Hydroxychloroquine Side Effects: What to Expect and When to Call Your Doctor

Hydroxychloroquine (Plaquenil) has been used for decades and has a relatively favorable safety profile compared to many other DMARDs. Most patients tolerate it well. However, like all medications, it can cause side effects — some minor and manageable, others requiring prompt medical attention. This guide covers what to realistically expect, how to minimize common side effects, and which warning signs require a call to your doctor.

Common Side Effects of Hydroxychloroquine

These side effects are the most frequently reported and are usually mild and manageable:

• Nausea and stomach upset: The most common side effect, especially when starting the medication. Taking hydroxychloroquine with food or milk significantly reduces this. Tablets can also be crushed and mixed with jam or jelly if swallowing is difficult.
• Diarrhea and vomiting: Usually occurs early in treatment and often improves over time. GI symptoms that persist beyond the first few weeks should be discussed with your doctor.
• Headache: Reported in some patients, typically mild and transient.
• Dizziness: Some patients report mild dizziness, especially at the start of therapy.
• Blurred vision (early): Mild, transient blurred vision can occur. This is different from the serious retinopathy described below — if vision changes are new, always report them to your doctor.
• Skin rash: Some patients develop a rash, which may be worsened by sunlight. Using sunscreen and sun-protective clothing is recommended for patients on hydroxychloroquine.
• Muscle weakness: Mild muscle weakness is occasionally reported. Significant or worsening weakness should be reported to your doctor.

Serious Side Effects: When to Call Your Doctor Immediately

The following side effects are rare but serious. Contact your healthcare provider or seek emergency care if you experience:

• Vision changes or vision loss: The most serious risk associated with hydroxychloroquine is retinopathy — damage to the retina. Symptoms include changes in color vision, difficulty seeing in low light, blurry central vision, or seeing halos. Retinopathy is more likely with doses exceeding 5 mg/kg/day, in patients older than 60, in those with kidney disease, and with long-term use (>5 years). This is why regular eye exams are required.
• Irregular heartbeat or chest pain: Hydroxychloroquine can prolong the QT interval, which can cause heart rhythm problems. The risk is higher when combined with other QT-prolonging drugs like azithromycin. Seek emergency care immediately for chest pain, palpitations, or fainting.
• Severe allergic reaction: Signs include rash spreading over large areas, difficulty breathing, swelling of face or throat, or anaphylaxis. Call 911 immediately.
• Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): Extremely rare but life-threatening skin conditions. Seek emergency care for widespread blistering, peeling skin, or a severe rash spreading rapidly.
• Low blood sugar (hypoglycemia): Hydroxychloroquine enhances the effects of insulin and oral diabetes medications, which can cause dangerously low blood sugar. Diabetic patients should monitor blood glucose carefully and discuss dose adjustments with their doctor.
• Mental or mood changes: Rare reports include nervousness, confusion, unusual thoughts, and irritability. Report significant mood changes to your doctor.

The Most Important Risk: Retinopathy

Hydroxychloroquine-induced retinopathy is the side effect that gets the most attention from clinicians — and for good reason. Although it is rare when the medication is taken at recommended doses, it can cause permanent vision loss if not caught early.

Here is what you need to know to protect your vision:

• Get a baseline eye exam within the first year of starting hydroxychloroquine
• For low-risk patients, repeat eye exam every 5 years after the baseline
• For high-risk patients (age >60, kidney disease, dose >5 mg/kg/day, concurrent tamoxifen use), annual exams are required
• Report any new vision changes to your doctor and ophthalmologist immediately
• Tell your eye doctor you are taking hydroxychloroquine so they can perform appropriate screening (BCVA, automated visual field, SD-OCT)

Tips to Manage Common Side Effects

• For nausea: Always take hydroxychloroquine with food or a glass of milk. Do not take on an empty stomach.
• For skin sensitivity: Use SPF 30+ sunscreen daily and wear protective clothing outdoors, as hydroxychloroquine can increase sun sensitivity.
• For antacid users: Space antacids and hydroxychloroquine at least 4 hours apart. Antacids reduce absorption of hydroxychloroquine.

Is Hydroxychloroquine Safe During Pregnancy?

Yes. Hydroxychloroquine is considered safe during pregnancy and is actively recommended by the American College of Rheumatology (ACR) for pregnant patients with lupus and rheumatoid arthritis. Studies have not demonstrated significant risk of major birth defects. If you are pregnant or planning a pregnancy, discuss your hydroxychloroquine use with your rheumatologist — continuing the medication is usually strongly encouraged.

For information on drug interactions that increase side effect risk, read our guide to Hydroxychloroquine Drug Interactions. If you're having trouble finding hydroxychloroquine at your pharmacy, medfinder can help.