HYDROXYCHLOROQUINE — 200 mg film‑coated tablets

Hydroxychloroquine is a 4-aminoquinoline compound first approved by the U.S. FDA in 1955, making it one of the oldest drugs still in widespread clinical use. Originally developed as an antimalarial, it has become a cornerstone of treatment for autoimmune diseases due to its immunomodulatory properties. It is structurally similar to chloroquine but has a more favorable safety profile, particularly with respect to ocular toxicity at therapeutic doses. During the COVID-19 pandemic, hydroxychloroquine gained global attention, but large clinical trials subsequently failed to demonstrate efficacy for COVID-19 treatment or prophylaxis .

Mechanism of action: The mechanisms of hydroxychloroquine are complex and incompletely understood. As a weak base, it accumulates in acidic intracellular compartments such as lysosomes and endosomes, raising their pH and inhibiting lysosomal hydrolases. This alkalinization disrupts antigen processing and presentation, reduces Toll-like receptor (TLR) signaling, and inhibits autophagy. It also downregulates the expression of CXCR4, inhibits HMGB1, alters intracellular calcium flux, and prevents thrombus formation . In autoimmune diseases, these actions result in reduced production of pro-inflammatory cytokines (IL-1, IL-6, TNF-α), decreased T-cell and B-cell activation, and attenuation of autoantibody production .

Clinical indications: Hydroxychloroquine is indicated for the treatment of systemic lupus erythematosus (SLE), discoid lupus erythematosus, and rheumatoid arthritis in adults. In SLE, it reduces disease flares, prevents organ damage, and improves long-term survival. It is also used off-label for other autoimmune conditions including Sjögren’s syndrome, sarcoidosis, and antiphospholipid syndrome. For malaria, it remains effective for treatment and prophylaxis in geographic regions without chloroquine resistance, but it is not recommended for Plasmodium falciparum acquired in areas with known resistance .

Pharmacokinetics: Hydroxychloroquine is rapidly absorbed after oral administration with high bioavailability (78-100%). It has an extremely large volume of distribution (111-285 L/kg or higher) due to extensive tissue binding, including concentration in erythrocytes and melanin-containing tissues. The drug accumulates slowly over weeks to months, with steady-state not reached for 3-6 months. Elimination is prolonged, with a terminal half-life of 40-50 days. Approximately 50% is excreted unchanged in urine, with the remainder metabolized via hepatic CYP enzymes (primarily CYP2D6, CYP3A4, and CYP2C8). Renal impairment significantly increases drug exposure and toxicity risk .

• Known hypersensitivity to hydroxychloroquine, chloroquine, or any 4-aminoquinoline compounds .
• Pre-existing maculopathy of the eye (retinal disease) .

• QT-prolonging drugs (amiodarone, moxifloxacin, halofantrine, Class IA/III antiarrhythmics, tricyclic antidepressants, antipsychotics): Increased risk of ventricular arrhythmias. Avoid or use with extreme caution .
• Tamoxifen: Concomitant use significantly increases risk of retinal toxicity .
• Macrolide antibiotics (azithromycin, clarithromycin, erythromycin): Increased risk of cardiovascular events and QT prolongation .
• Digoxin: Hydroxychloroquine may increase digoxin levels; monitor serum digoxin .
• Anti-diabetic drugs (insulin, sulfonylureas, metformin): Enhanced hypoglycemic effect; may require dose reduction of antidiabetic agents .
• Cyclosporine: Increased plasma cyclosporine levels reported .
• Antacids and kaolin: May decrease hydroxychloroquine absorption. Separate dosing by at least 4 hours .
• Cimetidine: May increase hydroxychloroquine levels; monitor for toxicity .
• Rifampicin: May decrease hydroxychloroquine efficacy; monitor clinical response .
• Neostigmine and pyridostigmine: Antagonism of effect; monitor .

• Pregnancy: FDA Category D (historically), but current data suggest small increased risk of major malformations; may be used if benefit outweighs risk. Many experts continue hydroxychloroquine in SLE during pregnancy to prevent flares .
• Lactation: Small amounts excreted in breast milk; compatible with breastfeeding according to AAP, but monitor infant .
• Pediatric use: Indicated for juvenile idiopathic arthritis and discoid SLE. Not recommended in children <31 kg (cannot safely divide 200 mg tablets) .
• Geriatric use: Increased risk of retinal toxicity; more frequent ophthalmologic screening recommended .
• Renal impairment: Significant renal impairment (eGFR <30 mL/min) increases drug exposure and risk of toxicity; dose adjustment or monitoring recommended. Bafna Pharmaceuticals label advises caution .
• Hepatic impairment: Severe hepatic impairment increases risk of hepatotoxicity; monitor LFTs closely .
• G6PD deficiency: Monitor for hemolytic anemia; use with caution .
• Porphyria: Avoid in patients with porphyria cutanea tarda (may exacerbate) .
• Psoriasis: Avoid in psoriasis (may increase risk of skin reactions) .

• Rheumatoid arthritis: Initial 400-600 mg daily. Chronic maintenance: 200 mg once daily or 400 mg daily (in single or divided doses). Minimum effective dose should not exceed 6.5 mg/kg/day based on ideal body weight. Discontinue if no improvement by 6 months .
• Systemic lupus erythematosus / Discoid lupus: 200 mg once daily or 400 mg once daily (or in two divided doses) .
• Malaria prophylaxis: 400 mg once weekly (adults), beginning 2 weeks before travel to endemic area, continuing weekly while in area, and for 4 weeks after leaving .
• Malaria treatment (uncomplicated): See full prescribing information for weight-based dosing (typically 800 mg initially, then 400 mg at 6, 24, and 48 hours) .
• Maximum daily dose: ≤6.5 mg/kg/day (based on ideal body weight). For obesity, use real weight with caution and keep under 400 mg/day for severely obese patients .
• Administration: Take with food or a glass of milk. Swallow tablets whole; do not crush or divide (tablets may have score line for ease of swallowing only, not for dose division) .

• Symptoms: Headache, visual disturbances, hypotension, convulsions, cardiac arrhythmias, followed by sudden respiratory depression and cardiac arrest. Children are particularly sensitive to overdose .
• Management: Immediate hospital transfer. No specific antidote. Emesis or gastric lavage if early. Activated charcoal may reduce absorption. Supportive care including cardiac monitoring, airway management, and seizure control .