Gastrointestinal/Thiopurine immunosuppressant

Thiopurines (azathioprine / mercaptopurine)

also: azathioprine · mercaptopurine · TPMT · IBD immunosuppression

Overview

Steroid-sparing immunosuppressants to MAINTAIN remission in IBD (and used in many autoimmune diseases + transplant). The TPMT check and the allopurinol interaction are heavily tested.

Mechanism

Azathioprine is metabolised to 6-mercaptopurine → purine antimetabolite → inhibits lymphocyte proliferation (immunosuppression). Metabolised by thiopurine methyltransferase (TPMT) — low TPMT activity → toxic accumulation.

Indications

IBD remission maintenance (Crohn's/UC)
Autoimmune disease (SLE, vasculitis, autoimmune hepatitis)
Transplant immunosuppression

The agents

Azathioprineprodrug of 6-MP

Check TPMT activity BEFORE starting (low → myelosuppression).

Mercaptopurine (6-MP)thiopurine

Also in ALL chemotherapy.

Adverse effects

Myelosuppression / bone marrow toxicityserious

Worse if low TPMT; monitor FBC.

Hepatotoxicity, pancreatitisserious

Increased infection + non-melanoma skin cancer / lymphoma riskcommon

Cautions & contraindications

Azathioprine + allopurinolall

Allopurinol (xanthine oxidase inhibitor) blocks an alternative metabolic route → toxic thiopurine accumulation → severe myelosuppression. Reduce dose drastically or avoid.

Absent/low TPMT activityall

Severe myelosuppression.

Interactions

Allopurinol/febuxostat (xanthine oxidase) → toxicity
Other myelosuppressants

Monitoring & kinetics

TPMT before starting; FBC + LFTs regularly

Oral. Slow onset (weeks–months) — a maintenance, not acute-flare, drug. IBD biologics (anti-TNF) cross-reference the dermatology systemic/biologic card.

Source: NICE — Crohn's / UC · BNF — Azathioprine