chloroquine
Brand: Aralen
Prototype Drug
Drug Class: aminoquinoline antiparasitic
Drug Family: antiparasitic
Subclass: 4-aminoquinoline antimalarial
Organ Systems: infectious-disease
Mechanism of Action
Accumulates in plasmodial digestive vacuoles; inhibits heme polymerase, preventing conversion of toxic free heme to non-toxic hemozoin; free heme accumulates and is toxic to the parasite. Active only against chloroquine-sensitive Plasmodium species.
plasmodial heme polymerase (hemozoin formation)
Indications
- malaria treatment and prophylaxis — chloroquine-sensitive Plasmodium (primarily P. vivax and P. ovale in non-resistant areas)
- extraintestinal amebiasis
- lupus and rheumatoid arthritis (at lower doses — replaced by hydroxychloroquine)
Contraindications
- chloroquine hypersensitivity
- retinal or visual field changes
- long QT syndrome (relative)
- G6PD deficiency (relative for treatment of P. vivax — hemolysis risk with primaquine combination)
Adverse Effects
Common
- GI upset
- headache
- pruritus (especially in dark-skinned patients)
- dizziness
Serious
- irreversible retinopathy (with long-term use)
- QTc prolongation/arrhythmias
- aplastic anemia
- seizures at high doses
- cardiomyopathy
Pharmacokinetics (ADME)
| Absorption | 89% oral bioavailability |
| Distribution | large Vd; concentrated in melanin-containing tissues (eyes, skin); distributes into red blood cells |
| Metabolism | hepatic (CYP3A4, CYP2D6) to active metabolite desethylchloroquine |
| Excretion | renal (50–60% unchanged) |
| Half-life | 1–2 months (terminal, due to tissue distribution) |
| Onset | 1–3 hours |
| Peak | 1–2 hours |
| Duration | once-weekly dosing for prophylaxis |
| Protein Binding | 50–65% |
| Vd | very large (250–800 L/kg) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| antacids/kaolin | reduce chloroquine absorption; separate by 4 hours | moderate |
| QTc-prolonging drugs | additive QTc prolongation; increased torsades risk | major |
| cyclosporine | chloroquine inhibits CYP3A4; increases cyclosporine levels | moderate |
Nursing Considerations
- For malaria prophylaxis, start 1–2 weeks before travel to a chloroquine-sensitive region and continue for 4 weeks after return.
- Monitor visual acuity and fundoscopy with long-term use (>1 year); retinopathy is irreversible and dose-related.
- For P. vivax/P. ovale malaria, chloroquine eliminates the blood stage only — primaquine is needed to eradicate liver hypnozoites and prevent relapse.
- Pruritus (particularly in Black patients) is a common, non-allergic adverse effect thought to be opioid receptor-mediated.
Clinical Pearls
- Chloroquine resistance in P. falciparum has spread globally, making chloroquine ineffective for falciparum malaria in most of the world except Haiti and parts of Central America; P. vivax resistance to chloroquine is also emerging in parts of Asia and Oceania.
- Chloroquine has an extraordinarily long half-life (1–2 months) due to its massive tissue distribution in melanin-containing tissues, making toxicity insidious and potentially prolonged after drug discontinuation.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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