Can gabapentin cause an elevation of serum gamma-glutamyltransferase (GGT)?/nA 76-year-old woman wi

Fråga: Can gabapentin cause an elevation of serum gamma-glutamyltransferase (GGT)? A 76-year-old woman with epilepsy has been treated with fenytoin for a long time. Three months ago, a switch to gabapentin (Neurontin) was initiated. Gamma-glutamyltransferase was then slightly elevated (3.59 ucat/l, reference <0,80), probably due to fenytoin use. Since then, the fenytoin dose has been gradually reduced and is now 100 mg b i d. The serum fenytoin concentration has been monitored and is decreasing as expected. When the fenytoin dose reduction was initiated, the patient started taking gabapentin 900 mg/d and the dose was later increased to 1200 mg/d. Two weeks ago, a further elevation of gamma-glutamyltransferase was noted (9 ucat/l). There was also a slight thrombocytosis. All other blood cell counts were normal, and so were the transaminases. A new blood sample was taken one week ago. The gamma-glutamyltransferase had not changed, but the thrombocyte count and all other test results were normal. The patient is feeling healthy and denies over-consumption of alcohol.

Sammanfattning: In the WHO database Intdis there are only a few cases of increased gamma-glutamyltransferase in patients taking gabapentin, and the connection to gabapentin has not been investigated. No documentation supporting the possibility of gabapentin causing liver damage was found in the literature. Gabapentin is not known to affect the pharmacokinetics of phenytoin during co-medication. Other causes for the elevated gamma-glutamyltransferase are investigated.

Svar: No information on liver dysfunction caused by gabapentin was found in Medline, Drugline or standard pharmacological literature. Liver damage and thrombocytopenia are both known adverse effects of fenytoin, although it seems unlikely that these would appear during cessation of fenytoin. Gabapentin does not interact pharmacokinetically with fenytoin, and should accordingly not cause increased levels of fenytoin during co-medication (1). In this patient, this assumption has also been confirmed by measurements of serum fenytoin levels.

The pre-clinical studies performed by the manufacturer indicated no risk of liver toxicity in animals, although there were no studies specifically examining hepatotoxicity (2).

In WHO´s adverse reactions database Intdis, there are four reports of increased gamma-glutamyltransferase and a total 64 reports of liver dysfunction in patients taking gabapentin. However, these reports are not evaluated regarding causality due to the differences of the reporting systems in the participating countries (3).

We recommend this case be reported to SADRAC (The Swedish Adverse Drug Reactions Advisory Committee).