Hydroxychloroquine

Hydroxychloroquine sulfate is an antimalarial and immunomodulatory agent with a well-established role in managing autoimmune disorders and preventing malaria. As a disease-modifying antirheumatic drug (DMARD), it modifies the underlying disease process rather than merely alleviating symptoms. Its mechanism involves altering lysosomal pH and inhibiting antigen presentation, which contributes to its efficacy in controlling systemic inflammation. This profile provides a comprehensive overview for healthcare professionals considering its therapeutic application.

Features

• Chemical name: Hydroxychloroquine sulfate
• Molecular formula: C₁₈H₂₆ClN₃O · H₂SO₄
• Available forms: Oral tablets (200 mg base equivalent to 155 mg base hydroxychloroquine sulfate)
• Half-life: Approximately 40 days
• Metabolism: Hepatic via CYP2D6, CYP3A4, CYP2C8
• Excretion: Renal (partial) and fecal
• Pregnancy category: C (requires risk-benefit assessment)

Benefits

• Provides long-term suppression of autoimmune activity in conditions like rheumatoid arthritis and systemic lupus erythematosus
• Reduces frequency and severity of disease flares through immunomodulatory action
• Demonstrates corticosteroid-sparing effects, minimizing long-term steroid complications
• Offers prophylactic protection against malaria in endemic regions
• Shows favorable safety profile relative to other DMARDs when monitored appropriately
• May improve lipid profiles and reduce thrombotic risk in certain patient populations

Common use

Hydroxychloroquine is primarily indicated for the treatment of uncomplicated malaria caused by Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. Its major therapeutic application lies in managing autoimmune conditions including rheumatoid arthritis, systemic lupus erythematosus, and discoid lupus erythematosus. Off-label uses include Sjögren’s syndrome, porphyria cutanea tarda, and certain photodermatoses. The drug’s immunomodulatory effects make it particularly valuable in controlling cutaneous and articular manifestations of autoimmune diseases.

Dosage and direction

Rheumatoid arthritis: Initial adult dose is 400-600 mg daily (as sulfate). Maintenance dose typically ranges from 200-400 mg daily based on response and tolerability.

Systemic lupus erythematosus: 400 mg once or twice daily initially, reducing to 200-400 mg daily for maintenance.

Malaria prophylaxis: 400 mg weekly starting 1-2 weeks before exposure and continuing for 4 weeks after leaving endemic area.

Administration should occur with food or milk to minimize gastrointestinal upset. Regular ophthalmologic examinations are mandatory due to retinal toxicity risk. Dosage adjustments are necessary in renal impairment and elderly patients.

Precautions

Baseline and quarterly ophthalmologic examinations are essential to monitor for retinal changes. Complete blood count, liver function tests, and renal function should be assessed periodically. Patients should be advised about potential photosensitivity and appropriate sun protection measures. Caution is advised in patients with hepatic disease, alcoholism, or concomitant hepatotoxic drugs. Regular monitoring for muscle weakness is recommended as myopathy may occur. Patients with glucose-6-phosphate dehydrogenase deficiency may develop hemolysis.

Contraindications

Hypersensitivity to hydroxychloroquine, 4-aminoquinoline compounds, or any component of the formulation. Contraindicated in patients with pre-existing retinal field changes attributable to 4-aminoquinoline compounds. Not recommended in patients with known porphyria. Avoid use in children for long-term therapy except for malaria treatment/prophylaxis. Concomitant use with other drugs known to cause retinal toxicity is contraindicated.

Possible side effect

Common (>10%): Nausea, abdominal cramps, diarrhea, headache, dizziness, pruritus Less common (1-10%): Skin eruptions, bleaching of hair, alopecia, anorexia, weight loss Rare (<1%): Retinopathy, corneal deposits, neuromyopathy, blood dyscrasias, cardiomyopathy Ophthalmic: Vortex keratopathy (corneal deposits), retinal pigmentary changes, visual field defects Neuropsychiatric: Anxiety, emotional lability, psychosis, seizures Dermatological: Photosensitivity, pigmentary changes, erythema multiforme

Drug interaction

Significant interactions:

• Digoxin (increased digoxin levels)
• Insulin and oral hypoglycemics (enhanced hypoglycemic effect)
• Cyclosporine (increased cyclosporine levels)
• Antacids (reduced absorption - separate administration by 4 hours)
• CYP2D6 substrates (potential altered metabolism)
• Drugs that prolong QT interval (additive effect)
• Mefloquine (increased seizure risk)

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 return to the regular weekly schedule. If the missed dose is not remembered until within 2 days of the next dose, omit the missed dose and resume the regular schedule.

Overdose

Symptoms include headache, drowsiness, visual disturbances, cardiovascular collapse, seizures, and hypokalemia. Cardiac manifestations include QRS and QT prolongation, heart block, and ventricular arrhythmias. Management involves immediate gastric lavage and activated charcoal within 1 hour of ingestion. Respiratory support and ECG monitoring are essential. Intravenous diazepam may control seizures. Potassium supplementation may be required for hypokalemia. Hemodialysis is not effective due to extensive tissue binding.

Storage

Store at controlled room temperature (20-25°C or 68-77°F). Protect from light and moisture. Keep in original container with tight closure. Keep out of reach of children. Do not use if tablets show signs of discoloration or deterioration. Dispense in light-resistant container.

Disclaimer

This information is intended for healthcare professionals and should not replace clinical judgment. Dosage must be individualized based on patient characteristics and response. Prescribers should consult full prescribing information before initiating therapy. Regular monitoring is essential for safe use. The benefits and risks should be carefully considered in each patient.

Reviews

Clinical studies demonstrate hydroxychloroquine’s efficacy in maintaining remission in autoimmune diseases. The 2019 ACR guidelines position it as a first-line therapy for mild to moderate SLE. Systematic reviews confirm its steroid-sparing benefits and favorable safety profile with appropriate monitoring. Malaria prophylaxis studies show 90-95% efficacy when compliance is maintained. Long-term observational data support its cardiovascular benefits in rheumatic diseases. Ongoing research continues to elucidate its mechanisms and potential applications in viral infections and metabolic disorders.