Hydroxychloroquine

Antimalarial (4-aminoquinoline), DMARD, Immunomodulator

Hydroxychloroquine

Plaquenil; mostly prescribed generically

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Summary

Classes

Antimalarial (4-aminoquinoline), DMARD, Immunomodulator

Pharmacy

Starting dose

200-400 mg PO daily; dose by actual body weight ≤5 mg/kg/d to reduce retinopathy risk (AAO 2016 guideline)

Preparations

200 mg tablets; 100 mg/5 mL suspension

US FDA Max

400 mg/d typical maintenance; weight-adjusted ceiling per ophthalmology guidance

Pharmacology

Routes

Oral

Onset

Rheumatologic effect at 6-12 weeks

Duration

Weeks (long half-life)

Half-life

~40 days (terminal; reflects extensive tissue distribution)

Bioavailability

70-75% (oral)

Pregnancy

Long-considered safe in pregnancy for lupus and other rheumatologic indications; benefits typically outweigh.^{[citation needed]}

Legal status

Rx-only in US

Purported mechanism

Hydroxychloroquine accumulates in lysosomes (lysosomotropic weak base), raising lysosomal pH and impairing endolysosomal antigen processing and TLR7/9 endosomal signaling; the net effect dampens innate immune activation and reduces autoantibody production in lupus and inflammation in rheumatoid arthritis.▲0▼ Retinal toxicity is the dose- and duration-limiting adverse effect (bull's eye maculopathy with photoreceptor damage); the 2016 American Academy of Ophthalmology guideline established the ≤5 mg/kg actual-body-weight ceiling and baseline + annual screening starting at year 5. QT prolongation and rare cardiomyopathy are recognized cardiac risks. The 2020 COVID-19 controversy is documented separately; HCQ does not have established benefit in COVID-19 and was eventually withdrawn from active recommendation.