Hydroxychloroquine (Plaquenil®): How it works, benefits, and risks

Hydroxychloroquine (Plaquenil®): How it works, benefits, and risks

By Dr. Jane B. Ayala, FACR and Dr. Thomas A. Rennie, FACR Board Certified in Internal Medicine and Rheumatology

Image Credits: Alain Pitton | NurPhoto | Getty Images

Explained the way we would discuss it with a patient in clinic.

 

What is hydroxychloroquine?

Hydroxychloroquine is a medication originally developed to treat malaria, but for many years it has been a core treatment for autoimmune diseases like lupus, rheumatoid arthritis, and some inflammatory arthritis conditions.

It is not an immunosuppressant in the way drugs like methotrexate or biologics are. Instead, it calms an overactive immune system.

It is one of our safest medications, does NOT lower the immune system, it modulates it. It is even recommended for pregnant patients, especially patients with lupus. 

 

How does hydroxychloroquine work?

In autoimmune diseases, the immune system is overactive and mistakenly attacks your own tissues. Hydroxychloroquine helps by:

  • Reducing immune system “over-signaling”
    It interferes with how immune cells communicate and process inflammatory signals.
  • Decreasing inflammation
    This helps reduce joint pain, swelling, rashes, fatigue, and other symptoms.
  • Stabilizing disease activity over time
    In lupus especially, it helps prevent disease flares and organ damage.

 

Think of it as turning down the volume on the immune system rather than shutting it off.

 

What are the benefits?

Hydroxychloroquine is one of the safest long-term medications we use in rheumatology.

Benefits include:

  • Reduces joint pain, swelling, rashes, and fatigue
  • Helps prevent disease flares (especially in lupus)
  • May protect organs like the kidneys and heart in lupus
  • Can improve cholesterol and blood sugar levels -- PEARL: decreases insulin resistance 
  • Allows lower doses of steroids like prednisone
  • Safe in pregnancy and breastfeeding (important for many patients)

 

Important: It works slowly. Most people notice benefit after 6–12 weeks, and full benefit may take 3–6 months.

 

What are the risks and side effects?

Most people tolerate hydroxychloroquine very well, but no medication is risk-free.

Common, usually mild side effects:

  • Nausea or upset stomach (often improves if taken with food)
  • Diarrhea
  • Headache
  • Skin darkening or mild rash

 

Rare but important risks:

Eye toxicity (retinopathy)

  • This is the most discussed risk, but it is rare, especially at proper dosing. We use 5mg/Kg/day dose!
  • Risk increases with:
    • High doses
    • Use longer than 5 years
    • Kidney disease

 

When monitored correctly, the risk is well under 1% in the first 5 years.

Very rare risks:

  • Muscle weakness or heart muscle effects (extremely uncommon and usually with long-term, high-dose use)


In summary, hydroxychloroquine is:

  • A cornerstone treatment in autoimmune disease
  • Effective, well-tolerated, and safe for long-term use
  • A medication that prevents flares and protects organs, not just treats symptoms

For most patients, the benefits greatly outweigh the risks, especially when properly dosed and monitored.

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