AZULFIDINE EN-TABS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZULFIDINE EN-TABS (AZULFIDINE EN-TABS).
Sulfasalazine is a prodrug that is cleaved by colonic bacteria to 5-aminosalicylic acid (5-ASA) and sulfapyridine. 5-ASA inhibits cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene synthesis. It also scavenges reactive oxygen species and inhibits NF-κB activation, leading to anti-inflammatory effects.
| Metabolism | Sulfasalazine is azo-reduced by colonic bacteria to form 5-ASA and sulfapyridine. 5-ASA is metabolized via N-acetylation (NAT1/NAT2) to N-acetyl-5-ASA and excreted renally. Sulfapyridine undergoes acetylation (NAT2), glucuronidation, and hydroxylation (CYP2C9) prior to renal elimination. |
| Excretion | Renal (50% as sulfapyridine metabolites, 33% as acetylsulfapyridine, 15% as sulfapyridine glucuronide, 2% as unchanged sulfapyridine; 15-20% as mesalamine metabolites), biliary/fecal (minimal, primarily mesalamine excreted in feces) |
| Half-life | Sulfapyridine: 12-15 hours (clinical context: dosing interval typically 6-12 hours due to sulfapyridine accumulation; mesalamine: 0.6-1.5 hours, not clinically relevant) |
| Protein binding | Sulfapyridine: 50-60% (primarily albumin), Mesalamine: 43% (albumin) |
| Volume of Distribution | Sulfapyridine: 0.1-0.3 L/kg (extensive tissue distribution); Mesalamine: 1-2 L/kg (large Vd, not clinically used) |
| Bioavailability | Sulfasalazine: oral bioavailability 10-20% (due to colonic bacterial cleavage); sulfapyridine: 100% absorbed from colon; mesalamine: 20-30% absorbed from colon (systemically); enteric-coated formulation reduces gastric absorption |
| Onset of Action | Oral: Entraric-coated tablets: 2-4 weeks (optimal therapeutic response in ulcerative colitis; rheumatoid arthritis: 4-8 weeks) |
| Duration of Action | 12-24 hours (based on sulfapyridine half-life; clinical effect sustained with regular dosing; full benefit may take weeks) |
500 mg orally twice daily, titrated to 1 g twice daily after 2 weeks for rheumatoid arthritis; 2 g daily in divided doses for ulcerative colitis.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | eGFR 30-60 mL/min: reduce dose by 25%; eGFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no dose adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Juvenile rheumatoid arthritis: 30-50 mg/kg/day in two divided doses, maximum 2 g/day; ulcerative colitis: 40-60 mg/kg/day in three to six divided doses, maximum 2 g/day. |
| Geriatric use | Start at lower end of dosing range (500 mg twice daily) due to potential renal impairment; monitor renal function and blood counts closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AZULFIDINE EN-TABS (AZULFIDINE EN-TABS).
| Breastfeeding | Excreted into breast milk; M/P ratio approximately 0.2-0.4 for sulfapyridine. Caution in infants with G6PD deficiency or jaundice; generally compatible with monitoring. |
| Teratogenic Risk | First trimester: No clear evidence of major malformations; sulfapyridine crosses placenta. Second/third trimester: Risk of neonatal hemolytic anemia, kernicterus, and glucose-6-phosphate dehydrogenase deficiency complications; avoid near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
Sulfasalazine is contraindicated in patients with known hypersensitivity to sulfonamides or salicylates. Fatalities due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported.
| Serious Effects |
["Hypersensitivity to sulfonamides, salicylates, or any component of the formulation","Intestinal or urinary obstruction","Porphyria","Severe hepatic or renal impairment","Infants under 2 years of age (not recommended)"]
| Precautions | ["Hypersensitivity reactions (including severe skin reactions, anaphylaxis)","Hematologic toxicity (monitor CBC; agranulocytosis, aplastic anemia, thrombocytopenia)","Hepatotoxicity (monitor LFTs; may cause fulminant hepatic necrosis)","Renal toxicity (maintain adequate fluid intake, monitor renal function)","Pulmonary toxicity (eosinophilic pneumonia, interstitial lung disease)","Oligospermia and infertility (reversible upon discontinuation)","Photosensitivity (avoid excessive sun exposure)","Folate deficiency (supplement folate as needed)"] |
| Food/Dietary |
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| Complete blood count, liver function tests, renal function tests, urinalysis; fetal ultrasound for growth and anatomy; neonatal bilirubin and G6PD screening if used near delivery. |
| Fertility Effects | May cause reversible oligospermia in males; no direct evidence of female infertility. |
| Take with food or milk to minimize gastrointestinal side effects. Avoid alcohol due to possible additive hepatotoxicity. No known significant food-drug interactions with this formulation. Maintain adequate fluid intake to reduce risk of renal crystalluria. |
| Clinical Pearls | AZULFIDINE EN-TABS (sulfasalazine enteric-coated) is a disease-modifying antirheumatic drug (DMARD) used primarily for rheumatoid arthritis and ulcerative colitis. The enteric coating reduces gastric irritation but may delay onset of action; therapeutic effect may take 8-12 weeks. Monitor for sulfonamide hypersensitivity (rash, fever, Stevens-Johnson syndrome), hepatotoxicity, and myelosuppression. Contraindicated in patients with porphyria or glucose-6-phosphate dehydrogenase deficiency. Dose titration required due to gastrointestinal intolerance. Active metabolite sulfapyridine is responsible for anti-inflammatory effects via inhibition of nuclear factor-kappa B. Urine and skin may turn orange-yellow. |
| Patient Advice | Take with food or milk to reduce stomach upset. Swallow tablets whole; do not crush or chew. · Your urine and skin may turn orange-yellow; this is harmless and due to the medication. · Report any signs of infection (fever, sore throat), unusual bleeding or bruising, severe rash, or yellowing of eyes/skin to your doctor immediately. · Avoid prolonged sun exposure and use sunscreen; may cause photosensitivity. · Drink plenty of fluids to prevent kidney stones. · Keep regular appointments for blood tests to monitor liver function and blood cell counts. |