The absorption of mexiletine is reduced following myocardial infarction,and very markedly reduced and delayed if diamorphineor morphine is used concurrently. A higher loading dose may beneeded if oral mexiletine is required during first few hoursfollowing a myocardial infarction.
A pharmacokinetic study showed that mean plasma levels of mexiletine (400 mg orally followed by 200mg 2 hrs later) in first 3 hrs were more than 50 % lower in 6 patients who had suffered a myocardial infarction and who had been given diamorphine 5 to 10mg or morphine 10 to 15mg than in 4 patients who had not been given opioids. In addition, AUC0-8 was 38.6 % lower in those who had received opioids (See reference number 1).
In a further study about prophylactic use of mexiletine, same authors found that plasma mexiletine levels 3 hrs after first oral dose were 31 % lower in 10 patients who had received opioids than in 6 patients who had not. These patients were from a subset who were subsequently shown not to have had a myocardial infarction (See reference number 1). In another similar trial of mexiletine in acute myocardial infarction,use of diamorphine was associated with low plasma mexiletine levels at 3 hours, and possible reduced efficacy of mexiletine. In this study, pretreatment with intravenous metoclopramide tended to reduce effect of diamorphine on mexiletine absorption,(See reference number 2) although this was not noted in other report (See reference number 1).
The reduced absorption of mexiletine would seem to result from inhibition of gastric emptying by opioids. Other mechanisms probably contribute to delayed clearance of mexiletine
An established interaction although information is limited. The delay and reduction in absorption would seem to limit value of oral mexiletine during first few hrs after a myocardial infarction, particularly if opioid analgesics are used. The manufacturer suggests that a higher load
ing dose of oral mexiletine may be preferable in this situation. Alternatively,an intravenous dose of mexiletine may be given. In addition, they note that it may be necessary to titrate dose against therapeutic effects and adverse effects (See reference number 3).
Pottage A,Campbell RWF, Achuff SC, Murray A, Julian DC, Prescott LF. The absorption oforal mexiletine in coronary care patients. Eur J Clin Pharmacol (1978) 13, 393–9.
Smyllie HC,Doar JW, Head CD, Leggett RJ. A trial of intravenous and oral mexiletine in acutemyocardial infarction. Eur J Clin Pharmacol (1984) 26, 537–42.
Mexitil (Mexiletine). Boehringer Ingelheim Ltd. UK Summary of product characteristics,May2003.