Issues for surgery
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
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.
Steroid exposure should be minimised prior to surgical procedures and increases in steroid dose to prevent adrenal insufficiency are not routinely required.
NB: The half-life of leflunomide is approximately 2 weeks (anything from 1 – 4 weeks); a prolonged period (five half-lives) off the drug would be required (or a washout procedure undertaken) to eliminate exposure. For specific information on the washout procedure, consult current product literature.
Emergency surgery
The patient should be closely monitored for signs of infection following emergency surgery.
Post-operative advice
Where continued pre-operatively – due to it’s long half-life (approx. 2 weeks), withholding doses of leflunomide in the immediate post-operative period would have little effect on reducing the risk of infection. A washout procedure may be necessary in the event of a severe, uncontrolled infection. A prolonged period (five half-lives) off the drug would be required to eliminate exposure. For specific information on the washout procedure, see current product information.
If discontinued, restart once wound healing is satisfactory.
Where leflunomide is continued, close monitoring of renal function is important so that inadvertent drug accumulation does not occur.
Interactions with common anaesthetic agents
Ropivacaine
Leflunomide is predicted to decrease the exposure to ropivacaine – be alert for reduced response to ropivacaine.
Interactions with other common medicines used in the perioperative period
Antimicrobials
Leflunomide is predicted to increase the exposure to benzylpenicillin and ciprofloxacin – manufacturer advises caution. Monitor for benzylpenicillin/ciprofloxacin adverse effects and adjust the dose as necessary.
Hepatotoxicity
See also Paracetamol below.
There is an increased risk of hepatotoxicity when leflunomide is used in combination with the following:
- clavulanic acid (found in co-amoxiclav)
- doxycycline
- flucloxacillin
Myelosuppression
Concomitant use of leflunomide 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 suggest that not all DMARDs carry equivalent infection risk profiles. Information regarding perioperative use of leflunomide in relation to post-operative complications is conflicting.
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 23rd June 2019]
Summary of Product Characteristics – Leflunomide 20mg Film-coated Tablets. Sandoz Limited. Accessed via www.medicines.org.uk 23/06/2019 [date of revision of the text January 2018]
Leflunomide. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 23rd June 2019]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 23rd June 2019]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 23rd June 2019]