Alternatives to Hydroxychloroquine: Practical Options and What to Watch For

If hydroxychloroquine isn’t working for you or you need to stop it, you still have solid choices. Which alternative fits depends on why you were on hydroxychloroquine — autoimmune disease (like lupus or rheumatoid arthritis) or malaria treatment/prophylaxis. Below I break down common alternatives, what they do, and the main safety checks you should know.

Drugs commonly used instead for autoimmune conditions

Methotrexate — a go-to for rheumatoid arthritis. It’s effective and often paired with folic acid to reduce side effects. Expect regular liver blood tests and blood counts while you’re on it.

Azathioprine — used for lupus and other autoimmune diseases. Before starting, many doctors check TPMT enzyme activity to lower the risk of severe blood problems. Watch for infections and routine blood monitoring.

Mycophenolate mofetil — often chosen for lupus that affects organs (kidneys, for example). It’s effective but raises infection risk and needs blood monitoring. Not safe in pregnancy.

Sulfasalazine and leflunomide — good options for inflammatory arthritis. Sulfasalazine is generally milder but can cause GI upset; leflunomide works well but needs liver monitoring and has long-lasting effects if stopped.

Biologic drugs — newer options like TNF inhibitors, rituximab, or belimumab are targeted therapies. They’re often used when conventional drugs don’t control disease. Expect screening for infections (TB, hepatitis) and careful follow-up with your specialist.

Alternatives for malaria treatment or prevention

If your use was for malaria, choices differ. Artemisinin-based combination therapies are standard for treatment in many regions. For prevention, mefloquine, doxycycline, or atovaquone-proguanil are commonly used depending on where you travel and your health profile. Talk to a travel clinic — they’ll match the right drug to the destination and your medical history.

Practical steps when switching off hydroxychloroquine

Talk to your prescribing clinician before stopping. Some drugs need a slow switch or overlap. Ask about baseline tests: eye exam history (hydroxychloroquine can cause retinopathy), liver and kidney labs, and blood counts depending on the new drug. If you start methotrexate or azathioprine, set up blood-work schedules and know infection signs to report.

Pregnancy, age, and other conditions matter. Mycophenolate and leflunomide are not safe in pregnancy. Older adults may need lower doses or more monitoring. If you have liver disease or frequent infections, that changes the safest choice.

Bottom line: there’s no one-size-fits-all replacement for hydroxychloroquine. The right option depends on your diagnosis, other health issues, and plans like pregnancy or travel. Ask your doctor for a clear plan: why the new drug, what tests you’ll need, and exactly what side effects to watch for.