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.
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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.
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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.
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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.
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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.
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Risk of malignancy |
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