Saara Rawn MD/PhD, Raj Carmona MBBS FRCPC

INDICATIONS (including off-label uses)

  • Rheumatoid arthritis, Psoriatic arthritis, Juvenile Idiopathic Arthritis.
  • Peripheral arthritis in patients with Spondyloarthritis (eg. ankylosing spondylitis). Inflammatory Bowel Disease (IBD)-related arthritis.
  • Ulcerative colitis

ADULT DOSING

  • Starting dose of 500 mg PO BID for 1 week, increasing by 500 mg weekly to maintenance 1000 mg PO BID
  • In IBD, doses of up to 4-6 g daily are used in 2-3 divided doses.

DOSE ADJUSTMENT

Hepatic Impairment

  • No dosage adjustments; use with caution.

Renal Impairment  

  • CrCl >50: No initial dose adjustment.
  • CrCl 10-50: 50% initial dose reduction (500 mg BID)
  • CrCl <10: 75% dose reduction (500 mg q daily)

MONITORING

  • Baseline:  CBC, AST, ALT, ALP, serum creatinine
  • Monthly for first 3-6 months: CBC, AST, ALT, then every 2-3 months thereafter.

CONTRAINDICATIONS

  • Hypersensitivity to salicylates, sulfonamides, or sulfasalazine. Urinary tract or intestinal obstruction. Porphyria.

COMMON SIDE EFFECTS AND ADVERSE REACTIONS

  • Sulfasalazine is considered to be generally safer than other DMARDS such as MTX and Leflunomide.  It is one of the “go to” DMARDs when a patient is considering pregnancy.
  • GI side-effects are most common: Nausea (RA 19%), dyspepsia (RA 13%), anorexia, gastric distress, vomiting
  • Central nervous system: Headache (RA 9%), dizziness
  • Dermatologic: Skin rash (RA 13%), pruritus, urticaria
  • Genitourinary: Oligospermia (reversible)
  • Hematologic: can cause agranulocytosis.  Leukopenia (RA 3%), thrombocytopenia (RA 1%), Heinz body anemia, hemolytic anemia
  • Hepatic: Abnormal hepatic function tests (RA 4%)

PREGNANCY AND LACTATION

  • Compared to background rates, sulfasalazine does not cause increases in miscarriage or fetal abnormalities.
  • If sulfasalazine is required by the mother, she may breastfeed, but careful observation of breastfed infants for diarrhea is advised.  In the newborn, it may cause kernicterus. If there is a concern, consultation with a specialist is recommended.

MECHANISM OF ACTION

  • In rheumatoid arthritis, sulfapyridine is traditionally thought to be the active moiety, but some studies show that the parent molecule (salicylic acid and sulfapyridine joined by an azo bond) may also have some independent activity. The mechanism of action in RA has not been identified. Some theories include: B cell activation inhibition, reduces interleukin-6 production, inhibits nuclear factor-kappa B (NFkB), inhibits TNF factor alpha expression of macrophages.

SUMMARY OF EVIDENCE (in development)

  • Weinblatt ME, et al. 1999. “Sulfasalazine treatment for rheumatoid arthritis: a meta-analysis of 15 randomized trials.” J Rheumatol 26:2123.
  • Fleischmann R et al. 2017 “Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis” RMD Open Jan 3;3(1):e000371.
  • Clegg DO et al. 1996. “Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A department of Veterans Affairs Cooperative Study.” Arthritis Rheum 29(12):2013.