Before starting

Required

• Baseline
  • ALT or AST
  • Blood pressure
  • Calculated glomerular filtration rate or Serum creatinine (for creatinine clearance)
  • Cervical screening · check this is up to date
  • Full blood count
  • Height
  • Liver function tests
  • TPMT assay
  • Weight
  • Vaccination status
  • Varicella Zoster Virus Immunity · if no history of chicken pox, shingles or varicella vaccination

Interpreting TPMT assay

Patients with absent TPMT activity should not receive thiopurine drugs.

Patients with reduced TPMT activity may be treated under specialist supervision.

Patients with intermediate (heterozygous) activity should receive a lower maintenance dose.

The British Society of Gastroenterology advises the following dosing schedule based on TPMT:

• Normal TPMT = 2mg/kg
• Low TPMT = 1mg/kg
• Very low TPMT = avoid

Vaccination status

Consider vaccination against pneumococcus and influenza prior to starting treatment.

Consider in patients at risk of infection

• Baseline
  • Hepatitis B
  • Hepatitis C
  • HIV

After started or dose changed

Dermatology patients

• More frequently than every 3 months
  • Full blood count
  • Liver function tests

Gastroenterology patients

• 14 days after starting; then at 4, 8, and 12 weeks; then 3 monthly
  • Full blood count
  • Full blood count
  • Serum creatinine (for creatinine clearance) or Calculated glomerular filtration rate
  • Liver function tests

Rheumatology patients

• Every 2 weeks until on stable dose for 6 weeks, then monthly
  • Full blood count
  • Serum creatinine (for creatinine clearance) or Calculated glomerular filtration rate
  • Albumin
  • ALT or AST

Patients at higher risk of toxicity

More frequent monitoring is appropriate in patients at higher risk of toxicity

Consider

• At week 4 and 16
  • Methylmercaptopurine to Thioguanine ratio

Ongoing once stable

Required

• Every 3 months
  • Albumin
  • ALT or AST
  • Full blood count
  • Serum creatinine (for creatinine clearance) or Calculated glomerular filtration rate
  • Liver function tests
  • Full blood count

Consider

• Annually
  • Methylmercaptopurine to Thioguanine ratio
• Periodically
  • Skin examination

Abnormal results

Monitor trends

Be aware of trends in results (e.g. gradual decreases in white blood cells or albumin, or increasing liver enzymes). A downward trend of FBC and neutrophil count or an upward trend in liver transaminases could be a sign of toxicity, even if the absolute levels are normal.

Respond to absolute levels

Consider stopping treatment and contacting a specialist any of the following develop:

Full blood count

• WCC less than 3.5 x 10⁹/L,
• Neutrophils less than 1.6 x 10⁹/L
• Unexplained eosinophilia more than 0.5x 10⁹/L
• Platelets less than 140 x 10⁹/L
• Unexplained fall in serum albumin less than 30g/L
• MCV greater than 105f/L (check B12, folate, thyroid-stimulating hormone levels – if abnormal treat, if normal discuss with specialist team)

Liver function

• AST and/or ALT greater than 100units/mL

Renal function

• Creatinine increase greater than 30% above baseline over 12 months
• Calculated GFR less than 60ml/min/1.73m² (repeat in 1 week, if still more than 30% from baseline, withhold and discuss with specialist team)

Notes

Vaccine use

Live vaccinations should not normally be given until at least three months after stopping immunosuppressive therapy.

However, long-term low-dose non-biological DMARDs (e.g. azathioprine in doses of or less than 3mg/kg/day) may not be immunosuppressive and so patients may receive live vaccines. Only consider vaccination with live vaccines for those on low-level immunosuppression after careful consideration of risks and benefits.

Advice to patients

Advise patients to seek urgent medical attention if they develop symptoms suggestive of:

• bone marrow suppression
• liver impairment
• specifically high fever or severe flu-like illness
• unexplained bleeding or bruising
• new onset jaundice

Advise patients to use sunscreens, wear protective clothing, and reduce sunlight exposure.

During serious infections

During a serious infection, azathioprine should be temporarily discontinued until the patient has recovered from the infection.

Bibliography

• Ledingham J, Gullick N, Irving K et al. BSR and BHPR Standards, Guidelines and Audit Working Group, BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs, Rheumatology, Volume 56, Issue 6, June 2017, Pages 865–868 [cited June 2020)
• Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press [cited 31/05/2020]
• Lamb CA, Kennedy NA, Raine T et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s107 [cited 30/07/2020]
• Meggitt SJ, Anstey AV, Mohd Mustapa MF et al. British Association of Dermatologists’ guidelines for the safe and effective prescribing of azathioprine 2011. Br J Dermatol 2011; 165; 711-734. Published October 2011 [cited 30/07/2020]
• National Institute for Health and Care Excellence (NICE). Crohn’s disease: management [NG129]. May 2019 [cited 31/07/2020]
• National Institute for Health and Care Excellence (NICE). Hepatitis B and C testing: people at risk of infection [PH43]. Dec 2012 [updated Mar 2013; cited June2020]
• National Institute for Health and Care Excellence (NICE). Ulcerative colitis: management [NG130]. May 2019 [cited 31/07/2020]
• Warner B, Johnston E, Arenas-Hernandez M et al. A practical guide to thiopurine prescribing and monitoring in IBD. Frontline Gastroenterology 2016;0:1–6. [cited 30/07/2020]
• NICE Clinical Knowledge Summaries (CKS). Crohn’s Disease. Updated Apr 2020 [cited 10/05/2020]
• Public Health England. Contraindications and special considerations: the green book, chapter 6. Published 20/03/2013. Last updated 26/10/2017 [cited 10/05/2020]
• Personal communication. Specialists at Guys and St Thomas’ NHS Foundation Trust. 11/05/2020

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