Comprehensive Guide to Hydroxychloroquine: Uses, Dosage, Side Effects, and More
What is Hydroxychloroquine?
Overview of Hydroxychloroquine
Generic Name: Hydroxychloroquine
Brand Name: Plaquenil, generics
Drug Group: Antimalarial, immunomodulatory (disease-modifying antirheumatic drug, DMARD)
Commonly Used For
- Treat rheumatoid arthritis (RA).
- Manage systemic lupus erythematosus (SLE).
- Prevent and treat malaria.
Key Characteristics
Form: Oral tablets (200 mg, 400 mg) (detailed in Dosage section).
Mechanism: Inhibits toll-like receptor signaling and lysosomal activity, reducing inflammation and parasite replication.
Approval: FDA-approved (1955 for Plaquenil) and EMA-approved for autoimmune diseases and malaria.
Indications and Uses of Hydroxychloroquine
Hydroxychloroquine is indicated for a range of autoimmune, infectious, and off-label conditions, leveraging its dual antimalarial and anti-inflammatory effects:
Rheumatoid Arthritis (RA): Alleviates joint pain, swelling, and stiffness, per rheumatology guidelines, supported by clinical trials showing improved American College of Rheumatology (ACR) scores within 6 months.
Systemic Lupus Erythematosus (SLE): Manages skin rashes, arthritis, and fatigue, reducing flare-ups, recommended in lupus treatment protocols with evidence of decreased anti-dsDNA levels.
Malaria Prevention and Treatment: Prevents and treats uncomplicated Plasmodium falciparum malaria, effective in chloroquine-sensitive regions, with infectious disease data.
Discoid Lupus Erythematosus (DLE): Investigated off-label to control chronic skin lesions, with dermatology-rheumatology evidence.
Porphyria Cutanea Tarda (PCT): Managed off-label to reduce photosensitivity and skin fragility, with hematology-dermatology studies.
Sjogren’s Syndrome: Explored off-label to alleviate dry eyes and mouth, with rheumatology research.
COVID-19 (Historical): Previously investigated off-label during the 2020 pandemic for viral load reduction, though efficacy is unproven, per recent infectious disease reviews.
Q Fever: Used off-label in chronic cases to prevent relapse, with infectious disease evidence.
Polymyalgia Rheumatica: Initiated off-label as an adjunct to steroids, with rheumatology data.
Chronic Urticaria: Applied off-label to manage refractory hives, with allergy-immunology studies.
Dosage of Hydroxychloroquine
Dosage for Adults
Rheumatoid Arthritis (RA):
- Initial: 400–600 mg daily (divided doses), maintenance: 200–400 mg daily, adjusted based on response after 4–12 weeks.
Systemic Lupus Erythematosus (SLE):
- 200–400 mg daily, with a maximum of 5 mg/kg of ideal body weight to minimize toxicity.
Malaria Prevention:
- 400 mg once weekly, starting 2 weeks before travel and continuing for 4 weeks after leaving endemic areas.
Malaria Treatment:
- 800 mg initially, followed by 400 mg at 6, 24, and 48 hours (total 2 g over 3 days), often with other antimalarials.
Dosage for Children (≥6 years)
Juvenile Idiopathic Arthritis (JIA) or Malaria:
- 5–6.5 mg/kg of ideal body weight daily (max 400 mg), under pediatric rheumatology or infectious disease supervision.
Dosage for Pregnant Women
Pregnancy Category C: Use only if benefits outweigh risks; consult an obstetrician, with fetal monitoring and dose adjustment based on weight.
Dosage Adjustments
Renal Impairment:
- Mild (CrCl 50–80 mL/min): No adjustment; monitor closely.
- Moderate to Severe (CrCl <50 mL/min): Reduce to 50% of dose; avoid if <10 mL/min.
Hepatic Impairment:
- Mild to moderate (Child-Pugh A or B): Use cautiously; severe (Child-Pugh C): Avoid due to limited data.
Concomitant Medications: Adjust if combined with QT-prolonging drugs (e.g., azithromycin); monitor ECG.
Elderly: Start with 200 mg daily; monitor for retinal and cardiac effects.
Weight-Based Dosing: Cap at 5 mg/kg of ideal body weight to reduce toxicity risk.
Additional Considerations
- Take this active ingredient with food or milk to reduce gastrointestinal upset.
