Threefold increase in theophylline serum concentration after addition of mexiletine

Ellison, Mark J.; Lyman, David J.; Miguel, Eduardo San

doi:10.1016/0735-6757(92)90078-c

Cited by 2 publications

(1 citation statement)

References 7 publications

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“…Nine studies ( n = 23 patients) report on mexiletine interacting with other drugs. 95 , 150 , 158 , 182 , 183 , 186 , 216 , 221 , 222 The majority [ n = 5 (56%) studies, 7 (30%) patients] of those studies report an interaction with theophylline. 95 , 158 , 182 , 183 , 216 Clearance of theophylline is reduced as a consequence of CYP1A2 inhibition by mexiletine, which results in increased (possibly toxic) theophylline blood levels.…”

Section: Resultsmentioning

confidence: 99%

Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review

et al. 2022

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While mexiletine has been used for over 40 years for prevention of (recurrent) ventricular arrhythmias and for myotonia, patient access has recently been critically endangered. Here we aim to demonstrate the effectiveness and safety of mexiletine in the treatment of patients with (recurrent) ventricular arrhythmias, emphasizing the absolute necessity of its accessibility. Studies were included in this systematic review (PROSPERO, CRD42020213434) if the efficacy or safety of mexiletine in any dose was evaluated in patients at risk for (recurrent) ventricular arrhythmias with or without comparison with alternative treatments (e.g. placebo). A systematic search was performed in Ovid MEDLINE, Embase, and in the clinical trial registry databases ClinicalTrials.gov and ICTRP. Risk of bias were assessed and tailored to the different study designs. Large heterogeneity in study designs and outcome measures prompted a narrative synthesis approach. In total, 221 studies were included reporting on 8970 patients treated with mexiletine. Age ranged from 0 to 88 years. A decrease in ventricular arrhythmias of >50% was observed in 72% of the studies for pre-mature ventricular complexes, 64% for ventricular tachycardia, and 33% for ventricular fibrillation. Electrocardiographic effects of mexiletine were small; only in a subset of patients with primary arrhythmia syndromes, a relative (desired) QTc decrease was reproducibly observed. As for adverse events, gastrointestinal complaints were most frequently observed (33% of the patients). In this systematic review, we present all the currently available knowledge of mexiletine in patients at risk for (recurrent) ventricular arrhythmias and show that mexiletine is both effective and safe.

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Section: Resultsmentioning

confidence: 99%

Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review

et al. 2022

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Effects of Mexiletine, a CYP1A2 Inhibitor, on Tizanidine Pharmacokinetics and Pharmacodynamics

Momo

Homma

Osaka

et al. 2010

The Journal of Clinical Pharma

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The aim of our study is to determine whether mexiletine, a CYP1A2 inhibitor, altered the pharmacokinetics and pharmacodynamics of tizanidine. Pharmacokinetics of tizanidine was examined in an open-label study in 12 healthy subjects after a single dose of tizanidine (2 mg) with and without mexiletine coadministration (50 mg, 3 times as a pre-treatment for a day and 2 times on the study day). Compared with tizanidine alone, mexiletine coadministration increased the peak plasma concentration (1.8 ± 0.8 vs. 5.3 ± 1.8 ng/mL), area under the curve (4.5 ± 2.2 vs. 15.4 ± 6.5 ng•h/mL) and the half-life (1.3 ± 0.2 vs. 1.8 ± 0.7 h) of tizanidine, respectively (P<0.05). Reduction in systolic blood pressure (−10 ± 8 vs. −24 ± 7 mmHg) and diastolic blood pressure (−10 ± 7 vs. −18 ± 8 mmHg) after tizanidine administration were also significantly enhanced by coadministration of mexiletine (P<0.01). Of the 15 patients treated with tizanidine and mexiletine, 4 suffered tizanidine-induced adverse effects such as drowsiness and dry mouth in the retrospective survey. Present results suggested that coadministration of mexiletine increased blood tizanidine concentrations and enhanced tizanidine pharmacodynamics in terms of reduction in blood pressure and adverse symptoms.3

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Threefold increase in theophylline serum concentration after addition of mexiletine

Cited by 2 publications

References 7 publications

Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review

Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review

Effects of Mexiletine, a CYP1A2 Inhibitor, on Tizanidine Pharmacokinetics and Pharmacodynamics

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