Mexiletine dosage

Hemodynamic effects - Small decreases in cardiac output and increases in systemic vascular resistance have occurred, with no significant negative inotropic effect. Blood pressure and pulse rate remain essentially unchanged. Mild depression of myocardial function has been observed following IV mexiletine (dosage form not available in the US) in patients with cardiac disease. 

After taking rifampicin 600 mg daily for 10 days, the half-life of a single 400-mg dose of mexiletine was redueed by 40% (from 8.5 to 5 hours) and the AUC fell by 39% in 8 healthy subjeets. The probable reason is that the rifampicin (a known, potent enzyme-indueer) inereases the metabolism and clearance of mexiletine. It seems likely that the mexiletine dosage will need to be increased during eoneurrent use. Monitor eoneurrent use well. 

Mexiletine has also shown significant efficacy in relieving chronic pain, especially pain due to diabetic neuropathy and nerve injury. The usual dosage is 450-750 mg/d orally. This application is off label. 

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. 

Plasma mexiletine levels are reduced by phenydoin. An increase in the dosage may be necessary. 

Information seems to be limited to this report but the interaction appears to be established. It seems likely that the fall in mexiletine levels will be clinically important in some individuals. Monitor for mexiletine efficacy, and where possible levels. Raise the dosage if necessary. 

The interaetion between theophylline and mexiletine is established and of elinical importanee. Monitor coneurrent use and reduee the theophylline dosage as necessary to prevent the development of theophylline toxieity. It has been suggested that 50% dose reduetions may be neeessary. It seems doubtful if the interaetion between theophylline and toeainide is elinically important but this needs eonfirmation. 

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