Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy

Abstract
We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydro-xylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period. Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long-term dapsone 50-100 mg daily, took cimetidine 1·6g daily concurrently for 3 months. At 3-weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298±849 ng/ml (mean+SD) at baseline to 3006±1131 ng/ml at week 3 of cimetidine (PPPPP<0·05), but this was not associated with any deterioration in control of the skin disorders. Hence, long-term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months. Cimetidine thus improves the therapeutic/toxic ratio of dapsone. Such a therapeutic strategy may be appropriate for patients who require high-dose dapsone, or those who are particularly susceptible to dapsone-induced haemotoxicity.