Hydroxychloroquine, most commonly prescribed for lupus and rheumatoid arthritis, causes digestive symptoms in a significant number of users and carries a small but real risk of eye damage with long-term use. Most side effects are mild and manageable, but a few rare ones, particularly involving the eyes and heart, require ongoing monitoring.
Digestive Side Effects
The most common complaints are nausea, diarrhea, stomach pain, vomiting, and loss of appetite. These tend to appear early in treatment and often improve after the first few weeks as your body adjusts. Taking the medication with food or splitting the dose (if your prescriber allows it) can reduce stomach upset considerably.
Skin and Hair Changes
Hydroxychloroquine can cause rashes, hives, itching, and increased sun sensitivity. Some people develop a blue-grey discoloration of the skin, particularly on the shins, face, or inside the mouth, after years of use. This happens because the drug promotes pigment deposits in the skin. The discoloration sometimes fades after stopping the medication, but in some cases it persists for months or longer.
Hair loss and changes in hair color are also reported. These are generally reversible once the drug is discontinued.
Eye Damage From Long-Term Use
The most serious concern with hydroxychloroquine is retinal toxicity, where the drug gradually damages the light-sensing cells at the back of the eye. This can lead to permanent vision loss if not caught early. The risk is low in the first five years of use but rises sharply after that, approaching 1% in people who have taken the drug for five to seven years or accumulated a total lifetime dose of 1,000 grams. Daily doses above 5 mg per kilogram of body weight also increase risk.
The tricky part is that early retinal damage causes no symptoms. By the time you notice vision changes, some damage may be irreversible. That’s why the American Academy of Ophthalmology recommends a baseline eye exam (including retinal imaging) soon after starting hydroxychloroquine, followed by annual screening. If you have no additional risk factors, annual screening can be deferred until after the first five years of use. If you have kidney disease, are taking a higher dose, or are also using tamoxifen, screening should start right away.
Heart-Related Risks
Hydroxychloroquine can affect the heart’s electrical system, causing a prolonged QT interval, which is a change in the heart’s rhythm that increases the risk of dangerous arrhythmias. An analysis of the World Health Organization’s global drug safety database found reports of both rhythm disturbances (including a potentially fatal arrhythmia called torsades de pointes) and conduction blocks, where electrical signals through the heart are delayed or interrupted. Two-thirds of the conduction problems were a type called atrioventricular block.
Heart failure has also been linked to prolonged use, particularly at higher doses. These cardiac effects are rare but more likely when the drug is combined with other medications that affect heart rhythm or when it’s taken at doses above the standard range. People with pre-existing heart conditions should be monitored more carefully.
Mood and Neurological Effects
Neuropsychiatric side effects are uncommon but documented. They range from irritability, anxiety, and difficulty sleeping to rare cases of psychosis. These reports are mostly limited to individual case studies rather than large trials, so the true frequency is hard to pin down. There is also weak evidence of a possible link between hydroxychloroquine and increased suicidal thoughts. If you notice significant mood changes after starting the medication, it’s worth bringing up at your next appointment.
Blood Sugar and Drug Interactions
Hydroxychloroquine can lower blood sugar, which matters most if you take insulin or other diabetes medications. The combination can push blood sugar too low, so glucose levels may need closer monitoring when you start or stop the drug.
Several other interactions are worth knowing about:
- Antacids reduce absorption of hydroxychloroquine. Take them at least four hours apart.
- Digoxin (a heart medication) levels can rise when combined with hydroxychloroquine, increasing the risk of toxicity.
- Seizure medications like carbamazepine and phenytoin may become less effective.
- Methotrexate and cyclosporine, both commonly prescribed alongside hydroxychloroquine for autoimmune conditions, can interact and may need dose adjustments.
Three drugs should not be taken with hydroxychloroquine at all due to dangerous heart rhythm interactions: dronedarone, pimozide, and thioridazine.
Safety During Pregnancy and Breastfeeding
Hydroxychloroquine is one of the few autoimmune medications considered compatible with pregnancy. Data from more than 250 pregnancies resulting in live births have shown no increase in birth defects. A survey of lupus specialists found that 69% continued prescribing it during pregnancy, and none reported seeing fetal toxicity from the drug. For women with lupus, stopping hydroxychloroquine during pregnancy can trigger disease flares that themselves pose risks to the pregnancy, so the current consensus generally favors continuing it.
The drug does pass into breast milk, but in very small amounts. Measurements in nursing mothers found that an infant would ingest roughly 0.06 to 0.2 mg per kilogram per day through breast milk, which is a tiny fraction of a therapeutic dose. Breastfeeding while taking hydroxychloroquine is generally considered safe.
Routine Monitoring
Unlike many other medications for autoimmune diseases, hydroxychloroquine does not require regular blood work. Routine lab monitoring (complete blood counts, liver or kidney function tests) is not generally necessary unless you’re also taking another medication that demands it, or your specialist requests it for a specific clinical reason. The main ongoing monitoring commitment is the annual eye exam, which becomes increasingly important the longer you stay on the drug.