Sulfasalazine interactions

Conditions

Conditions in which Sulfasalazine needs care, as documented in this source.

• Colitis

  Major

  Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

  31 sources

  1. "Product Information. Omnipen (ampicillin)." Wyeth-Ayerst Laboratories (2002):
  2. "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome (2002):
  3. "Product Information. Zinacef (cefuroxime)." Glaxo Wellcome (2002):
  4. "Product Information. Cleocin (clindamycin)." Pharmacia and Upjohn (2002):
  5. "Product Information. Macrobid (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  6. "Product Information. Macrodantin (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  7. "Product Information. Amoxil (amoxicillin)." SmithKline Beecham (2001):
  8. "Product Information. Merrem (meropenem)." Astra-Zeneca Pharmaceuticals (2001):

  Show all 31 sourcesShow fewer sources

  9. "Product Information. Coly-Mycin M Parenteral (colistimethate)." Parke-Davis (2001):
  10. "Product Information. Lincocin (lincomycin)." Pharmacia and Upjohn (2001):
  11. "Product Information. Cubicin (daptomycin)." Cubist Pharmaceuticals Inc (2003):
  12. "Product Information. Xifaxan (rifaximin)." Salix Pharmaceuticals (2004):
  13. "Product Information. Doribax (doripenem)." Ortho McNeil Pharmaceutical (2007):
  14. "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc (2009):
  15. "Product Information. Vibativ (telavancin)." Theravance Inc (2009):
  16. "Product Information. Teflaro (ceftaroline)." Forest Pharmaceuticals (2010):
  17. "Product Information. Penicillin G Sodium (penicillin G sodium)." Sandoz Inc (2022):
  18. "Product Information. Dalvance (dalbavancin)." Durata Therapeutics, Inc. (2014):
  19. "Product Information. Orbactiv (oritavancin)." The Medicines Company (2014):
  20. "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions (2017):
  21. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
  22. "Product Information. Polymyxin B Sulfate (polymyxin B sulfate)." AuroMedics Pharma LLC (2022):
  23. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  24. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  25. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
  26. "Product Information. Aemcolo (rifamycin)." Aries Pharmaceuticals, Inc. (2018):
  27. "Product Information. Fetroja (cefiderocol)." Shionogi USA Inc (2019):
  28. "Product Information. Biaxin (clarithromycin)." AbbVie US LLC (2019):
  29. "Product Information. Zithromax (azithromycin)." Pfizer U.S. Pharmaceuticals Group (2021):
  30. "Product Information. E.E.S.-400 Filmtab (erythromycin)." Arbor Pharmaceuticals (2018):
  31. "Product Information. Priftin (rifapentine)." sanofi-aventis (2020):

• Hematologic Diseases

  Major

  The use of sulfonamides has been associated with hematologic toxicity, including methemoglobinemia, sulfhemoglobinemia, leukopenia, granulocytopenia, eosinophilia, hemolytic anemia, aplastic anemia, purpura, clotting disorder, thrombocytopenia, hypofibrinogenemia, and hypoprothrombinemia. Acute dose-related hemolytic anemia may occur during the first week of therapy due to sensitization, while chronic hemolytic anemia may occur with prolonged use. Patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency should be observed closely for signs of hemolytic anemia. Therapy with sulfonamides should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Complete blood counts should be obtained regularly, especially during prolonged therapy (>2 weeks), and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice.

  25 sources

  1. Barak S, Shaked Y, Bar A, Samra Y "Drug-induced post-surgical hemorrhage resulting from trimethoprim-sulphamethoxazole." Int J Oral Maxillofac Surg 18 (1989): 206-7
  2. Chan M, Beale D, Moorhead J "Acute megaloblastosis due to cotrimoxazole." Br J Clin Pract 34 (1980): 87-8
  3. Damergis J, Stoker J, Abadie J "Methemoglobinemia after sulfamethoxazole and trimethoprim therapy." JAMA 249 (1983): 590-1
  4. Finland M, Strauss E, Peterson O "Sulfadiazine." JAMA 251 (1984): 1467-74
  5. Kuipers EJ, Vellenga E, de Wolf JT, Hazenberg BP "Sulfasalazine induced agranulocytosis treated with GM-CSF." J Rheumatol 19 (1992): 621-2
  6. Youssef PP, Bertouch JV "Sulphasalazine induced aplastic anaemia." Aust N Z J Med 22 (1992): 391-2
  7. Keisu M, Ekman E "Sulfasalazine associated agranulocytosis in sweden 1972-1989: clinical features, and estimation of its incidence." Eur J Clin Pharmacol 43 (1992): 215-8
  8. "Product Information. Gantranol (sulfamethoxazole)." Roche Laboratories, Nutley, NJ.

