Merck Manual

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Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Reviewed/Revised May 2022 | Modified Sep 2022
Topic Resources

Sulfonamides are synthetic bacteriostatic antibiotics Overview of Antibacterial Drugs Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more Overview of Antibacterial Drugs 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 Trimethoprim and Sulfamethoxazole Trimethoprim is available as a single drug or in combination with sulfamethoxazole (a sulfonamide antibiotic). The drugs act synergistically to block sequential steps in bacterial folate metabolism... read more ). 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.

Indications for Sulfonamides

Sulfonamides are active against

Topical sulfonamides can be used to treat the following:

Contraindications to Sulfonamides

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 Kernicterus Kernicterus is brain damage caused by unconjugated bilirubin deposition in basal ganglia and brain stem nuclei. Normally, bilirubin bound to serum albumin stays in the intravascular space. However... read more in the fetus or neonate.

Sulfonamides enter breast milk.

Adverse Effects of Sulfonamides

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

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 for Sulfonamides

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.

Drugs Mentioned In This Article

Drug Name Select Trade
AK-Sulf , Bleph-10, Carmol, Cetamide, Klaron, Mexar, Ocu-Sul , Ovace, Ovace Plus, RE-10 , Rosula NS, Seb-Prev, Sodium Sulamyd, Sulf-10
No brand name available
Azulfidine, Azulfidine En-Tabs, Sulfazine , Sulfazine EC
Primsol, Proloprim, TRIMPEX
Silvadene, SSD, SSD AF, Thermazene
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20
Folacin , Folicet, Q-TABS
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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