Rechallenge of Lamotrigine After Rash: A Systematic Review

Objective: This study aims to characterize the rate of successful rechallenge considering the risk of recurrence of cutaneous adverse reactions with reintroduction of lamotrigine, as well as how to characterize cutaneous reactions appropriately, and important considerations in deciding whether to attempt reintroduction of lamotrigine.

Data Sources: A systematic review was conducted of PubMed, SCOPUS, and Web of Science databases. Search terms included lamotrigine, rash, and rechallenge or reintroduction.

Study Selection: The resulting articles (59) were imported into Covidence. After screening and application of inclusion/exclusion criteria, 11 articles were included.

Data Extraction and Synthesis: Variables extracted included study design, age of patient, lamotrigine dosing regimen, concomitant valproate use, use of other concomitant enzyme-inducing antiepileptic drugs, rash timing after starting lamotrigine, rash description, rash diagnosis, dermatologist evaluation, skin biopsy, hospitalization, time from initial rash onset until rechallenge, rechallenge lamotrigine dosing regimen, and response.

Results: There were 106 cases of rechallenge of lamotrigine. Over half (57%) of patients were female, and the average age was 35 years. Time from discontinuation of lamotrigine until rechallenge ranged from 1 week to 26 months, and there were 12 cases that continued lamotrigine without interruption or by reducing the dose. Patients who were rechallenged with lamotrigine successfully typically started the rechallenge with either 5 mg or 12.5 mg daily with a gradual upward titration until reaching desired dose. Successful rechallenge occurred in 84% of cases; reasons for unsuccessful rechallenge included severe or intolerable rash or other symptoms. Only 3 out of 106 cases had a dermatologist confirm the initial rash diagnosis.

Conclusions: Lamotrigine has been rechallenged safely in select cases; however, it is critical to confirm that the initial rash did not have specific features of a severe rash in order to proceed with safe reintroduction of lamotrigine. This article analyzes the cases in the literature to date and gives recommendations for how to assess whether to rechallenge lamotrigine.