Drug Interactions between clozapine and procainamide

CONTRAINDICATED: The use of clozapine with other potentially myelotoxic agents including procainamide may increase the risk and/or severity of hematologic toxicity. Clozapine alone is associated with a significant risk of agranulocytosis, defined as an absolute neutrophil count (ANC) of less than 500/mm3. During premarketing trials in the U.S., at a time when the need for close monitoring of white blood cell counts was already recognized, the cumulative incidence of agranulocytosis at one year was estimated to be approximately 1.3%. The incidence has decreased postmarketing under a weekly WBC count monitoring system. Although the mechanism of clozapine-induced agranulocytosis is unknown, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression. The use of procainamide itself has been associated with agranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia, and thrombocytopenia in approximately 0.5% of patients. A fatality rate of 3% has been reported for agranulocytosis associated with clozapine and 20% to 25% for agranulocytosis associated with procainamide.

GENERALLY AVOID: Like other Class IA antiarrhythmic agents, procainamide can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval such as clozapine may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: The use of clozapine in combination with other agents having a well-known potential to cause agranulocytosis or otherwise suppress bone marrow function is considered contraindicated. The concurrent use of procainamide with other medications that can prolong the QT interval should preferably be avoided unless benefits are anticipated to outweigh the risks.

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