Fever, skin rashes, urticaria; nausea, vomiting, or diarrhea; stomatitis, conjunctivitis, arthritis, aseptic meningitis, exfoliative dermatitis; bone marrow depression, thrombocytopenia, hemolytic anemia (in glucose-6-phosphate dehydrogenase [G6PD] deficiency) or aplastic anemia, granulocytopenia, leukemoid reactions; hepatitis, polyarteritis nodosa, vasculitis, Stevens-Johnson syndrome; reversible hyperkalemia; and many others have been reported. Because of the risk of Stevens-Johnson syndrome, patients with a previous rash with receipt of trimethoprim-sulfamethoxazole should not be rechallenged.
Patients intolerant to trimethoprim-sulfamethoxazole can often be desensitized. While a number of desensitization protocols exist, one effective method is giving 0.004 mg trimethoprim/0.02 mg sulfamethoxazole as oral suspension and increasing the dose tenfold each hour to achieve a final dose of 160 mg trimethoprim/500 mg sulfamethoxazole.
Older sulfonamides were relatively insoluble and would precipitate in urine. The most commonly used sulfonamides presently (sulfamethoxazole) are quite soluble, and the old admonition to force fluids is no longer warranted. However, patients with toxoplasmosis receiving high-dose sulfadiazine, one of the older sulfonamides, commonly experience crystalluria. Sulfonamides have been implicated in interstitial nephritis.