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

Plaquenil (hydroxychloroquine) has an excellent safety record compared to many other disease-modifying medications used in autoimmune conditions. Most patients tolerate it well and take it for years or even decades. However, there are some side effects—ranging from minor and temporary to rare but serious—that every patient should know about before starting therapy.

Common Side Effects of Plaquenil

The most common side effects of Plaquenil are gastrointestinal and typically mild. They are most common when first starting the medication and often improve over time. These include:

• Nausea and stomach upset
• Vomiting or diarrhea
• Headache
• Dizziness or lightheadedness
• Skin rash or itching (pruritus)
• Insomnia or trouble sleeping

Tip to reduce GI side effects: Always take Plaquenil with food or a glass of milk. Taking it on an empty stomach significantly increases the likelihood of nausea.

Retinal Toxicity: The Most Important Long-Term Risk

The most significant long-term side effect of Plaquenil is retinopathy—damage to the retina of the eye. This is the risk your doctor is monitoring when they order regular eye exams. Here's what you need to know:

• Retinal toxicity is related to cumulative dose and duration of treatment—the risk increases after 5 years of use, especially at doses exceeding 5 mg/kg/day of actual body weight
• Early retinal damage often has no symptoms—which is why regular eye monitoring is critical
• If not detected early, retinal damage can be irreversible and may progress to permanent vision loss
• Risk factors include: doses >5 mg/kg/day, duration >5 years, kidney disease, concurrent tamoxifen use, and pre-existing macular disease

Monitoring schedule: A baseline eye exam should be done within the first year. For low-risk patients, annual exams can begin after 5 years. For high-risk patients (those with the risk factors above), annual exams should start sooner.

Call your doctor immediately if: you develop blurred vision, trouble focusing, distorted vision, blind spots, difficulty reading, changes in color vision, or increased sensitivity to light.

Cardiac Side Effects

Serious cardiac side effects are rare but can be life-threatening:

• QT prolongation and ventricular arrhythmias: Plaquenil can prolong the QT interval, increasing the risk of dangerous heart rhythm abnormalities, especially when combined with other QT-prolonging drugs (such as azithromycin).
• Cardiomyopathy: Rare cases of cardiomyopathy (weakening of the heart muscle) have been reported, usually with long-term use.

Seek emergency care if: you experience fast or pounding heartbeats, chest pain, fluttering in your chest, shortness of breath, or sudden dizziness that feels like you might faint.

Hypoglycemia (Low Blood Sugar)

Plaquenil can enhance the effects of insulin and other blood sugar-lowering medications, sometimes causing severe hypoglycemia (low blood sugar) even in patients without diabetes. Symptoms include shakiness, sweating, confusion, and in severe cases, loss of consciousness. Diabetic patients should monitor their blood sugar closely when starting or adjusting Plaquenil.

Serious Skin Reactions

While mild rash is common, rare but severe skin reactions can occur with Plaquenil:

• Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN): Life-threatening skin conditions with blistering and peeling
• DRESS Syndrome: Drug Reaction with Eosinophilia and Systemic Symptoms—a serious multi-organ hypersensitivity reaction

Seek emergency care if: you develop fever, sore throat, burning eyes, widespread blistering or peeling skin, or a red-purple rash that is spreading rapidly.

Blood Cell Changes

Plaquenil can rarely cause changes in blood cell counts, including low red blood cells (anemia), low white blood cells (leukopenia), or low platelets (thrombocytopenia). Patients with G6PD (glucose-6-phosphate dehydrogenase) deficiency are at higher risk of hemolytic anemia. Regular CBC monitoring during therapy can catch these issues early.

Side Effects vs. Lupus/RA Symptoms: What's What?

One challenge for lupus and RA patients is distinguishing medication side effects from their underlying disease symptoms. Fatigue, rash, and joint pain can be caused by both lupus and Plaquenil (rarely). If you're experiencing new or worsening symptoms after starting Plaquenil, talk to your rheumatologist—don't just stop taking the medication on your own.

For more information on what medications can make Plaquenil side effects worse, see: Plaquenil Drug Interactions: What to Avoid.