Azulfidine®(sulfasalazine)

INDICATIONS AND USAGE AZULFIDINE Tablets are indicated: in the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis; and for the prolongation of the remission period between acute attacks of ulcerative colitis.

CONTRAINDICATIONS AZULFIDINE Tablets are contraindicated in: Patients with intestinal or urinary obstruction, Patients with porphyria as sulfonamides have been reported to precipitate an acute attack, Patients hypersensitive to sulfasalazine, its metabolites, sulfonamides, or salicylates.

WARNINGS Hepatic, Renal, and Hematologic Toxicity or Other Conditions Only after critical appraisal should AZULFIDINE Tablets be given to patients with hepatic or renal damage or blood dyscrasias. Deaths associated with the administration of sulfasalazine have been reported from hypersensitivity reactions, agranulocytosis, aplastic anemia, other blood dyscrasias, renal and liver damage, irreversible neuromuscular and central nervous system changes, and fibrosing alveolitis. The presence of clinical signs such as sore throat, fever, pallor, purpura, or jaundice may be indications of serious blood disorders or hepatotoxicity. Complete blood counts, as well as urinalysis with careful microscopic examination, should be done frequently in patients receiving AZULFIDINE. AZULFIDINE should be discontinued and the patient evaluated if significant hematological or hepatic toxicity occurs.• Oligospermia and Infertility: Oligospermia and infertility have been observed in men treated with sulfasalazine; however, withdrawal of the drug appears to reverse these effects.• Serious Infections: Serious and fatal infections, including sepsis and pneumonia, have been reported. Some infections were associated with agranulocytosis, neutropenia, or myelosuppression. Discontinue AZULFIDINE if a patient develops a serious infection.• Hypersensitivity Reactions: Severe hypersensitivity reactions may include internal organ involvement, such as hepatitis, nephritis, myocarditis, mononucleosis-like syndrome, hematological abnormalities, and/or pneumonitis.• Severe Cutaneous Adverse Reactions: DRESS, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), exfoliative dermatitis, and acute generalized exanthematous pustulosis (AGEP) have been reported.• PRECAUTIONS General: AZULFIDINE should be given with caution to patients with severe allergy or bronchial asthma. Adequate fluid intake must be maintained to prevent crystalluria and stone formation. Patients with glucose-6-phosphate dehydrogenase deficiency should be observed closely for signs of hemolytic anemia.• Information for Patients: Patients should be informed of the possibility of adverse reactions and of the need for careful medical supervision. Sulfasalazine may produce an orange-yellow discoloration of the urine or skin.• Laboratory Tests: Complete blood counts and liver function tests should be performed before starting AZULFIDINE and every second week during the first three months of therapy.• Drug Interactions: Reduced absorption of folic acid and digoxin have been reported when administered concomitantly with sulfasalazine.• Carcinogenesis: Two-year oral carcinogenicity studies showed statistically significant increase in urinary bladder transitional cell papillomas in male rats, renal pelvic/ureter tumors in female rats, and hepatocellular adenoma or carcinoma in mice at highest dose.• Pregnancy: There are no adequate and well-controlled studies in pregnant women. Sulfasalazine and its metabolites pass through the placenta and are present in human milk.• Nursing Mothers: Caution should be exercised when AZULFIDINE is administered to a nursing mother. Reports of bloody stools or diarrhea in breastfed infants.• Pediatric Use: Safety and effectiveness in pediatric patients below the age of 2 years have not been established.

ADVERSE REACTIONS The most common adverse reactions associated with sulfasalazine are anorexia, headache, nausea, vomiting, gastric distress, and apparently reversible oligospermia. These occur in about one-third of the patients.• Less frequent adverse reactions include: pruritus, urticaria, rash, fever, Heinz body anemia, hemolytic anemia, and cyanosis.• Blood dyscrasias: aplastic anemia, agranulocytosis, leukopenia, megaloblastic anemia, purpura, thrombocytopenia, methemoglobinemia, myelodysplastic syndrome.• Hypersensitivity reactions: erythema multiforme, SJS/TEN, DRESS, anaphylaxis, serum sickness syndrome, interstitial lung disease, vasculitis, fibrosing alveolitis, pericarditis, allergic myocarditis, lupus erythematosus-like syndrome, hepatitis and hepatic necrosis, fulminant hepatitis.• Gastrointestinal reactions: hepatitis, hepatic failure, pancreatitis, bloody diarrhea, impaired folic acid absorption, stomatitis.• Central Nervous System reactions: transverse myelitis, convulsions, meningitis, peripheral neuropathy, mental depression, vertigo, hearing loss, hallucinations.• Renal reactions: toxic nephrosis, nephritis, nephrotic syndrome, crystalluria.• Other reactions: urine discoloration and skin discoloration.• Postmarketing Reports: myocarditis, hepatotoxicity, folate deficiency, nephrolithiasis, angioedema, AGEP.

DESCRIPTION AZULFIDINE Tablets contain sulfasalazine, 500 mg, for oral administration. Therapeutic Classification: Anti-inflammatory agent. Chemical Designation: 5-([p-(2-pyridylsulfamoyl)phenyl]azo) salicylic acid. Molecular Formula: C18H14N4O5S. Inactive ingredients: magnesium stearate, povidone, silica (colloidal anhydrous), starch (pregelatinized).