Could serum levels of lamotrigine be elevated due to an interaction with gabapentin or omeprazole?

Fråga: "Could serum levels of lamotrigine be elevated due to an interaction with gabapentin or omeprazole? Is a serum level of lamotrigine of 82 umol/L likely to be lethal?

The question concerns a child of school age with an encephalopathy and epilepsy. He is treated with the abovementioned medications. A lamotrigine serum level of 82 umol/L is measured hours before the kid´s condition rapidly deteriorates (the serum concentration has previously been within the "therapeutic" range, 6-40 umol/L). He later presents with the clinical picture of septicaemia. Pneumococcal bacteremia is diagnosed. The outcome of the episode is fatal. The questioner wants to know whether the abovementioned treatment decisions might have contributed to the outcome."

Sammanfattning: There is no basis in the published literature for the assumption that the elevated lamotrigine concentration noted in the present case was due to interaction with gabapentin or omeprazole. Neither does available evidence support the notion of the recorded lamotrigine concentration as a cause of the fatal outcome of this case, which, given available information, was by all probability caused by pneumococcal septicaemia.

Svar: The standard literature and Medline does not cite any described interactions between lamotrigine and gabapentin or omeprazole. Lamotrigine is metabolised thorugh hepatic glucuronidatrion. Gabapentin is mainly excreted renally, whereas omeprazole undergoes hepatic oxidative metabolism through cytochrome enzymes. There are no theoretical reasons to assume that these medications would cause decreased clearance of lamotrigine, and thus an elevated serum concentration. A more likely, though unprovable, cause of the pre-terminal elevated lamotrigine serum concentration is an effect of severe intercurrent illness on hepatic biotransformation.

We could find one case reported in the literature where death was attributed to lamotrigine overdose. The post-mortem concentration of lamotrigine in this case was reported to be 210 umol/L. However, the exact manner of death was undetermined (1). There are no other recorded cases of death which could be directly attributed to lamotrigine overdose (2,3). A number of cases of lamotrigine intoxication were plasma concentrations have been recorded are available in the literature. A 55-year old woman presented with stupor after overdosing lamotrigine. Her plasma concentration on admission was 134 umol/L. Her ECG was normal and recovery unremarkable (4). Another intoxication case presented with ataxia and nystagmus. She had a plasma level of 70 umol/L. She recovered completely (5). Yet another case describes ataxia and nystagmus with a plasma level of 139 umol/L, and complete recovery (6). There is one case were a two year old accidentally ingested 800 mg of lamotrigine. He developed seizures but recovered completely. Remarkably, his serum concentration was only 15 umol/L two hours following ingestion (7). Finally, our experience from therapeutic drug monitoring of lamotrigine, where we occasionally see concentrations in the size of the present case does not indicate that these levels would generally be associated with any life-threatening symptomatology. Levine B, Jufer RA, Smialek JE. Lamotrigine distribution in two postmortem cases. J Anal Toxicol 2000;24(7):635-7. Richens A. Safety of lamotrigine. Epilepsia 1994;35(suppl 5):S37-40. Wong IC, Mawer GE, Sander JW. Adverse event monitoring in lamotrigine patients: a pharmacoepidemiologic study in the United Kingdom. Epilepsia 2001;42(2):237-44. Sbei M, Campellone JV. Stupor from lamotrigine toxicity. Epilepsia 2001;42(8):1082-83. Blankenhorn V, Hoffman H-G, Polatschek B. Acute intoxication with the new antiepileptic drug lamotrigin in a suicide attempt. O´Donnell J, Bateman DN. Lamotrigine overdose in an adult. J Toxicol Clin Toxicol 2000;38(6):659-60. Briassoulis G, Kalabalikis P, Tamiolaki M, Hatzis T. Lamotrigine childhood overdose. Pediatr Neurol 1998;19:239-42.