sulfasalazine
Azulfidine, Azulfidine EN-tabs

Available forms
Available by prescription only
Suspension: 250 mg/5 ml
Tablets (with or without enteric coating): 500 mg

Indications and dosages
 Mild to moderate ulcerative colitis, adjunctive therapy in severe ulcerative colitis. Adults: Initially, 3 to 4 g P.O. daily in evenly divided doses. Maintenance dosage is 2 g P.O. daily in divided doses q 6 hours. May need to start with 1 to 2 g initially, with a gradual increase in dose to minimize adverse reactions.
Children older than age 2: Initially, 40 to 60 mg/kg P.O. daily, divided into three to six doses; then 30 mg/kg daily in four doses. Maximum, 2 g daily. May need to start at lower dose if GI intolerance occurs.
 Rheumatoid arthritis (enteric-coated tablets). Adults: 2 g daily P.O. in two evenly divided doses. Start at lower dosage to minimize adverse GI effects.
 Patients with polyarticular-course juvenile rheumatoid arthritis who have responded inadequately to salicylates or other NSAIDs. Children age 6 and older: 30 to 50 mg/kg P.O. daily in two divided doses. Maximum dose is 2 g daily. To reduce possible GI intolerance, start with one-quarter to one-third of planned maintenance dose and increase weekly until reaching maintenance dose at 1 month.

Pharmacodynamics
Antibacterial action: Exact mechanism of action of drug in ulcerative colitis is unknown; it’s believed to be a prodrug metabolized by intestinal flora in the colon. One metabolite (5-aminosalicylic acid or mesalamine) is responsible for the anti-inflammatory effect; the other metabolite (sulfapyridine) may be responsible for antibacterial action and for some adverse effects.

Pharmacokinetics
Absorption: Absorbed poorly from the GI tract after oral administration; 70% to 90% is transported to the colon where intestinal flora metabolize drug to its active ingredients-sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory)-which exert their effects locally. Sulfapyridine is absorbed from the colon, but only a small portion of 5-aminosalicylic acid is absorbed.
Distribution: Human data on sulfasalazine distribution are lacking; animal studies have identified drug and metabolites in serous fluid, liver, and intestinal walls. Parent drug and both metabolites cross the placental barrier.
Metabolism: Cleaved by intestinal flora in the colon.
Excretion: Systemically absorbed sulfasalazine is excreted chiefly in urine; some parent drug and metabolites appear in breast milk. Plasma half-life is about 6 to 8 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to salicylates or sulfonamides or to other drugs containing sulfur, such as thiazides, furosemide, or oral sulfonylureas. Also contraindicated in pregnant women, breast-feeding women, infants and children younger than age 2, and patients with porphyria or severe renal or hepatic dysfunction. Sulfasalazine is also contraindicated in patients with intestinal or urinary tract obstructions because of the risk of local GI irritation and crystalluria.
  Use cautiously in patients with mild to moderate renal or hepatic dysfunction, severe allergies, asthma, blood dyscrasia, or G6PD deficiency.

Interactions
Drug-drug. Antacids: Increases systemic absorption and hazard of toxicity. Monitor patient closely.
Antibiotics that alter intestinal flora: May interfere with conversion of sulfasalazine to sulfapyridine and 5-aminosalicylic acid, decreasing its effectiveness. Monitor patient closely.
Digoxin, folic acid: Sulfasalazine may reduce GI absorption of these drugs. Monitor patient closely.
Oral anticoagulants: Enhances anticoagulant effects. Monitor patient for bleeding.
Oral antidiabetics including sulfonylureas: Enhances hypoglycemic effects. Monitor blood glucose levels.
Urine acidifying agents, such as ammonium chloride and ascorbic acid: Increases risk of crystalluria. Monitor patient closely.
Drug-lifestyle. Sun exposure: May cause photosensitivity. Advise patient to take precautions.

Adverse reactions
CNS: headache, depression, seizures, hallucinations, tinnitus.
GI: nausea, vomiting, diarrhea, abdominal pain, anorexia, stomatitis.
GU: toxic nephrosis with oliguria and anuria, crystalluria, hematuria, oligospermia, infertility.
Hematologic: agranulocytosis, aplastic anemia, megaloblastic anemia, thrombocytopenia, leukopenia, hemolytic anemia.
Hepatic: jaundice.
Skin: erythema multiforme (Stevens-Johnson syndrome), generalized skin eruption, epidermal necrolysis, exfoliative dermatitis, photosensitivity, urticaria, pruritus.
Other: hypersensitivity reactions, serum sickness, drug fever, anaphylaxis, bacterial and fungal superinfection.

Effects on lab test results
• May increase AST and ALT levels.
• May decrease hemoglobin and granulocyte, platelet, and WBC counts.

Overdose and treatment
Signs and symptoms of overdose include dizziness, drowsiness, headache, unconsciousness, anorexia, abdominal pain, nausea, and vomiting. More severe complications, including hemolytic anemia, agranulocytosis, dermatitis, acidosis, sensitivity reactions, and jaundice, may be fatal.
 Treat by gastric lavage, if ingestion has occurred within the preceding 4 hours, followed by correcting acidosis, encouraging patient to drink, and alkalinizing urine to enhance solubility and excretion. If kidney function is normal, encourage patient to drink. If anuria is present, restrict fluids and salt, and treat appropriately. Catheterization of the ureters may be indicated for complete renal blockage by crystals.

Special considerations
• Most adverse effects involve the GI tract; minimize reactions and facilitate absorption by spacing doses evenly and giving drug after food.
• Drug colors urine and it may color skin orange-yellow.
• Don’t give antacids with enteric-coated sulfasalazine; they may alter absorption.
• Sulfasalazine alters results of urine glucose tests using cupric sulfate (Benedict’s reagent or Clinitest).
• Discontinue drug if signs of toxicity or hypersensitivity occur; if hematologic abnormalities are accompanied by sore throat, pallor, fever, jaundice, purpura, or weakness; if crystalluria is accompanied by renal colic, hematuria, oliguria, proteinuria, urinary obstruction, urolithiasis, increased BUN levels, or anuria; if severe diarrhea indicates pseudomembranous colitis; or if severe nausea, vomiting, or diarrhea persists.
• Perform CBC, including differential white cell count, and liver function tests before starting therapy and every second week during the first 3 months of therapy. During the second 3 months, perform the same tests once monthly and, thereafter, once every 3 months and as clinically indicated. Also perform urinalysis and an assessment of renal function periodically during treatment.
• Serum sulfapyridine level determinations may be useful because levels above 50 mcg/ml appear to be linked to an increased risk of adverse reactions.
Breast-feeding patients
• Drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Contraindicated in patients younger than age 2 months.

Patient education
• Tell patient that sulfasalazine normally turns urine orange-yellow. Warn that skin may also turn orange-yellow and that drug may permanently stain soft contact lenses yellow.
• Advise patient to take drug after meals to reduce GI distress and to facilitate passage into intestines.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use