hydroxychloroquine
antimalarial / DMARD· Brands: Plaquenil, QuineproxPO
Mechanism of action
Hydroxychloroquine is a 4-aminoquinoline derivative that exerts its effects by raising intravesicular pH within lysosomes and endosomes, thereby interfering with antigen processing and presentation. It also inhibits Toll-like receptor signaling, reducing pro-inflammatory cytokine release, and has immunomodulatory properties. In malaria, it is thought to act by concentrating in the acidic vacuoles of the parasite, preventing the detoxification of haem, which is toxic to the parasite.
Pharmacokinetics
Hydroxychloroquine is well absorbed orally, with peak plasma concentrations reached within 2 to 3 hours. It has a very large volume of distribution, extensive tissue binding, and a prolonged elimination half-life of approximately 40 to 50 days. The drug is partially metabolised in the liver, with some metabolites retaining activity, and is excreted primarily in the urine. Because of its long half-life, steady-state concentrations take several months to achieve.
Indications & dosing
Malaria prophylaxis
Start 1 week before travel and continue for 4 weeks after leaving endemic area.
- adult · PO: 400 mg once weekly · Start 1 week before travel and continue for 4 weeks after leaving endemic area.
Malaria treatment
Follow with 400 mg at 6, 12, 24, and 48 hours. Used for chloroquine-sensitive strains.
- adult · PO: 800 mg single dose · Follow with 400 mg at 6, 12, 24, and 48 hours. Used for chloroquine-sensitive strains.
Rheumatoid arthritis
Initial dose 400 mg daily; maintenance 200-400 mg daily. Monitor for retinal toxicity.
- adult · PO: 200–400 mg daily · Initial dose 400 mg daily; maintenance 200-400 mg daily. Monitor for retinal toxicity.
Systemic lupus erythematosus
Initial dose 400 mg daily; maintenance 200-400 mg daily. Monitor for retinal toxicity.
- adult · PO: 200–400 mg daily · Initial dose 400 mg daily; maintenance 200-400 mg daily. Monitor for retinal toxicity.
Contraindications & precautions
- Hypersensitivity to hydroxychloroquine or other 4-aminoquinolines · Risk of anaphylaxis.
- Pre-existing retinopathy or maculopathy · Hydroxychloroquine can cause irreversible retinal damage.
- Porphyria · Can precipitate acute porphyric attacks.
- Psoriasis · May exacerbate psoriasis.
- Perform baseline and regular ophthalmological examinations to monitor for retinal toxicity.
- Caution in patients with hepatic or renal impairment; dose adjustment may be required.
- Caution with drugs that prolong the QT interval.
- Monitor blood glucose, especially in patients receiving antidiabetic therapy.
- Caution in G6PD deficiency.
Adverse effects
- Gastrointestinal upset (nausea, diarrhoea)
- Headache
- Skin rash and pruritus
- Retinopathyserious
- QT prolongation and ventricular arrhythmiasserious
- Hypoglycaemiaserious
- Cardiomyopathyserious
- Agranulocytosisserious
Renal & hepatic adjustment
- eGFR 0–30: Reduce dose by 50% of the usual dose in severe renal impairment (eGFR < 30 mL/min). No adjustment needed for mild to moderate impairment.
- Hepatic impairment (severe): Use with caution; consider dose reduction and monitor for adverse effects.
Monitoring, pregnancy & toxicity
- Ophthalmological examination for retinal toxicity · Baseline and at least annually (more frequently if high risk)
- ECG for QT interval · Baseline and periodically in patients at risk of QT prolongation
- Complete blood count · Periodically during long-term therapy
- Liver function tests · Periodically during long-term therapy
- Pregnancy: Hydroxychloroquine is generally considered safe in pregnancy when indicated (e.g., for SLE or malaria prophylaxis). Available data suggest low risk of congenital malformations. Continue treatment if clinically necessary.
- Toxicity: QT interval prolongation, ventricular arrhythmias, and cardiac arrest in severe overdose · Continuous ECG monitoring; correct electrolyte abnormalities; consider isoprenaline or temporary pacing for torsades de pointes.
- Toxicity: Hypoglycaemia · Frequent blood glucose monitoring; treat with intravenous glucose or glucagon if needed.
- Toxicity: Retinal toxicity (maculopathy) with long-term use · Discontinue hydroxychloroquine if toxicity is suspected; refer to ophthalmologist.
- Toxicity: CNS toxicity: seizures, coma, and respiratory depression in severe overdose · General supportive care; administer activated charcoal if recent ingestion; benzodiazepines for seizures; mechanical ventilation if needed.
Clinical notes
It is considered safe for malaria prophylaxis in pregnancy, but should be used in autoimmune disease under specialist guidance.
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BNF; local formulary