  Show all 25 sourcesShow fewer sources

  9. "Product Information. Gantrisin (sulfisoxazole)." Roche Laboratories (2001):
  10. "Product Information. Sulfadiazine (sulfadiazine)." Eon Labs Manufacturing Inc (2001):
  11. Peppercorn MA "Sulfasalazine. Pharmacology, clinical use, toxicity, and related new drug development." Ann Intern Med 101 (1984): 377-86
  12. Jacobson IM, Kelsey PB, Blyden GT, Demirjian ZN, Isselbacher KJ "Sulfasalazine-induced agranulocytosis." Am J Gastroenterol 80 (1985): 118-21
  13. Wheelan KR, Cooper B, Stone MJ "Multiple haematologic abnormalities associated with sulfasalazine." Ann Intern Med 97 (1982): 726-7
  14. Pena JM, Gonzalez-Garcia JJ, Garcia-Alegria J, Barbado FJ, Vazquez JJ "Thrombocytopenia and sulfasalazine." Ann Intern Med 102 (1985): 277-8
  15. Davies GE, Palek J "Selective erythroid and magakaryocytic aplasia after sulfasalazine administration." Arch Intern Med 140 (1980): 1122
  16. Guillemin F, Aussedat R, Guerci A, Lederlin P, Trechot P, Pourel J "Fatal agranulocytosis in sulfasalazine treated rheumatoid arthritis." J Rheumatol 16 (1989): 1166-7
  17. Mitrane MP, Singh A, Seibold JR "Cholestasis and fatal agranulocytosis complicating sulfasalazine therapy: case report and review of the literature." J Rheumatol 13 (1986): 969-72
  18. Mechanick JI "Coombs' positive hemolytic anemia following sulfasalazine therapy in ulcerative colitis: case reports, review, and discussion of pathogenesis." Mt Sinai J Med 52 (1985): 667-70
  19. Betkowski AS, Lubin A "Sulfamethoxazole-related antiplatelet antibody." Blood 82 (1993): 1683
  20. Gales BJ, Gales MA "Granulocyte-colony stimulating factor for sulfasalazine-induced agranulocytosis." Ann Pharmacother 27 (1993): 1052-4
  21. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):
  22. Bates CM "HIV medicine: drug side effects and interactions." Postgrad Med J 72 (1996): 30-6
  23. "Product Information. Zonegran (zonisamide)." Elan Pharmaceuticals (2001):
  24. Hopkinson ND, Garcia FS, Gumpel JM "Haematological side-effects pf sulphasalazine in inflammatory arthritis." Br J Rheumatol 28 (1989): 414-7
  25. Logan EC, Williamson LM, Ryrie DR "Sulphasalazine associated pancytopenia may be caused by acute folate deficiency." Gut 27 (1986): 868-72

• Hypersensitivity, Immediate

  Major

  The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Sulfonamide therapy should be stopped at once if a rash develops.

  53 sources

  1. Johnson M, Goodwin D, Shands J "Trimethoprim-sulfamethoxazole anaphylactoid reactions in patients with AIDS: case reports and literature review." Pharmacotherapy 10 (1990): 413-16
  2. Hofer T, Becker EW, Weigand K, Berg PA "Demonstration of sensititzed lymphocytes to trimethoprim/sulfamethoxazole and ofloxacin in a patient with cholestatic hepatitis." J Hepatol 15 (1992): 262-3
  3. Stevenson D, Christie D, Haas J "Hepatic injury in a child caused by trimethoprim-sulfamethoxazole." Pediatrics 61 (1978): 864-6
  4. Smith E, Light J, Filo R, Yum M "Interstitial nephritis caused by trimethoprim-sulfamethoxazole in renal transplant recipients." JAMA 244 (1980): 360-1
  5. Fischl M, Dickinson G, LaVoie L "Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for pneumocystis carinii pneumonia in AIDS." JAMA 259 (1988): 1185-9
  6. Whittington R "Toxic epidermal necrolysis and co-trimoxazole." Lancet 2 (1989): 574
  7. Kelly W, Dooley D, Lattuada C, Smith C "A severe, unusual reaction to trimethoprim-sulfamethoxazole in patients infected with human immunodeficiency virus." Clin Infect Dis 14 (1992): 1034-9
  8. Horak J, Mertl L, Hrabal P "Severe liver injuries due to sulfamethoxazole-trimethoprim and sulfamethoxydiazine." Hepatogastroenterology 31 (1984): 199-200

