Introduction/Objectives:

During the period from March 2005 to April 2008 Croatian Agency for Medicinal Products and Medical Devices (Agency) received 10 reports of ADRs associated with lamotrigine. Three of those were severe ADRs including Stevens Johnson syndrome and hypersensitivity including multi-systemic symptoms and 5 rashes that have not developed systemic signs (therapy was suspended). Lamotrigine is a well established antiepileptic known to be responsible for hypersensitivity reactions manifested through skin reactions. These kinds of ADRs are potentially life threatening if not recognized on time. The objective was to analyze and identify risk factors in cases of severe skin rashes associated with lamotrigine therapy.

Participants, Materials/Methods:

Review of collected ADRs from Agency's database by the keyword lamotrigine and evaluation of these reports.

Results:

Review of three cases of severe skin rashes caused by lamotrigine.

Case 1: 16-year-old patient within few weeks of combined therapy with lamotrigine 75 mg and valproate 450 mg daily experienced febrile reaction, exfoliative rash, had difficulties swallowing, sore throat and generalized maculopapular rash. At the same time, Beta Hemolytic Streptococcus (BHS) was isolated and he received benzatin-fenoxymetil penicillin, antihistamines and corticosteroids but progression of symptoms continued. Lamotrigine was discontinued, patient recovered.

Case 2: 4-year-old infant started receiving 10 mg lamotrigine daily with valproate 45 mg and clonazepam 1 g as a standard therapy. Twenty days afterwards mononucleosis like symptoms, maculo-papular rash, enlarged spleen and lymph nodes along with high fever (40°C) developed. Lamotrigin was discontinued and patient recovered within 3 days.

Case 3: 14-year-old female patient received valproate 750 mg. Within 43 days of receiving concomitant lamotrigine 25 mg daily she experienced vulval redness and itching, diarrhea and rash indicating systemic hypersensitivity reaction. Reaction ceased upon discontinuation of lamotrigine.

Conclusions:

In the presented cases we identified the cause of the severe ADRs as a result of given risk factors: too high dose, pediatric patients, interaction with valproate, drug-induced rash not recognized due to BHS infection respectively. The severity of rash in the reviewed cases and development of more severe symptoms has usually been related to duration of exposure to lamotrigine and it is not possible to predict reliably which rashes will prove to be serious or life threatening. That is why lamotrigine should ordinarily be discontinued at first signs of rash, unless the rash is clearly not drug related.