Hydroxychloroquine is an oral disease-modifying antirheumatic drug (DMARD) with immunomodulatory properties, derived from chloroquine with an improved safety profile. It is primarily indicated for the management of autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and for the prophylaxis and treatment of uncomplicated malaria caused by susceptible strains of plasmodium. Its mechanism involves altering acidic intracellular organelles, which impacts antigen processing and cytokine production, leading to downstream immunosuppressive effects. This profile provides a comprehensive overview for healthcare professionals considering its therapeutic application.

Features

• Chemical structure: 4-Aminoquinoline compound
• Available formulations: 200mg and 400mg oral tablets (as hydroxychloroquine sulfate)
• Bioavailability: Approximately 74% following oral administration
• Half-life: Elimination half-life ranges from 40 to 50 days
• Metabolism: Hepatic, via cytochrome P450 enzymes (CYP2D6, CYP3A4, CYP2C8)
• Excretion: Primarily renal (with unchanged drug and metabolites)
• Pregnancy category: FDA Category C (requires risk-benefit assessment)

Benefits

• Provides long-term suppression of autoimmune disease activity and reduces frequency of flares in conditions like SLE
• Demonstrates corticosteroid-sparing effects, allowing reduction of glucocorticoid doses and associated adverse effects
• Offers prophylactic efficacy against malaria in endemic regions with chloroquine-sensitive plasmodium species
• May improve lipid profiles and reduce thrombotic risk in patients with autoimmune conditions
• Shown to retard radiographic progression in rheumatoid arthritis when used as part of combination therapy
• Generally well-tolerated with a predictable side effect profile when appropriately monitored

Common use

Hydroxychloroquine is principally prescribed for the management of autoimmune inflammatory conditions, including systemic lupus erythematosus (for cutaneous and joint manifestations, and for reducing disease flares) and rheumatoid arthritis (as a monotherapy or in combination with other DMARDs). It is also indicated for the prophylaxis and treatment of acute attacks of malaria caused by Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. Off-label uses may include Sjögren’s syndrome, cutaneous lupus erythematosus, and porphyria cutanea tarda, though evidence supporting these applications varies.

Dosage and direction

Dosage must be individualized based on indication, patient weight, and renal/hepatic function. For autoimmune diseases: usual adult dose is 400–600 mg daily initially, then reduced to a maintenance dose of 200–400 mg daily. For malaria prophylaxis: 400 mg once weekly, starting 1–2 weeks before travel and continuing for 4 weeks after leaving endemic area. For malaria treatment: 800 mg initially, followed by 400 mg at 6, 24, and 48 hours. Administer with food or milk to minimize gastrointestinal upset. Regular ophthalmologic screening is mandatory due to retinopathy risk.

Precautions

Baseline and annual ophthalmologic examinations are essential to monitor for irreversible retinopathy. Use with caution in patients with hepatic impairment, severe gastrointestinal disorders, or neurological conditions. Periodic complete blood count should be performed. May exacerbate psoriasis or porphyria. Caution advised in patients with G6PD deficiency due to hemolysis risk. Educate patients on the importance of adherence to monitoring schedules. Not recommended in children under 6 years except for malaria prophylaxis/treatment where benefits outweigh risks.

Contraindications

Hypersensitivity to hydroxychloroquine, 4-aminoquinoline compounds, or any component of the formulation. Contraindicated in patients with pre-existing macular changes or visual field defects. Avoid use in patients with known retinal toxicity from previous quinoline use. Not recommended in patients with severe hepatic or renal impairment without close monitoring. Contraindicated in long-term therapy in children except for specific indications under specialist supervision.

Possible side effect

Common: nausea, abdominal cramps, diarrhea, headache, dizziness, skin rash, pruritus.
Serious but rare: irreversible retinopathy, corneal deposits, cardiomyopathy, conduction disorders, hematologic abnormalities (agranulocytosis, aplastic anemia), severe hypoglycemia, neuromyopathy, psychiatric disturbances (including anxiety, hallucinations).
Ocular side effects require immediate discontinuation and specialist referral. Most gastrointestinal effects are dose-dependent and may resolve with dose reduction.

Drug interaction

May potentiate effects of digoxin, insulin, and oral hypoglycemics. Concurrent use with hepatotoxic drugs or other DMARDs may increase toxicity risk. Drugs that alter renal function or urinary pH may affect excretion. CYP450 inducers (e.g., rifampin) may reduce efficacy; inhibitors may increase levels. Avoid concomitant use with drugs known to prolong QT interval (e.g., macrolides, antipsychotics). May reduce efficacy of typhoid and rabies vaccines.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next dose. Do not double the dose. For weekly malaria prophylaxis: if a dose is missed, take it as soon as possible, then resume the regular weekly schedule. If the missed dose is not remembered until within 2 days of the next dose, skip the missed dose. Consistent adherence is critical for prophylactic efficacy.

Overdose

Overdose can be fatal; symptoms include headache, drowsiness, visual disturbances, cardiovascular collapse, seizures, and hypokalemia. Immediate medical attention is required. Management is supportive: gastric lavage if recent ingestion, activated charcoal, and meticulous electrolyte monitoring (particularly potassium). Respiratory and cardiac support may be necessary. There is no specific antidote.

Storage

Store at controlled room temperature (20–25°C). Protect from light and moisture. Keep in original container with child-resistant closure. Do not store in bathroom or damp areas. Keep out of reach of children and pets. Dispose of unused medication via take-back programs; do not flush.

Disclaimer

This information is intended for healthcare professionals and should not replace clinical judgment. Prescribers must verify indications, contraindications, and dosing based on current guidelines and individual patient factors. Patients should be counseled on risks, benefits, and monitoring requirements. Off-label use should be evidence-based and documented. The prescriber is responsible for staying updated with emerging safety data.

Reviews

Clinical studies and meta-analyses support the efficacy of hydroxychloroquine in reducing disease activity in SLE and RA, with particular benefit in cutaneous and articular manifestations. Long-term observational data confirm its corticosteroid-sparing effect and overall acceptable safety profile with appropriate monitoring. Its role in malaria prophylaxis remains valuable in specific geographic regions. Ongoing research continues to refine its place in therapy, particularly concerning rare adverse effects like retinopathy and cardiotoxicity. Patient-reported outcomes often reflect improved quality of life due to reduced symptom burden and disease progression.