  Show all 53 sourcesShow fewer sources

  9. Gibson J "Recurrent trimethoprim-associated fixed skin eruption." Br Med J 284 (1982): 1529-30
  10. Holdcroft C, Ellison R "Trimethoprim-sulfamethoxazole reaction simulating pneumocystis carinii pneumonia." AIDS 5 (1991): 1029-42
  11. Steinbrecher U, Mishkin S "Sulfamethoxazole-induced hepatic injury." Dig Dis Sci 26 (1981): 756-9
  12. Rudra T, Webb D, Evans A "Acute tubular necrosis following co-trimoxazole therapy." Nephron 53 (1989): 85-6
  13. Ulstad D, Ampel N, Shon B, Galgiani JN, Cutcher AB "Reaction after re-exposure to trimethoprim-sulfamethoxazole." Chest 95 (1989): 937-8
  14. Heer M, Altorfer J, Burger H, Walti M "Bullous esophageal lesions due to co-trimoxazole: an immune-mediated process?" Gastroenterology 88 (1985): 1954-7
  15. Pisanty S, Brayer L "Erythema multiforme-like eruption due to sulfadiazine." J Dent Med 20 (1965): 154-7
  16. Robson M, Levi J, Dolberg L, Rosenfeld J "Acute tubulo-interstitial nephritis following sulfadiazine therapy." Isr J Med Sci 6 (1970): 561-6
  17. Finland M, Strauss E, Peterson O "Sulfadiazine." JAMA 251 (1984): 1467-74
  18. Goadsby P, Donaghy A, Lloyd A, Wakefield D "Acquired immunodeficiency syndrome (AIDS) and sulfadiazine-associated acute renal failure." Ann Intern Med 107 (1987): 783-4
  19. Carbone L, Bendixen B, Appel G "Sulfadiazine-associated obstructive nephropathy occurring in a patient with the acquired immunodeficiency syndrome." Am J Kidney Dis 12 (1988): 72-5
  20. Tenant-Flowers M, Boyle M, Carey D, et al. "Sulphadiazine desenitization in patients with AIDS and cerebral toxoplasmosis." AIDS 5 (1991): 311-5
  21. Leroux JL, Ghezail M, Chertok P, Blotman F "Hypersensitivity reactions to sulfasalazine: skin rash, fever, hepatitis and activated lymphocytes." Clin Exp Rheumatol 10 (1992): 427
  22. "Product Information. Gantranol (sulfamethoxazole)." Roche Laboratories, Nutley, NJ.
  23. "Product Information. Gantrisin (sulfisoxazole)." Roche Laboratories (2001):
  24. "Product Information. Sulfadiazine (sulfadiazine)." Eon Labs Manufacturing Inc (2001):
  25. Peppercorn MA "Sulfasalazine. Pharmacology, clinical use, toxicity, and related new drug development." Ann Intern Med 101 (1984): 377-86
  26. Kanner RS, Tedesco FJ, Kalser MH "Azulfidine- (sulfasalazine-) induced hepatic injury." Am J Dig Dis 23 (1978): 956-8
  27. Losek JD, Werlin SL "Sulfasalazine hepatotoxicity." Am J Dis Child 135 (1981): 1070-2
  28. Fich A, Schwartz J, Braverman D, Zifroni A, Rachmilewitz D "Sulfasalazine hepatotoxicity." Am J Gastroenterol 79 (1984): 401-2
  29. Yaffe BH, Korelitz BI "Sulfasalazine pneumonitis." Am J Gastroenterol 78 (1983): 493-4
  30. Ribe J, Benkov KJ, Thung SN, Shen SC, LeLeiko NS "Fatal massive hepatic necrosis: a probable hypersensitivity reaction to sulfasalazine." Am J Gastroenterol 81 (1986): 205-8
  31. Averbuch M, Halpern Z, Hallak A, Topilsky M, Levo Y "Sulfasalazine pneumonitis." Am J Gastroenterol 80 (1985): 343-5
