Indications for Hydroxychloroquine
Hydroxychloroquine is primarily indicated for the treatment of systemic lupus erythematosus, rheumatoid arthritis, chronic discoid lupus erythematosus, and malaria (both treatment of uncomplicated cases and prophylaxis in non-resistant areas). 1
FDA-Approved Indications
Rheumatologic Indications
- Systemic Lupus Erythematosus (SLE): Recommended for all patients with SLE regardless of disease activity or severity 2
- Rheumatoid Arthritis: For adult patients, typically at doses of 200-400 mg daily 1
- Chronic Discoid Lupus Erythematosus: For adult patients, typically at doses of 200-400 mg daily 1
Infectious Disease Indications
- Treatment of uncomplicated malaria due to P. falciparum, P. malariae, P. ovale, and P. vivax 1
- Prophylaxis of malaria in geographic areas where chloroquine resistance is not reported 1
Off-Label Dermatologic Indications
- Porphyria cutanea tarda: Low-dose regimen (125 mg chloroquine twice weekly) 3
- Cutaneous sarcoidosis 3
- Dermatomyositis with skin manifestations 3
Other Potential Uses (Less Evidence)
Important Limitations of Use
Not Recommended For:
- Treatment of complicated malaria
- Treatment of chloroquine or hydroxychloroquine-resistant strains of Plasmodium
- Treatment of malaria in geographic areas with known chloroquine resistance
- Prevention of relapses of P. vivax or P. ovale (not active against liver hypnozoites)
- COVID-19: Strong recommendation against use based on high-certainty evidence showing no mortality benefit and increased risk of adverse effects 5, 6
Dosing Considerations
Standard Dosing
- Rheumatologic conditions: 200-400 mg daily (either once daily or in divided doses) 1
- Malaria prophylaxis: 400 mg once weekly for adults, starting 2 weeks before travel to endemic area and continuing for 4 weeks after leaving 1
- Maximum recommended dose: ≤5.0 mg/kg based on actual body weight to minimize retinal toxicity risk 2, 5
Special Populations
- Renal impairment: Reduce dose by 25% for eGFR <30 ml/min per 1.73 m² 5
- Pregnancy: Generally considered safe if clinically indicated 5
Monitoring Requirements
Baseline Assessment
- Complete blood count
- Liver function tests
- Renal function tests
- G6PD levels (especially in at-risk populations)
- ECG (particularly in patients with cardiac risk factors)
- Ophthalmologic examination
Ongoing Monitoring
- Ophthalmologic examination: Starting after 5 years of use (or after 1 year if additional risk factors exist), then every 6-12 months 2, 5
- Regular monitoring of liver function, complete blood count, and renal function
Major Adverse Effects
Ocular Toxicity
- Retinopathy is the most significant dose-limiting toxicity
- Risk factors: daily dose >5 mg/kg, duration >10 years, age >65 years, renal disease, concurrent tamoxifen use 2
Other Adverse Effects
- Cardiac: QT prolongation, conduction abnormalities, cardiomyopathy
- Hematologic: Hemolytic anemia (especially with G6PD deficiency)
- Neurologic: Headache, dizziness, confusion, seizures
- Dermatologic: Skin rashes, hyperpigmentation, lichenoid eruptions
- Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea
Contraindications
- Hypersensitivity to 4-aminoquinoline compounds
- Pre-existing retinopathy or visual field changes
- Long-term therapy in children
Clinical Pearls
- Hydroxychloroquine is considered a valuable drug with an excellent benefit-risk profile when properly dosed and monitored
- Blood levels of HCQ >0.6 mg/L may be associated with lower risk of lupus nephritis flare
- Retinopathy risk is very low (<2%) for the first 10 years of treatment when using ≤5.0 mg/kg/day based on actual body weight
- The drug should not be stopped casually for borderline findings on ophthalmologic examination
By following these guidelines for appropriate use and monitoring, hydroxychloroquine remains an important therapeutic option for patients with autoimmune conditions and specific infectious diseases.