Intestinal anti-inflammatory (prodrug of 5-ASA + sulfapyridine)
Sulfasalazine is an anti-inflammatory medicine used to treat ulcerative colitis (active disease and maintenance of remission) and rheumatoid arthritis. It is composed of 5-aminosalicylic acid (5-ASA) linked to sulfapyridine; in the colon, gut bacteria split them and 5-ASA exerts the local anti-inflammatory effect. It should be used under medical supervision, with regular laboratory monitoring.
Also known as: Salazopyrin, Azulfidine, sulfasalazine
Sulfasalazine, like mesalazine, may inhibit TPMT and increase azathioprine toxicity.
Sulfasalazine (like mesalazine, its active metabolite) inhibits TPMT, the enzyme that inactivates 6-mercaptopurine — the active metabolite of azathioprine. TPMT inhibition shifts metabolism towards 6-thioguanine production, increasing the risk of myelosuppression (leucopenia, thrombocytopenia, anaemia). This interaction is classic in inflammatory bowel disease (IBD), where azathioprine is an immunomodulator and sulfasalazine is anti-inflammatory — both used simultaneously in moderate to severe IBD. The sulfasalazine label does not directly mention azathioprine, but the TPMT mechanism is established in the literature and documented in the azathioprine label (metabolism via TPMT). Monitor blood counts weekly during the first month, then monthly; reduce the azathioprine dose by 25–50% when starting the aminosalicylate; watch for signs of infection and anaemia.
Azathioprine + sulfasalazine: TPMT inhibition by sulfasalazine — risk of additive myelotoxicity. Monitor blood counts and reduce azathioprine dose.
TPMT inhibition by sulfasalazine with increased active azathioprine metabolites.
Periodic blood count.
Myelosuppression.
Monitor blood count and azathioprine dose.
DailyMed (FDA) — approved Sulfasalazine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d967092f-9685-446b-b7b8-17821e29417b ; approved Azathioprine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5116b22b-1460-5535-e063-6394a90acbe5 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sulfasalazine may reduce folic acid absorption and its effect, especially with long-term use.
The sulfasalazine label documents that "reduced absorption of folic acid and digoxin have been reported when these agents were administered concomitantly with sulfasalazine" and that "sulfasalazine inhibits the absorption and metabolism of folic acid, which may interfere with folic acid supplementation". The mechanism involves sulfapyridine (a sulfasalazine metabolite) which inhibits the reduced folate carrier (RFC) intestinal transporter. This interaction is particularly relevant in women of childbearing age with IBD (risk of neural tube defects) and in patients with megaloblastic anaemia or high-dose sulfasalazine. Supplement with folic acid 1 mg/day (or 5 mg if planning pregnancy) and monitor serum folate levels, haemoglobin and MCV; consider divided doses of sulfasalazine to minimise sulfapyridine exposure.
Folic acid + sulfasalazine: sulfasalazine reduces intestinal folate absorption (sulfapyridine). Supplement and monitor folate levels.
Inhibition of the intestinal folate transporter by sulfapyridine (a sulfasalazine metabolite).
Monitor blood count and signs of megaloblastic anaemia.
Megaloblastic anaemia.
Consider folic acid supplementation in patients on long-term therapy, especially with anaemia or pregnancy.
DailyMed (FDA) — approved Sulfasalazine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d967092f-9685-446b-b7b8-17821e29417b ; approved Folic acid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0baa10dd-6d1d-4946-8236-566451132da3 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Food may reduce sulfasalazine absorption but improves gastrointestinal tolerance.
Take with food to reduce gastric intolerance.
EMC-UK (MHRA) — approved Sulfasalazine SmPC: https://www.medicines.org.uk/emc/product/6686/smpc
Sulfasalazine and its metabolites may accumulate in renal impairment.
Use with caution and monitor renal function.
EMC-UK (MHRA) — approved Sulfasalazine SmPC: https://www.medicines.org.uk/emc/product/6686/smpc
Sulfasalazine contains sulfapyridine (a sulphonamide); it may cause severe allergic reactions.
Do not use in patients with sulphonamide allergy.
EMC-UK (MHRA) — approved Sulfasalazine SmPC: https://www.medicines.org.uk/emc/product/6686/smpc
Sulfasalazine interferes with folic acid; supplement folate during pregnancy and use with caution in the 3rd trimester.
Maintain folic acid supplementation (e.g. 1 mg/day) throughout pregnancy.
Compatible with breastfeeding; monitor the newborn (sulfapyridine theoretical concerns).
No specific additional contraception.
EMC-UK (MHRA) — approved Sulfasalazine SmPC: https://www.medicines.org.uk/emc/product/6686/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Intestinal anti-inflammatory (prodrug) for ulcerative colitis: the therapeutic action resides mainly in the 5-aminosalicylic acid (5-ASA) released in the colon. Frequent adverse reactions (anorexia, headache, nausea, reversible oligospermia) related to systemic sulfapyridine.
Sulfasalazine is cleaved by the colonic bacterial flora into sulfapyridine (carrier) and 5-ASA (active moiety). 5-ASA locally inhibits the COX and lipoxygenase pathways, reducing prostaglandins, leukotrienes and neutrophil chemotaxis/degranulation in the mucosa.
<15% of SSZ absorbed as the parent drug (serum peak ~6 µg/mL at 6 h, 3-12 h); sulfapyridine is well absorbed from the colon (bioavailability ~60%); 5-ASA is poorly absorbed (bioavailability 10-30%). Sulfapyridine and 5-ASA peaks ~10 h after dosing (transit to the colon).
Uncleaved SSZ is partially metabolised (acetylation); sulfapyridine is extensively metabolised in the liver (acetylation, hydroxylation with conjugation) — the acetylation phenotype influences toxicity; 5-ASA is N-acetylated in the intestinal epithelium and liver. Renal excretion of metabolites.
Half-life of IV sulfasalazine ~7.4 h; half-life of sulfapyridine ~10 h (acetylation dependent); renal excretion of sulfapyridine and metabolites, with faecal elimination of unabsorbed 5-ASA.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