  32. Gabazza EC, Taguchi O, Yamakami T, Machishi M, Ibata H, Suzuki S, Matsumoto K, Kitagawa T, Yamamoto J "Pulmonary infiltrates and skin pigmentation associated with sulfasalazine." Am J Gastroenterol 87 (1992): 1654-7
  33. Poland GA, Love KR "Marked atypical lymphocytosis, hepatitis, and skin rash in sulfasalazine drug allergy." Am J Med 81 (1986): 707-8
  34. Hamadeh MA, Atkinson J, Smith LJ "Sulfasalazine-induced pulmonary disease." Chest 101 (1992): 1033-7
  35. Williams T, Eidus L, Thomas P "Fibrosing alveolitis, bronchiolitis obliterans, and sulfasalazine therapy." Chest 81 (1982): 766-8
  36. Valcke Y, Pauwels R, Van der Straeten M "Bronchoalveolar lavage in acute hypersensitivity pneumonitis caused by sulfasalazine." Chest 92 (1987): 572-3
  37. Taffet SL, Das KM "Sulfasalazine. Adverse effects and desensitization." Dig Dis Sci 28 (1983): 833-42
  38. Pearl RK, Nelson RL, Prasad ML, Orsay CP, Abcarian H "Serious complications of sulfasalazine." Dis Colon Rectum 29 (1986): 201-2
  39. Sotolongo RP, Neefe LI, Rudzki C, Ishak KG "Hypersensitivity reaction to sulfasalazine with severe hepatotoxicity." Gastroenterology 75 (1978): 95-9
  40. Wang KK, Bowyer BA, Fleming CR, Schroeder KW "Pulmonary infiltrates and eosinophilia associated with sulfasalazine." Mayo Clin Proc 59 (1984): 343-6
  41. Haines JD, Jr "Hepatotoxicity after treatment with sulfasalazine." Postgrad Med 79 (1986): 193-4,
  42. Faintuch J, Mott CB, Machado MC "Pancreatitis and pancreatic necrosis during sulfasalazine therapy." Int Surg 70 (1985): 271-2
  43. Marinos G, Riley J, Painter DM, McCaughan GW "Sulfasalazine-induced fulminant hepatic failure." J Clin Gastroenterol 14 (1992): 132-5
  44. Namias A, Bhalotra R, Donowitz M "Reversible sulfasalazine-induced granulomatous hepatitis." J Clin Gastroenterol 3 (1981): 193-8
  45. Gremse DA, Bancroft J, Moyer MS "Sulfasalazine hypersensitivity with hepatotoxicity, thrombocytopenia, and erythroid hypoplasia." J Pediatr Gastroenterol Nutr 9 (1989): 261-3
  46. Marinac JS, Stanford JF "A severe hypersensitive reaction to trimethoprim-sulfamethoxazole in a patient infected with human immunodeficiency virus." Clin Infect Dis 16 (1993): 178-9
  47. Rubin R "Sulfasalazine-induced fulminant hepatic failure and necrotizing pancreatitis." Am J Gastroenterol 89 (1994): 789-91
  48. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):
  49. Roujeau JC, Kelly JP, Naldi L, et al. "Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis." N Engl J Med 333 (1995): 1600-7
  50. Bates CM "HIV medicine: drug side effects and interactions." Postgrad Med J 72 (1996): 30-6
  51. Kawada A, Kobayashi T, Noguchi H, Hiruma M, Ishibashi A, Marshall J "Fixed drug eruption induced by sulfasalazine." Contact Dermatitis 34 (1996): 155-6
  52. Moore RD, Fortgang I, Keruly J, Chaisson RE "Adverse events from drug therapy for human immunodeficiency virus disease." Am J Med 101 (1996): 34-40
  53. "Product Information. Zonegran (zonisamide)." Elan Pharmaceuticals (2001):

