Hydroxychloroquine sulfate is a disease-modifying antirheumatic drug (DMARD) with a well-established profile in clinical practice. Originally developed for its antimalarial properties, its potent immunomodulatory and anti-inflammatory effects have made it a fundamental therapeutic agent in the management of autoimmune conditions. This medication works by interfering with antigen processing and toll-like receptor signaling, leading to a downregulation of the immune response. Its favorable safety and tolerability profile, coupled with its oral administration, have secured its position as a first-line and long-term maintenance therapy for millions of patients worldwide.

Features

• Active Ingredient: Hydroxychloroquine Sulfate
• Standard Tablet Strengths: 200 mg (equivalent to 155 mg base) and, less commonly, 100 mg
• Pharmacologic Class: 4-Aminoquinoline compound, classified as an Antimalarial and Disease-Modifying Antirheumatic Drug (DMARD)
• Mechanism of Action: Exact mechanism in autoimmune diseases is multifactorial and incompletely understood but is believed to involve raising the pH of intracellular vesicles, inhibiting antigen presentation, Toll-like receptor (TLR) signaling, and cytokine production.
• Administration: Oral tablet, taken with food or milk to minimize gastrointestinal upset.
• Bioavailability: Rapid and nearly complete absorption from the gastrointestinal tract.
• Half-Life: Extremely long, with a terminal elimination half-life of approximately 40-50 days due to extensive tissue binding and slow release.
• Metabolism: Partially metabolized in the liver by the cytochrome P450 system (CYP2D6, CYP3A4, CYP2C8) into active and inactive metabolites.
• Excretion: Primarily excreted renally, with a smaller portion eliminated in feces.

Benefits

• Effective Disease Control: Provides significant symptomatic relief from pain, swelling, and stiffness associated with autoimmune arthritis and lupus.
• Disease Modification: Helps to slow the progression of joint damage in rheumatoid arthritis and reduce the frequency and severity of disease flares in systemic lupus erythematosus (SLE).
• Steroid-Sparing Effect: Allows for the reduction of corticosteroid dosage, thereby mitigating the risk of long-term steroid-related adverse effects such as osteoporosis, diabetes, and cataracts.
• Favorable Long-Term Safety Profile: Generally well-tolerated for chronic use with a predictable and often manageable side effect profile when monitored appropriately.
• Reduction of Systemic Complications: In SLE, it is associated with a reduced risk of thrombotic events, organ damage, and improved lipid profiles.
• Convenient Dosing: Typically administered once or twice daily, promoting high rates of patient adherence to the treatment regimen.

Common use

Hydroxychloroquine is FDA-approved for the treatment of uncomplicated malaria (due to susceptible strains of Plasmodium vivax, P. malariae, P. ovale, and P. falciparum), chronic discoid lupus erythematosus, and systemic lupus erythematosus (SLE). It is also approved for the treatment of acute and chronic rheumatoid arthritis in adults. Beyond its approved indications, it holds an essential place in off-label management for other autoimmune conditions such as Sjögren’s syndrome, palindromic rheumatism, and cutaneous manifestations of lupus. Its use is almost always chronic in these contexts, aimed at long-term disease control and remission maintenance.

Dosage and direction

Dosing is critically based on ideal body weight to minimize the risk of irreversible retinal toxicity. The maximum recommended daily dose is ≤5.0 mg/kg real body weight.

• Rheumatoid Arthritis & Lupus (Adults): The initial dose is typically 400 mg to 600 mg (310 mg to 465 mg base) administered orally once daily or in divided doses. After a good response is observed (usually 4-12 weeks), the dose is often reduced by 50% and maintained at 200 mg to 400 mg (155 mg to 310 mg base) daily.
• Malaria Prophylaxis: 400 mg (310 mg base) once weekly, starting 1-2 weeks before travel to an endemic area and continuing for 4 weeks after leaving.
• Malaria Treatment: A loading dose followed by a second dose 6-8 hours later, a third dose on day 2, and a final dose on day 3 (specific mg/kg dosing protocols must be followed).
• Administration: Tablets should be taken with a meal or a glass of milk to reduce the potential for gastrointestinal irritation.

Crucial Note: Dosing must be individualized by a physician. Patients must never self-adjust their dose.

Precautions

• Ophthalmologic Monitoring: Mandatory baseline ophthalmologic examination within the first year of starting therapy, followed by annual screenings after 5 years of use (or more frequently for patients with additional risk factors: high dose, renal impairment, pre-existing retinal disease, age >60 years). This monitors for irreversible retinopathy.
• Cardiac Monitoring: Use with caution in patients with pre-existing cardiac disease or those on other drugs that prolong the QT interval, as hydroxychloroquine can cause conduction disorders.
• Hepatic and Renal Impairment: Dose adjustment or avoidance may be necessary in patients with severe hepatic or renal impairment due to altered metabolism and excretion.
• Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: Can cause hemolysis in patients with G6PD deficiency; screening should be considered in at-risk populations.
• Psoriasis: May exacerbate psoriasis; use with extreme caution in patients with this condition.
• Porphyria: May exacerbate porphyria; is contraindicated in patients with porphyria cutanea tarda.
• Myasthenia Gravis: May exacerbate muscle weakness in patients with myasthenia gravis.

