Clinical evidence,mechanism, importance and management
A man taking perphenazine 8mg twice daily developed marked psychosis soon after starting to take disulfiram 100mg daily (See reference number 1). His serum perphenazine levels had fallen from a range of 2 to 3 nanomol/L to less than 1 nanomol/L. Doubling dosage of perphenazine had little effect, and no substantial clinical improvement or rise in serum levels occurred until he was given intramuscular perphenazine enantate 50mg weekly, at which point levels rose to about 4 nanomol/L. The results of clinical biochemical tests suggested that disulfiram was acting as an enzyme inducer, resulting in increased metabolism and clearance of perphenazine. However,disulfiram normally acts as an enzyme inhibitor. Too little is known to assess general importance of this interaction, and there seems to be no information about an interaction with other phenothiazines.
1. Hansen LB,Larsen N-E. Metabolic interaction between perphenazine and disulfiram. Lancet (1982) ii, 1472.