• Intestinal Obstruction

  Major

  The use of sulfasalazine is contraindicated in patients with intestinal obstruction. Approximately one-third of orally administered sulfasalazine is systemically absorbed from the small intestine, while the majority is metabolized by intestinal bacteria to 5-aminosalicylic acid (5-ASA) that remains in the colonic lumen and gets excreted in the feces.

  1 source

  1. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):

• Kidney Diseases

  Major

  Sulfonamides and their metabolites are eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from sulfonamides due to decreased drug clearance. Dosage adjustments may be necessary and modifications should be based on the degree of renal impairment and severity of infection. Additionally, sulfonamides may cause renal toxicity secondary to crystalluria, including uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine. Hydration (8 oz. glass of water with each dose and throughout the day) and adequate urinary output (> 1.5 L/day) should be maintained during sulfonamide administration. Renal function tests and urinalysis should be performed weekly or as often as indicated by the patient's status. Rarely, alkalinization of the urine is necessary.

  48 sources

  1. Smith E, Light J, Filo R, Yum M "Interstitial nephritis caused by trimethoprim-sulfamethoxazole in renal transplant recipients." JAMA 244 (1980): 360-1
  2. Rudra T, Webb D, Evans A "Acute tubular necrosis following co-trimoxazole therapy." Nephron 53 (1989): 85-6
  3. Cryst C, Hammar S "Acute granulomatous interstitial nephritis due to co-trimoxazole." Am J Nephrol 8 (1988): 483-8
  4. Robson M, Levi J, Dolberg L, Rosenfeld J "Acute tubulo-interstitial nephritis following sulfadiazine therapy." Isr J Med Sci 6 (1970): 561-6
  5. Finland M, Strauss E, Peterson O "Sulfadiazine." JAMA 251 (1984): 1467-74
  6. Goadsby P, Donaghy A, Lloyd A, Wakefield D "Acquired immunodeficiency syndrome (AIDS) and sulfadiazine-associated acute renal failure." Ann Intern Med 107 (1987): 783-4
  7. Sahai J, Heimberger R, Collins K, Kaplowitz L, Polk R "Sulfadiazine-induced crystalluria in a patient with the acquired immunodeficiency syndrome: a reminder." Am J Med 84 (1988): 791-2
  8. Carbone L, Bendixen B, Appel G "Sulfadiazine-associated obstructive nephropathy occurring in a patient with the acquired immunodeficiency syndrome." Am J Kidney Dis 12 (1988): 72-5

  Show all 48 sourcesShow fewer sources

  9. Christin S, Baumelou A, Bahri S, Ben Hmida M, Deray G, Jacobs C "Acute renal failure due to sulfadiazine in patients with AIDS." Nephron 55 (1990): 233-4
  10. Simon D, Brosius F, Rothstein D "Sulfadiazine crystalluria revisited." Arch Intern Med 150 (1990): 2379-84
  11. Molina J, Belenfant X, Doco-Lecompte T, et al. "Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis." AIDS 5 (1991): 587-9
  12. Marques L, Silva M, Madeira E, Santos O "Obstructive renal failure due to therapy with sulfadiazine in an AIDS patient." Nephron 62 (1992): 361
  13. Hekster C, Vree T "Clinical pharmacokinetics of sulphonamides and their N4-acetyl derivatives." Antibiot Chemother 31 (1982): 22-118
  14. Adam W, Dawborn J "Urinary excretion and plasma levels of sulphonamides in patients with renal impairment." Australas Ann Med 19 (1970): 250-4
  15. Madsen S "A comparative study of the excretion of sulfonamide-metabolites in cases of renal failure and hepatitis." Chemotherapy 11 (1966): 1-9
  16. Andreasen F, Elsborg L, Husted S, Thomsen O "Pharmacokinetics of sulfadiazine and trimethoprim in man." Eur J Clin Pharmacol 14 (1978): 57-67
  17. Bergan T, Brodwall E, Vik-Mo H, Anstad U "Pharmacokinetics of sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function." Infection 7 (1979): s382-7
  18. Ortengren B, Fellner H, Bergan T "Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part 2: Comparative pharmacokinetics of five sulphonamides." Infection 7 Suppl 4 (1979): s367-70
  19. Stachowska B, Senczuk W "Studies on kinetics of sulfadiazine and trimethoprim excretion in man." Int J Clin Pharmacol Ther Toxicol 25 (1987): 81-5
  20. Mannisto PT, Mantyla R, Mattila J, Nykanen S, Lamminsivu U "Comparison of pharmacokinetics of sulphadiazine and sulphamethoxazole after intravenous infusion." J Antimicrob Chemother 9 (1982): 461-70
