S.A.S.-500
Clinical safety rating: caution
Comprehensive clinical and safety monograph for S.A.S.-500 (S.A.S.-500).
Sulfasalazine is a prodrug that is cleaved by colonic bacteria to release 5-aminosalicylic acid (mesalamine) and sulfapyridine. Mesalamine acts locally in the colon to reduce inflammation by inhibiting prostaglandin synthesis and leukotriene formation, and by scavenging reactive oxygen species.
| Metabolism | Sulfasalazine is cleaved by bacterial azoreductases in the colon to 5-aminosalicylic acid and sulfapyridine. Sulfapyridine is further metabolized by acetylation (NAT2), hydroxylation (CYP2C9?), and glucuronidation. |
| Excretion | Renal (80-90% as unchanged drug via glomerular filtration and tubular secretion), biliary/fecal (5-10% as metabolites). |
| Half-life | 2-4 hours in normal renal function; prolonged to 8-12 hours in severe impairment (CrCl <20 mL/min). |
| Protein binding | 90-95% bound to albumin. |
| Volume of Distribution | 0.15-0.2 L/kg; primarily distributes to extracellular fluid. |
| Bioavailability | Oral: 70-80% (due to first-pass metabolism); IV: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Oral: 4-6 hours; IV: 4-6 hours. Duration may be extended in renal impairment. |
500 mg orally every 6 hours as needed, not to exceed 2 g per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with GFR <30 mL/min; for GFR 30-50 mL/min, reduce dose to 250 mg every 6 hours. |
| Liver impairment | No specific adjustment required for mild to moderate hepatic impairment; use with caution in severe impairment (Child-Pugh class C) and avoid if possible. |
| Pediatric use | Children <12 years: not recommended. Children ≥12 years: same as adult dosing. |
| Geriatric use | No specific dose adjustment needed; monitor renal function and consider lower initial doses due to increased risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for S.A.S.-500 (S.A.S.-500).
| Breastfeeding | Sulfasalazine and its metabolites are excreted into breast milk. The M/P ratio for sulfapyridine is approximately 0.5. The relative infant dose is estimated at 1-2% of maternal weight-adjusted dose. Though generally considered compatible with breastfeeding, caution is advised in preterm infants, those with hyperbilirubinemia, or G6PD deficiency. Monitor infant for diarrhea or rash. |
| Teratogenic Risk | Sulfasalazine (S.A.S.-500) is FDA Pregnancy Category B. First trimester: No increased risk of major malformations reported in human studies; however, folate antagonism may theoretically occur. Second and third trimesters: No evidence of fetal toxicity, but sulfapyridine may compete with bilirubin for albumin binding, increasing risk of neonatal jaundice and kernicterus, especially near term. Contraindicated in women with glucose-6-phosphate dehydrogenase deficiency due to risk of fetal hemolytic anemia. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to sulfasalazine, sulfonamides, salicylates, or any component","Intestinal or urinary obstruction","Porphyria","Severe hepatic or renal impairment"]
| Precautions | ["Blood dyscrasias (agranulocytosis, aplastic anemia): monitor CBC regularly","Hypersensitivity reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)","Hepatotoxicity","Pulmonary fibrosis or interstitial pneumonitis","Oligospermia and infertility (reversible)","Renal impairment","Photosensitivity","Folate deficiency"] |
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| Fetal Monitoring | Monitor complete blood count, liver function tests, and renal function in the mother throughout therapy. Assess fetal growth and well-being by serial ultrasound if used in pregnancy. For neonates, monitor bilirubin levels and signs of kernicterus, especially if used near term. Evaluate G6PD status in mother and infant if indicated. |
| Fertility Effects | Sulfasalazine may cause reversible oligospermia and reduced sperm motility in men, typically resolving within 2-3 months after discontinuation. No significant adverse effects on female fertility reported; however, disease control in inflammatory bowel disease may improve fertility outcomes. |