When you have G6PD deficiency, even a common pill can trigger a dangerous drop in red blood cells. This isn’t theoretical-it happens in hospitals every day. A 42-year-old man in Ohio was given methylene blue for methemoglobinemia without being tested for G6PD deficiency. Within 48 hours, his hemoglobin plunged from 14.2 g/dL to 5.8 g/dL. He needed three units of blood. This isn’t rare. In fact, 68% of people with G6PD deficiency report at least one hemolytic episode, often because their doctor didn’t know the risks.

What Is G6PD Deficiency?

G6PD deficiency is a genetic condition that affects how your red blood cells handle stress. The enzyme glucose-6-phosphate dehydrogenase helps protect those cells from damage caused by oxidative stress. When this enzyme doesn’t work properly, your red blood cells break down too easily-especially when exposed to certain drugs, foods, or infections. It’s not something you can outgrow. It’s not curable. But it’s completely preventable-if you know what to avoid.

It’s most common in people with ancestry from Africa, the Mediterranean, Southeast Asia, and the Middle East. In some parts of sub-Saharan Africa, one in five people carries the gene. In the U.S., about 1 in 10 African American males has it. Many people never know they have it until they’re given a dangerous medication-or until their child is born with jaundice that won’t go away.

Why Certain Medications Are Dangerous

Not all drugs are risky. But about 87 medications on the WHO’s Essential Medicines List can cause hemolysis in people with G6PD deficiency. These aren’t obscure drugs-they’re commonly prescribed.

• Rasburicase-used to treat tumor lysis syndrome. The FDA has a black box warning: it causes 100% hemolysis in deficient patients. One case reported in the American Journal of Emergency Medicine involved a 28-year-old who received rasburicase without testing. His hemoglobin dropped to 3.1 g/dL. He needed 10 units of blood.
• Methylene blue-used for methemoglobinemia. In G6PD-deficient patients, it causes severe hemolysis in 95% of cases. It’s ironic: a drug meant to fix oxygen delivery in the blood can destroy red blood cells in people with this deficiency.
• Primaquine-used to treat malaria. For people with Class I or II G6PD deficiency, it’s deadly. WHO guidelines now require testing before use. In Thailand, after making G6PD testing mandatory before primaquine, hemolytic crises dropped from 15.2% to 0.3%.
• Dapsone-used for leprosy and some skin conditions. At doses above 50mg daily, it causes hemolysis in 80% of deficient patients.

Even drugs you might assume are safe can be risky. Sulfonylureas like glyburide (used for diabetes) carry warnings on their labels, but the evidence is weak-only 17 cases ever documented since 1965. Yet, 92% of their packaging still includes the warning. This creates confusion and unnecessary fear.

Safe Alternatives

The good news? You don’t have to go without treatment. There are safe alternatives for almost every risky drug.

• For malaria prevention: Use atovaquone-proguanil (Malarone) instead of primaquine. A 2021 study of 1,245 travelers with G6PD deficiency showed 95% avoided hemolysis using this combo.
• For malaria treatment: Artemisinin-based combination therapies (like artemether-lumefantrine) are safe in all G6PD deficiency classes.
• For methemoglobinemia: Instead of methylene blue, use ascorbic acid (vitamin C) or exchange transfusion if severe.
• For tumor lysis syndrome: Use allopurinol instead of rasburicase. It’s slower but safe.
• For pain relief: Avoid aspirin and high-dose acetaminophen. Stick to low-dose acetaminophen or ibuprofen-both are generally safe at standard doses.

One of the biggest breakthroughs is tafenoquine, a new drug approved in 2018 for radical cure of malaria. It’s more effective than primaquine-but only if you’ve been tested for G6PD deficiency first. The FDA requires testing before prescribing it. This is a model for how drug safety should work.

Testing Is Not Optional

Many people think G6PD deficiency only affects men. It doesn’t. About 15% of women with the gene can still have hemolysis due to how X-chromosome inactivation works. So if your mother had jaundice as a baby, or your uncle had a bad reaction to a drug, you could be at risk.

Testing is simple. The fluorescent spot test gives results in 15 minutes. It’s 98.7% accurate. In Saudi Arabia, after making newborn screening mandatory, hospital admissions for hemolytic crises dropped by 78% between 2010 and 2020.

But here’s the catch: you can’t test during or right after a hemolytic episode. Your red blood cells are young and still have enough enzyme to mask the deficiency. You need to wait at least three months after an episode for an accurate result. If you’ve had unexplained anemia after taking a drug, get tested after the recovery period.

What to Do If You’ve Never Been Tested

If you’re from a high-risk region, or you’ve had unexplained jaundice, dark urine after taking a drug, or a family history of anemia, get tested. Don’t wait for a crisis.

Here’s your checklist:

1. Ask your doctor for a G6PD test-especially if you’re planning surgery, pregnancy, or travel to a malaria-endemic area.
2. If you’re pregnant, get tested before taking any new medication. Your baby may inherit the deficiency.
3. Keep a list of unsafe drugs and show it to every new provider. Print it out. Put it in your wallet.
4. Wear a medical alert bracelet that says “G6PD Deficient.”
5. Ask for a copy of your test results. Don’t rely on old charts or memory.

People who get proper education and avoid triggers have a 92% chance of never having a hemolytic episode. Those who don’t? 62% will have at least one by age 40.

What About Fava Beans and Infections?

Yes, fava beans can trigger hemolysis. That’s why it’s sometimes called “favism.” But not everyone with G6PD deficiency reacts to them. It depends on the variant. Mediterranean variants are more sensitive. African variants less so.

Infections-like pneumonia or the flu-can also trigger hemolysis. That’s because they create oxidative stress. If you’re sick and you have G6PD deficiency, avoid NSAIDs like ibuprofen unless approved by your doctor. Stick to acetaminophen. Stay hydrated. Monitor for dark urine or fatigue.

Future Hope

There’s progress. In January 2024, the FDA approved the first point-of-care G6PD test that gives results in 8 minutes with 99.1% accuracy. That’s huge for emergency rooms and clinics without labs.

Researchers are also testing N-acetylcysteine (NAC), a common antioxidant, to protect red blood cells during exposure to risky drugs. Early lab results show it reduces hemolysis by 75% when given with primaquine.

By 2035, experts believe preventable deaths from G6PD deficiency could be nearly eliminated in countries with good healthcare. But right now, 85% of deaths happen in places without testing programs. That’s not a medical problem-it’s a systems problem.

Final Thought: Knowledge Saves Lives

G6PD deficiency isn’t a death sentence. It’s a condition you manage with awareness. The drugs aren’t evil. The condition isn’t rare. The problem is silence. Too many people don’t know they have it. Too many doctors don’t ask. Too many patients don’t speak up.

If you’ve ever had dark urine after taking a pill, or if your child had jaundice that didn’t go away, get tested. If you’re prescribed a new drug, ask: “Is this safe for G6PD deficiency?” Don’t assume it is. Write it down. Keep a list. Tell your pharmacist. Your life might depend on it.