  21. Ohnhaus EE, Spring P "Elimination kinetics of sulfadiazine in patients with normal and impaired renal function." J Pharmacokinet Biopharm 3 (1975): 171-9
  22. Ortengren B, Magni L, Bergan T "Development of sulphonamide-trimethoprim combinations for urinary tract infections. part 3: pharmacokinetic characterization of sulphadiazine and sulphamethoxazole." Infection 7 (1979): s371-81
  23. Bergan T, Brodwall EK "Human pharmacokinetics of a sulfamethoxazole-trimethoprim combination." Acta Med Scand 192 (1972): 483-92
  24. Adam WR, Henning M, Dawborn JK "Excretion of trimethoprim and sulphamethoxazole in patients with renal failure." Aust N Z J Med 3 (1973): 383-7
  25. Kremers P, Duvivier J, Heusghem C "Pharmacokinetic studies of co-trimoxazole in man after single and repeated doses." J Clin Pharmacol 14 (1974): 112-7
  26. Rieder J, Schwartz DE, Fernex M, et al. "Pharmacokinetics of the antibacterial combination sulfamethoxazole plus trimethoprim in patients with normal or impaired kidney function." Antibiot Chemother 18 (1974): 148-98
  27. Bergan T, Brodwall EK, Vik-Mo H, Anstad U "Pharmacokinetics of sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function." Infection 7 (1979): s382-7
  28. Patel RB, Welling PG "Clinical pharmacokinetics of co-trimoxazole (trimethoprim-sulphamethoxazole)." Clin Pharmacokinet 5 (1980): 405-23
  29. Gleckman R, Gantz NM, Joubert DW "Intravenous sulfamethoxazole-trimethoprim: pharmacokinetics, therapeutic indications, and adverse reactions." Pharmacotherapy 1 (1981): 206-11
  30. Vergin H, Ferber H, Zimmermann I, Neurath GB "Single and multiple dose kinetics of co-tetroxazine and co-trimoxazole in patients." Int J Clin Pharmacol Ther Toxicol 19 (1981): 350-7
  31. Mannisto PT, Mantyla R, Mattila J, Nykanen S, Lamminsivu U "Comparison of pharmacokinetics of sulphadiazine and sulphamethoxazole after intravenous infusion." J Antimicrob Chemother 9 (1982): 461-70
  32. Cohen M, Pocelinko R "Renal transport mechanisms for the excretion of sulfisoxazole." J Pharmacol Exp Ther 185 (1973): 703-12
  33. Shermantine M, Gambertoglio J, Amend W, Vincenti F, Oie S "Pharmacokinetics of sulfisoxazole in renal transplant patients." Antimicrob Agents Chemother 28 (1985): 535-9
  34. Boisvert A, Barbeau G, Belanger PM "Pharmacokinetics of sulfisoxazole in young and elderly subjects." Gerontology 30 (1984): 125-31
  35. Kaplan SA, Weinfeld RE, Abruzzo CW, Lewis M "Pharmacokinetic profile of sulfisoxazole following intravenous, intramuscular, and oral administration to man." J Pharm Sci 61 (1972): 773-8
  36. Klotz U "Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid." Clin Pharmacokinet 10 (1985): 285-302
  37. Dwarakanath AD, Michael J, Allan RN "Sulphasalazine-induced renal failure." Gut 33 (1992): 1006-7
  38. Marques LP, Silva MT, Madeira EP, Santos OR "Obstructive renal failure due to therapy with sulfadiazine in an AIDS patient." Nephron 62 (1992): 361
  39. "Product Information. Gantranol (sulfamethoxazole)." Roche Laboratories, Nutley, NJ.
  40. "Product Information. Gantrisin (sulfisoxazole)." Roche Laboratories (2001):
  41. Sasson JP, Dratch PL, Shortsleeve MJ "Renal US findings in sulfadiazine-induced crystalluria." Radiology 185 (1992): 739-40
  42. "Product Information. Sulfadiazine (sulfadiazine)." Eon Labs Manufacturing Inc (2001):
  43. Farinas MC, Echevarria S, Sampedro I, Gonzalez A, Perez del Molino A, Gonzalez-Macias J "Renal failure due to sulphadiazine in AIDS patients with cerebral toxoplasmosis." J Intern Med 233 (1993): 365-7
  44. Hein R, Brunkhorst R, Thon WF, Schedel I, Schmidt RE "Symptomatic sulfadiazine crystalluria in AIDS patients: a report of two cases." Clin Nephrol 39 (1993): 254-6
  45. Erturk E, Casemento JB, Guertin KR, Kende AS "Bilateral acetylsulfapyridine nephrolithiasis associated with chronic sulfasalazine therapy." J Urol 151 (1994): 1605-6
  46. Schroder H, Campbell DE "Absorption, metabolism, and excretion of salicylazosulfapyridine in man." Clin Pharmacol Ther 13 (1972): 539-51
  47. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):
  48. Becker K, Jablonowski H, Haussinger D "Sulfadiazine-associated nephrotoxicity in patients with the acquired immunodeficiency syndrome." Medicine 75 (1996): 185-94

