UK Clinical Pharmacy Association

Azathioprine – as Immunosuppressant & DMARD

Issues for surgery

For suppression of transplant rejection – risk of rejection if omitted (see Transplant anti-rejection medication drug records).

For rheumatology, dermatology and inflammatory bowel disease (IBD) conditions – risk of perioperative flare in disease activity if omitted (see Further information).

Risk of post-operative infection if continued (see Further information).

Advice in the perioperative period

Elective surgery 

Rheumatology indications 
Continue.

Individualised decisions should be made for procedures considered to have a high risk of infection and should be balanced against the risk of disease flare (see Further information). The surgical team and the patient’s rheumatologist should be involved in the planning for elective surgery.

Steroid exposure should be minimised prior to surgical procedures, and increases in steroid dose to prevent adrenal insufficiency are not routinely required.

Other indications (e.g. dermatology indications, IBD indications)

The decision to continue should be made on an individual patient basis in conjunction with the surgical team and the patient’s specialist.

If the decision is made to stop azathioprine prior to surgery, it should be stopped 2 weeks pre-operatively. Withdrawal should be a gradual process performed under close monitoring owing to the risk of severe worsening of the condition if stopped suddenly.

Emergency surgery 

The patient should be closely monitored for signs of infection following emergency surgery.

Post-operative advice

For high-risk surgical procedures or where there are patient factors that may increase surgical infection risk, i.e. age and/or co-morbidity, consider withholding azathioprine in the immediate post-operative period.

If discontinued, restart once wound healing is satisfactory.

Where azathioprine is continued, close monitoring of renal function is important so that inadvertent drug accumulation does not occur.

Interactions with common anaesthetic agents

Non-depolarising neuromuscular blocking drugs (NMBDs)

Antagonism of the neuromuscular blocking effects of non-depolarising NMBDs has been reported with azathioprine, but other evidence suggests there is no clinically relevant interaction. Azathioprine probably inhibits phosphodiesterase activity at the motor nerve terminal resulting in release of acetylcholine. Any effects occurring seem likely to be managed by routine dose titration of the NMBDs and standard post-operative care.

Interactions with other common medicines used in the perioperative period

None.

Further information

Rheumatoid arthritis (RA) flare

RA flares develop in 10-20% of patients undergoing surgery and have a potential to impact adversely on post-operative recovery. In addition, active RA increases infection risk, further complicating decisions regarding DMARD interruption.

Infection risk

Some data suggests that not all DMARDs carry the same infection risk. There are limited data available regarding use of azathioprine and perioperative infection. A retrospective study of joint surgeries in rheumatoid arthritis patients found that two-thirds of patients receiving DMARDs, including azathioprine, demonstrated no association with perioperative infection.

References

Ledingham J, Gullick N, Irving K et al. Rheumatology Guidelines. The British Society of Rheumatology and British Health Professionals in Rheumatology. BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs. Rheumatology. 2017; 56(6):865-68 and online supplementary information www.rheumatology.oxfordjournals.org [Accessed on 2nd June 2019]

Summary of Product Characteristics – Azathioprine 50mg Tablets. Accord-UK Ltd. Accessed via www.medicines.org.uk 2/06/2019 [date of revision of the text October 2017]

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 2nd June 2019]

Azathioprine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 2nd June 2019]

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed on 2nd June 2019]