      Document 0050
 DOCN  DRG0050
 UNIQUE IDENTIFIER        DRG-0197
 NAME OF SUBSTANCE        Mexiletine hydrochloride [USAN 1996]
 REGISTRY NUMBER          5370-01-4
 STANDARD CHEMICAL NAME   2-Propanamine, 1-(2,6-dimethylphenoxy)-,
                          hydrochloride [USAN 1996]
 SYNONYMS                 1-Methyl-2-(2,6-xyloxy)ethylamine
                          hydrochloride [USAN 1996]
 SYNONYMS                 Mexitil [USAN 1996]
 SYNONYMS                 Katen [Merck Index 1989]
 SYNONYMS                 Ritalmex [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 242
 SECONDARY SOURCE ID      Ko 1173 Cl [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits the inward sodium
                          current, thus reducing the rate of rise of
                          the action potential, Phase 0. Mexiletine
                          hydrochloride is well absorbed (approximately
                          90 percent) from the gastrointestinal tract.
                          Its first-pass metabolism is low. Peak blood
                          levels are reached in 2-3 hours. In normal
                          subjects, plasma elimination half-life is
                          10-12 hours. The drug is 50-60 percent bound
                          to plasma protein, with a volume of
                          distribution of 5-7 liters/kg. Mexiletine
                          hydrochoride is metabolized by the liver, and
                          approximately 10 percent is excreted
                          unchanged by the kidney. Acidification
                          accelerates the rate of excretion of the
                          drug, and alkalinization retards it.
                          Mexiletine plasma levels of at least 0.5
                          mcg/ml are generally required for therapeutic
                          response. [PDR 1995]
 DISEASES STUDIED/TREATED Relief or reduction of pain in HIV-associated
                          peripheral neuropathy [NIAID ACTG 242]
 CLASSIFICATION CODE      Analgesic [NIAID ACTG 242]
 CLASSIFICATION CODE      Cardiac depressant (anti-arrhythmic) [USAN
                          1996]
 OTHER MAJOR USES         Treatment of documented ventricular
                          tachycardia that are life threatening [PDR
                          1995]
 SUBSTANCE INTERACTIONS   No interactions were observed with commonly
                          employed antianginal, antihypertensives, and
                          anticoagulants. Lowered mexiletine plasma
                          levels were reported for concurrent use with
                          some hepatic enzyme inducers such as
                          rifampin, phenytoin, or phenobarbital.
                          Concurrent use with theophylline may increase
                          plasma theophylline levels. [PDR 1995]
 ADVERSE EFFECTS          Adverse effects may include gastrointestinal
                          distress, dizziness or lightheadedness,
                          tremor, and coordination difficulties. [PDR
                          1995]
 CONTRAINDICATIONS        Contraindicated in cardiogenic shock, or
                          pre-existing second or third degree AV block
                          (if no pacemaker is present). Should be used
                          with caution in patients with structural
                          heart disease. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Class 1B antiarrhythmic
                          compound, with electrophysiologic properties
                          similar to lidocaine [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C11H18ClNO [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 215.72 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 203-205 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in water and in
                          alcohol [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa 9.2 [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white
                          crystalline powder with slightly bitter taste
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 150, 200, and 250 mg gelatin
                          capsules. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTIONS: Store below 30 C (86
                          F). [PDR 1995]
 MANUFACTURERS            Boehringer Ingelheim Pharmaceuticals Inc
 REFERENCES               Kwok DW, Kerr CR, McErlane KM.
                          Pharmacokinetics of mexiletine enantiomers in
                          healthy human subjects. A study of the in
                          vivo serum protein binding, salivary
                          excretion and red blood cell distribution of
                          the enantiomers. Xenobiotica 1995
                          Nov;25(10):1127-42.
 REFERENCES               Morita H, Hirabayashi K, Nozaki S, Ohmori K,
                          Yoshikawa K, Matsuo H. Chronic effect of oral
                          mexiletine administration on left ventricular
                          contractility in patients with congestive
                          heart failure: a study based on mitral
                          regurgitant flow velocity measured by
                          continuous-wave Doppler echocardiography. J
                          Clin Pharmacol 1995 May;35(5):478-83.
 REFERENCES               Lein B. Potential therapy for painful
                          neuropathy. PI Perspect. 1995 May;(no 16):11.
 REFERENCES               Murakawa Y, Inoue H, Kuo TT, Sezaki K,
                          Nakajima T, Usui M, Yamashita T, Ajiki K,
                          Oikawa N, Sugimoto T, et al. Prolongation of
                          intraventricular conduction time associated
                          with fatal [correction of fetal] impairment
                          of defibrillation effeciency during treatment
                          with class I antiarrhythmic agents. J
                          Cardiovasc Pharmacol 1995 Feb;25(2):194-9.
 REFERENCES               Kemper CA, Ganer A, Kent G, Deresinski S.
                          Double-blind placebo(P)-controlled cross-over
                          study fails to show benefit of mexiletine
                          (MX) in painful neuropathy. Natl Conf Hum
                          Retroviruses Relat Infect (2nd). 1995 Jan 29-
                          Feb 2;:171.
 REFERENCES               Kempton J, Manoukian A, Levine B, Smialek J.
                          A mexiletine intoxication. J Anal Toxicol
                          1994 Oct:18(6):346-7.
 REFERENCES               Rohrig TP, Harty LE. Postmortem distribution
                          of mexiletine in a fatal overdose. J Anal
                          Toxicol 1994 Oct;18(6):354-6.
 REFERENCES               Chabal C, Jacobson L, Mariano A, Chaney E,
                          Britell CW. The use of oral mexiletine for
                          the treatment of pain after peripheral nerve
                          injury. Anesthesiology. 1992 Apr;76(4):513-7.
 REFERENCES               Stracke H, Meyer UE, Schumacher HE, Federlin
                          K. Mexiletine in the treatment of diabetic
                          neuropathy. Diabetes Care. 1992
                          Nov;15(11):1550-5.
 REFERENCES               Kent GP, Ganer A, Deresinski SC. The safety
                          and efficacy of mexiletine in HIV-associated
                          painful peripheral neuropathy (PPN). Int Conf
                          AIDS. 1991 Jun 16-21;7(1):199 (abstract no.
                          M.B.2068).
 ENTRY MONTH              9403
 LAST REVISION DATE       960417
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
