Mexiletine adverse effects

CIMETIDINE, RANITIDINE ANTIARRHYTHMICS-AMIODARONE, FLECAINIDE, MEXILETINE, PROCAINAMIDE, PROPAFENONE Likely t plasma concentrations of these antiarrhythmics and risk of adverse effects Cimetidine inhibits CYP2D6-mediated metabolism of flecainide, mexiletine, procainamide and propafenone. Ranitidine is a much weaker CYP2D6 inhibitor. Cimetidine is a potent inhibitor of organic cation transport in the kidney, and the elimination of procainamide is impaired Monitor PR and BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider alternative acid suppression therapy... 

Mexiletine is a class Ib antidysrhythmic drug, similar in action to lidocaine, but it can be given orally. Its adverse effects occur in up to 50% of patients (1) and withdrawal is often necessary (2). The most common adverse effects are on the cardiovascular and central nervous systems. The pharmacokinetics, clinical use, and adverse effects and interactions of mexiletine have been reviewed widely (3-8). 

In addition to its use as an antidysrhythmic drug, mexiletine has also been used in the treatment of various types of neuropathic pain and dystonias (9,10). The adverse effects in these circumstances have been reported (11-13) and reviewed (14). 

In an open study of the antidystonic effect of mexiletine (200 mg/day increasing to a maximum of 800 mg/day) in spasmodic torticollis in six patients, mexiletine produced significant improvement and there were no adverse effects in five of the six patients in the other patient dizziness occurred at the highest dose and required a reduction in dosage (11). 

Mexiletine has been used to treat painful peripheral neuropathy in patients with HIV infection, without any evidence of efficacy (15,16). In one study of 22 patients, nine had adverse effects probably related to mexiletine, including nausea in five, vomiting in four, and abdominal pain, diarrhea, dizziness, insomnia, rises in liver enzymes, and skin rash in one patient each (15). Adverse effects in seven patients required dosage reduction in four cases and withdrawal in three (because of a rash in one case and gastrointestinal effects in two). 

In a double-blind, placebo-controlled, crossover study of the use of mexiletine in 20 patients with neuropathic pain with prominent allodynia the dosage was titrated to maximum of 900 mg/day or until dose-limiting adverse effects occurred. Mexiletine produced little beu-eficial effect and the two most common adverse effects were nausea aud sedatiou (12). Other adverse effects that occurred iu oue or two patients each included insomnia, trismus, headache, agitation, nightmares, and tremor. 

The commonest adverse effects of mexiletine are on the nervous system, and include centrally mediated gastrointestinal distress (38%), light-headedness (20%), tremor (12%), and coordination difficulties (11%). The figures in parentheses are quoted from a study in which mexiletine was compared with quinidine (26). Other reported adverse effects include changes in sleep habit, weakness, headache, visual problems, and nervousness. Slurred speech, dysarthria, diplopia, and ataxia have also been reported (18). 

Mexiletine is mainly cleared polymorphically by CYP2D6 in the liver, and poor metabolizers and the slower among the extensive metabolizers have a higher incidence of mild adverse effects (nausea and light-headedness) (43). However, renal insufficiency can also be associated with an increase in plasma mexiletine concentrations (44). 

Murray KT, Barbey JT, Kopelman HA, Siddoway LA, Echt DS, Woosley RL, Roden DM. Mexiletine and tocai-nide a comparison of antiarrhythmic efficacy, adverse effects, and predictive value of lidocaine testing. Clin Pharmacol Ther 1989 45(5) 553-61. 

Gass IB drugs are less state-dependent blockers of fast Na+ channels, and they decrease the APD. The uses for lidocaine, mexiletine, and tocainide are discussed, as are the metabolism and adverse effects of lidocaine. 

The pharmacokinetics of mexiletine were not altered by cimeti-dine or ranitidine. Cimetidine can reduce the gasitric adverse effects of mexiletine. 

The interaction between caffeine and mexiletine appears to be established, but its clinical importance is uncertain. Some of the adverse effects of mexiletine might be partially due to caffeine-retention (from drinking tea, coffee, cola drinks, etc.). In excess, caffeine can cause jitteriness, tremor and insomnia. It has also been suggested that the caffeine test for liver function might be impaired by mexiletine. Be alert for these possible effects. 

Nervous system Mexiletine 600-1500 mg/ day has been investigated in nine patients with refractory chronic headache. Although it was much more effective or more effective than previous medications, adverse effects such as nausea, fatigue, tremor, dizziness, incoordination, and, to a lesser extent, palpitation led to withdrawal in most patients [78 ]. 

MEXILETINE PROPAFENONE t serum levels of mexiletine Propafenone inhibits CYP2D6-mediated metabolism of mexiletine no case reports of adverse clinical effects but is potential for proarrhythmias Monitor ECG closely... 

Mexiletine is similar to lignocaine (lidocaine) but is effective by the oral route (t) 10 h). It has been used for ventricular arrhythmias especially those complicating myocardial infarction. The drug is usually poorly tolerated. Adverse reactions are almost universal and dose-related and include nausea. 

Flaker GC, Beach CL, Chapman D. Adverse side effects associated with mexiletine. Qin Progr Electrophysiol Pacing 1986 4 602-7. 

Adverse reactions Minor side effects of lidocaine are drowsiness, dizziness, paresthesia, and euphoria. More serious side effects include CNS and cardiovascular effects. Tocainide and mexiletine both have a high incidence of Gl side effects (nausea and vomiting) and CNS side effects (dizziness, numbness, and paresthesias). Additionally, tocainide has a 15% incidence of rash and may cause agranulocytosis. 

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