If hydroxychloroquine isn’t right for you — because of side effects, interactions, or lack of response — there are several other medicines that work for the same problems. Below I break down practical alternatives by condition, explain how they differ, and offer quick safety tips so you can discuss options with your doctor.
For rheumatoid arthritis (RA): methotrexate is the most common next step. It’s a low-dose immune suppressant given weekly and often combined with folic acid to reduce side effects. If methotrexate doesn’t control symptoms, doctors may add or switch to sulfasalazine, leflunomide, or one of the newer targeted drugs called biologics — for example, TNF inhibitors like etanercept or adalimumab. Biologics are very effective but need infection screening and regular monitoring.
For systemic lupus erythematosus (SLE): hydroxychloroquine is first-line, but alternatives include mycophenolate mofetil (especially for kidney involvement), azathioprine for chronic control, and cyclophosphamide for severe flares. Newer options such as belimumab target B cells and can help people with active lupus despite standard therapy.
For malaria: if hydroxychloroquine isn’t suitable due to resistance or side effects, artemisinin-based combination therapies (ACTs) are the go-to in most regions. For certain strains, atovaquone-proguanil, doxycycline, or mefloquine are used for treatment and prevention. Choice depends on where the infection was acquired and local resistance patterns.
For viral uses such as COVID-19: hydroxychloroquine is not recommended. Proven options depend on the illness stage — antiviral drugs like remdesivir, oral antivirals when appropriate, and monoclonal antibodies for high-risk patients have clearer evidence. Vaccination and supportive care remain essential.
Pick an alternative with your clinician based on your diagnosis, other health issues, and monitoring limits. Key questions to ask: what tests will I need, how fast will the drug work, and what are the common side effects? For immune suppressants, watch for infection signs and get vaccinations before starting when possible. For drugs that affect liver or blood counts, regular bloodwork is essential. Always tell your doctor about other medicines and supplements to avoid dangerous interactions.
One more practical note: some alternatives carry specific risks you need to plan for. Methotrexate and mycophenolate are toxic in pregnancy — use reliable contraception and discuss family planning well before switching. Methotrexate requires weekly dosing, folic acid, and routine blood tests for liver enzymes and blood counts. Leflunomide can stay in the body for months, and may need a drug washout if pregnancy is planned. Biologics often need TB screening and sometimes hepatitis testing before you start. For antibiotics and malaria drugs, follow local guidelines and travel clinic advice. Keep a written list of symptoms to report and a schedule for labs so nothing slips through the cracks.
If cost or access is a concern, ask about patient assistance programs or generic versions — many effective drugs have affordable generics. If you notice new vision changes, persistent cough, fever, or unexplained bruising after switching drugs, contact your provider promptly.
