CIMETIDINE IMPROVES THE THERAPEUTIC TOXIC RATIO OF DAPSONE IN PATIENTS ON CHRONIC DAPSONE THERAPY

We have previously shown that cimetidine, given concurrently for 2 wee ks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydroxylamine metabolite of dapsone. The aim of the present study was to examine the effect of thi s combination on the benefit/toxic ratio of dapsone over a longer peri od. Eight patients (six dermatitis herpetiformis, one linear IgA disea se, one folliculitis decalvans) on long-term dapsone 50-100 mg dairy, took cimetidine 1.6 g daily concurrently for 3 months. At 3-weekly int ervals, a clinical assessment was made, plasma dapsone and methaemoglo bin were measured, and parameters of oxidative haemolysis were monitor ed. The dapsone level rose from 2298 +/- 849 ng/ml (mean +/- SD) at ba seline to 3006 +/- 1131 ng/ml at week 3 of cimetidine (P < 0.01). This rise in plasma dapsone was sustained during cimetidine administration , falling to 2446 +/- 954 ng/ml when cimetidine was stopped (P < 0.02) . The methaemoglobin fell from 5.5 +/- 2.2% (mean +/- SD) at baseline to 3.9 +/- 1.1% at week 3 (P < 0.01), and remained low until week 12, when there was a return to baseline values (P < 0.01). The haemoglobin did not change from the baseline of 12.7 +/- 0.3 g/dl (mean +/- SD), and other parameters of haemolysis were unaltered, There was a fall in the visual analogue score for headache (P < 0.05), but this was not a ssociated with any deterioration in control of the skin disorders. Hen ce, long-term concurrent cimetidine results in increased plasma dapson e levels without increased haemolysis, and is accompanied by reduced m ethaemoglobinaemia for more than 2 months, Cimetidine thus improves th e therapeutic/toxic ratio of dapsone. Such a therapeutic strategy may be appropriate for patients who require high-dose dapsone, or those wh o are particularly susceptible to dapsone-induced haemotoxicity.