Studies in patients and
in vitro investigations have shown that fluoxetine and its
metabolite, norfluoxetine, inhibit CYP2D6, the
enzyme that metabolises
mexiletine. Paroxetine would be expected to interact similarly. Fluvoxamine increases the AUC of
mexiletine by 55% due to its effects on CYP1A2.
There appear to be no reported interactions with fluoxetine, but given the way it interacts with other CYP2D6 substrates it would seem prudent to be alert for increased and prolonged effects if it is given with
mexiletine. Similar caution seems warranted with
fluvoxamine.