LETTERS TO THE EDITOR
CAUTION I N THE USE OF TOCAINIDE We read with interest the article by Puniani and Bertorini4 concerning the beneficial effects of tocainide in muscle cramps and spasms due to neuromuscular disease. However, we caution against the use of this drug for the treatment of unpleasant but non-life-threatening symptoms of neuromuscular disease. The authors reported no serious side-effects of tocainide therapy, and only 1 subject of the 9 cases had minor side-effect symptoms. Previous reports have suggested that 10% to 20% of patients stop treatment because of gastrointestinal or neurological side-effects2 However, the serious hematological complications of tocainide are of greater concern and include neutropenia, agranulocytosis, thrombocytopenia, and rarely aplastic anemia. The incidence of serious blood dyscrasias has been reported as O.lS%.' Blood dyscrasias commonly occur within 3 months of commencing treatment and may be anticipated by hematological monitoring, but withdrawal of therapy may not always he associated with r e ~ o v e r y . ~ In view of the serious side-effects, tocainide therapy is now recommended only for life-threatening symptomatic ventricular arrhythmias in patients unresponsive to other treatments or in whom other treatments are contra-indi~ated.~ We suggest that similar strictures be applied to the use of tocainide treatment for cramps and spasms. Tocainide should be considered only in cases in which more conventional treatment has failed and then only with strict supervision of blood counts. John EmClague, MRCP Richard H.T. Edwards, PhD, FRCP University Department of Medicine Royal Liverpool University Hospital Liverpool, England L69 3BX
1. Curtis T A : Aplastic anemia due to tocainide (Reply to letter). N EngJ Med 1986;314:583. 2. Kutalek SP, Morganroth J, Horowitz LN: Tocainide: A new oral antiarrhythmic agent. Ann Intern Med 1985;103:387391. 3. Morrill GB: Tocainide-induced aplastic anemia. Drug Intell Clin Phann 1989;23:90-91.
Letters to the Editor
4. Puniani TS, Bertorini TE: Tocainide therapy in muscle cramps and spasms due to neuromuscular disease. Muscle Nerve 1991;14:280-285. 5. Data Sheet for Tonocard. Astra Pharmaceuticals Ltd 1990.
CAUTION I N THE USE OF TOCAINIDE: A REPLY The comments of JE Clague and RHT Edwards regarding our article4 are well appreciated hut several points should be clarified. Our patients used smaller doses than those prescribed in patients with cardiac arrhythmias,' and some of the reported side effects, particularly the neurological ones, are dose related, frequently transient and, disappear with discontinuation of the drug.' Their absence in our patients is likely due to the lbw dosage used. We discussed the possible cardiac complications, which are rare and occur in very ill individuals. The hematological complications also appear to be rare and have occurred in 0.03% in 550,000 patients treated between the time the drug was introduced in the U.S.A. and 1986." Many of the patients with these complications were also using other bone marrow depressants.' These side effects seem to occur in the first few months of therapy. Patients should be carefully monitored during this period, as we did with ours throughout the treatment period. It is noteworthy that some of our patients had been previously treated with other drugs with less than satisfactory response. Other drugs used in the treatment of myotonia are also known to cause side effects that can be severe, including bone marrow depression, and sometimes also cause cardiac conduction abnormalities, particularly in patients with myotonic d y ~ t r o p h y .We ~ have emphasized that tocainide is useful in treating disablmg muscle spasms. In two patients, muscle spasms even caused difficulty in swallowing4 which did not respond to other treatments but was relieved with tocainide.
MUSCLE & NERVE
December 1991
1247
We thus believe that tocainide is a useful agent in patients with myotonia and painful muscle spasms but should be used with caution. The patients should be carefully monitored and made fully aware of its side effects. Tulio E. Bertorini, MD Trilok S. Puniani, MD Department of Neurology University of Tennessee, Memphis Memphis Neurosciences Center Memphis, Tennessee 38163
1248
Letters to the Editor
1. Horn HR, Hadidian Z, Johnson JL, et al: Safety evaluation of tocainide in the American Emergency Use Program. Amer Heart J 1980;100:1037- 1040. 2. Kutalek SP, Morganroth J, Horowitz LN: Tocainide: A new oral antiarrhythmic agent. Ann Int Med 1985;103:387-391. 3. Munsant T: Therapy of tnyotonia: A double blind evaluation of diphenylhydantoin, procainamide and placebo. Neurology 1967;17:359-367. 4. Puniani TS, Bertorini TE: Tocainide therapy in muscle cramps and spasms due to neuromuscular disease. Muscle Nerue 1991;14:280-285. 5. True C: Aplastic anemia due to tocainide (Reply to Letter). N Engl J Med 1986;314:583.