• Liver Diseases

  Major

  Hepatotoxicity, including jaundice, diffuse hepatocellular necrosis, hypersensitivity hepatitis and hepatic failure, has rarely been reported in patients receiving sulfonamides. In addition, sulfonamides are partially metabolized by the liver and may accumulate in patients with hepatic impairment. Therapy with sulfonamides should be administered cautiously in patients with liver disease.

  49 sources

  1. Kowdley K, Keeffe E, Fawaz K "Prolonged cholestasis due to trimethoprim-sulfamethoxazole." Gastroenterology 102 (1992): 2148-50
  2. Basista MP "Randomized study to evaluate efficacy and safety of ofloxacin vs trimethoprim and sulfamethoxazole in treatment of uncomplicated urinary tract infection." Urology 37 (1991): 21-7
  3. Hofer T, Becker EW, Weigand K, Berg PA "Demonstration of sensititzed lymphocytes to trimethoprim/sulfamethoxazole and ofloxacin in a patient with cholestatic hepatitis." J Hepatol 15 (1992): 262-3
  4. Stevenson D, Christie D, Haas J "Hepatic injury in a child caused by trimethoprim-sulfamethoxazole." Pediatrics 61 (1978): 864-6
  5. Horak J, Mertl L, Hrabal P "Severe liver injuries due to sulfamethoxazole-trimethoprim and sulfamethoxydiazine." Hepatogastroenterology 31 (1984): 199-200
  6. Steinbrecher U, Mishkin S "Sulfamethoxazole-induced hepatic injury." Dig Dis Sci 26 (1981): 756-9
  7. Alberti-Flor JJ, Hernandez ME, Ferrer JP, Howell S, Jeffers L "Fulminant liver failure and pancreatitis associated with the use of sulfamethoxazole-trimethoprim." Am J Gastroenterol 84 (1989): 1577-9
  8. Ransohoff D, Jacobs G "Terminal hepatic failure following a small dose of sulfamethoxazole-trimethoprim." Gastroenterology 80 (1981): 816-9

  Show all 49 sourcesShow fewer sources

  9. Finland M, Strauss E, Peterson O "Sulfadiazine." JAMA 116 (1941): 2641-7
  10. Hekster C, Vree T "Clinical pharmacokinetics of sulphonamides and their N4-acetyl derivatives." Antibiot Chemother 31 (1982): 22-118
  11. Madsen S "A comparative study of the excretion of sulfonamide-metabolites in cases of renal failure and hepatitis." Chemotherapy 11 (1966): 1-9
  12. Andreasen F, Elsborg L, Husted S, Thomsen O "Pharmacokinetics of sulfadiazine and trimethoprim in man." Eur J Clin Pharmacol 14 (1978): 57-67
  13. Ortengren B, Fellner H, Bergan T "Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part 2: Comparative pharmacokinetics of five sulphonamides." Infection 7 Suppl 4 (1979): s367-70
  14. Stachowska B, Senczuk W "Studies on kinetics of sulfadiazine and trimethoprim excretion in man." Int J Clin Pharmacol Ther Toxicol 25 (1987): 81-5
  15. Mannisto PT, Mantyla R, Mattila J, Nykanen S, Lamminsivu U "Comparison of pharmacokinetics of sulphadiazine and sulphamethoxazole after intravenous infusion." J Antimicrob Chemother 9 (1982): 461-70
  16. Ortengren B, Magni L, Bergan T "Development of sulphonamide-trimethoprim combinations for urinary tract infections. part 3: pharmacokinetic characterization of sulphadiazine and sulphamethoxazole." Infection 7 (1979): s371-81
  17. Bergan T, Brodwall EK "Human pharmacokinetics of a sulfamethoxazole-trimethoprim combination." Acta Med Scand 192 (1972): 483-92
  18. Kremers P, Duvivier J, Heusghem C "Pharmacokinetic studies of co-trimoxazole in man after single and repeated doses." J Clin Pharmacol 14 (1974): 112-7
  19. Patel RB, Welling PG "Clinical pharmacokinetics of co-trimoxazole (trimethoprim-sulphamethoxazole)." Clin Pharmacokinet 5 (1980): 405-23
  20. Gleckman R, Gantz NM, Joubert DW "Intravenous sulfamethoxazole-trimethoprim: pharmacokinetics, therapeutic indications, and adverse reactions." Pharmacotherapy 1 (1981): 206-11
  21. Vergin H, Ferber H, Zimmermann I, Neurath GB "Single and multiple dose kinetics of co-tetroxazine and co-trimoxazole in patients." Int J Clin Pharmacol Ther Toxicol 19 (1981): 350-7
  22. Mannisto PT, Mantyla R, Mattila J, Nykanen S, Lamminsivu U "Comparison of pharmacokinetics of sulphadiazine and sulphamethoxazole after intravenous infusion." J Antimicrob Chemother 9 (1982): 461-70
  23. Boisvert A, Barbeau G, Belanger PM "Pharmacokinetics of sulfisoxazole in young and elderly subjects." Gerontology 30 (1984): 125-31
  24. Kaplan SA, Weinfeld RE, Abruzzo CW, Lewis M "Pharmacokinetic profile of sulfisoxazole following intravenous, intramuscular, and oral administration to man." J Pharm Sci 61 (1972): 773-8
  25. Oie S, Gambertoglio JG, Fleckenstein L "Comparison of the disposition of total and unbound sulfisoxazole after single and multiple dosing." J Pharmacokinet Biopharm 10 (1982): 157-72
  26. Khan AK, Truelove SC, Aronson JK "The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man." Br J Clin Pharmacol 13 (1982): 523-8
  27. Klotz U "Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid." Clin Pharmacokinet 10 (1985): 285-302
  28. Leroux JL, Ghezail M, Chertok P, Blotman F "Hypersensitivity reactions to sulfasalazine: skin rash, fever, hepatitis and activated lymphocytes." Clin Exp Rheumatol 10 (1992): 427
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  32. Peppercorn MA "Sulfasalazine. Pharmacology, clinical use, toxicity, and related new drug development." Ann Intern Med 101 (1984): 377-86
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  36. Fich A, Schwartz J, Braverman D, Zifroni A, Rachmilewitz D "Sulfasalazine hepatotoxicity." Am J Gastroenterol 79 (1984): 401-2
  37. Ribe J, Benkov KJ, Thung SN, Shen SC, LeLeiko NS "Fatal massive hepatic necrosis: a probable hypersensitivity reaction to sulfasalazine." Am J Gastroenterol 81 (1986): 205-8
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• Porphyrias

