Adverse Reactions during Salicylazosulfapyridine Therapy and the Relation with Drug Metabolism and Acetylator Phenotype

TLDR

Most toxic symptoms of salicylazosulfapyridine are linked to high serum total sulfapyridine concentrations (>50 µg/mL). The study aimed to show that temporary cessation or dose reduction can alleviate sulfapyridine‑related toxicity. Reintroduction of a therapeutic dose was achieved by starting low and gradually increasing it, with regular blood monitoring and acetylator phenotype assessment recommended. Among 28 patients with side effects—most slow acetylators taking ≥4 g/day—dose reduction or temporary cessation allowed continuation in 26 patients, with symptom improvement coinciding with lowered total sulfapyridine levels and no correlation with salicylazosulfapyridine or its metabolites. Published in N Engl J Med 289:491–495 (1973).

Abstract

Most of the toxic symptoms ascribed to salicylazosulfapyridine can be related to high serum concentrations of total sulfapyridine (>50 μg per milliliter). No such correlation is observed with serum concentrations of salicylazosulfapyridine, sulfapyridine metabolites or the other metabolite of salicylazosulfapyridine, 5-aminosalicylic acid. The majority of 28 patients with side effects were taking 4 g or more of salicylazosulfapyridine per day, and most of them were slow acetylator phenotypes. The sulfapyridine-related toxic symptoms can be overcome if salicylazosulfapyridine is stopped temporarily or reduced in dosage. By this method, the therapy could be continued in 26 out of 28 patients who exhibited side effects. A decrease in serum total sulfapyridine concentration coincided with the improvement of the symptoms. Reintroduction of a therapeutic dose of salicylazosulfapyridine was achieved by an initially small dose, which was then gradually increased. Regular blood examination in patients during the initial therapy or during change of dosage is indicated, and patients' acetylator phenotype should be ascertained. (N Engl J Med 289:491–495, 1973)