Mexiletine Opioids

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

D6 Amiodarone, cimetidine, quinidine, SSRIs Antidepressants, flecainide, lidocaine, mexiletine, opioids... 

A study in 8 healthy subjects found that a single 600-microgram dose of intravenous atropine reduced the rate of absorption of a single 400-mg oral dose of mexiletine, but the mexiletine AUC remained unaffected. Intravenous metoclopramide 10 mg hastened the absorption of mexiletine but similarly did not affect the AUC. Metoclopramide tended to reverse the effect of diamorphine on plasma mexiletine levels in one clinical trial (see also Mexiletine + Opioids , p.268). 

Opioids such as diamorphine, pethidine, and pentazocine strongly inhibit gastric emptying and greatly reduce the absorption rate of paracetamol. Codeine, however, has no significant effect on paracetamol absorption. Morphine and diamorphine have been shown to reduce the absorption of antiarrhyth-mics such as mexiletine in patients with myocardial infarction. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

OPIOIDS MEXILETINE 1. Absorption of oral mexiletine is 1 by co-administration with morphine or diamorphine 2. Methadone may t mexiletine levels 1. Uncertain but thought to be due to an opioid-induced delay in gastric emptying 2. Methadone inhibits CYP2D6-mediated metabolism of mexiletine 1. Watch for poor response to mexiletine consider starting at a higher or using the intravenous route 2. Monitor PR, BP and ECG closely watch for mexiletine toxicity... 

A pharmacokinetic study showed that the mean plasma levels of mexiletine (400 mg orally followed by 200 mg 2 hours later) in the first 3 hours were more than 50% lower in 6 patients who had suffered a myocardial infarction and who had been given diamorphine 5 to 10 mg or morphine lOto 15 mg than in 4 patients who had not been given opioids. In addition, the AUCo.8 was 38.6% lower in those who had received opioids. ... 

In a further study about the prophylactic use of mexiletine, the same authors found that plasma mexiletine levels 3 hours after the 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. 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 meto-clopramide tended to reduce the effect of diamorphine on mexiletine absorption, although this was not noted in the other report. ... 

The reduced absorption of mexiletine would seem to result from inhibition of gastric emptying by the opioids. Other mechanisms probably contribute to the delayed clearance of mexiletine. 

An established interaction although information is limited. The delay and reduction in the absorption would seem to limit the value of oral mexiletine during the first few hours after a myocardial infarction, particularly if opioid analgesics are used. The manufacturer suggests that a higher load-... 

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