G6PD Deficiency and Medications: How to Prevent Hemolysis

• By Celeste Marwood
• 12 Nov, 2025
• 1 Comments

When you have G6PD deficiency, your red blood cells don’t have enough of a key enzyme to protect them from damage. This isn’t something you can see or feel until something triggers it-like a common medication. A single pill can send your hemoglobin crashing, causing fatigue, dark urine, jaundice, and even life-threatening anemia. The good news? Almost all of these crises are preventable. You don’t need to live in fear. You just need to know which drugs to avoid and how to make sure your doctors do too.

What Happens When G6PD Deficiency Meets Certain Drugs

G6PD deficiency means your body can’t make enough NADPH, which keeps your red blood cells safe from oxidative stress. When you take certain medications, they create free radicals that your cells can’t handle. The result? Your red blood cells burst-this is hemolysis. It doesn’t happen with every drug, but with about 87 known triggers, it’s easy to accidentally cross the line.

Some of the most dangerous drugs include rasburicase, used to treat tumor lysis syndrome. The FDA requires a G6PD test before giving it-because if you’re deficient, one dose can drop your hemoglobin to dangerously low levels. In one case reported in the American Journal of Emergency Medicine, a 28-year-old man’s hemoglobin fell to 3.1 g/dL after receiving rasburicase without testing. He needed 10 units of blood. Another drug, methylene blue, is used for methemoglobinemia, but in G6PD-deficient people, it causes hemolysis in 95% of cases. There’s no safe dose if you’re deficient.

Then there’s primaquine, the go-to drug for curing relapsing malaria. For decades, doctors assumed it was safe if given in low doses. But in people with Class I or II G6PD deficiency-common in Mediterranean and Asian populations-it causes complete hemolysis. In Thailand, before mandatory testing, 15% of malaria patients had severe hemolytic episodes after primaquine. After testing became routine, that number dropped to 0.3%.

Medications You Must Avoid

Not all drugs are equally dangerous. Some are outright banned for G6PD-deficient patients. Others are risky only at high doses or in certain variants. Here’s what you need to know:

• Rasburicase - Absolute contraindication. Never use without confirmed normal G6PD levels.
• Methylene blue - High risk. Use only if no alternatives exist and you’ve been tested.
• Primaquine - Requires quantitative G6PD testing. Not safe for Class I or II.
• Dapsone - Used for leprosy and skin conditions. Hemolysis risk spikes above 50mg daily.
• Sulfonamides - Antibiotics like sulfamethoxazole. Risk varies, but avoid unless absolutely necessary.
• Nitrofurantoin - Common UTI drug. Avoid in G6PD deficiency.
• Aspirin (high doses) - More than 600mg daily can trigger hemolysis.
• Chloroquine - Safe. Used in malaria prevention for G6PD-deficient travelers.
• Tafenoquine - Newer alternative to primaquine. Requires testing before use.
• