Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.
2 min synopsisUK scopeSources checked 27 Aug 2026Clinical review pending
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Severe conventional-DMARD toxicity
Visual change, syncope or arrhythmia on hydroxychloroquine; fever, mucosal ulceration, bruising or haemolysis on sulfasalazine; or jaundice, cytopenia, severe infection, pregnancy or progressive neuropathy on leflunomide requires urgent interruption and assessment.
Action: Withhold the suspected drug, arrange syndrome-directed same-day testing and specialist advice, treat infection or cardiac instability immediately, and start accelerated leflunomide elimination when severe toxicity or pregnancy makes rapid drug removal necessary.
Synopsis
Choose and monitor hydroxychloroquine, sulfasalazine or leflunomide according to disease, time to effect and comorbidity, while preventing retinal, cardiac, marrow, hepatic, infection and reproductive harm.
Hydroxychloroquine is slower and less powerfully immunosuppressive than methotrexate, but is valuable in lupus and milder inflammatory arthritis and is compatible with pregnancy and breastfeeding.
Dose hydroxychloroquine by actual body weight and keep long-term exposure at no more than 5 mg/kg/day, usually 200–400 mg daily, to reduce retinal risk.
RCOphth no longer recommends routine baseline retinal testing for every new user; annual monitoring starts after five years, or after one year when risk factors such as eGFR below 60, tamoxifen or dose above 5 mg/kg/day are present.
Key red flags
New paracentral visual disturbance, reading difficulty or colour change on hydroxychloroquine needs prompt ophthalmic assessment, although early retinal toxicity may be asymptomatic.
Hydroxychloroquine cardiac pattern
Syncope, conduction block, QT prolongation, ventricular thickening or unexplained biventricular failure after prolonged exposure needs cardiology and drug review.
Investigation priorities
01
First-line shared baselineFirst stepFirst line
Establish blood, liver, renal, infection and reproductive safety before selecting among the three DMARDs.
Management branches
Selection stepMatch medicine to disease and life plan
A conventional DMARD is required and methotrexate is insufficient, unsuitable or not preferred.
Choose hydroxychloroquine for lupus or milder disease when retinal dose can be safe; choose sulfasalazine for appropriate peripheral arthritis and reproductive compatibility.
Choose leflunomide for active rheumatoid or psoriatic arthritis when once-daily potent therapy fits liver, blood pressure, infection and pregnancy constraints.
Key medicines
HydroxychloroquineGive 200–400 mg orally daily with food, keeping the long-term average at no more than 5 mg/kg actual body weight each day; use an alternating 200 mg and 400 mg schedule when needed to achieve a safe average.
SulfasalazineStart 500 mg orally once daily and increase by 500 mg each week to 2 g daily in divided doses; a specialist may increase to 3 g daily when response and blood monitoring permit.
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.