Issues for surgery
For rheumatology and dermatology conditions – risk of perioperative flare in disease activity if omitted (see Further information).
Risk of post-operative infection if continued (see Further information).
Potential risk of QT-interval prolongation if continued (see Interactions with common anaesthetic agents and Interactions with other common medicines used in the perioperative period)
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.
Steroid exposure should be minimised prior to surgical procedures and increases in steroid dose to prevent adrenal insufficiency are not routinely required.
Dermatology 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 hydroxychloroquine 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
If discontinued, restart once wound healing is satisfactory.
Where hydroxychloroquine is continued, close monitoring of renal function is important so that inadvertent drug accumulation does not occur.
Interactions with common anaesthetic agents
Neuromuscular blocking drugs (NMBDs)
A report described respiratory insufficiency during the recovery period following surgery, which was attributable to the additive effects of chloroquine with NMBDs. Hydroxychloroquine would be expected to interact similarly. Monitor the outcome of concurrent use, expecting an alteration in recovery time.
QT-interval prolongation
Also see Interactions with other common medicines used in the perioperative period.
Hydroxychloroquine may increase the QT-interval, although there is no evidence of such an effect. Some consider concurrent use with other drugs that can prolong the QT-interval might increase the risk.
Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include:
- desflurane, isoflurane, sevoflurane
- thiopental (theoretical)
The possibility of QT-interval prolongation with concomitant administration of hydroxychloroquine and the above listed medications is only theoretical; however, it may be prudent to monitor ECG with concurrent use if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia).
Interactions with other common medicines used in the perioperative period
QT-interval prolongation
Hydroxychloroquine may increase the QT-interval, although there is no evidence of such an effect. Some consider concurrent use with other drugs that can prolong the QT-interval might increase the risk. These include:
- ciprofloxacin*
- clarithromycin*
- domperidone**
- droperidol*
- erythromycin – particularly intravenous*
- granisetron**
- haloperidol*
- loperamide – increased risk with high doses*
- ondansetron*
- prochlorperazine – only a theoretical risk*
*monitor ECG with concurrent use if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia)
** no documented reaction, but bear interaction in mind especially in presence of additional risk factors
Antimicrobials
See also QT-interval prolongation above.
Aminoglycoside antibiotics (e.g. gentamicin) could potentiate the direct blocking action of hydroxychloroquine at the neuromuscular junction.
Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring. Consult current product literature.
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. In a retrospective study looking at joint surgeries in RA patients, two-thirds of patients receiving DMARDs including hydroxychloroquine demonstrated no association with perioperative infection. Specialists do not consider hydroxychloroquine to be an immunosuppressant and as such recommend that it can be safely continued throughout the perioperative period irrespective of the infection risk associated with the surgery.
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 26th June 2019]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 26th June 2019]
Summary of Product Characteristics – Plaquenil®- Hydroxychloroquine sulphate 200mg Film-coated Tablets. Zentiva. Accessed via www.medicines.org.uk 26/06/2019 [date of revision of the text August 2018]