If the concentration of the sulfonamide is sufficiently high and its aqueous solubility is sufficiently low, the free drug or its metabolites may form crystals and cause bleeding or complete obstruction of the kidneys. Combinations of sulfa compounds have been developed for the purpose of lowering the dosage of individual components to reduce the chance of crystalluria (e.g., triple sulfas, such as the trisulfapyrimidines).
The sulfonamides do cause hypersensitivity reactions (e.g., rashes, eosinophilia, and drug fever) in a small number of patients. Other rare allergic reactions include vasculitis, photosensitivity, agranulocytosis, and thrombocytopenia. Stevens-Johnson syndrome is also associated with sulfonamide use; it is characterized by fever, malaise, erythema multiforme, and ulceration of the mucous membranes of the mouth and genitalia. Hemolytic anemia may develop in persons with a genetic deficiency of red blood cell glucose-6-phosphate dehydrogenase (G6PD).
Sulfonamides compete for sites on plasma proteins that are responsible for the binding of bilirubin. As a result, less bilirubin is bound, and in the newborn, the unbound bilirubin can be deposited in the basal ganglia and subthalamic nuclei, causing kernicterus, a toxic encephalopathy. For this reason, sulfonamides should not be administered to newborns or to women during the last 2 months of pregnancy.
Significant drug-drug interactions are those that potentiate the effects of other agents and require dosage modification. These include certain anticoagulants, hy-poglycemic sulfonylureas, and hydantoin anticonvul-sants.
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