G6PD Deficiency and Medications: How to Prevent Hemolysis

Imagine taking a common medicine for an infection, only to have your red blood cells start breaking down within hours. For someone with G6PD deficiency, this isn’t a hypothetical scenario-it’s a real, life-threatening risk. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency affects around 400 million people worldwide, and most don’t even know they have it until they’re exposed to a trigger. The good news? Hemolysis isn’t random. It’s preventable. The key is knowing which medications to avoid and getting tested before taking anything new.

What G6PD Deficiency Actually Does

G6PD is an enzyme your red blood cells need to fight off oxidative damage. Think of it like a shield. When you take certain drugs, smoke, eat fava beans, or get an infection, your body produces reactive molecules that can tear up red blood cells. Normally, G6PD helps neutralize those molecules. But if you’re deficient, your shield is weak or missing. Without it, red blood cells burst open-this is hemolysis. Hemoglobin can drop from normal levels (14 g/dL) to below 7 g/dL in less than a week. That’s not just fatigue-it’s organ stress, kidney damage, and possible death if not treated fast.

The condition is inherited, carried on the X chromosome. That’s why it’s more common in males, but about 15% of females with the gene can still have symptoms because of how X-chromosome inactivation works. It’s not rare. In parts of Africa, one in five people carries the gene. In the Mediterranean and Southeast Asia, rates are similar. And it’s not just a childhood issue-it lasts your whole life.

Medications That Can Trigger Hemolysis

There are 87 medications currently flagged by the WHO as dangerous for people with G6PD deficiency. But you don’t need to memorize them all. Focus on the big ones that cause the most harm:

• Rasburicase-Used to treat tumor lysis syndrome. This drug generates hydrogen peroxide. In G6PD-deficient patients, it causes near-universal hemolysis. The FDA issued a Black Box Warning in January 2023. Never give it without testing first.
• Methylene blue-Used for methemoglobinemia. It’s ironic: the treatment for one blood problem can cause another. Studies show 95% of G6PD-deficient patients have severe hemolysis after a single dose. In one case, a patient’s hemoglobin dropped from 14.2 to 5.8 in 48 hours.
• Primaquine-A malaria drug. For decades, it was the go-to for killing dormant liver parasites. But it’s extremely risky. Class I and II G6PD variants have 100% hemolysis risk at standard doses. WHO now requires testing before use.
• Dapsone-Used for leprosy and some skin conditions. Above 50mg daily, it causes hemolysis in 80% of deficient patients. Even lower doses can be dangerous in sensitive individuals.
• Sulfonamides-Including trimethoprim-sulfamethoxazole (Bactrim). While not all sulfonamides are equally dangerous, the risk is high enough that many clinicians avoid them entirely in known cases.

Some drugs have vague warnings on their labels. For example, sulfonylureas like glyburide (used for diabetes) carry G6PD precautions in 92% of global package inserts-but only 17 documented cases exist since 1965. Experts say these warnings are often based on fear, not evidence. Still, when in doubt, avoid.

Safe Alternatives

You don’t have to go without treatment. Safe options exist for nearly every condition:

• Malaria prevention: Use atovaquone-proguanil (Malarone) instead of primaquine. For travelers, it’s 95% effective and completely safe for G6PD-deficient people.
• Malaria treatment: Artemisinin-based combination therapies (ACTs) are safe in all G6PD classes. Tafenoquine is now approved-but only if you’ve had a quantitative G6PD test confirming you’re not severely deficient.
• Methemoglobinemia: Use ascorbic acid (vitamin C) instead of methylene blue. It’s slower, but safe. In emergencies, exchange transfusion may be needed.
• Infections: Most antibiotics like amoxicillin, cephalexin, and azithromycin are safe. Avoid sulfa drugs unless no alternatives exist.
• Pain relief: Acetaminophen (paracetamol) is fine. Avoid high-dose aspirin and NSAIDs like naproxen in acute hemolytic episodes.

Testing: When and How

The biggest problem? Most people aren’t tested until after they’re already sick. That’s too late. The best time to test is before any new medication is given-or better yet, at birth.

Point-of-care tests now exist that give results in under 15 minutes. The STANDARD G6PD Test System, approved by the FDA in January 2024, delivers 99.1% accuracy in just eight minutes. In emergency rooms, this can prevent deadly mistakes. In newborn screening programs, it’s saved lives. Saudi Arabia reduced hemolytic crisis admissions by 78% after implementing universal newborn testing.

But here’s the catch: you can’t test right after a hemolytic episode. Your body is still rebuilding red blood cells. The new ones have normal enzyme levels, so the test will falsely look normal. Wait at least three months after the last crisis for an accurate result.

Quantitative testing is essential. Fluorescent spot tests are good for screening, but they don’t tell you how severe your deficiency is. Class II (Mediterranean variant) patients need stricter avoidance than Class III (common African variant). Genetic testing can identify your exact mutation, but it’s expensive and not always necessary if you’re avoiding triggers.

What to Do If You’re Diagnosed

If you or your child has been diagnosed:

1. Get a medical alert bracelet. It should say “G6PD DEFICIENT-AVOID OXIDATIVE DRUGS.”
2. Keep a printed list of unsafe medications. Update it yearly. The WHO and NIH have free downloadable lists.
3. Teach your family and caregivers. A nurse in Texas gave methylene blue to a G6PD-deficient patient because no one knew the risk. He needed three blood transfusions.
4. Carry a copy of your test results. Many doctors don’t know G6PD details. Be your own advocate.
5. Ask before taking any new drug-even over-the-counter ones. Herbal supplements like naphthalene (mothballs) and vitamin K analogs can also trigger hemolysis.

One study found that 92% of patients who received full education on triggers had zero hemolytic episodes over five years. Those who didn’t? Only 38% stayed safe. Knowledge isn’t just helpful-it’s lifesaving.

Global Gaps and Progress

You’d think this would be standard care by now. But only 18 of 47 African countries have national G6PD screening programs. In the U.S., only 12 states require newborn testing, even though 1 in 10 African American males has the condition. The Global Fund has invested $127 million to fix this in malaria zones. The WHO now lists G6PD testing as essential for safe malaria treatment.

Research is moving fast. A 2024 study showed N-acetylcysteine (NAC) can protect red blood cells from oxidative damage when given with primaquine. That could open the door to safer malaria treatment for millions. Phase I trials for enzyme replacement therapy start in late 2024. In the future, we might be able to fix the enzyme itself.

Right now, though, prevention is still the only proven method. No surgery. No long-term drugs. Just awareness and avoidance.

Final Advice

If you’re from a region with high G6PD prevalence-Africa, the Mediterranean, Southeast Asia-or if you have family members with unexplained anemia, get tested. Don’t wait for a crisis. If you’re prescribed a new medication, ask: “Is this safe for someone with G6PD deficiency?” If the answer isn’t clear, get a second opinion. For every person who dies from a preventable hemolytic episode, there are dozens more who suffer, are hospitalized, or lose weeks of work.

The tools to prevent this are here. The science is solid. The question isn’t whether we can stop it. It’s whether we will.