- Use a consistent daily schedule to maintain steady blood levels.
- Avoid antacids within 4 hours of dosing to prevent absorption interference.
How to Use Hydroxychloroquine
Administration:
Oral: Swallow tablets whole with water or a meal, avoiding crushing or chewing.
Divide doses if >400 mg daily to improve tolerability.
Timing: Take at the same time each day, preferably with breakfast or dinner.
Monitoring: Watch for vision changes, muscle weakness, or signs of arrhythmias (e.g., palpitations); report changes immediately.
Additional Tips:
- Store at 20–25°C (68–77°F), protecting from light and moisture.
- Keep out of reach of children due to overdose risk.
- Schedule baseline and annual eye exams (e.g., retinal imaging) to monitor for toxicity.
- Use sunscreen and protective clothing to reduce photosensitivity during therapy.
- Educate patients on recognizing early retinal symptoms (e.g., blurred vision, color changes) and reporting promptly.
Contraindications for Hydroxychloroquine
Hypersensitivity: Patients with a known allergy to Hydroxychloroquine, chloroquine, or 4-aminoquinoline derivatives.
Retinopathy: Contraindicated in pre-existing macular degeneration or severe retinal disease due to toxicity risk.
Severe Cardiac Conditions: Avoid in patients with QT prolongation, bradycardia, or heart block without pacemaker.
Porphyria: Contraindicated in porphyria cutanea tarda or other porphyrias due to exacerbation risk.
Psoriasis: Avoid in severe psoriasis as it may trigger flares.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: Contraindicated due to hemolysis risk.
Severe Hepatic Disease: Contraindicated in Child-Pugh Class C due to impaired metabolism.
Warnings & Precautions for Hydroxychloroquine
General Warnings
Retinal Toxicity: Risk of irreversible maculopathy with long-term use (>5 years); perform annual screening after 5 years.
Cardiotoxicity: Risk of QT prolongation and cardiomyopathy; monitor ECG in at-risk patients.
Hypoglycemia: Risk in diabetic patients; monitor glucose levels.
Myopathy/Neuropathy: Risk with prolonged use; assess muscle strength periodically.
Bone Marrow Suppression: Rare risk of agranulocytosis; monitor CBC.
Additional Warnings
Hepatotoxicity: Rare liver enzyme elevation; check LFTs in hepatic disease.
Psoriasis Exacerbation: Risk of flares; avoid unless benefits outweigh risks.
Seizure Risk: Rare exacerbation; discontinue if seizures occur.
Hypersensitivity Reactions: Rare Stevens-Johnson syndrome; stop if severe.
Ocular Effects: Risk of corneal deposits; monitor with slit-lamp exams.
Use in Specific Populations
Pregnancy: Category C; use with caution, monitoring fetal outcomes.
Breastfeeding: Use caution; monitor infant for effects.
Elderly: Higher risk of retinal and cardiac toxicity; start with lower doses.
Children: Safe for JIA or malaria with supervision.
Renal/Hepatic Impairment: Adjust or avoid based on severity.
Additional Precautions
- Inform your doctor about retinal disease, heart conditions, or G6PD deficiency before starting this medication.
- Avoid prolonged sun exposure to reduce photosensitivity risk.
- Use with caution in patients with a history of mental health disorders due to rare neuropsychiatric effects.
Overdose and Management of Hydroxychloroquine
Overdose Symptoms
Nausea, vomiting, or drowsiness.
Severe cases: Hypoglycemia, seizures, or cardiac arrest (QT prolongation).
Vision changes, confusion, or hypotension as early signs.
Coma or respiratory failure with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer activated charcoal if ingestion is recent, monitor vital signs, and provide IV fluids.
Specific Treatment: No specific antidote; use diazepam for seizures and sodium bicarbonate for QT prolongation under specialist guidance.
Monitor: Check ECG, glucose, and eye function for 24–48 hours; assess for arrhythmias.
Patient Education: Advise against self-adjusting doses and to store safely away from children.
Additional Notes
- Overdose risk is significant; store securely and limit access.
- Report persistent symptoms (e.g., severe vision loss, irregular heartbeat) promptly.
