What is the recommended dose of Azathioprine (immunosuppressive medication) for treating ulcerative colitis?

Azathioprine Dosing in Ulcerative Colitis

The recommended dose of azathioprine for ulcerative colitis is 2-2.5 mg/kg/day orally, initiated during hospitalization for acute severe disease or as maintenance therapy for steroid-dependent patients. 1

Standard Dosing Protocol

Initial dosing should be 2-2.5 mg/kg/day, which represents the evidence-based standard across multiple high-quality guidelines. 1

• The 2019 British Society of Gastroenterology guidelines specifically recommend azathioprine 1.5-2.5 mg/kg/day for steroid-dependent ulcerative colitis 1
• The 2017 ECCO guidelines support thiopurines at standard dosing for patients with mild to moderate disease who have experienced early or frequent relapse on mesalamine, or who are steroid-dependent 1
• Mercaptopurine can be used as an alternative at 0.75-1.5 mg/kg/day 1

Clinical Context for Initiation

Azathioprine should be started in specific clinical scenarios:

• During hospitalization for acute severe ulcerative colitis (ASUC) after response to rescue therapy with infliximab or ciclosporin, initiated at day 7 in clinical responders 1
• For steroid-dependent disease, defined as inability to reduce prednisolone below 20 mg/day or relapse within 6 weeks of stopping steroids 1
• For patients requiring two or more steroid courses per year to maintain remission 1

Dose Escalation Strategy

For patients who fail to respond after at least 3 months at standard dosing (2 mg/kg/day), dose escalation may be attempted:

• Increase in increments of 0.5 mg/kg/day up to a maximum of 2.5 mg/kg/day 2
• Doses above 2.5 mg/kg/day are less likely to be efficacious and carry substantially higher risk of adverse reactions, particularly leukopenia 2
• Response to dose escalation is more likely when the maximum dose remains ≤2.5 mg/kg/day (55% response rate) compared to doses >2.5 mg/kg/day (17% response rate) 2

Comparative Efficacy Evidence

Azathioprine at 2 mg/kg/day demonstrates superior efficacy compared to 5-ASA:

• In steroid-dependent ulcerative colitis, azathioprine 2 mg/kg/day achieved clinical and endoscopic remission with steroid discontinuation in 53% of patients versus 21% with 5-ASA 3.2 g/day (OR 4.78,95% CI 1.57-14.5) 3
• In steroid-resistant and steroid-dependent disease, azathioprine reduced steroid consumption and clinical relapses by approximately 75% over 3 years 4
• Remission with complete steroid elimination was achieved in 64-69% of patients during the first three years of treatment 4

Monitoring Requirements

Essential monitoring includes:

• Full blood count within 4 weeks of starting therapy, then every 6-12 weeks to detect neutropenia 1
• Liver function tests at the same intervals 1
• Thiopurine methyltransferase (TPMT) activity measurement before treatment is debated but not universally recommended, as it does not identify all patients at risk of neutropenia 1

Common Pitfalls and Caveats

Critical safety considerations:

• Profound neutropenia and sepsis can develop rapidly despite monitoring, requiring vigilance 1
• Nausea is common, occurring in approximately 29% of patients (7 of 24 in one trial) and may require drug discontinuation 5
• Transient leukopenia, hepatotoxicity, and pancreatitis can occur 1, 6
• Long-term risks include elevated risk of lymphoproliferative disorders, non-melanoma skin cancers, myeloid disorders, and urinary tract cancers, requiring shared decision-making about duration of therapy 1

Timing considerations:

• Azathioprine has historically been considered to have a slow onset of action, but intravenous loading studies suggest clinical response may occur within 4 weeks 6
• When used as maintenance after calcineurin inhibitors (ciclosporin/tacrolimus), azathioprine should be introduced while the patient is still receiving the calcineurin inhibitor, serving as a "bridge" until therapeutic effects are achieved 1

Combination Therapy Context

When used with infliximab for acute severe ulcerative colitis:

• Azathioprine should be started at day 7 in patients with clinical response to infliximab 1
• Combination therapy with infliximab plus azathioprine demonstrates synergistic effects, raising infliximab levels and reducing antibody formation 1
• The UC SUCCESS study showed combination therapy achieved 40% remission at week 16 versus 22% with infliximab alone 1