Table 1

Recommendations for the safe use of azathioprine in neurology patients

Recommended actions and advice
Dose and efficacy of azathioprine
  • Check TMPT levels before starting azathioprine—complete TMPT deficiency; do not use azathioprine, borderline levels; administer reduced dose and monitor carefully.

  • Warn patient that azathioprine may take as long as a year or longer to take full effect.

Blood monitoring
  • Carry out fortnightly blood tests (full blood count, urea and electrolytes, liver function tests) when starting or changing azathioprine dose. Once on a stable dose for 6 weeks, reduce the frequency to monthly for 3 months and then every 12 weeks while continuing azathioprine.

  • Weekly initial blood monitoring is reasonable for higher risk patients.

  • Warn patients to report jaundice or unexplained bruising.

  • Use MCV and lymphocyte count to gauge azathioprine compliance.

  • Consider azathioprine metabolite testing in higher risk patients or those who are poorly responsive to therapy; check 6-MMP and 6-TG levels and ratio at 4 weeks after starting or changing dose of azathioprine, then 12–16 weeks after starting, and then annually:

    • Very low or absent 6-TG and 6-MMP levels: likely poor compliance or rarely poor absorption—educate patient.

    • Low 6-TG (<235 pmol/8×108) and low 6-MMP levels: subtherapeutic dosing—increase azathioprine dose and recheck levels.

    • Low 6-TG (<235 pmol/8×108) and high 6-MMP levels (or 6-MMP:6-TG ratio >11): hypermethylation—split dose or reduce azathioprine dose and add allopurinol (see text) and recheck.

    • Therapeutic 6-TG (235–450 pmol/8×108) levels and 6-MMP levels<5700 pmol/8×108: therapeutic—continue azathioprine dose but if no clinical response then likely class resistance and consider changing to alternative immunosuppressive.

    • High 6-TG (>450 pmol/8×108) and 6-MMP (>5700 pmol/8×108) levels: supratherapeutic—reduce azathioprine dose and recheck levels.

  • Establish local shared-care protocols for the safe administration of azathioprine in the community.

Pregnancy and breast-feeding
  • It is possible to use azathioprine during pregnancy but discuss risk and benefits with patient.

  • Azathioprine is considered safe for breast-feeding mothers.

  • Azathioprine should not be started de novo in pregnant women.

  • Seek specialist advice and enlist the aid of maternal medicine units.

Drug interactions
  • Check interactions between azathioprine and other medications in the BNF.

  • Important interactions to remember are with allopurinol (reduce azathioprine dose), ACE inhibitors and warfarin.

Risk of infection
  • Check VZV exposure or serology and hepatitis, HIV and EBV status before starting azathioprine; seek specialist advice if evidence of infection.

  • Give the pneumococcal vaccine before starting azathioprine and the influenza vaccine annually.

  • Advise patients to inform pharmacy staff of azathioprine use prior to vaccination.

Risk of malignancy
  • Inform patients that the risk of malignancy with azathioprine is considered low in neurology patients but photoprotection with UVA blockers is recommended.

  • ACE, ACE converting enzyme; BNF, British National Formulary; EBV, Epstein Barr virus; MCV, mean corpuscular volume; 6-MMP, 6-methylmercaptopurine; 6-TG, 6-thioguanine;TPMT, thiopurine methyltransferase; UVA, ultraviolet A; VZV, varicella zoster virus.