Alternatives to Hydroxychloroquine If You Can't Fill Your Prescription

Hydroxychloroquine (Plaquenil) is a cornerstone medication for millions of people living with lupus and rheumatoid arthritis. When you can't find it at your pharmacy, the most important first step is to contact your prescribing doctor immediately — do not stop hydroxychloroquine abruptly without medical guidance. That said, understanding your alternatives can help you have an informed conversation with your provider about what to do next.

This guide covers the main alternatives to hydroxychloroquine — organized by the condition it treats — and explains the key differences patients should know.

Important: Don't Stop Hydroxychloroquine Without Talking to Your Doctor

Hydroxychloroquine is a slow-acting drug. It can take 3 to 6 months to build up full therapeutic effect — and can take just as long to wash out of your system. Stopping it abruptly can trigger lupus flares or worsening RA. Before making any changes, call your rheumatologist or prescribing physician.

Alternatives for Rheumatoid Arthritis (RA)

Hydroxychloroquine is classified as a conventional synthetic DMARD (csDMARD). The following medications share this classification and are commonly used for RA:

Methotrexate

Methotrexate is the most commonly prescribed first-line DMARD for rheumatoid arthritis and is often combined with hydroxychloroquine in what's called "triple therapy" (methotrexate + sulfasalazine + hydroxychloroquine). If hydroxychloroquine isn't available, your rheumatologist may adjust your methotrexate dose or add a different agent.

Key differences: Methotrexate requires regular blood tests to monitor liver function and blood counts; hydroxychloroquine does not. Methotrexate is NOT safe during pregnancy, while hydroxychloroquine is generally considered safe.

Sulfasalazine (Azulfidine)

Sulfasalazine is another conventional DMARD approved for RA. It is often used in combination therapy with methotrexate and hydroxychloroquine (triple therapy). It's a reasonable alternative when hydroxychloroquine is temporarily unavailable.

Key differences: Sulfasalazine can cause GI upset in some patients and requires periodic CBC monitoring. It should not be used in patients with sulfonamide allergies.

Leflunomide (Arava)

Leflunomide is a DMARD that inhibits T-cell proliferation and is FDA-approved for rheumatoid arthritis and psoriatic arthritis. It works differently from hydroxychloroquine and is considered when patients don't respond to or cannot tolerate hydroxychloroquine.

Key differences: Leflunomide requires liver monitoring and is absolutely contraindicated in pregnancy. It has a very long half-life and requires a "washout" procedure if it needs to be discontinued quickly.

Alternatives for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine is unique in lupus treatment because it addresses multiple aspects of the disease — inflammation, disease flares, organ damage prevention, and even cardiovascular protection. No single drug fully replicates all of these benefits. However, the following may be considered by your rheumatologist:

Azathioprine (Imuran)

Azathioprine is an immunosuppressant used for moderate-to-severe lupus. It provides broader immune suppression than hydroxychloroquine and is often used for lupus nephritis and other organ-threatening disease. It requires regular CBC and liver monitoring.

Belimumab (Benlysta)

Belimumab is a biologic DMARD FDA-approved specifically for systemic lupus erythematosus and lupus nephritis in adults. It targets B-lymphocyte stimulator (BLyS) proteins that drive lupus activity. While not a direct replacement for hydroxychloroquine, it may be appropriate for patients whose disease is not controlled adequately.

Key differences: Belimumab is much more expensive than hydroxychloroquine (often thousands of dollars monthly without insurance) and is given by IV infusion or subcutaneous injection. It's typically reserved for moderate-to-severe SLE not controlled by other agents.

Alternatives for Malaria Prophylaxis

If you're taking hydroxychloroquine for malaria prevention and can't find it, there are alternative antimalarials. Work with an infectious disease specialist or travel medicine clinic to determine the best option based on your destination and travel itinerary:

• Atovaquone/proguanil (Malarone): Taken daily; often preferred for short trips
• Doxycycline: Widely available antibiotic with antimalarial properties; taken daily
• Mefloquine: Weekly dosing; not suitable for all patients due to neuropsychiatric side effects

What to Tell Your Doctor When You Can't Fill Hydroxychloroquine

When you contact your rheumatologist or prescriber, be prepared to share:

• How many days of medication you have left
• Which pharmacies you've already tried
• Whether your disease is currently well-controlled or flaring
• Any other medications you're currently taking (for interaction screening)

The Bottom Line

While alternatives to hydroxychloroquine exist, none offer the exact same safety profile, affordability, and breadth of benefit — especially for lupus. Before switching, try harder to find hydroxychloroquine in stock. Read our guide on how to find hydroxychloroquine near you, or use medfinder to have pharmacies checked on your behalf. If supply is genuinely unavailable, your doctor is your best resource for a safe, personalized next step.