hydroxychloroquine
Brand: Plaquenil
Prototype: chloroquine
Drug Class: aminoquinoline antiparasitic/DMARD
Drug Family: antiparasitic
Subclass: 4-aminoquinoline used primarily as DMARD
Organ Systems: infectious-diseaseimmunologymusculoskeletal
Mechanism of Action
Similar to chloroquine for antimalarial activity; additionally accumulates in lysosomes and inhibits TLR7/TLR9 signaling by preventing endosomal acidification, reducing autoimmune cytokine production — the basis for its DMARD activity.
plasmodial heme polymerase; toll-like receptors (TLR7/TLR9) in immune cells
Indications
- malaria prophylaxis and treatment (chloroquine-sensitive)
- systemic lupus erythematosus (SLE) — reduces flares and mortality
- rheumatoid arthritis (DMARD)
- Sjögren's syndrome
Contraindications
- hydroxychloroquine hypersensitivity
- pre-existing retinopathy or macular disease
Adverse Effects
Common
- GI upset
- skin discoloration (blue-gray)
- headache
Serious
- retinopathy (irreversible — dose and duration dependent)
- cardiomyopathy (rare)
- QTc prolongation (less than chloroquine)
- agranulocytosis (rare)
Pharmacokinetics (ADME)
| Absorption | 74% oral bioavailability |
| Distribution | large Vd; extensively distributed to tissues, especially eyes and skin |
| Metabolism | hepatic (desethylhydroxychloroquine — active metabolite) |
| Excretion | renal (40–50%) and fecal |
| Half-life | 40–50 days (long terminal half-life) |
| Onset | 2–4 weeks (for DMARD effects) |
| Peak | 3.2 hours |
| Duration | once or twice daily |
| Protein Binding | 45% |
| Vd | very large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| digoxin | hydroxychloroquine may increase digoxin levels | moderate |
| QTc-prolonging drugs | additive QTc prolongation | moderate |
| metformin | increased risk of lactic acidosis in renal impairment | minor |
Nursing Considerations
- Baseline ophthalmologic examination is mandatory before initiating therapy; annual fundoscopy and Humphrey visual field testing required after 5 years of therapy (or earlier for high-risk patients).
- Administer with food to reduce GI adverse effects.
- For SLE: therapeutic benefits take weeks to months to manifest; counsel patients not to stop therapy prematurely.
- Monitor CBC and LFTs annually; screen for G6PD deficiency in high-risk patients.
Clinical Pearls
- Hydroxychloroquine reduces mortality and lupus flare rates by 30–50% in SLE patients, and should be continued indefinitely unless toxicity develops; it is one of the only medications proven to reduce cardiovascular events and thrombosis in SLE.
- Hydroxychloroquine retinopathy risk is related to dose (>5 mg/kg lean body weight per day) and duration (>5 years); safe dosing is critical since retinopathy is irreversible.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.