Merck Manual

Please confirm that you are a health care professional




Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version

Sulfonamides are synthetic bacteriostatic antibiotics that competitively inhibit conversion of p-aminobenzoic acid to dihydropteroate, which bacteria need for folate synthesis and ultimately purine and DNA synthesis. Humans do not synthesize folate but acquire it in their diet, so their DNA synthesis is less affected.

Sulfonamides include the following:

  • Mafenide

  • Sulfacetamide

  • Sulfadiazine

  • Sulfadoxine

  • Sulfamethizole

  • Sulfamethoxazole

  • Sulfanilamide

  • Sulfasalazine

  • Sulfisoxazole

Three sulfonamides, sulfisoxazole, sulfamethizole, and sulfasalazine, are available as single drugs for oral use. Sulfamethoxazole is coformulated with trimethoprim (as TMP/SMX). Sulfadoxine combined with pyrimethamine is available for oral use.

Sulfonamides available for topical use include silver sulfadiazine and mafenide burn cream, sulfanilamide vaginal cream and suppositories, and sulfacetamide ophthalmic.


Sulfonamide resistance is widespread, and resistance to one sulfonamide indicates resistance to all.


Most sulfonamides are readily absorbed orally and, when applied to burns, topically. Sulfonamides are distributed throughout the body. They are metabolized mainly by the liver and excreted by the kidneys. Sulfonamides compete for bilirubin-binding sites on albumin.


Sulfonamides are active against

  • A broad spectrum of gram-positive and many gram-negative bacteria

  • Plasmodium and Toxoplasma species

Sulfasalazine can be used orally for inflammatory bowel disease.

Sulfonamides are most commonly used with other drugs (eg, for nocardiosis, urinary tract infection, and chloroquine-resistant falciparum malaria).

Topical sulfonamides can be used to treat the following:

  • Burns: Silver sulfadiazine and mafenide acetate

  • Vaginitis: Vaginal cream and suppositories with sulfanilamide

  • Superficial ocular infections: Ophthalmic sulfacetamide


Sulfonamides are contraindicated in patients who have had an allergic reaction to them or who have porphyria.

Sulfonamides do not eradicate group A streptococci in patients with pharyngitis and should not be used to treat group A streptococcal pharyngitis.

Use During Pregnancy and Breastfeeding

Evidence regarding an association between sulfonamides and birth defects is mixed. Animal studies with sulfonamides show some risk, and adequate studies have not been done in pregnant women.

Use near term and in breastfeeding mothers is contraindicated, as is use in patients < 2 months of age (except as adjunctive therapy with pyrimethamine to treat congenital toxoplasmosis). If used near term during pregnancy or in neonates, these drugs increase blood levels of unconjugated bilirubin and increase risk of kernicterus in the fetus or neonate.

Sulfonamides enter breast milk.

Adverse Effects

Adverse effects of sulfonamides can result from oral and sometimes topical sulfonamides; effects include

  • Hypersensitivity reactions, such as rashes, Stevens-Johnson syndrome, vasculitis, serum sickness, drug fever, anaphylaxis, and angioedema

  • Crystalluria, oliguria, and anuria

  • Hematologic reactions, such as agranulocytosis, thrombocytopenia, and, in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, hemolytic anemia

  • Kernicterus in neonates

  • Photosensitivity

  • Neurologic effects, such as insomnia, and headache

Hypothyroidism, hepatitis, and activation of quiescent systemic lupus erythematosus may occur in patients taking sulfonamides. These drugs can exacerbate porphyrias.

Incidence of adverse effects is different for the various sulfonamides, but cross-sensitivity is common.

Sulfasalazine can reduce intestinal absorption of folate (folic acid). Thus, use of this drug may trigger folate deficiency in patients with inflammatory bowel disease, which also reduces absorption, especially if dietary intake is also inadequate.

Mafenide may cause metabolic acidosis by inhibiting carbonic anhydrase.

Dosing Considerations

To avoid crystalluria, clinicians should hydrate patients well (eg, to produce a urinary output of 1200 to 1500 mL/day). Sulfonamides can be used in patients with renal insufficiency, but peak plasma levels should be measured and sulfamethoxazole levels should not exceed 120 mcg/mL.

Sulfonamides can potentiate sulfonylureas (with consequent hypoglycemia), phenytoin (with increased adverse effects), and coumarin anticoagulants.

Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
Professionals also read

Also of Interest


View All
Overview of Lyme Disease
Overview of Lyme Disease
3D Models
View All
3D Model