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Sulfamethoxazole Side Effects

Applies to sulfamethoxazole: compounding powder, oral tablet.

Hypersensitivity adverse events

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]

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]

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]

Hematologic

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

Renal

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]

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]

Gastrointestinal

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]

Hepatic

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]

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

Endocrine

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

References

1. Johnson M, Goodwin D, Shands J (1990) "Trimethoprim-sulfamethoxazole anaphylactoid reactions in patients with AIDS: case reports and literature review." Pharmacotherapy, 10, p. 413-16

2. Schattner A, Rimon E, Green L, Coslovsky R, Bentwich Z (1988) "Hypoglycemia induced by co-trimoxazole in AIDS." BMJ, 297, p. 742

3. Hofer T, Becker EW, Weigand K, Berg PA (1992) "Demonstration of sensititzed lymphocytes to trimethoprim/sulfamethoxazole and ofloxacin in a patient with cholestatic hepatitis." J Hepatol, 15, p. 262-3

4. Stevenson D, Christie D, Haas J (1978) "Hepatic injury in a child caused by trimethoprim-sulfamethoxazole." Pediatrics, 61, p. 864-6

5. Smith E, Light J, Filo R, Yum M (1980) "Interstitial nephritis caused by trimethoprim-sulfamethoxazole in renal transplant recipients." JAMA, 244, p. 360-1

6. Fischl M, Dickinson G, LaVoie L (1988) "Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for pneumocystis carinii pneumonia in AIDS." JAMA, 259, p. 1185-9

7. Whittington R (1989) "Toxic epidermal necrolysis and co-trimoxazole." Lancet, 2, p. 574

8. Kelly W, Dooley D, Lattuada C, Smith C (1992) "A severe, unusual reaction to trimethoprim-sulfamethoxazole in patients infected with human immunodeficiency virus." Clin Infect Dis, 14, p. 1034-9

9. Horak J, Mertl L, Hrabal P (1984) "Severe liver injuries due to sulfamethoxazole-trimethoprim and sulfamethoxydiazine." Hepatogastroenterology, 31, p. 199-200

10. Gibson J (1982) "Recurrent trimethoprim-associated fixed skin eruption." Br Med J, 284, p. 1529-30

11. Holdcroft C, Ellison R (1991) "Trimethoprim-sulfamethoxazole reaction simulating pneumocystis carinii pneumonia." AIDS, 5, p. 1029-42

12. Steinbrecher U, Mishkin S (1981) "Sulfamethoxazole-induced hepatic injury." Dig Dis Sci, 26, p. 756-9

13. Gutt L, Feder J, Feder R, Grammer LC, Shaughnessy MA, Patterson R (1988) "Corneal ring formation after exposure to sulfamethoxazole." Arch Ophthalmol, 106, p. 726-7

14. Fernandez-Rivas M, Rebolleda G, De La Hoz B, Losada E (1991) "Conjunctivitis after oral administration of sulfamethoxazole." Ann Allergy, 66, p. 272

15. Rudra T, Webb D, Evans A (1989) "Acute tubular necrosis following co-trimoxazole therapy." Nephron, 53, p. 85-6

16. Ulstad D, Ampel N, Shon B, Galgiani JN, Cutcher AB (1989) "Reaction after re-exposure to trimethoprim-sulfamethoxazole." Chest, 95, p. 937-8

17. Heer M, Altorfer J, Burger H, Walti M (1985) "Bullous esophageal lesions due to co-trimoxazole: an immune-mediated process?" Gastroenterology, 88, p. 1954-7

18. Ransohoff D, Jacobs G (1981) "Terminal hepatic failure following a small dose of sulfamethoxazole-trimethoprim." Gastroenterology, 80, p. 816-9

19. Marinac JS, Stanford JF (1993) "A severe hypersensitive reaction to trimethoprim-sulfamethoxazole in a patient infected with human immunodeficiency virus." Clin Infect Dis, 16, p. 178-9

20. Roujeau JC, Kelly JP, Naldi L, et al. (1995) "Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis." N Engl J Med, 333, p. 1600-7

21. McCue J, Zandt J (1991) "Acute psychoses associated with the use of ciprofloxacin and trimethoprim-sulfamethoxazole." Am J Med, 90, p. 528-9

22. Basista MP (1991) "Randomized study to evaluate efficacy and safety of ofloxacin vs trimethoprim and sulfamethoxazole in treatment of uncomplicated urinary tract infection." Urology, 37, p. 21-7

23. Borucki MJ, Matzke DS, Pollard R (1988) "Tremor induced by trimethoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome (AIDS)." Ann Intern Med, 109, p. 77-8

24. Joffe A, Farley J, Linden D, Goldsand G (1989) "Trimethoprim-sulfamethoxazole-associated aseptic meningitis: case reports and review of the literature." Am J Med, 87, p. 332-8

25. Bovino J, Marcus D (1982) "The mechanism of transient myopia induced by sulfonamide therapy." Am J Ophthalmol, 94, p. 99-102

26. Liu L, Seward S, Crumpacker C (1986) "Intravenous trimethoprim-sulfamethoxazole and ataxia." Ann Intern Med, 104, p. 448

27. Gregor JC, Zilli CA, Gotlib IH (1993) "Acute psychosis associated with oral trimethoprim-sulfamethoxazole therapy." Can J Psychiatry, 38, p. 56-8

28. Barak S, Shaked Y, Bar A, Samra Y (1989) "Drug-induced post-surgical hemorrhage resulting from trimethoprim-sulphamethoxazole." Int J Oral Maxillofac Surg, 18, p. 206-7

29. Chan M, Beale D, Moorhead J (1980) "Acute megaloblastosis due to cotrimoxazole." Br J Clin Pract, 34, p. 87-8

30. Damergis J, Stoker J, Abadie J (1983) "Methemoglobinemia after sulfamethoxazole and trimethoprim therapy." JAMA, 249, p. 590-1

31. Betkowski AS, Lubin A (1993) "Sulfamethoxazole-related antiplatelet antibody." Blood, 82, p. 1683

32. Cryst C, Hammar S (1988) "Acute granulomatous interstitial nephritis due to co-trimoxazole." Am J Nephrol, 8, p. 483-8

33. Kowdley K, Keeffe E, Fawaz K (1992) "Prolonged cholestasis due to trimethoprim-sulfamethoxazole." Gastroenterology, 102, p. 2148-50

34. Sugarman B (1985) "Trimethoprim-sulfamethoxazole, pseudomembranous colitis, and spinal cord injury." South Med J, 78, p. 711-3

35. Alberti-Flor JJ, Hernandez ME, Ferrer JP, Howell S, Jeffers L (1989) "Fulminant liver failure and pancreatitis associated with the use of sulfamethoxazole-trimethoprim." Am J Gastroenterol, 84, p. 1577-9

36. Simma B, Meister B, Deutsch J, Sperl W, Fend F, Ofner D, Margreiter R, Vogel W (1995) "Fulminant hepatic failure in a child as a potential adverse effect of trimethoprim-sulphamethoxazole." Eur J Pediatr, 154, p. 530-3

37. Johnson JA, Kappel JE, Sharif MN (1993) "Hypoglycemia secondary to trimethoprim/sulfamethoxazole administration in a renal transplant patient." Ann Pharmacother, 27, p. 304-6

Frequently asked questions

Further information

Sulfamethoxazole side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

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