OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Sulfadoxine-Pyrimethamine – Fansidar®

DRUG CLASS

Antiinfective Agents; Antimalarial Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULAS AND STRUCTURES

ANNOTATED BIBLIOGRAPHY

References updated: 10 January 2026

Abbreviations: TMP-SMZ, trimethoprim and sulfamethoxazole; DRESS, drug reaction with eosinophilia and systemic symptoms; iv, intravenous; HLA, human leukocyte antigen.

• Zimmerman HJ. Sulfonamides. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 606-9.

  (Expert review of the sulfonamides and sulfones published in 1999; sulfonamides are thought to cause clinically apparent liver injury in 0.5-1.0% of recipients generally with a sudden onset within 14 days of starting, often with immunoallergic features and a hepatocellular or mixed pattern of injury; mortality may be as high as 10%).
• Moseley RH. Sulfonamides. Hepatotoxicity of antimicrobials and antifungal agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 463-82.

  (Review of hepatotoxicity of antibiotics including sulfonamides).
• MacDougall C. Sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1011-1021.

  (Textbook of pharmacology and therapeutics).
• Vinetz JM. Chemotherapy of malaria. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 967-986.

  (Textbook of pharmacology and therapeutics, mentions that the combination of sulfadoxine and pyrimethamine was a primary treatment for uncomplicated P. falciparum malaria, but is no longer recommended because of a high rate of resistance and its potential for liver and hypersensitivity related adverse events).
• Lowe J, Smith M. The chemotherapy of leprosy in Nigeria; with an appendix on glandular fever and exfoliative dermatitis precipitated by sulfones. Int J Lepr 1949; 17: 181-95. [PubMed: 15399690]

  (Summary of clinical results in using sulfones in 227 patients with leprosy described "Glandular fever and exfoliative dermatitis precipitated by sulfones" in the appendix: occurring mostly in adult men, the dermatitis in 2%, glandular fever in 12% which was marked by fever, lymphadenitis, splenomegaly and jaundice in some cases: initial description of sulfone-syndrome).
• Fries J, Siragenian R. Sulfonamide hepatitis. Report of a case due to sulfamethoxazole and sulfisoxazole. N Engl J Med 1966; 274: 95-7. [PubMed: 5901208]

  (60 year old woman developed jaundice after 4 days of sulfamethoxazole with fever, arthralgias and rash [bilirubin 8.4 mg/dL, ALT 360 U/L, Alk P 2.5 times ULN], with positive rechallenge within 30 hours of starting sulfisoxazole [AST 396 U/L, Alk P 1.5 times ULN]).
• Dujovne CA, Chan CH, Zimmerman HJ. Sulfonamide hepatic injury. Review of the literature and report of a case due to sulfamethoxazole. N Engl J Med 1967; 277: 785-8. [PubMed: 6046676]

  (Classic description of sulfonamide hepatotoxicity: case report of a 38 year old man who developed jaundice after 14 days of sulfamethoxazole [3rd exposure] with positive rechallenge; review of the literature on over 100 cases: usual latency of 1-4 weeks, shorter on rechallenge, rash and fever common).
• Espiritu CR, Kim TS, Levine RA. Granulomatous hepatitis associated with sulfadimethoxine hypersensitivity. JAMA 1967; 202: 985-8. [PubMed: 5630747]

  (24 year old man developed rash and jaundice within a week of starting sulfadimethoxine [bilirubin 4.2 mg/dL, AST 72 U/L, Alk P ~ twice ULN], liver biopsy showing granulomatous hepatitis; and rapid recovery).
• Iwarson S, Lundin P. Multiple attacks of jaundice associated with repeated sulfonamide treatment. Acta Med Scand 1979; 206: 219-22. [PubMed: 495230]

  (Four women, ages 20, 30, 35 and 68 years, who had repeated episodes of liver injury after sulfonamides with shortening of latency upon re-exposure, but no worsening of injury [usually hepatocellular] or slowing of resolution, which ranged from 4-12 weeks).
• Døssing M, Andreasen PB. Drug-induced liver disease in Denmark. An analysis of 572 cases of hepatotoxicity reported to the Danish Board of Adverse Reactions to Drugs. Scand J Gastroenterol 1982; 17: 205-11. [PubMed: 6982502]

