Hydroxychloroquine alternatives: safe options for malaria and autoimmune disease

Hydroxychloroquine (HCQ) gets mentioned a lot, but it’s not the only choice for malaria prevention or treating autoimmune conditions like lupus and rheumatoid arthritis. If HCQ isn’t right for you—because of side effects, eye concerns, or lack of effect—there are clear alternatives. Below I’ll lay out common options, what they do, and practical safety notes so you can have a focused conversation with your doctor.

Alternatives by condition

For malaria (prevention or treatment):

- Artemisinin-based combination therapies (ACTs): The frontline treatment in many parts of the world. Fast acting and usually effective against drug-resistant malaria strains. Side effects are generally mild but vary by combination.

- Atovaquone–proguanil (Malarone): Good for travel prophylaxis and treatment. Well tolerated, but cost is higher than older drugs.

- Doxycycline: Often used for prevention during travel. Cheap and effective, but it can cause sun sensitivity and isn’t recommended in pregnancy or for young children.

- Mefloquine: Effective for many regions but can cause vivid dreams or mood changes in some people. Avoid if you have certain psychiatric conditions.

- Chloroquine: Works only where malaria is still sensitive to it. Many regions have resistance, so it’s less reliable in parts of Africa and Asia.

For autoimmune diseases (lupus, RA, other rheumatologic conditions):

- Methotrexate: A common first-line option for RA. It reduces joint damage but needs regular blood tests for liver function and blood counts. Folic acid is often prescribed alongside it.

- Sulfasalazine and leflunomide: Oral alternatives that can work alone or with methotrexate. Each has its own monitoring needs—liver tests and blood counts are standard.

- Azathioprine and mycophenolate mofetil: Used more often in lupus and organ-sparing strategies. They suppress the immune system and increase infection risk; regular labs and dose checks are required.

- Biologic drugs (TNF inhibitors like etanercept, adalimumab; B-cell therapy like rituximab; and targeted drugs for lupus like belimumab): These are powerful options when conventional drugs fail. They work fast for many patients but come with infection risks and higher costs.

How to choose and safety tips

Choosing an alternative depends on why HCQ isn’t suitable—eye toxicity, poor response, or other medical issues. Ask your doctor about the drug’s benefits for your exact condition, monitoring needs (CBC, liver tests, pregnancy testing), and infection risks. Never stop HCQ or switch meds suddenly without medical advice—some conditions flare if treatment is interrupted abruptly.

Watch for red flags: worsening vision, unexplained bruising, new fevers, or signs of liver trouble (jaundice, severe nausea). Pregnant or breastfeeding? Mention that up front—some drugs are unsafe in pregnancy.

Bottom line: there are solid, well-studied alternatives for both malaria and autoimmune care. A good plan pairs the right drug with the right monitoring and follow-up. Talk openly with your clinician about symptoms, lifestyle, costs, and how quickly you need relief—those details decide the best alternative for you.