Chloroquine and Hydroxychloroquine: Dosage and Usage
Malaria Treatment
For uncomplicated malaria in chloroquine-sensitive regions, administer chloroquine phosphate at a total dose of 25 mg/kg body weight over 3 days, divided as 10 mg/kg at 0 hours, 10 mg/kg at 24 hours, and 5 mg/kg at 48 hours for children, or 1,500 mg total (600 mg, 600 mg, 300 mg at 0,24, and 48 hours) for adults. 1
Treatment Regimens by Patient Population
Adults:
- Total dose: 1,500 mg chloroquine (approximately 25 mg/kg body weight) over 3 days 1
- Dosing schedule: 600 mg at 0 hours, 600 mg at 24 hours, 300 mg at 48 hours 1
Pediatric Patients:
- Total dose: 25 mg/kg body weight over 3 days 1
- Dosing schedule: 10 mg/kg at 0 hours, 10 mg/kg at 24 hours, 5 mg/kg at 48 hours 1
Pregnant Women:
- Use the adult dosing regimen 1
- Chloroquine is safe during pregnancy 1
- Monitor carefully for hypoglycemia if quinine is used as alternative 1
Chloroquine-Resistant Areas
In regions with documented chloroquine resistance, chloroquine should NOT be used as first-line therapy. 1, 2 The FDA label explicitly states hydroxychloroquine is not recommended for treatment of chloroquine-resistant strains or malaria acquired in areas where chloroquine resistance occurs 2.
Alternative first-line options include:
- Artemether-lumefantrine: 4 tablets (20mg artemether + 120mg lumefantrine per tablet) twice daily for 3 days for patients over 35kg, taken with fatty meal 3
- Atovaquone-proguanil (Malarone): Weight-based dosing for 3 days 1
- Mefloquine: 15 mg/kg (max 750 mg) once, then 10 mg/kg (max 500 mg) 12 hours later 1
Treatment Failure Protocol
If symptoms persist 48-72 hours after starting chloroquine, switch immediately to a second-line antimalarial drug. 1 Repeat thick blood smear to assess parasitemia reduction 1. Alternative drugs include sulfadoxine-pyrimethamine, tetracycline, quinine, or mefloquine, depending on local parasite sensitivity patterns 1.
Adjunctive Therapy for P. vivax and P. ovale
Add primaquine 15 mg daily for 14 days (adults) or 0.3 mg/kg/day (children) after chloroquine to achieve radical cure and prevent relapses. 1
Critical caveat: Screen for G-6-PD deficiency before primaquine administration 1. In populations with severe G-6-PD deficiency (notably Asians), limit primaquine to maximum 5 days to prevent life-threatening hemolysis 1.
Malaria Prophylaxis
For prophylaxis in chloroquine-sensitive areas, administer 400 mg (adults) or 6.5 mg/kg up to 400 mg (pediatric patients ≥31 kg) once weekly, beginning 2 weeks before travel, continuing during exposure, and for 4 weeks after leaving the endemic area. 2
Hydroxychloroquine is NOT recommended for prophylaxis in areas with documented chloroquine resistance. 2 Use mefloquine 250 mg weekly instead 1.
High-Risk Groups for Chemoprophylaxis During Epidemics
Consider prophylaxis for:
- Children under 5 years, especially those with malnutrition, anemia, or debilitating diseases 1
- Pregnant women 1
- Persons with compromised health status at increased risk for complications 1
Autoimmune Disease Treatment
Rheumatoid Arthritis
For rheumatoid arthritis, initiate hydroxychloroquine at 400-600 mg daily, then reduce to a chronic maintenance dose of 200-400 mg once daily (or divided into two doses). 2
Systemic Lupus Erythematosus
For systemic lupus erythematosus, administer hydroxychloroquine 200-400 mg once daily (or divided into two doses). 2
Chronic Discoid Lupus Erythematosus
For chronic discoid lupus erythematosus, administer hydroxychloroquine 200-400 mg once daily (or divided into two doses). 2
Mechanism in Autoimmune Disorders
Hydroxychloroquine functions as a disease-modifying anti-rheumatic drug through immunosuppressive activity, reducing T-cell and B-cell hyperactivity and pro-inflammatory cytokine gene expression 4. The drug employs pH-dependent inhibition of endosome, lysosome, and trans-Golgi network functioning, along with immunomodulatory actions and autophagy inhibition 5.
Critical Safety Warnings
Cardiac Toxicity
Fatal or life-threatening cardiomyopathy and ventricular arrhythmias have been reported with hydroxychloroquine. 2 QTc interval prolongation occurs at therapeutic doses, with median increases of 12-26 ms at peak concentrations 6. Cardiac monitoring is required, particularly when combining with other QT-prolonging medications 2.
Retinal Toxicity
Irreversible retinal damage is related to cumulative dosage and treatment duration. 2 Perform baseline retinal examination before initiating therapy and regular monitoring during treatment 2.
Severe Skin Reactions
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have been reported 2.
Contraindications and Precautions
Absolute contraindications:
- Hypersensitivity to 4-aminoquinoline compounds 2
- Psoriasis (may worsen) 2
- Porphyria (hepatotoxicity reported in porphyria cutanea tarda) 2
Monitor for:
- Myelosuppression (discontinue if occurs) 2
- Renal toxicity (consider phospholipidosis in connective tissue disorders) 2
- Hepatotoxicity 2
- Bone health effects with long-term use (inhibits osteoblastic and osteoclastic activity) 7
Dosing Considerations
Higher chloroquine doses (50-70 mg/kg total) are well tolerated in children but show limited efficacy against resistant strains carrying pfcrt 76T allele (57-67% cure rates) 6. Standard dosing remains preferred unless specifically indicated for resistant parasites in controlled settings 6.