Chloroquine: 7 Uses, Side Effects, And Monitoring

Author: Reviewed by Dr. Reviewed by Dr. A. F. Oakley, Dermatologist, Hamilton, New Zealand. DermNet NZ Editor in Chief: Dr. Amanda Oakley, Dermatologist, Hamilton, New Zealand. September 2024.

What is chloroquine?

Chloroquine is a 4-aminoquinoline antimalarial drug. It is now infrequently used for malaria due to widespread resistance but remains valuable for treating rheumatic diseases such as rheumatoid arthritis and dermatological conditions. Hydroxychloroquine has largely replaced it for these uses owing to a lower risk of retinal toxicity.

Chloroquine phosphate and chloroquine hydrochloride are given orally, typically as a 200 mg tablet containing 155 mg base. Chloroquine sulfate is given by injection.

History of chloroquine

Chloroquine was first synthesised in Germany in 1934 but not widely used until 1947. An aldehyde and acetone were combined to form p-aminophenyl-α-pyridyl carbinol, which was then reacted with chloroquine.

It was discovered to inhibit Plasmodium falciparum growth in 1944 and introduced for malaria prophylaxis during World War II by the Allies. In 1955, chloroquine resistance emerged in Thailand and the Philippines, spreading globally by the 1960s. By 1983, resistance was confirmed in over 110 countries.

Chloroquine’s immunomodulatory effects were recognised in the 1950s, leading to its use in lupus erythematosus (1956) and rheumatoid arthritis (1962). Retinal toxicity concerns prompted hydroxychloroquine’s development in 1959.

Pharmacology of chloroquine

Mechanism of action

Chloroquine concentrates in parasite food vacuoles, raising pH and inhibiting haem polymerase. This prevents toxic haem dimerization, causing parasite death. It also inhibits protein synthesis, DNA/protein interactions, glutathione reductase, and protein kinase C.

In rheumatic diseases, chloroquine impairs antigen presentation, reduces cytokine production (IL-1, IL-6, TNF-α), and inhibits phospholipase A2, decreasing prostaglandin/chemotaxis.

Absorption

Chloroquine is rapidly absorbed (bioavailability ~90%). Peak plasma levels occur 1–2 hours post-dose. Food reduces absorption by ~20%. Steady-state levels take 2–3 months.

Distribution

Chloroquine binds 50–65% to plasma proteins and distributes widely (volume ~800 L). It concentrates in melanin-rich organs (eyes, skin, liver) and cells (leucocytes, liver, spleen, kidneys, lungs, heart). CSF levels are 100–200 times lower than plasma.

Metabolism

Chloroquine undergoes partial hepatic metabolism to monodesethylchloroquine (active, longer half-life) and bisdesethylchloroquine. ~30% is demethylated.

Excretion

Elimination half-life is 3–5 days (metabolite 9 days). 70% renal excretion (50% unchanged, 20–30% metabolites); 25% biliary/faecal. Acidic urine increases elimination. Dose reduction needed in renal impairment.

Uses of chloroquine

• Malaria prophylaxis (0.5 g/week)
• Malaria treatment (1 g then 0.5 g at 6, 24, 48 hours)
• Am oe biasis
• Rheumatoid arthritis (250 mg/day)
• Systemic lupus erythematosus
• Porphyria cutanea tarda
• Dermatological conditions: discoid lupus erythematosus, polymorphous light eruption, solar urticaria, lichen planopilaris, erosive lichen planus

Dose of chloroquine

Malaria prophylaxis

Adults: 310 mg base (500 mg salt) weekly, starting 1–2 weeks before travel, continuing 4 weeks after. Children: 5 mg base/kg/week.

Malaria treatment

Adults: 620 mg base (1 g salt), then 310 mg at 6, 24, 48 hours. Children: 10 mg base/kg, then 5 mg/kg at 6, 24, 48 hours.

Rheumatic disease

Adults: 155 mg base (250 mg salt) daily. Maximum 2.5 mg/kg/day. Children: 3–5 mg/kg/day.

Response takes 4–12 weeks; full effect 4–6 months. Reduce dose if no improvement after 6 months.

Dose adjustments

Chloroquine side effects

Gastrointestinal

Nausea, vomiting, diarrhoea (transient, minimised by taking with meals or dose reduction). Abdominal pain, anorexia.

Dermatological

Pruritus (most common, 464+ cases across 29 studies, occurs within 3 months). Hyperpigmentation (blue-grey/brown-black, nails/mucosa common, resolves slowly). Alopecia, Photosensitivity, Exfoliative dermatitis, Erythema annulare centrifugum, Lichen planus.

Ocular

Retinopathy (irreversible bull’s eye maculopathy >1 year use, 2.5 mg/kg/day). Risk factors: renal/hepatic disease, age >60, obesity. Corneal deposits (reversible, <3 years), Myopia/cataracts, Keratitis, Photophobia.

Neuromuscular

Neuromyopathy (proximal weakness, depressed reflexes, elevated CK, EMG changes, resolves 2–6 months post-discontinuation). Psychosis, Seizures, Ototoxicity, Peripheral neuropathy.

Cardiovascular

QT prolongation, Bradycardia, Cardiomyopathy, Hypotension (IV).

Haematological

Agranulocytosis, Aplastic anaemia, Haemolysis (G6PD deficiency), Thrombocytopenia.

Hepatic

Acute hepatitis (rare).

Chloroquine monitoring

• Baseline: FBC, LFT, RFT, G6PD, ECG, visual acuity, Amsler grid, fields, colour testing
• 3 months: Repeat tests, fundus exam
• 6–12 months then annually: FBC, LFT, RFT, visual fields, colour testing
• High risk: 3-monthly exams first year
• Stop if: Visual acuity <6/12, fields <10°/white, colour vision deteriorates

Drug interactions with chloroquine

• Increases chloroquine levels: cimetidine
• Decreases chloroquine levels: aluminium/magnesium antacids, kaolin
• Increased toxicity: amiodarone (QT), ciclosporin (levels), cimetidine
• Decreased efficacy: metopirone (11-β-hydroxylase)

Chloroquine toxicity

Acute ingestion

Adults: 1 g base usually tolerated; >3 g potentially fatal. Children: 15–20 mg/kg fatal. Symptoms: Nausea, vomiting, diarrhoea, headache, drowsiness, visual changes, convulsions, coma, arrhythmias, hypotension.

Management

Activated charcoal if <30 min. Supportive: diazepam (seizures), sodium bicarbonate (QRS widening), epinephrine (hypotension), diazepam/propofol (arrhythmias). Antidote: epinephrine 5–15 μg/min IV infusion.

Alternatives to chloroquine

• Malaria: atovaquone-proguanil, doxycycline, mefloquine
• Rheumatology: hydroxychloroquine, methotrexate, sulfasalazine, leflunomide, biologics
• Dermatology: hydroxychloroquine, quinacrine

Frequently asked questions about chloroquine

What are the most common side effects of chloroquine?

Gastrointestinal upset (nausea, diarrhoea) and pruritus. Most resolve with dose reduction or discontinuation.

Does chloroquine cause permanent vision damage?

Yes, retinopathy can cause irreversible bull’s eye maculopathy with prolonged use. Regular screening essential.

Is chloroquine safe in pregnancy?

Compatible in pregnancy; widely used for malaria prophylaxis. Avoid high doses.

How long does chloroquine stay in the body?

Elimination half-life 3–5 days; metabolite up to 9 days. Full clearance months.

Can chloroquine be used in children?

Yes, weight-based dosing for malaria. Avoid long-term in rheumatology unless essential.

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