MUSCLE & NERVE
December 1991
CAUTION I N THE USE OF TOCAINIDE We read with interest the article by Puniani and Bertorini4 concerning the beneficial effects of tocainide in muscle cramps and spasms due to neuromuscular disease. However, we caution against the use of this drug for the treatment of unpleasant but non-life-threatening symptoms of neuromuscular disease. The authors reported no serious side-effects of tocainide therapy, and only 1 subject of the 9 cases had minor side-effect symptoms. Previous reports have suggested that 10% to 20% of patients stop treatment because of gastrointestinal or neurological side-effects2 However, the serious hematological complications of tocainide are of greater concern and include neutropenia, agranulocytosis, thrombocytopenia, and rarely aplastic anemia. The incidence of serious blood dyscrasias has been reported as O.lS%.' Blood dyscrasias commonly occur within 3 months of commencing treatment and may be anticipated by hematological monitoring, but withdrawal of therapy may not always he associated with r e ~ o v e r y . ~ In view of the serious side-effects, tocainide therapy is now recommended only for life-threatening symptomatic ventricular arrhythmias in patients unresponsive to other treatments or in whom other treatments are contra-indi~ated.~ We suggest that similar strictures be applied to the use of tocainide treatment for cramps and spasms. Tocainide should be considered only in cases in which more conventional treatment has failed and then only with strict supervision of blood counts. John EmClague, MRCP Richard H.T. Edwards, PhD, FRCP University Department of Medicine Royal Liverpool University Hospital Liverpool, England L69 3BX
1. Curtis T A : Aplastic anemia due to tocainide (Reply to letter). N EngJ Med 1986;314:583. 2. Kutalek SP, Morganroth J, Horowitz LN: Tocainide: A new oral antiarrhythmic agent. Ann Intern Med 1985;103:387391. 3. Morrill GB: Tocainide-induced aplastic anemia. Drug Intell Clin Phann 1989;23:90-91.
Letters to the Editor
4. Puniani TS, Bertorini TE: Tocainide therapy in muscle cramps and spasms due to neuromuscular disease. Muscle Nerve 1991;14:280-285. 5. Data Sheet for Tonocard. Astra Pharmaceuticals Ltd 1990.
CAUTION I N THE USE OF TOCAINIDE: A REPLY The comments of JE Clague and RHT Edwards regarding our article4 are well appreciated hut several points should be clarified. Our patients used smaller doses than those prescribed in patients with cardiac arrhythmias,' and some of the reported side effects, particularly the neurological ones, are dose related, frequently transient and, disappear with discontinuation of the drug.' Their absence in our patients is likely due to the lbw dosage used. We discussed the possible cardiac complications, which are rare and occur in very ill individuals. The hematological complications also appear to be rare and have occurred in 0.03% in 550,000 patients treated between the time the drug was introduced in the U.S.A. and 1986." Many of the patients with these complications were also using other bone marrow depressants.' These side effects seem to occur in the first few months of therapy. Patients should be carefully monitored during this period, as we did with ours throughout the treatment period. It is noteworthy that some of our patients had been previously treated with other drugs with less than satisfactory response. Other drugs used in the treatment of myotonia are also known to cause side effects that can be severe, including bone marrow depression, and sometimes also cause cardiac conduction abnormalities, particularly in patients with myotonic d y ~ t r o p h y .We ~ have emphasized that tocainide is useful in treating disablmg muscle spasms. In two patients, muscle spasms even caused difficulty in swallowing4 which did not respond to other treatments but was relieved with tocainide.
MUSCLE & NERVE
December 1991
1247
We thus believe that tocainide is a useful agent in patients with myotonia and painful muscle spasms but should be used with caution. The patients should be carefully monitored and made fully aware of its side effects. Tulio E. Bertorini, MD Trilok S. Puniani, MD Department of Neurology University of Tennessee, Memphis Memphis Neurosciences Center Memphis, Tennessee 38163
1248
Letters to the Editor
1. Horn HR, Hadidian Z, Johnson JL, et al: Safety evaluation of tocainide in the American Emergency Use Program. Amer Heart J 1980;100:1037- 1040. 2. Kutalek SP, Morganroth J, Horowitz LN: Tocainide: A new oral antiarrhythmic agent. Ann Int Med 1985;103:387-391. 3. Munsant T: Therapy of tnyotonia: A double blind evaluation of diphenylhydantoin, procainamide and placebo. Neurology 1967;17:359-367. 4. Puniani TS, Bertorini TE: Tocainide therapy in muscle cramps and spasms due to neuromuscular disease. Muscle Nerue 1991;14:280-285. 5. True C: Aplastic anemia due to tocainide (Reply to Letter). N Engl J Med 1986;314:583.
MUSCLE & NERVE
December 1991
