Tocainide toxicity

When used with other class IB antiarrhythmic drugs, tocainide toxicity may be increased without significant gain in antiarrhythmic efficacy. 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

Some rare toxic effects that may result from tocainide therapy are a lupus-fike syndrome, skin rash, pulmonary complications, and hematologic abnormalities, eg, agranulocytosis (1,2,24). 

ADM INI STERI NG TOCAIN IDE AN D M EXILETIN E Tocainide and mexiletine are administered at 8-hour intervals and with food (or an antacid) to prevent gastrointestinal upset. In addition, administering tocainide with food may offer some protection gainst toxicity because the absoq> tion rate is slowed in the presence of food. 

These drug s are contraindicated in those with a known hypersensitivity to any component of the preparation. The topical anesthetics are used cautiously in patients receiving Class I antiarrhytiimic drug s such as tocainide and mexiletine because the toxic effects are additive and potentially synergistic. 

These are Class IB drugs with actions similar to those of lidocaine. These agents can be administered orally. Mexiletine [mex IL e teen] is used for chronic treatment of ventricular arrhythmias associated with previous myocardial infarction. Tocainide [toe KAY nide] is used for treatment of ventricular tachyarrhythmias. Tocainide has pulmonary toxicity, which may lead to pulmonary fibrosis. 

Engler R, Ryan W, LeWinter M, Bluestein H, Karliner JS. Assessment of long-term antiarrhythmic therapy studies on the long-term efficacy and toxicity of tocainide. Am J Cardiol 1979 43(3) 612-18. 

Lidocaine, mexiletine, and tocainide rarely cause typical local anesthetic toxicity (ie, CNS stimulation, including convulsions) cardiovascular depression (usually minor) and allergy (usually rashes but may extend to anaphylaxis). Tocainide may cause agranulocytosis. These drugs may also precipitate arrhythmias, but this is less common than with class lA drugs. Hyperkalemia increases cardiac toxicity. 

Foirence E, Covinsky JO, Mullen C. A seizure induced by concurrent lidocaine-tocainide therapy — Is it just a case of additive toxicity Drug Intell Clin Pharm (1986) 20, 56-9. 

Caffeine clearance is reduced by 30 to 60% by mexiletine, resulting in raised serum caffeine levels. Whether this might result in caffeine toxicity is uncertain. Lidocaine, flecainide and tocainide do not appear to affect caffeine clearance. Caffeine does not significantly alter mexiletine levels. 

Serum theophylline levels are increased by mexiletine and toxicity may occur. Tocainide has only a small and probably clinically unimportant effect on theophylline pharmacokinetics. 

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