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Sulfamethoxazole Side Effects

Applies to sulfamethoxazole: compounding powder, oral tablet


Hypotension, pulmonary edema, and elevated serum transaminases have been reported following administration of trimethoprim-sulfamethoxazole to patients with HIV infection. Cholestatic jaundice, thought to be due to hypersensitivity, has been reported with sulfamethoxazole alone.

The use of sulfonamide antibiotics, including sulfamethoxazole, is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis, although these phenomena are rare as a whole.[Ref]

Hypersensitivity reactions most commonly present as an urticarial rash. Rare cases of anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome have been reported. Hypersensitivity reactions may be more likely in patients with the Acquired Immunodeficiency Syndrome (AIDS).[Ref]

Nervous system

Neurologic side effects are uncommon and include headache, depression, and hallucinations.[Ref]

Rare cases of aseptic meningitis associated with trimethoprim-sulfamethoxazole have been reported. In addition, reversible tremors, ataxia, catatonia, and seizures have been observed in patients with AIDS.

A single case of acute psychosis has been associated with the routine use of oral trimethoprim-sulfamethoxazole (TMP-SMX). This reaction is believed to be due to the SMX component of the drug.[Ref]


Methemoglobinemia induced by sulfamethoxazole has been reported.

There is in vitro evidence for a sulfamethoxazole-associated antiplatelet antibody. Serologic studies (flow cytometry) on a man with profound and symptomatic thrombocytopenia, associated with trimethoprim-sulfamethoxazole (TMP-SMX), revealed significant SMX-dependent platelet-reactive antibody. These findings are consistent with a diagnosis of SMX-induced immune thrombocytopenia.[Ref]

Hematologic side effects are unusual and include thrombocytopenia, leukopenia, agranulocytosis, and hemolytic, megaloblastic, and aplastic anemias.[Ref]


Sulfamethoxazole may induce sulfa crystal precipitation in renal tubules. Rare cases of interstitial nephritis and tubular necrosis have been reported and are thought to be due to a hypersensitivity mechanism.[Ref]

Renal side effects occur occasionally, probably due to sulfa crystalluria. These side effects may be less likely with adequate hydration. Frequent monitoring of serum creatinine and urinalysis is recommended during sulfamethoxazole therapy in patients with renal insufficiency. Acute interstitial nephritis has rarely been observed with trimethoprim-sulfamethoxazole, but may be due to the trimethoprim component.[Ref]


Gastrointestinal side effects, such as nausea and vomiting, are usually mild. Diarrhea and hepatitis are infrequent.[Ref]

Rare cases of pancreatitis associated with sulfamethoxazole have been reported.[Ref]


Cholestatic hepatitis associated with sulfamethoxazole therapy may present with other signs of hypersensitivity, such as rash, fever, and eosinophilia.[Ref]

Hepatic side effects are rare but can be serious. Isolated cases of jaundice due to cholestasis have been reported. Fulminant hepatic failure has occurred in a few patients treated with trimethoprim-sulfamethoxazole and is likely due to the sulfamethoxazole component. Frequent monitoring of liver function tests during sulfamethoxazole therapy is recommended in patients with liver dysfunction.[Ref]


Sulfamethoxazole, like other sulfonamides, may induce hypoglycemia by stimulating pancreatic islet cells to secrete insulin. A single case of hypoglycemic stupor associated with trimethoprim-sulfamethoxazole has been reported. This patient also had AIDS, may have had another viral infection, and was on other medications.[Ref]

Endocrine side effects including hypoglycemia have been reported rarely.[Ref]


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It is possible that some side effects of sulfamethoxazole may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.
