UK Clinical Pharmacy Association

Sulfasalazine

Issues for surgery

For rheumatology 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 

IBD indications 

Continue.

Rheumatology indications

Continue.

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

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 specialist should be involved in the planning for elective surgery.

If the decision is made to stop sulfasalazine prior to surgery, it should be stopped 2 weeks pre-operatively.

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 sulfasalazine in the immediate post-operative period.

If discontinued, restart once wound healing is satisfactory.

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

Ensure that the correct formulation of sulfasalazine is prescribed – see Further information.

Interactions with common anaesthetic agents

Local anaesthetics

The manufacturers suggest that the effects of topical prilocaine/lidocaine may be additive with drugs that can cause methaemoglobinaemia – they name sulfasalazine – use with caution.

Interactions with other common medicines used in the perioperative period

Antimicrobials

Since the effects of sulfasalazine depend on release of the active metabolite, 5-aminosalicylic acid, by bacterial metabolism in the gut any drug that reduces the intestinal microflora, such as antimicrobials, may reduce the production of the active metabolite. However, a decrease in clinical effect does not seem to have been seen.

Hepatotoxicity

Also see Paracetamol below.
There is an increased risk of hepatotoxicity when sulphasalazine is used in combination with the following:

  • clavulanic acid (found in co-amoxiclav)
  • doxycycline
  • flucloxacillin

Myelosuppression

Concomitant use of sulfasalazine with the following can increase the risk of myelosuppression:

  • co-trimoxazole
  • linezolid
  • trimethoprim

Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring of LFTs and/or haematological abnormalities. Consult current product literature.

Paracetamol

Both sulfasalazine and paracetamol increase the risk of hepatotoxicity. Whilst single perioperative doses of paracetamol should not pose a problem, continued post-operative treatment may require close monitoring of LFTs.

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 sulfasalazine and perioperative infection. A retrospective study found sulfasalazine was associated with a lower risk of perioperative infection compared to other DMARD.

Crystalluria and kidney stone formation

Sulfasalazine causes crystalluria and kidney stone formation, hence adequate fluid intake should be ensured during treatment.

Prescribing information

There are different licensed preparations of sulfasalazine and it is important to ensure that the correct product is prescribed for the correct indication. Whilst all products are licensed for use in IBD indications, only sulfasalazine enteric-coated tablets (Salazopyrin® EN-Tabs) are licensed for use in rheumatology.

References

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 3rd June 2019]

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

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 3rd June 2019]

Krause ML and Matteson EL. Perioperative management of the patient with rheumatoid arthritis. World J Orthop. 2014;5(3):283-291.

Sulfasalazine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 18th May 2019]

Summary of Product Characteristics – Salazopyrin® EN-Tabs 500mg Tablets. Pfizer Limited. Accessed via www.medicines.org.uk 8/06/2019 [date of revision of the text February 2014]