Toxic epidermal necrolysis lamotrigine

Published and unpublished cases of Stevens-Johnson syndrome (n = 43) and toxic epidermal necrolysis (n = 14) associated with lamotrigine have been reviewed (44). The patients with Stevens-Johnson syndrome were younger than those with toxic epidermal necrolysis (21 versus 31 years) the median time to onset for both reactions was 17 days the median dosage at onset (50 mg for Stevens-Johnson syndrome, 87.5 mg for toxic epidermal necrolysis) did not differ significantly. Valproate comedication was present in 74% and 64% of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis respectively. In three patients, toxic epidermal necrolysis occurred in the context of the anticonvulsant hypersensitivity syndrome. 

Stevens-Johnson syndrome, and 3 as suggestive of Stevens-Johnson syndrome two deaths were reported. Rashes associated with one or more symptoms of hypersensitivity reactions occurred in 19 children. Of 29 patients with Stevens-Johnson syndrome, toxic epidermal necrolysis, or hypersensitivity reactions, for whom precise details were available, 83% were taking lamotrigine with concomitant valproate and 85% were taking lamotrigine dosages higher than recommended. 

Although serious skin rashes have been reported with traditional anticonvulsants, the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis with these drugs appears to be lower than with lamotrigine. Data from the Saskatchewan Health Plan suggest that the risk of serious rashes is in the order of 0.9 1000 (1.4 1000 in children) for phenytoin, 0.6 1000 (1.4 1000 in children) for carbamaze-pine, and 0 1000 for valproate, but Stevens-Johnson syndrome constituted only a small minority of these cases (47). 

Co-administration of valproate is one of the most important risk factors for skin reactions to lamotrigine valproate co-medication was present in 74 and 64% of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis respectively (44). 

Two reports have described patients who presented with toxic epidermal necrolysis after erroneous substitution of terbinafine with lamotrigine [189, 190 ]. 

Duparc A, Lasek A, Gros C, Delaporte E, Van der Linden T, Modiano P. Toxic epidermal necrolysis caused by erroneous substitution of lamotrigine for terbinaflne. Ann Dermatol Venereol 2010 137(11) 736-8. 

In a prospective study, the incidence of rash was calculated in 237 patients who were taking lamotrigine for bipolar I disorder in Korea, of whom 30 developed a rash at a median time of onset of 16 days [162. In two cases the rash was serious, but none developed Stevens-Johnson sjmdrome or toxic epidermal necrolysis. 

Intravenous immunoglobulin was successfully given to a patient with epilepsy and toxic epidermal necrolysis, which appeared after 2 weeks of treatment with lamotrigine and valproate [177 ]. 

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