  (572 reports of drug induced liver injury from 1968-78 were analyzed, representing 6% of total adverse reaction reports and 12% of those that were fatal; halothane accounted for 25% of cases, chlorpromazine 9%, sulfonamides 9%, antituberculosis agents 7%, oxyphenisatin 4% and methyldopa 2%).
• Olsen VV, Loft S, Christensen KD. Serious reactions during malaria prophylaxis with pyrimethamine-sulfadoxine. Lancet 1982; 2: 994. [PubMed: 6127497]

  (Briefly described case of 60 year old woman traveler who developed severe jaundice after 5 weeks of pyrimethamine-sulfadoxine [Fansidar] with fever and eosinophilia, ultimately recovered).
• Koch-Weser J, Hodel C, Leimer R, Styk S. Adverse reactions to pyrimethamine/sulfadoxine. Lancet 1982; 2: 1459. [PubMed: 6129527]

  (Industry response to letter by Olsen [1982] stressing the safety of Fansidar; among 1.5 million exposed persons, only 24 cases of liver reactions have been reported to sponsor).
• Lazar HP, Murphy RL, Phair JP. Fansidar and hepatic granulomas. Ann Intern Med 1985; 102: 722. [PubMed: 3985527]

  (Two women, aged 69 and 75 years, taking sulfadoxine and pyrimethamine for prophylaxis against malaria developed fever, rash and enzyme elevations with liver biopsies showing granulomas).
• Selby CD, Ladusans EJ, Smith PG. Fatal multisystemic toxicity associated with prophylaxis with pyrimethamine and sulfadoxine (Fansidar). Br Med J (Clin Res Ed) 1985; 290: 113-4. [PMC free article: PMC1415474] [PubMed: 3155635]

  (60 year old traveler developed fever and rash 3 weeks after starting Fansidar [bilirubin rising to 22.5 mg/dL, Alk P 809 U/L, ALT 89 U/L], dying two weeks later with severe rash and renal failure).
• Curley RK, Macfarlane AW. Fatal multisystemic toxicity associated with prophylaxis with pyrimethamine and sulfadoxine. Br Med J (Clin Res Ed) 1985; 290: 471-2. [PMC free article: PMC1417750] [PubMed: 2857586]

  (Toxic epidermal necrolysis [TEN] arose after 9 days of sulfasalazine and subsequent jaundice with little information on enzymes; death appeared to be complication of TEN and corticosteroid use with herpes, septicemia, and shock).
• Murphy RL, Phair JP. Systemic reaction to pyrimethamine-sulfadoxine. J Fam Pract 1986; 22: 375-6. [PubMed: 3958686]

  (75 year old woman developed fever, rash, eosinophilia, and cholestatic liver enzymes [AST 53 U/L, Alk P 364 U/L] without jaundice after 4 weeks of sulfadoxine-pyrimethamine therapy; liver biopsy showed granulomas).
• Wejstal R, Lindberg J, Malmvall BE, Norkrans G. Liver damage associated with Fansidar. Lancet 1986; 1: 854-5. [PubMed: 2870335]

  (Seven cases of jaundice attributed to sulfadoxine-pyrimethamine [Fansidar] prophylaxis against malaria; cases arose after 2-12 weeks of therapy, were usually hepatocellular and 6 were jaundiced [bilirubin 0.7-15.2 mg/dL, Alk P 1-2 times normal, ALT 20-90 times normal], resolving within 4-12 weeks of stopping).
• Zitelli BJ, Alexander J, Taylor S, Miller KD, Howrie DL, Perez TH, Van Thiel DH. Fatal hepatic necrosis due to sulfadoxine-pyrimethamine (Fansidar). Ann Intern Med 1987; 106: 393-5. [PubMed: 2949680]

  (15 year old girl developed fever, rash and jaundice after third weekly dose of sulfadoxine-pyrimethamine [bilirubin rising from 0.6 to 8.5 mg/dL, ALT 763 U/L, Alk P 669 U/L, atypical lymphocytosis]; patient ultimately died of acute liver failure).
• Phillips-Howard PA, West LJ. Serious adverse drug reactions to pyrimethamine-sulphadoxine, pyrimethamine-dapsone and to amodiaquine in Britain. J R Soc Med 1990; 83: 82-5. [PMC free article: PMC1292502] [PubMed: 2138674]

  (Spontaneous reporting of serious liver injury in 1:75,000 prescriptions for pyrimethamine-dapsone [Maloprim] for malaria prophylaxis in the UK).
• Friis H, Andreasen PB. Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987. J Intern Med 1992; 232: 133-8. [PubMed: 1506809]

