The use of cimetidine to reduce dapsone‐dependent methaemoglobinaemia in dermatitis herpetiformis patients

1. We have attempted to reduce dapsone‐dependent methaemoglobinaemia formation in six dermatitis herpetiformis patients stabilised on dapsone by the co‐administration of cimetidine. 2. In comparison with control, i.e. dapsone alone, methaemoglobinaemia due to dapsone fell by 27.3 +/‐ 6.7% and 26.6 +/‐ 5.6% the first and second weeks after commencement of cimetidine administration. The normally cyanotic appearance of the patient on the highest dose of dapsone (350 mg day‐ 1), underwent marked improvement. 3. There was a significant increase in the trough plasma concentration of dapsone (2.8 +/‐ 0.8 x 10(‐5)% dose ml‐1) at day 21 in the presence of cimetidine compared with control (day 7, 1.9 +/‐ 0.6 x 10(‐5)% dose ml‐1, P less than 0.01). During the period of the study, dapsone‐mediated control of the dermatitis herpetiformis in all six patients was unchanged. 4. Trough plasma concentrations of monoacetyl dapsone were significantly increased (P less than 0.05) at day 21 (1.9 +/‐ 1.0 x 10(‐5)% dose ml‐ 1) compared with day 7 (1.6 +/‐ 0.9 x 10(‐5)% dose ml‐1:control). 5. Over a 12 h period, 20.6 +/‐ 8.9% (day 0) of a dose of dapsone was detectable in urine as dapsone hydroxylamine. Significantly less dapsone hydroxylamine was recovered from urine at day 14 (15.0 +/‐ 8.4) in the presence of cimetidine, compared with day 0 (control: P less than 0.05). 6. The co‐administration of cimetidine may be of value in increasing patient tolerance to dapsone, a widely used, effective, but comparatively toxic drug.