A CLUSTER OF CASES OF SEVERE CARDIOTOXICITY AMONG KALA-AZAR PATIENTS TREATED WITH A HIGH-OSMOLARITY LOT OF SODIUM ANTIMONY GLUCONATE

In India, sodium antimony gluconate is the drug of choice for kala-aza r. Due to increasing unresponsiveness to this drug in the current epid emic that began in the early 1970s, daily doses of 20 mg/kg/day for 30 days or more is recommended as opposed to che 10 mg/kg/day dose for 6 -10 days used in the past. Of the 130-150 patients treated annually at our center with locally made sodium antimony gluconate, serious cardi otoxicity has occurred in less than 10%. During April 1995 at the Univ ersity Hospital in Varanasi, we encountered life-threatening cardiotox icity after 3-28 days of therapy in each of the eight patients being t reated with a new lot of this drug made by a different manufacturer. O f the eight patients, six each developed congestive heart failure and/ or prolongation of the corrected QT interval (QTc), and three died as a direct consequence of drug-induced toxicities. In three instances, t he life-threatening complications occurred with a cumulative dose of l ess than 300 mg/kg. In patients with prolonged QTc, ventricular premat ure beats and ventricular tachycardia were recorded; in one patient, t he ventricular tachycardia progressed to torsade de pointes, culminati ng in ventricular fibrillation and death. Since switching to different lots of this drug, we have not seen further clustering of dangerous c ardiotoxicity. The antimony content of the implicated drug was compara ble with that in lots from other manufacturers that did not show overt toxicity, but the osmolarity was approximately 300 mOsm/L higher. The simple technique of measuring of osmolarity may help identify inappro priately manufactured drug.