Contraindications

Hydroxychloroquine is contraindicated in patients with:

• Known hypersensitivity to 4-aminoquinoline compounds (e.g., chloroquine, hydroxychloroquine).
• Preexisting retinal field changes attributable to any 4-aminoquinoline compound.
• Long-term use in children is contraindicated except for the treatment of juvenile idiopathic arthritis (JIA) under strict specialist supervision.

Possible side effect

The majority of side effects are dose-related and often reversible upon dose reduction or discontinuation.

• Common: Gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal cramps), headache, dizziness, skin rash, and pruritus.
• Ophthalmologic: The most serious adverse reaction is irreversible retinopathy with visual field defects (paracentral scotomas). Corneal deposits (vertillata) may also occur but are usually benign and reversible.
• Neuromuscular: Skeletal muscle myopathy or neuropathy leading to progressive weakness and atrophy of proximal muscle groups.
• Neuropsychiatric: Irritability, nervousness, emotional changes, nightmares, psychosis, and seizures.
• Dermatologic: Hair bleaching, alopecia, and skin pigmentation changes.
• Hematologic: Rare reports of bone marrow suppression, including agranulocytosis, aplastic anemia, and thrombocytopenia.
• Cardiac: Cardiomyopathy, conduction disturbances (e.g., bundle branch block, atrioventricular block), and QT interval prolongation.

Drug interaction

Hydroxychloroquine has the potential for significant interactions:

• QT-Prolonging Agents: Concomitant use with other drugs known to prolong the QT interval (e.g., antiarrhythmics like amiodarone, antipsychotics, macrolide antibiotics, fluoroquinolones) increases the risk of life-threatening cardiac arrhythmias, including Torsades de Pointes.
• Digoxin: Hydroxychloroquine may increase serum digoxin levels.
• Insulin and Oral Hypoglycemics: May enhance the effects of these drugs, increasing the risk of hypoglycemia.
• Mefloquine: Co-administration may increase the risk of convulsions.
• Antiepileptics (e.g., carbamazepine, phenytoin): May lower antiepileptic levels, reducing their efficacy.
• Cyclosporine: Concomitant use may increase cyclosporine plasma levels.
• Praziquantel: Hydroxychloroquine may reduce the bioavailability and effectiveness of praziquantel.
• CYP2D6 Substrates: Hydroxychloroquine inhibits CYP2D6 and may increase levels of drugs metabolized by this enzyme (e.g., metoprolol, dextromethorphan, some antidepressants).

Missed dose

• If a dose is missed, it should be taken as soon as it is remembered.
• However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not double the dose to make up for the missed one.
• Patients should maintain their regular dosing schedule and inform their physician of any significant pattern of missed doses.

Overdose

Hydroxychloroquine overdose is extremely dangerous and can be rapidly fatal due to cardiovascular collapse. Symptoms of acute toxicity can occur within 30 minutes of ingestion and include headache, drowsiness, visual disturbances, cardiovascular collapse, convulsions, hypokalemia, and sudden respiratory and cardiac arrest. Management is supportive and must occur in a hospital setting with intensive care capabilities. Treatment may include prompt gastric lavage, activated charcoal (within the first hour), early mechanical ventilation, and aggressive management of hypokalemia and cardiac arrhythmias. There is no specific antidote.

Storage

• Store at room temperature, between 20°C to 25°C (68°F to 77°F).
• Keep in the original container, tightly closed, and protected from light and moisture.
• Keep out of reach of children and pets.
• Do not flush medications down the toilet or pour them into a drain. Dispose of unused medication through a medicine take-back program or according to FDA guidelines.

Disclaimer

This information is for educational and informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting or stopping any medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content provided has been compiled from various medical sources but may not be exhaustive or reflect the most up-to-date, product-specific prescribing information.

Reviews

• “As a rheumatologist with over 20 years of experience, hydroxychloroquine remains a bedrock therapy in my practice for both lupus and RA. Its steroid-sparing benefit is invaluable for long-term patient health.” – Dr. E.L., MD, Rheumatology
• “Managing my SLE has been a journey, but adding hydroxychloroquine was a turning point. My joint pain and fatigue are significantly better, and I’ve had far fewer flares. The peace of mind is worth the annual eye check.” – Patient A., 42
• “From a pharmacological standpoint, its immunomodulatory mechanisms, while complex, provide a unique and effective approach to calming systemic autoimmunity with a generally manageable side effect profile when monitored correctly.” – Clinical Pharmacist Specialist
• “The requirement for diligent ophthalmologic surveillance cannot be overstated. It is the single most important factor in preventing the rare but devastating complication of retinopathy.” – Dr. S.K., MD, Ophthalmology
• “It took about three months to feel the full effect, but the improvement in my rheumatoid arthritis symptoms was profound. I can now perform daily tasks with much less discomfort.” – Patient R., 58