What are the uses of Plaquenil (hydroxychloroquine)?

Plaquenil (Hydroxychloroquine) Uses

Plaquenil is FDA-approved for treating uncomplicated malaria, malaria prophylaxis in chloroquine-sensitive areas, rheumatoid arthritis, systemic lupus erythematosus, and chronic discoid lupus erythematosus in adults. 1

FDA-Approved Indications

Malaria Treatment and Prevention

• Treatment of uncomplicated malaria caused by Plasmodium falciparum, P. malariae, P. ovale, and P. vivax in adults and children 1
• Prophylaxis of malaria in geographic areas where chloroquine resistance is not reported 1
• Not recommended for complicated malaria, chloroquine-resistant strains, or prevention of P. vivax/P. ovale relapses (requires additional 8-aminoquinoline therapy for radical cure) 1

Rheumatic and Autoimmune Diseases

• Rheumatoid arthritis in adults: Initial dosing 400-600 mg daily, maintenance 200-400 mg daily 1
• Systemic lupus erythematosus (SLE) in adults: 200-400 mg daily 1
• Chronic discoid lupus erythematosus in adults: 200-400 mg daily 1

Guideline-Recommended Uses

Lupus Nephritis and SLE

The KDIGO 2024 guidelines strongly recommend hydroxychloroquine for all patients with SLE, including those with lupus nephritis, unless contraindicated. 2

The benefits include:

• Reduced disease flares (HR 2.50 for flares when stopped vs. continued) 2
• Lower rates of progressive kidney damage and slower progression of kidney disease 2
• Decreased cardiovascular and thrombotic events, particularly in patients with antiphospholipid antibodies 2
• Improved lipid profile and better bone mass preservation 2
• Safe in pregnancy with decreased lupus activity and no harm to the fetus 2
• Potential mortality reduction in lupus nephritis patients (very low certainty evidence) 2

Chronic Q Fever

• The CDC recommends combination therapy with doxycycline (100 mg twice daily) plus hydroxychloroquine (200 mg three times daily) for 18-24 months for chronic Q fever 3
• Hydroxychloroquine alkalinizes the phagosomal compartment, allowing doxycycline to achieve bactericidal activity against C. burnetii 3
• Do not use for acute Q fever (doxycycline alone is recommended) 3

Mechanism of Action

Hydroxychloroquine works through multiple pathways:

• Increases pH in intracellular vesicles (endosomes, lysosomes), inhibiting pH-dependent proteases and affecting protein processing 2, 4
• Interferes with antigen processing in macrophages and antigen-presenting cells, diminishing peptide-MHC class II complex formation and down-regulating immune responses 4
• Reduces inflammatory cytokines including TNF-α and IL-6 2
• Antimalarial effect through accumulation of cytotoxic heme that poisons Plasmodium parasites 2

COVID-19: Not Recommended

The WHO and CDC do not support hydroxychloroquine use for COVID-19 treatment or prophylaxis. 3

• Initial in vitro antiviral activity against SARS-CoV-2 did not translate to clinical benefit 3
• Patients with rheumatic diseases on chronic hydroxychloroquine should continue their medication during COVID-19 due to immunomodulatory effects and risk of disease flares 3

Critical Dosing and Monitoring

Dosing Guidelines

• Maximum dose: 5 mg/kg actual body weight to minimize retinal toxicity 2, 3
• Doses of 2-3 mg/kg/day may be inadequate and associated with higher flare rates 2
• Target blood level >0.6 mg/L may be associated with lower risk of lupus nephritis flare 2
• Renal impairment: Reduce dose by 25% if eGFR <30 mL/min/1.73 m² 2, 3

Pre-Treatment Screening

• Check G6PD levels in men of African, Asian, or Middle Eastern origin before starting to avoid hemolysis risk 2, 3
• Baseline ophthalmologic examination is required before initiating therapy 3

Ongoing Monitoring

• Annual ophthalmologic screening should begin after 1 year in high-risk patients (tamoxifen use, eGFR <60, dose >5 mg/kg/day) or after 5 years in low-risk patients 2, 3
• Retinopathy risk increases with duration: 0.5% after 6 years, 7.5% in long-term users generally, and >20% after 20 years of treatment 2
• Monitor for cardiomyopathy with high cumulative exposure (rare but potentially fatal) 2, 1

Important Contraindications and Warnings

• Absolute contraindication: Hypersensitivity to 4-aminoquinoline compounds 1
• Avoid in psoriasis (may worsen disease) 1
• Avoid in porphyria (hepatotoxicity reported in porphyria cutanea tarda) 1
• Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported 1
• Fatal cardiomyopathy and ventricular arrhythmias have been reported 1