  (Adverse drug reaction reports in Denmark from 1978 to 1987; 62 cases [5%] were attributed to either TMP-SMZ or SMZ alone but none to sulfadoxine-pyrimethamine).
• Pillans PI. Drug associated hepatic reactions in New Zealand: 21 years’ experience. N Z Med J 1996; 109: 315-9. [PubMed: 8816722]

  (Adverse drug reaction reports identified 943 liver injuries over 21 years in New Zealand; TMP-SMZ accounted for 29 (ranking 9th), 1 case being fatal).
• Slatore CG, Tilles SA. Sulfonamide hypersensitivity. Immunol Allergy Clin North Am 2004; 24: 477-90, vii. PMID: 15242722 [PubMed: 15242722]

  (Review of mechanisms of hypersensitivity to sulfonamides).
• Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl 2004; 10: 1018-23. [PubMed: 15390328]

  (Among ~50,000 liver transplants done in the US between 1990 and 2002, 270 [0.5%] were done for drug induced acute liver failure, 3 of which were attributed to sulfasalazine and 1 to TMP-SMZ but none to sulfadoxine-pyrimethamine).
• Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, Garcia-Ruiz E, Garcia-Munoz B, et al.; Spanish Group for the Study of Drug-Induced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005; 129: 512-21. [PubMed: 16083708]

  (Reports to a Spanish network between 1994-2004, included 461 cases of drug induced liver disease; sulfonamides were not mentioned in the top 19 causes [drugs with 5 or more cases]).
• Garcia Rodriguez LA, Ruigomez A, Jick H. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol 2005; 40: 1095-1101. [PubMed: 16165719]

  (Among 103 cases of fulminant drug induced liver injury reported to a Swedish registry between 1966 and 2002, 6 cases were attributed to TMP-SMZ, 3 to sulfonamides and 1 to sulfasalazine but none to sulfadoxine-pyrimethamine [~10% overall]).
• Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol 2010; 105: PMID: 2396-404. [PubMed: 20648003]

  (313 cases of drug induced liver injury were seen over a 12 year period at a large hospital in Bangalore, India; dapsone accounted for 17 cases [5.4%] of which 2 were fatal, and TMP-SMZ accounted for 7 cases [2.2%], but none attributed to sulfadoxine-pyrimethamine).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury including 12 due to sulfonamides [9%], 9 due to TMP-SMZ, and 3 due to sulfasalazine but none to sulfadoxine-pyrimethamine).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, including 39 attributed to antimicrobial agents, but none to sulfonamides).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 31 cases were attributed to TMP-SMZ, 2 cases to dapsone, but none to sulfadoxine-pyrimethamine).
• Chalasani N, Reddy KRK, Fontana RJ, Barnhart H, Gu J, Hayashi PH, Ahmad J, et al. Idiosyncratic drug induced liver injury in African-Americans is associated with greater morbidity and mortality compared to Caucasians. Am J Gastroenterol 2017; 112: 1382-8. [PMC free article: PMC5667647] [PubMed: 28762375]

  (Among 985 patients enrolled in a US prospective database of drug induced liver injury between 2004 and 2016, SMZ/TMP was the most implicated medication among 144 African Americans [7.6%], but ranked fifth among 841 Caucasians [3.6%] behind amoxicillin-clavulanate, nitrofurantoin, anabolic steroids and isoniazid).
• Fontana RJ, Kleiner DE, Chalasani N, Bonkovsky H, Gu J, Barnhart H, Li YJ, et al. The impact of patient age and corticosteroids in patients with sulfonamide hepatotoxicity. Am J Gastroenterol. 2023;118:1566-1575.. [PMC free article: PMC10511659] [PubMed: 36848311]

  (Among 105 cases of sulfonamide induced liver injury enrolled in a prospective U.S. database between 2004 and 2020, 93 were attributed to TMP-SMZ, 9 to sulfasalazine, 2 to dapsone, 1 to sulfadiazine, but none to sulfadoxine-pyrimethamine).
• Bessone F, Hernandez N, Medina-Caliz I, García-Cortés M, Schinoni MI, Mendizabal M, Chiodi D, et al. Drug-induced liver injury in Latin America: 10-year experience of the Latin American DILI (LATINDILI) Network. Clin Gastroenterol Hepatol. 2025;23:89-102.. [PubMed: 38992407]

  (Among 483 cases of drug-induced liver injury enrolled in a prospective Latin American database, only 3 were attributed to TMP-SMZ, 3 to sulfadiazine, 2 to dapsone, and one to sulfasalazine).