Generic Name

Plaquenil

Mechanism

*Plaquenil* primarily exerts its effects through immunomodulation and lysosomal activity:
• Alters lysosomal pH → inhibits antigen processing and presentation.
• Reduces Toll‑like receptor (TLR) signaling → decreases pro‑inflammatory cytokine production (IFN‑α, IL‑6, TNF‑α).
• Blocks calcium influx in immune cells → dampens B‑cell activation and autoantibody production.

These actions collectively produce anti‑inflammatory and antirheumatic effects.

Pharmacokinetics

• Absorption: ~70‑80 % oral bioavailability; peak plasma concentration 1–2 h post‑dose.
• Distribution: Extensive tissue penetration (retina, heart, liver). Large volume of distribution (~97 L/kg).
• Metabolism: Hepatic via CYP3A4, CYP2D6, and CYP2C8; metabolites largely inactive.
• Elimination: Renal excretion; half‑life ~2–3 months, allowing for once‑daily dosing.

Indications

• Rheumatoid arthritis and systemic lupus erythematosus (SLE).
• Dermatologic conditions: discoid lupus, psoriasis, chronic urticaria.
• Antimalarial prophylaxis (malaria) and treatment.
• Mosquito‑borne viral infections (e.g., Ebola)—investigational.

Contraindications

• Known sensitivity to hydroxychloroquine.
• Retinal disease: pre‑existing maculopathy, advanced glaucoma, or cone‑rod dystrophies.
• Severe kidney disease: eGFR < 30 mL/min/1.73 m².
• Pregnancy: category C; consider alternatives unless benefits outweigh risks.
• Cardiac rhythm disorders: prolongs QT interval—avoid with other QT‑prolonging drugs.
• Cytopenias or myelosuppression: concurrent use with immunosuppressants may increase risk.

Dosing

• Rheumatic diseases:
• Start at 200–400 mg/day, maximum 400 mg/day.
• Adjust based on patient weight and renal function.
• Malaria prophylaxis: 500 mg weekly (weekly high‑dose regimen) or 400 mg daily for 7 days pre‑travel.
• Lupus flare: 200–400 mg twice daily for 4–8 weeks, then taper to maintenance dose.

Adverse Effects

• Common
• Gastrointestinal: nausea, vomiting, abdominal pain.
• Dermatologic: rash, pruritus, photosensitivity.
• CNS: headache, dizziness.
• Serious
• Retinopathy: blurred vision, central scotoma.
• Myopathy: proximal muscle weakness.
• Cardiac: arrhythmias, QT prolongation.
• Hepatotoxicity: elevated transaminases.
• Severe hemolytic anemia in G6PD deficiency.

Monitoring

• Baseline and ocular:
• Comprehensive eye exam with automated retinal photography (EHR‑DFA) before starting, then annually.
• AUS‑A‑EL (Automated Full-Field Electroretinogram) < 1 year before therapy in high‑risk patients.
• Laboratory:
• CBC, CMP at baseline, 1–2 weeks after initiation, then every 3–6 months.
• Liver enzymes every 3–6 months or when clinically indicated.
• Cardiac:
• Baseline ECG in patients with QT risk; repeat if adding QT‑prolonging meds or if symptoms arise.
• Pregnancy:
• Amniotic fluid monitoring for fetal toxicity when used in pregnancy.

Clinical Pearls

• Weight‑based dosing: 5–6 mg/kg/day of Plaquenil is optimal for rheumatologic indications—helps avoid over‑exposure while maintaining efficacy.
• Renal function adjustment: For eGFR 30–60 mL/min/1.73 m², reduce dose to 200 mg/day; below 30 mL/min, consider discontinuation.
• Photo‑protection: Counsel patients on sun‑block use and avoid intense UV exposure to mitigate photosensitivity.
• Drug interactions: Avoid concomitant azithromycin, ritonavir, and other QT‑prolonging agents; monitor QTc.
• Pregnancy considerations: Though category C, hydroxychloroquine may reduce pre‑eclampsia risk in SLE; weigh benefits versus risks.
• Eye‑exam timing: Annual retinal evaluation is sufficient for most patients in low‑dose therapy (< 200 mg/day); consider earlier screening if high‑dose or prolonged use.

Plaquenil remains a cornerstone in the management of autoimmune disease, offering a favorable safety profile when monitored appropriately.