Introduction
Chloroquine is a 4-aminoquinoline compound that has been used clinically since the 1940s. Originally developed as an antimalarial agent, it has since found applications in rheumatology and has been investigated for various viral infections. This aminoquinoline derivative remains an important therapeutic agent despite the emergence of resistance in some malaria-endemic regions.
Mechanism of Action
Chloroquine exerts its antimalarial effects through multiple mechanisms. As a weak base, it accumulates in the acidic food vacuoles of Plasmodium parasites, raising the pH and interfering with hemoglobin degradation. It inhibits heme polymerase, leading to toxic heme accumulation that is lethal to the parasite. Additionally, chloroquine may interfere with parasitic nucleic acid synthesis.
In autoimmune conditions, chloroquine appears to work through immunomodulatory effects, including inhibition of antigen presentation, Toll-like receptor signaling, and cytokine production. It also accumulates in lysosomes, raising intracellular pH and affecting various enzymatic processes.
Indications
FDA-Approved Indications:- Treatment of uncomplicated malaria due to susceptible strains of P. vivax, P. malariae, P. ovale, and P. falciparum
- Prophylaxis of malaria in specific geographic regions with chloroquine-sensitive parasites
- Treatment of extraintestinal amebiasis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Discoid lupus erythematosus
- Photosensitivity disorders
- Porphyria cutanea tarda
Dosage and Administration
Malaria Treatment:- Adults: 1 g (600 mg base) initially, followed by 500 mg (300 mg base) at 6, 24, and 48 hours
- Pediatric: 10 mg/kg base (maximum 600 mg base) initially, followed by 5 mg/kg base at 6, 24, and 48 hours
- Adults: 500 mg (300 mg base) weekly, starting 1-2 weeks before exposure and continuing for 4 weeks after leaving endemic area
- Pediatric: 5 mg/kg base weekly (maximum 300 mg base)
- Adults: 250-500 mg daily (150-300 mg base)
- Renal impairment: Use with caution; consider dose reduction
- Hepatic impairment: Use with caution; monitor closely
- Geriatric: Initiate at lower end of dosing range
- Pregnancy: FDA Category C; may be used when benefits outweigh risks
Pharmacokinetics
Absorption: Rapid and nearly complete from GI tract (89%) Distribution: Extensive tissue binding; Vd: 100-800 L/kg; crosses placenta and enters breast milk Protein Binding: Approximately 55% to plasma proteins Metabolism: Hepatic via CYP2C8, CYP3A4, and CYP2D6 to active metabolites Elimination: Renal excretion (50-70%), with 25% as unchanged drug; elimination half-life: 20-60 daysContraindications
- Hypersensitivity to chloroquine or other 4-aminoquinolines
- Retinal field changes attributable to chloroquine
- Psoriasis (may exacerbate condition)
- Porphyria (may precipitate acute attacks)
Warnings and Precautions
Black Box Warning:- Irreversible retinal damage with long-term use
- Cardiomyopathy with prolonged therapy
- Hematologic toxicity: May cause bone marrow suppression
- Neuropsychiatric effects: May exacerbate psychosis, seizures
- Hypoglycemia: Significant risk, especially in diabetics
- Neuromuscular toxicity: May worsen myasthenia gravis
- G6PD deficiency: May cause hemolysis
Drug Interactions
Major Interactions:- Digoxin: Chloroquine may increase digoxin levels
- CYP2D6 substrates: May increase levels of metoprolol, flecainide, others
- Antacids: May decrease absorption (separate administration by 4 hours)
- Mefloquine: Increased seizure risk
- Ampicillin: Reduced ampicillin bioavailability
- Ciclosporin: Increased ciclosporin levels
- Cimetidine: May decrease chloroquine metabolism
- Insulin/Oral hypoglycemics: Enhanced hypoglycemic effect
Adverse Effects
Common (>10%):- Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramps
- Dermatologic: Pruritus, skin eruptions, hair bleaching
- Neurologic: Headache, dizziness
- Ocular: Retinopathy, corneal deposits, blurred vision
- Cardiac: Cardiomyopathy, conduction defects, hypotension
- Hematologic: Pancytopenia, aplastic anemia, agranulocytosis
- Hepatic: Hepatitis, elevated transaminases
- Neuropsychiatric: Psychosis, seizures, extrapyramidal symptoms
Monitoring Parameters
Baseline:- Complete ophthalmologic exam including visual fields
- CBC with differential
- Liver function tests
- Renal function tests
- ECG (if cardiac risk factors present)
- G6PD screening in at-risk populations
- Annual ophthalmologic exams after 5 years of use (more frequent if high risk)
- Periodic CBC and LFTs
- Regular cardiac assessment with prolonged therapy
- Blood glucose monitoring in diabetics
- Neurologic assessment if symptoms develop
Patient Education
- Take with food to minimize GI upset
- Complete full course for malaria treatment
- For prophylaxis: Continue for 4 weeks after leaving endemic area
- Report any visual changes, muscle weakness, or unusual bleeding/bruising immediately
- Use sun protection due to photosensitivity risk
- Inform all healthcare providers of chloroquine use
- Do not crush or break tablets
- Store in original container away from moisture
References
1. FDA Prescribing Information: Chloroquine Phosphate Tablets 2. WHO Guidelines for Malaria, 2022 3. American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016) 4. Katzung BG. Basic & Clinical Pharmacology. 15th ed. 5. Micromedex® DrugDex® Evaluations 6. UpToDate: Chloroquine drug information 7. NIH LiverTox: Clinical and Research Information on Drug-Induced Liver Injury 8. British National Formulary (BNF) 85, March 2023
Note: This information is for educational purposes only. Always consult appropriate prescribing information and clinical guidelines before initiating therapy.