Hydroxychloroquine Prescribing and Monitoring

Hydroxychloroquine is an antimalarial immunomodulator used in systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, antiphospholipid syndrome and cutaneous lupus. In lupus it reduces flares, organ damage, thrombosis and mortality, and every patient with lupus without a contraindication should receive it.

Dose ceiling. The retinal toxicity risk depends on cumulative dose and on the daily dose in mg/kg of actual body weight, not on the total daily dose alone.

Onset. Benefit builds over 3 to 6 months; stopping raises flare risk within months.

Usual regimen. Hydroxychloroquine 200 to 400 mg orally once daily with food, never more than 5 mg/kg of actual body weight daily.

• Weight 40 kg: maximum 200 mg daily. Weight 60 kg: 300 mg daily. Weight 80 kg or more: 400 mg daily.
• Rheumatoid arthritis: 200 to 400 mg daily, started at 400 mg and reduced to 200 mg daily once disease is controlled.
• Lupus: 200 to 400 mg daily within the weight limit; 200 mg daily may be enough for long-term maintenance in controlled disease.
• Alternate-day schedules, for example 400 mg and 200 mg on alternate days, reach an average daily dose within 5 mg/kg where tablets are only available as 200 mg.

Combination. Used alone for mild disease, or with methotrexate, sulfasalazine, mycophenolate or biologics for active disease.

Antiphospholipid syndrome and pregnancy. Continue throughout pregnancy and breastfeeding.

Kidney impairment. eGFR 60 mL/min or more: no change. eGFR under 60 mL/min raises retinal risk, so use the lower end of the dose; eGFR under 30 mL/min: reduce by 25 to 50% (for example 200 mg daily).

Liver impairment. Use with caution; reduce the dose in severe impairment.

Obesity. Dose by actual body weight but cap at 400 mg daily.

Older adults. Higher macular risk; check retinal screening earlier and dose to the lower limit.

Pregnancy and breastfeeding. Compatible with both; stopping in pregnancy raises lupus flare risk, including foetal heart block risk with anti-Ro antibodies.

Interactions.

• Antacids, calcium and kaolin: separate by 4 hours.
• QT-prolonging drugs (macrolides, quinolones, ondansetron, antipsychotics, citalopram, methadone, artemether-lumefantrine): additive risk; check ECG and electrolytes.
• Tamoxifen: higher retinal toxicity risk.
• Insulin and sulphonylureas: increased hypoglycaemia.
• Digoxin, ciclosporin, penicillamine, agalsidase: levels or effect altered.

Safety warnings. Retinopathy, QT prolongation, hypoglycaemia, cardiomyopathy and myopathy (rare), skin hyperpigmentation, neuropsychiatric effects, and haemolysis in glucose-6-phosphate dehydrogenase deficiency (rare at these doses).

Regional. Do not rely on this dose for malaria prevention; chloroquine-resistant malaria is widespread in East Africa, so give a suitable antimalarial for travel or residence in endemic areas.

Retinal screening. Baseline eye examination within the first year, then yearly after 5 years of use, or from year 1 if risk factors are present: dose over 5 mg/kg, eGFR under 60 mL/min, tamoxifen use, pre-existing macular disease, or age over 60. Use optical coherence tomography with visual fields; add fundus autofluorescence where available.

Other monitoring. Blood pressure, weight (to recalculate the dose), and a baseline ECG if other QT-prolonging drugs or cardiac disease are present. Full blood count and liver tests at baseline and with symptoms.

Stop and escalate. Stop at once and refer for any suspected retinal toxicity (parafoveal ring scotoma on screening, new visual symptoms). Stop for severe skin reactions or proven cardiomyopathy. Review disease control before any planned stopping.