Side Effects of Hydroxychloroquine
Common Side Effects
- Nausea (10–20%, managed with food)
- Headache (5–15%, relieved with rest)
- Dizziness (5–10%, decreases with time)
- Rash (3–8%, managed with antihistamines)
- Abdominal Pain (2–6%, reduced with divided doses)
These effects may subside with adaptation.
Serious Side Effects
Seek immediate medical attention for:
- Ocular: Retinopathy or maculopathy with vision loss.
- Cardiac: QT prolongation, torsades de pointes, or cardiomyopathy.
- Hematologic: Agranulocytosis or hemolysis in G6PD deficiency.
- Neurological: Seizures or psychosis.
- Allergic: Stevens-Johnson syndrome or anaphylaxis.
Additional Notes
Regular monitoring with annual ophthalmologic exams (e.g., fundus autofluorescence) is essential after 5 years of use.
ECG monitoring is recommended in patients with cardiac risk factors or on QT-prolonging drugs.
Patients with G6PD deficiency should have baseline and periodic hemoglobin checks.
Report any unusual symptoms (e.g., halos around lights, muscle weakness) immediately to a healthcare provider.
Long-term use (>5 years) requires specialist oversight for retinal and cardiac health.
Drug Interactions with Hydroxychloroquine
This active ingredient may interact with:
- QT-Prolonging Drugs: Increases arrhythmia risk (e.g., amiodarone, azithromycin); monitor ECG.
- Antidiabetic Agents: Enhances hypoglycemia (e.g., insulin); adjust dose.
- Antacids: Reduces absorption; separate by 4 hours.
- Immunosuppressants: Potentiates immunosuppression (e.g., methotrexate); monitor.
- Digoxin: Increases levels; check digoxin levels.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Use this antimalarial as prescribed for autoimmune or malaria treatment, following the daily schedule.
Monitoring: Report vision changes, heart palpitations, or signs of infection immediately.
Lifestyle: Avoid excessive sun exposure; wear protective clothing.
Diet: Take with meals; avoid antacids near dosing.
Emergency Awareness: Know signs of overdose or retinal damage; seek care if present.
Follow-Up: Schedule regular check-ups every 3–6 months to monitor eyes, heart, and blood counts.
Pharmacokinetics of Hydroxychloroquine
Absorption: Oral, peak at 2–4 hours; bioavailability ~70–75%.
Distribution: Volume of distribution ~40–50 L/kg; concentrates in tissues (e.g., liver, retina).
Metabolism: Hepatic via CYP2D6, CYP3A4, and CYP2C8 to active metabolites.
Excretion: Primarily renal (20–30% unchanged); half-life 40–50 days.
Half-Life: 40–50 days, with accumulation over months.
Pharmacodynamics of Hydroxychloroquine
This drug exerts its effects by:
Inhibiting toll-like receptor (TLR) signaling, reducing pro-inflammatory cytokines in RA and SLE.
Interfering with heme polymerase in Plasmodium, killing malaria parasites.
Exhibiting dose-dependent risks of retinopathy and QT prolongation.
Storage of Hydroxychloroquine
Temperature: Store at 20–25°C (68–77°F); protect from light and moisture.
Protection: Keep in original container, away from heat and humidity.
Safety: Store in a secure location out of reach of children due to toxicity risk.
Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Hydroxychloroquine treat?
A: This medication treats arthritis, lupus, and malaria.
Q: Can this active ingredient cause vision changes?
A: Yes, retinal issues are possible; get regular eye exams.
Q: Is Hydroxychloroquine safe for children?
A: Yes, for JIA or malaria with supervision.
Q: How is this drug taken?
A: Orally as tablets, with food.
Q: How long is Hydroxychloroquine treatment?
A: Months to years for autoimmune diseases, weeks for malaria.
Q: Can I use Hydroxychloroquine if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 1955 (Plaquenil) for RA, SLE, and malaria.
European Medicines Agency (EMA): Approved for autoimmune diseases and malaria prophylaxis.
Other Agencies: Approved globally for rheumatologic and infectious use; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Plaquenil (Hydroxychloroquine) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Hydroxychloroquine Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Hydroxychloroquine: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Hydroxychloroquine.
- WHO’s inclusion of Hydroxychloroquine for malaria and autoimmune diseases.
- Arthritis & Rheumatology. (2022). Hydroxychloroquine in SLE.
- Peer-reviewed article on Hydroxychloroquine efficacy (note: access may require a subscription).
