16.
8. Mockenhaupt M, Messenheimer J, Tennis P, Schlingmann J. Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology 2005;64(7):1134-8.
9. Tay YK, Huff JC, Weston WL. Mycoplasma pneumoniae infection is associated with Stevens–Johnson syndrome, not erythema multiforme (von Hebra). J Am Acad Dermatol1996;35(5 Pt 1):757–60.
10. Rzany B, Correia O, Kelly JP, Naldi L, Auquier A, Stern R. Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis during first weeks of antiepileptic therapy: a casecontrol study. Study group of the international case control study on severe cutaneous adverse reactions. Lancet 1999;353(9171):2190-4.
11. Bocquet H, Farmer M, Bressieux JM, Barzegar C, Jullien M, Soto B, et al. Lyell syndrome and Stevens-Johnson syndrome caused by lamotrigine. Ann Dermatol Venereol 1999;126(1):46- 8.
12. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30(2):239-45.
13. Yalcin B, Karaduman A. Stevens-Johnson syndrome associated with concomitant use of lamotrigine and valproic acid. J Am Acad Dermatol 2000;43(5 Pt 2):898-9.
14. Gidal BE, Sheth R, Parnell J, Maloney K, Sale M. Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Epilepsy Res 2003;57(2-3):85-93.