Chloroquine phosphate is a well-established antimalarial agent with additional immunomodulatory applications. This 4-aminoquinoline compound has been a cornerstone in malaria prophylaxis and treatment for decades, demonstrating reliable efficacy against Plasmodium species in non-resistant regions. Beyond its antiparasitic properties, chloroquine exhibits anti-inflammatory effects through lysosomal inhibition and cytokine modulation, making it valuable in managing autoimmune conditions. Its well-characterized pharmacokinetic profile and extensive clinical experience support its continued therapeutic relevance when used according to established guidelines.

Features

• Chemical name: 7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline phosphate
• Molecular formula: C₁₈H₂₆ClN₃·2H₃PO₄
• Molecular weight: 515.87 g/mol
• Appearance: White crystalline powder
• Solubility: Freely soluble in water
• Mechanism: Inhibits hemozoin biocrystallization in malaria parasites; modulates immune responses through pH-dependent mechanisms
• Bioavailability: Approximately 90% oral absorption
• Protein binding: 55% bound to plasma proteins
• Half-life: 20-60 days (extensive tissue distribution)

Benefits

• Provides rapid clinical improvement in acute malaria attacks when caused by chloroquine-sensitive strains
• Offers convenient once-weekly dosing for malaria prophylaxis in appropriate regions
• Demonstrates disease-modifying effects in autoimmune conditions through immunomodulatory action
• Exhibits favorable safety profile when administered within recommended dosage guidelines
• Enables flexible oral administration without requirement for clinical supervision in most cases
• Maintains cost-effectiveness compared to newer antimalarial alternatives in susceptible areas

Common use

Chloroquine is primarily indicated for the prophylaxis and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also used as second-line therapy for extraintestinal amebiasis. In rheumatology, chloroquine finds application in the management of discoid and systemic lupus erythematosus, and rheumatoid arthritis unresponsive to first-line agents. The drug’s immunomodulatory properties have shown benefit in conditions such as porphyria cutanea tarda and photodermatitis when other treatments prove inadequate.

Dosage and direction

Malaria prophylaxis: Adults: 500 mg (300 mg base) orally once weekly, beginning 1-2 weeks before exposure and continuing for 4 weeks after leaving endemic area. Pediatric dose: 8.3 mg/kg (5 mg/kg base) weekly, not to exceed adult dose.

Acute malaria treatment: Adults: Initial dose 1 g (600 mg base) orally, followed by 500 mg (300 mg base) at 6, 24, and 48 hours. Total dose 2.5 g (1.5 g base) over 48 hours. Pediatric dose: 10 mg/kg base initially, then 5 mg/kg base at 6, 24, and 48 hours.

Rheumatoid arthritis: Adults: 250-500 mg (150-300 mg base) daily orally. Maximum dose should not exceed 4 mg/kg ideal body weight daily.

Administration with meals or milk minimizes gastrointestinal discomfort. Tablets should be swallowed whole without crushing or chewing.

Precautions

Regular ophthalmologic examinations (including visual acuity, slit-lamp, funduscopic, and visual field testing) are mandatory every 6-12 months during long-term therapy due to risk of irreversible retinopathy. Hepatic function should be monitored periodically, as chloroquine is metabolized in the liver. Patients with glucose-6-phosphate dehydrogenase deficiency should be monitored for hemolysis. Caution is advised in patients with history of epilepsy, psoriasis, or myasthenia gravis, as chloroquine may exacerbate these conditions. Use during pregnancy requires careful risk-benefit assessment, though it is considered relatively safe for malaria prophylaxis.

Contraindications

Hypersensitivity to 4-aminoquinoline compounds. Pre-existing retinal or visual field changes attributable to 4-aminoquinoline compounds. Concurrent administration with gold therapy or phenylbutazone in rheumatoid arthritis patients. Use in patients with known porphyria. Prophylaxis against P. falciparum in regions with known chloroquine resistance. Concomitant use with other drugs known to cause retinal toxicity.

Possible side effect

Common (≥1%): Headache, dizziness, nausea, vomiting, diarrhea, abdominal cramps, pruritus (especially in black patients), skin eruptions, bleaching of hair, and keratopathy (visible as vortex keratopathy on slit-lamp examination).

Serious (<1%): Irreversible retinopathy with visual field defects, ototoxicity (tinnitus, hearing loss), cardiomyopathy, neuromyopathy, blood dyscrasias (aplastic anemia, agranulocytosis, thrombocytopenia), psychiatric disturbances (including psychosis, depression, anxiety), and severe hypoglycemia.

Dermatological: Exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity, and pigmentation changes.

Drug interaction

Chloroquine may potentiate the effects of digoxin and cyclosporine due to decreased clearance. Concurrent use with hepatotoxic drugs increases risk of liver damage. Antacids and kaolin reduce absorption—separate administration by at least 4 hours. May increase risk of convulsions when used with other epileptogenic drugs. Enhances effects of insulin and oral hypoglycemics. Cimetidine inhibits chloroquine metabolism, increasing plasma levels. Amphetamine and cocaine levels may be increased due to urinary alkalinization. May decrease antibody response to live typhoid vaccine.

Missed dose

If a weekly prophylactic dose is missed, administer as soon as possible. If remembered near the time of the next dose, skip the missed dose and resume regular schedule. Do not double doses. For daily treatment regimens, take the missed dose as soon as remembered unless it is almost time for the next dose. Maintain regular interval between doses to avoid accumulation.

Overdose

Chloroquine overdose is extremely dangerous and potentially fatal, with death occurring within hours. Symptoms include headache, drowsiness, visual disturbances, cardiovascular collapse, convulsions, and sudden respiratory and cardiac arrest. Hypokalemia is a characteristic finding. Management requires immediate gastric lavage (within 1 hour) followed by activated charcoal. Respiratory support and early intubation may be necessary. Intravenous diazepam may reduce cardiovascular toxicity. Potassium replacement should be aggressive but monitored carefully. Epinephrine is contraindicated. Serum chloroquine levels guide management but treatment should not await laboratory confirmation.

Storage

Store at controlled room temperature (20-25°C/68-77°F) in tight, light-resistant containers. Keep away from moisture and excessive heat. Do not freeze. Keep out of reach of children and pets. Discard any unused medication after the expiration date. Do not transfer to other containers as this may affect stability.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Chloroquine is a prescription medication that should only be used under appropriate medical supervision. Healthcare providers should consult full prescribing information before administration. Resistance patterns should be verified before use for malaria prophylaxis or treatment. The benefits and risks must be carefully evaluated for each patient, particularly regarding long-term therapy. Actual clinical use should follow current guidelines and local regulations.

Reviews

“Chloroquine remains invaluable for vivax malaria in our region. The weekly dosing schedule provides excellent compliance for prophylaxis, though we always screen for G6PD deficiency first.” - Tropical Medicine Specialist, Southeast Asia

“While its use in rheumatoid arthritis has declined with biologics, chloroquine still has a place in our armamentarium for selected patients who cannot tolerate or access newer agents. Ophthalmic monitoring is non-negotiable.” - Rheumatologist, EU

“The cardiac toxicity in overdose situations is dramatic and requires intensive care management. We maintain strict protocols for its use in our hospital given the narrow therapeutic window.” - Clinical Toxicologist, US

“Despite resistance concerns, chloroquine’s cost-effectiveness makes it important in resource-limited settings for non-falciparum malaria. We combine it with primaquine for radical cure when appropriate.” - Public Health Physician, Africa