Translation of a-t 2023; 54: 24
 

SIDE EFFECTS

VALPROIC ACID PLUS METHOTREXATE: INTERACTION WARNING

The New Zealand medicines regulatory authority Medsafe is currently indicating an interaction between the antiepileptic drug valproic acid (ERGENYL, generics) and the folic acid antagonist methotrexate (LANTAREL, generics) (1). The background to this is two literature reports in which significantly decreased serum concentrations of valproic acid are described during treatment with methotrexate (at high doses in a patient with lymphatic leukaemia in childhood and at a low dose in a patient with psoriasis), in each case accompanied by seizures (2,3). The day after the use of methotrexate the valproic acid level decreased to a quarter (2) or a fifth (3) of the value measured previously. The cause is suspected to be a displacement of valproic acid from the plasma protein binding resulting in a more rapid metabolism via the liver (1-3).

The New Zealand product information now recommends monitoring the clinical response to the antiepileptic drug when valproic acid and methotrexate are used at the same time and if necessary checking the valproic acid level and adapting the dose accordingly. Where this is medically reasonable, in the event of a clinically relevant interaction an alternative to methotrexate should be considered (1). Since February 2023 the interaction has also been indicated in US product information (4).

The German product information contains no reference to the interaction (5,6). The European Medicines Agency (EMA) is currently not planning any corresponding measures and makes reference to the national authorities (7). The Federal Institute for Drugs and Medical Devices (BfArM) in turn believes that the responsibility lies with the European Pharmacovigilance Committee PRAC and describes the assessment of the interaction as "not yet complete" (8).

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