Allergic skin rash with lamotrigine and concomitant valproate therapy: evidence for an increased risk

Abstract

-Cutaneous rash is one of the commonest adverse events associated with lamotrigine. We assessed whether the risk is increased in patients receiving concomitant valproate therapy in a population of 103 adult patients with intractable epilepsy, who had lamotrigine added to their treatment. Of the 33 patients taking valproate, 10 (30%) developed a rash, whilst of the 70 not taking valproate, only 6 (8%) developed a rash. This suggests a significantly higher risk of cutaneous rash when starting lamotrigine in patients already taking valproate (p<0.02).KEY WORDS: allergic skin rash, antiepileptic drugs, lamotrigine, valproate. Rash cutâneo com lamotrigina e concomitante uso de valproate, evidências de maior riscoRESUMO -Rash cutâneo é um dos efeitos adversos mais comuns associados ao início de tratamento com lamotrigina, uma nova medicação antiepiléptica. Avaliamos se esse risco é maior em pacientes medicados concomitantemente com valproato em 103 pacientes adultos com epilepsia refratária, que tiveram lamotrigina adicionada a seu tratamento. Dez dos 33 pacientes (30%) que faziam uso de valproato e 6 (8%) dos 70 pacientes que não usaram valproato desenvolveram rash. Isto sugere que existe maior risco de desenvolver rash cutâneo quando se adiciona lamotrigina em pacientes em uso de valproato (p<0,02). PALAVRAS-CHAVE: rash cutâneo, drogas antiepilépticas, lamotrigina, valproato.Cutaneous rash is a well established adverse effect of phenytoin, carbamazepine, and has also been reported with lamotrigine (LTG) therapy. It is very rare with valproate (VPA). The overall rate of skin rash in patients receiving lamotrigine is approximately 3%There have been suggestions of a higher incidence of skin rash in patients receiving LTG therapy with concomitant VPA 2 .To further investigate this observation, we reviewed all case records of adult inpatients with refractory epilepsy at the assessment unit of Chalfont Centre for Epilepsy, admitted between 1991 and 1993, to identify patients who had LTG added to their therapy. We noted whether side effects were recorded after its introduction.

A Study on the Adverse Drug Reactions Induced by Anti Epileptic Drugs in the Epileptic Patients

“…Sodium valproate interferes with the metabolism of LAM by inhibiting hepatic glucuronides, leading to increased LAM blood levels. According to other studies incidence of Lamotrigine induced rash in epileptic patients is 8-20% and the chance of developing skin rashes with combination of Sodium Valproate and Lamotrigine has also been proved (Li et al, 1996;Ghaffarpour et al, 2005;Mohammed, 2007). Monotherapy with Sodium valproate caused weight gain in 4 patients.…”

Therapeutic Safety Monitoring: What to Look for and When to Look for It

“…61 Allergic rash occurs at a higher rate when patients are already taking VPA. [62][63][64] Valproate is a powerful inhibitor of lamotrigine metabolism, resulting in much higher serum levels of lamotrigine in the presence of VPA compared with enzyme-inducing AEDs. However, the mechanism of increased rash with the combination of lamotrigine and VPA is not fully explained by an increase in lamotrigine levels.…”

Oral Health of Epileptic Patients in Rural Rajasthan

“…Xerostomia and stomatitis have been reported rarely as a side effects of Carbamazepine. 8 and rash that may involve the oral cavity has been associated with lamotrigine and can be exacerbated by the concomitant use of valproic acid.…”