Dosing and uses of Azulfidine, Azulfidine EN (sulfasalazine)
Adult dosage forms and strengths
tablet
- 500mg
tablet, enteric coated (delayed release)
- 500mg
Ulcerative Colitis
Mild to moderate cases, adjunctive therapy in severe cases, and prolongation of remission
3-4 g/day PO divided TID after meals; may start 1-2 g qDay
Rheumatoid Arthritis
Inadequate response or intolerance to salicylates or other NSAIDs
Enteric coated: 2-3 g/day PO divided TID after meals; may start 0.5-1 g qDay
Crohn Disease (Off-label)
3-6 g/day PO divided TID after meals
Administration
Take after meals
Administer in equally divided doses
Pediatric dosage forms and strengths
tablet
- 500mg
tablet, enteric coated (delayed release)
- 500 mg
Ulcerative Colitis
Mild to moderate cases, adjunctive therapy in severe cases, and prolongation of remission
<6 years old: Safety and efficacy not established
6 years or older
- Initial: 40-60 mg/kg/day PO divided q4-8hr after meals
- Maintenance: 30 mg/kg/day PO divided q6hr after meals
Juvenile Rheumatoid Arthritis
Polyarticular course with inadequate response to salicylates or other NSAIDs
<6 years old: Safety and efficacy not established
6 years or older: Gradually titrate at weekly intervals up to 30-50 mg/kg/day PO divided BID after meals; not to exceed 2 g/day
Azulfidine, Azulfidine EN (sulfasalazine) adverse (side) effects
>10%
Anorexia (~33%)
Headache (~33%)
Nausea (~33%)
Vomiting (~33%)
Gastric distress (~33%)
Apparently reversible oligospermia (~33%)
<1%
Skin rash
Pruritus
Urticaria
Fever
Heinz body anemia
Hemolytic anemia
Cyanosis
Postmarketing Reports
Blood dyscrasias: Pseudomononucleosis
Cardiac disorders: Myocarditis
Hepatobiliary disorders: reports of hepatotoxicity, including elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, hepatitis cholestatic, cholestasis and possible hepatocellular damage including liver necrosis and liver failure; some of these cases were fatal; 1 case of Kawasaki-like syndrome
Immune system disorders: Anaphylaxis
Metabolism and nutrition system disorders: Folate deficiency
Renal and urinary disorders: Nephrolithiasis
Respiratory, thoracic and mediastinal disorders: Oropharyngeal pain
Skin and subcutaneous tissue disorders: Angioedema, purpura
Vascular disorders: Pallor
Warnings
Contraindications
Hypersensitivity to sulfasalazine or its metabolites, to sulfonamides, or to salicylates
Intestinal or urinary tract obstruction
Porphyria
Cautions
Severe allergy or bronchial asthma
Blood dyscrasias; serious infections reported, including fatal sepsis and pneumonia; some infections were associated with agranulocytosis, neutropenia, or myelosuppression
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis
Severe hypersensitivity reported; may include internal organ involvement, such as hepatitis, nephritis, myocarditis, mononucleosis-like syndrome (ie, pseudomononucleosis), hematological abnormalities (including hematophagic histiocytosis), and/or pneumonitis including eosinophilic infiltration
Anemia
Gout
Hepatic/renal impairment
Hypochlorhydria
Hypoprothrombinemia
Thyrotoxicosis
Vitamin K deficiency
Ensure adequate hydration to prevent crystalluria
May cause orange discoloration of the urine or skin
Pregnancy and lactation
Pregnancy category: B; D if used for prolonged periods or near term; increased potential for kernicterus in the newborn
Oral sulfasalazine inhibits the absorption and metabolism of folic acid which may interfere with folic acid supplementation and protection from neural tube defects
Lactation: Excreted into human breast milk; caution with breastfeeding, some reports of bloody stools or diarrhea in human milk fed infants of mothers taking sulfasalazine
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Azulfidine, Azulfidine EN (sulfasalazine)
Mechanism of action
Sulfasalazine is a prodrug that is metabolized to its active components, sulfapyridine and 5-aminosalicylic acid (5-ASA; mesalamine); beneficial effects are predominantly from the anti-inflammatory properties of 5-ASA, which inhibits leukotriene synthesis and lipoxygenase
Absorption
Bioavailability: <15% of parent drug; 60% (sulfapyridine); 10-30% (5-ASA)
Peak plasma time: 6 hr; 10 hr (sulfapyridine and 5-ASA)
Peak plasma concentration: 6 mcg/mL
Distribution
Protein bound: >99% to albumin; 70% (sulfapyridine)
Vd: 7.5 L
Metabolism
Approximately 90% of sulfasalazine is converted by colon bacteria into its active components, sulfapyridine and mesalamine
Elimination
Half-life: 10.4-14.8 hr (sulfapyridine)
Renal clearance: 37%
Excretion: Urine (systematically absorbed sulfapyridine and 5-ASA); feces (majority of 5-ASA)
