Sulfasalazine

Fatalities associated with severe reactions, including agranulocytosis, aplastic anemia, and other blood dyscrasias, have occurred; discontinue use at first sign of rash or signs of serious adverse reactions. The presence of clinical signs such as sore throat, fever, pallor, or purpura may be indicative of a serious blood disorder. Use with extreme caution in patients with blood dyscrasias; monitor CBC frequently.

Deaths from irreversible neuromuscular and CNS changes have been reported.

Severe skin reactions (some fatal), including Stevens-Johnson syndrome (SJS), exfoliative dermatitis, and toxic epidermal necrolysis (TEN), have occurred with sulfonamides (including sulfasalazine), most commonly during the first month of treatment; discontinue use at first sign of skin rash, mucosal lesions, or any other sign of dermatologic toxicity.

Deaths from fibrosing alveolitis have been reported.

May decrease folic acid absorption.

Nausea, vomiting, and abdominal discomfort commonly occur; titration of dose and/or using the enteric coated formulation may decrease GI adverse effects.

Fatalities associated with hepatic damage have occurred; discontinue use at first sign of jaundice or hepatotoxicity.

Severe and life-threatening reactions, including drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, have been reported. Fever or lymphadenopathy may be present prior to rash development. Other severe hypersensitivity reactions may include internal organ involvement, such as hepatitis, nephritis, myocarditis, mononucleosis-like syndrome, hematologic abnormalities (including hematophagic histiocytosis), and/or pneumonitis including eosinophilic infiltration. Discontinue treatment for severe reactions and evaluate promptly.

Serious infections (some fatal), including sepsis and pneumonia, have been reported. Infections may be associated with agranulocytosis, neutropenia, or myelosuppression. Monitor for signs/symptoms of infection during and after sulfasalazine therapy and promptly evaluate if infection occurs; discontinue therapy for serious infections. Use cautiously in patients with a history of recurring or chronic infections or with underlying conditions or concomitant therapy which may predispose them to infectious complications.

In males, oligospermia (rare) and infertility have been reported; usually reverses upon discontinuation.

Traditionally, concerns for cross-reactivity have extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides and antibiotic sulfonamides. A nonantibiotic sulfonamide compound which contains the arylamine structure and therefore may cross-react with antibiotic sulfonamides is sulfasalazine (Zawodniak 2010). T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes. Disease-related concerns:

Use with caution in patients with severe allergies or bronchial asthma.

Use with caution in patients with G6PD deficiency; hemolytic anemia may occur (dose related).

Use with extreme caution in patients with impaired hepatic function.

Use with extreme caution in patients with renal impairment. Maintain adequate hydration to prevent crystalluria and stone formation. Special populations:

Patients classified as slow acetylators may be at increased risk for adverse reactions due to a prolonged half-life of sulfapyrazine (metabolite of sulfasalazine). Dosage form specific issues:

Delayed release: Use in patients with ulcerative colitis who cannot take uncoated sulfasalazine tablets because of GI intolerance, and in whom there is evidence that this intolerance is not primarily the result of high blood levels of sulfapyridine and its metabolites (eg, patients experiencing nausea and vomiting with the first few doses of the drug, patients in whom a reduction in dosage does not alleviate the adverse GI effects).

Discontinue if tablets are noted to pass without disintegrating. Other warnings/precautions:

May cause skin and urine discoloration (orange/yellow).