  Major

  The use of sulfonamides is contraindicated in patients with porphyria, since these drugs can precipitate an acute attack.

  2 sources

  1. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):
  2. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division (1998):

• Urethral Obstruction

  Major

  The use of sulfasalazine tablets is contraindicated in patients with urinary obstruction.

  1 source

  1. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):

• Crystalluria

  Moderate

  Crystalluria can occur during sulfonamide therapy due to precipitation of the sulfonamide and/or its N4-acetyl metabolite in the urinary tract. Renal toxicity such as uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine has been reported. Hydration (8 oz. glass of water with each dose and throughout the day) and adequate urinary output (> 1.5 L/day) should be maintained during sulfonamide administration. Patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk for the development of crystalluria and lithiasis and should be encouraged to consume additional amounts of liquid or given intravenous fluid. Renal function tests and urinalysis should be performed weekly during prolonged therapy (> 2 weeks). Rarely, alkalinization of the urine is necessary.

  12 sources

  1. Robson M, Levi J, Dolberg L, Rosenfeld J "Acute tubulo-interstitial nephritis following sulfadiazine therapy." Isr J Med Sci 6 (1970): 561-6
  2. Finland M, Strauss E, Peterson O "Sulfadiazine." JAMA 251 (1984): 1467-74
  3. Sahai J, Heimberger R, Collins K, Kaplowitz L, Polk R "Sulfadiazine-induced crystalluria in a patient with the acquired immunodeficiency syndrome: a reminder." Am J Med 84 (1988): 791-2
  4. Simon D, Brosius F, Rothstein D "Sulfadiazine crystalluria revisited." Arch Intern Med 150 (1990): 2379-84
  5. Molina J, Belenfant X, Doco-Lecompte T, et al. "Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis." AIDS 5 (1991): 587-9
  6. "Product Information. Gantranol (sulfamethoxazole)." Roche Laboratories, Nutley, NJ.
  7. "Product Information. Gantrisin (sulfisoxazole)." Roche Laboratories (2001):
  8. Sasson JP, Dratch PL, Shortsleeve MJ "Renal US findings in sulfadiazine-induced crystalluria." Radiology 185 (1992): 739-40

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  9. "Product Information. Sulfadiazine (sulfadiazine)." Eon Labs Manufacturing Inc (2001):
  10. Hein R, Brunkhorst R, Thon WF, Schedel I, Schmidt RE "Symptomatic sulfadiazine crystalluria in AIDS patients: a report of two cases." Clin Nephrol 39 (1993): 254-6
  11. Erturk E, Casemento JB, Guertin KR, Kende AS "Bilateral acetylsulfapyridine nephrolithiasis associated with chronic sulfasalazine therapy." J Urol 151 (1994): 1605-6
  12. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):

• Folic Acid Deficiency

  Moderate

  Sulfasalazine may interfere with the absorption of dietary folic acid. Folate deficiency and megaloblastic anemia have been reported. Therapy with sulfasalazine should be administered cautiously in patients with preexisting folate deficiency or anemia secondary to folate deficiency. Folic acid supplementation (1 mg/day) is recommended in all patients during prolonged therapy.

  3 sources

  1. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  2. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):
  3. Halsted CH, Gandhi G, Tamura T "Sulfasalazine inhibits the absorption of folates in ulcerative colitis." N Engl J Med 305 (1981): 1513-7

• Glucosephosphate Dehydrogenase Deficiency

  Moderate

  Sulfasalazine may cause hemolytic anemia in patients with glucose-6 phosphate dehydrogenase deficiency. This reaction is frequently dose related. It is recommended to observe these patients closely for signs of hemolytic anemia, and if toxic reactions occur, the drug should be discontinued immediately.

  1 source

  1. "Product Information. Azulfidine (sulfasalazine)." Pharmacia and Upjohn (2001):