Is there a risk for interaction between lamotrigine and paracetamol (acetaminophen)?

Fråga: Is there a risk for interaction between lamotrigine and paracetamol (acetaminophen)?

Sammanfattning: Paracetamol seems to increase the elimination of lamotrigine to a small extent. This is probably of little clinical significance. However, in a patient where adequate anticonvulsive control has been difficult to obtain, these changes might be of interest. It is prudent to follow plasma levels of lamotrigine during regular co-administration of paracetamol.

Svar: Both paracetamol and lamotrigine are to a large extent glucuronidated, 55 and 63 per cent respectively. A further 38 per cent of paracetamol is metabolised to other forms of conjugates (1). Data on the remaining 30 per cent of lamotrigine is lacking. Less than 10 per cent of both drugs is excreted in the urine unchanged (1).

The cytochrome P450 isoenzymes CYP1A2, CYP2E1 and CYP3A4 are involved in the metabolism of paracetamol and are responsible for the formation of N-acetyl-p-benzoquinoneimine, a cytotoxic intermediate (2).

Drugs inducing these specific isoenzymes, might increase paracetamol´s hepatotoxicity when the latter is given in high doses. In vivo and in vitro studies have, however, not shown lamotrigine to be an inducer or an inhibitor of hepatic drug metabolising enzymes (3)

A study involving eight healthy volunteers showed that 2.7 g paracetamol daily reduced the AUC (area under the curve) of a 300 mg dose of lamotrigine by 20 per cent and shortened the half-life by 15 per cent (4). These changes are small and probably of little clinical significance in the majority of patients.