SULFAPYRIDINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFAPYRIDINE (SULFAPYRIDINE).
Sulfapyridine is a sulfonamide antibiotic that inhibits bacterial dihydropteroate synthase, blocking folate synthesis and thereby nucleic acid production. It also has anti-inflammatory and immunomodulatory effects in dermatologic conditions through unknown mechanisms.
| Metabolism | Primarily hepatic via N-acetylation (N-acetyltransferase 2, NAT2) and glucuronidation; also undergoes hydroxylation. Excreted renally. |
| Excretion | Renal: approximately 70–80% (30% as unchanged drug, remainder as metabolites, primarily N4-acetylsulfapyridine); biliary/fecal: minor (<5%). |
| Half-life | Terminal elimination half-life: 6–10 hours (prolonged in renal impairment or slow acetylators); clinical context: requires dosing adjustment in renal insufficiency. |
| Protein binding | Approximately 50–70% bound to albumin. |
| Volume of Distribution | Vd: 0.25–0.35 L/kg; clinical meaning: indicates distribution primarily into extracellular fluid, with limited tissue penetration. |
| Bioavailability | Oral: 85–100% (well absorbed from gastrointestinal tract). |
| Onset of Action | Oral: onset of bacteriostatic effect within 24–48 hours after achieving steady-state; not used parenterally. |
| Duration of Action | Duration: 12–24 hours after a single oral dose; sustained with multiple daily dosing; clinical notes: trough levels should be monitored to maintain therapeutic concentration. |
500 mg orally four times daily for initial treatment of dermatitis herpetiformis; maintenance dose 500 mg daily to 1.5 g daily in divided doses.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: administer every 8-12 hours. CrCl <10 mL/min: administer every 12-24 hours. Avoid use in severe renal impairment. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B or C: avoid use due to potential accumulation and hepatotoxicity. |
| Pediatric use | Not recommended for children due to risk of kernicterus and adverse effects; safety not established. |
| Geriatric use | Start at lower end of dosing range; monitor renal function and for adverse effects; increased risk of sulfonamide-induced reactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SULFAPYRIDINE (SULFAPYRIDINE).
| Breastfeeding | Sulfapyridine is excreted into breast milk. The milk-to-plasma (M/P) ratio is approximately 0.45. Low levels are unlikely to cause adverse effects in healthy term infants, but caution is advised in premature, ill, or G6PD-deficient infants due to potential for hemolysis or kernicterus. |
| Teratogenic Risk | First trimester: Sulfapyridine, a sulfonamide, crosses the placenta. There is a potential risk of neural tube defects and other malformations based on animal studies, but human data are limited. Second and third trimesters: Sulfonamides compete with bilirubin for albumin binding, increasing the risk of kernicterus in the neonate if administered near term. Use is generally avoided after 32 weeks gestation. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to sulfonamides, porphyria, severe hepatic or renal impairment, pregnancy (especially near term) and lactation, infants <2 months (except for congenital toxoplasmosis).
| Precautions | Severe hypersensitivity reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hematologic toxicity (agranulocytosis, hemolytic anemia in G6PD deficiency), hepatotoxicity, renal toxicity. Discontinue if rash or signs of hypersensitivity. |
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| Fetal Monitoring | Monitor maternal complete blood count, renal function, and hepatic function. Fetal ultrasound may be considered in first trimester exposure. Neonatal bilirubin levels should be monitored if administered near term. |
| Fertility Effects | No specific human data on fertility impairment. Animal studies have not shown significant effects on fertility at therapeutic doses. |