sulfasalazine (Rx)

>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

Contraindications

Hypersensitivity to sulfasalazine or its metabolites, to sulfonamides, or to salicylates

Intestinal or urinary tract obstruction

Porphyria

Cautions

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue at first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity

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; if signs or symptoms are present, the patient should be evaluated immediately; Sulfasalazine drug should be discontinued if an alternative etiology for signs or symptoms cannot be established

Administer tablets with caution to patients with severe allergy or bronchial asthma; adequate fluid intake must be maintained in order to prevent crystalluria and stone formation; patients with glucose-6 phosphate dehydrogenase deficiency should be observed closely for signs of hemolytic anemia; reaction is frequently dose-related; if toxic or hypersensitivity reactions occur, the drug should be discontinued immediately

Oligospermia and infertility reported; however, withdrawal of drug appears to reverse these effects

Infections

• Blood dyscrasias; serious infections reported, including fatal sepsis and pneumonia
• Some infections were associated with agranulocytosis, neutropenia, or myelosuppression; discontinue therapy if patient develops a serious infection
• Closely monitor patients for the development of signs and symptoms of infection during and after treatment
• Frequently perform complete blood counts, as well as urinalysis with careful microscopic examination; discontinue treatment while awaiting results of blood tests;

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.

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)