Safety of Long‐Term Lamotrigine in Epilepsy

Abstract

Summary:Purpose: To examine the safety of lamotrigine (LTG) used in general practice to treat epilepsy.Methods: Information was collected on 11,316 patients who were included in a noninterventional observational cohort study conducted by means of Prescription-Event Monitoring (PEM). A follow-up study provided information on the first 3,994 patients who had taken LTG for 3 6 months. Incidence density (ID) measurements were used to rank the frequency of the reported events.Results: Rash was the most frequently reported nonepileptiform event (ID, 19.7/1,000 patient-months) in the first month of treatment and resulted in LTG being stopped in 2% of the 11,316 patients. Rash was reported more frequently among children aged 2-12 years (ID, 29.4/1,000 patient-months) than adults. Other events associated with the use of LTG included headache, drowsiness, nausea, vomiting, malaise, and lassitude.Rare serious events possibly associated with LTG included 12 cases reported as Stevens-Johnson syndrome, four cases of neutropenia, three cases of thrombocytopenia, and two cases of disseminated intravascular coagulation. There were also individual cases of leucopenia, a meningitic reaction, acute renal failure, hepatotoxicity, and a "lupus-like'' reaction possibly associated with the drug. No foetal abnormalities were specifically associated with the use of the drug in pregnancy. No death was attributed to LTG.Conclusions: Patients had severe epilepsy, inadequately controlled by other antiepileptic agents. The results of these two studies suggest that LTG is acceptably safe when used for the treatment of refractory epilepsy. Key Words: LamotrigineEpilepsy-Drug safety-Prescription-Event MonitoringRash.Lamotrigine (LTG) is a relatively new antiepileptic agent (AED) initially licensed as add-on therapy for seizures inadequately controlled by other drugs. LTG is therefore usually prescribed for patients with chronic, severe epilepsy, already being treated by other agents. The safety of LTG in these patients is of importance to both neurologists and general practitioners (GPs).A study was conducted by Prescription-Event Monitoring (PEM) to establish the safety of LTG. PEM identified events over an observation period of -6 months. As LTG is routinely intended for long-term use, a follow-up study was carried out to identify long-latency events in those patients who took the drug for >6 months.We report the results of the PEM study and the follow-up study.

Lamotrigine

“…Headache (37%), nausea (22%), abnormal coordination (12%), and skin rash (10%) were not statistically significant (35) ( Table 3). Available evidence suggests that LTG is well tolerated at higher maintenance doses (up to 700 mg/day) (36) and during long-term therapy (37).…”

Interchangeability among therapeutic equivalents of lamotrigine: evaluation of quality of life

“…The reduction observed in vitality caused by formulation B, although not significant, may be related to the increase in mean plasma concentration of LTG which can promote the occurrence of side effects (nausea, headache, depression, irritability and skin rash) (Mackay et al, 1997). Formulation C of LTG showed improvement only on the sociability domain of the QOLIE-31, reducing the final score of quality of life, but the alterations were not considered statistically significant (Table III).…”

Late side-effects of valproate and lamotrigine

“…1,18,19 Rare studies have reported side-effects after chronic use of LTG (ex, 6 months). 20 The study of Mackay et al 21 evaluated adverse-effects six months after LTG introMoreira B, Thomé-Souza S, Valente K duction. Rash and Steven-Johnsons syndrome were earlier manifestations, observed during introduction.…”