Hydroxychloroquine (HCQ) is an antimalarial and immunomodulatory drug derived from chloroquine. Its mechanism of action varies depending on the condition being treated:

Antimalarial:

HCQ accumulates in parasitic lysosomes, raising pH and inhibiting heme polymerase, which is essential for detoxifying heme. This leads to toxic heme accumulation and parasite death.

Immunomodulatory:

Inhibits antigen presentation, cytokine production, and toll-like receptor signaling.

Stabilizes lysosomal membranes, reducing inflammatory responses.

Antiviral (Experimental):

May interfere with viral entry and replication by altering endosomal pH

Hydroxychloroquine is indicated for:

Rheumatologic Diseases:

Rheumatoid arthritis (RA).

Systemic lupus erythematosus (SLE).

Juvenile idiopathic arthritis (JIA).

Malaria:

Prophylaxis and treatment of uncomplicated malaria (in chloroquine-sensitive regions).

Off-Label Uses:

Chronic Q fever, sarcoidosis, porphyria cutanea tarda.

Investigational use in viral infections (e.g., COVID-19, though evidence is limited).

Adults:

Rheumatologic Diseases: 200–400 mg daily (max 6.5 mg/kg/day to reduce toxicity).

Malaria Prophylaxis: 400 mg once weekly, starting 1–2 weeks before travel and continuing for 4 weeks after return.

Malaria Treatment: 800 mg initially, followed by 400 mg at 6, 24, and 48 hours.

Children:

Rheumatologic Diseases: 5–6.5 mg/kg/day (max 400 mg/day).

Malaria Prophylaxis: 5 mg/kg once weekly (max 400 mg).

Special Populations:

Renal Impairment: Reduce dose or avoid in severe impairment.

Hepatic Impairment: Use with caution; monitor LFTs

Common: Nausea, diarrhea, headache, rash.

Serious:

Ocular Toxicity: Retinopathy (irreversible vision loss; risk increases with cumulative dose >1000 g).

Cardiotoxicity: QT prolongation, cardiomyopathy.

Hematologic: Agranulocytosis, thrombocytopenia.

Neurologic: Seizures, peripheral neuropathy.

Hypoglycemia: Especially in diabetics

Ocular Monitoring:

Baseline and annual eye exams (visual acuity, fundoscopy, visual fields).

Discontinue if retinopathy is suspected.

Cardiac Monitoring:

ECG for QT prolongation in high-risk patients.

Pregnancy/Lactation:

Category C: Use only if benefits outweigh risks.

Excreted in breast milk; avoid breastfeeding.

G6PD Deficiency:

Risk of hemolysis; monitor CBC

Hydroxychloroquine interacts with:

QT-Prolonging Drugs:

Antiarrhythmics (e.g., amiodarone), macrolides (e.g., azithromycin) – additive risk of arrhythmias.

Antidiabetics:

Enhanced hypoglycemic effect (monitor blood glucose).

Digoxin:

Increased digoxin levels (monitor serum levels).

Mefloquine:

Increased risk of seizures.

Cimetidine:

Increased HCQ levels (avoid combination).

Generic: Hydroxychloroquine sulfate.

Brand Names: Plaquenil (US), Quinoric (UK).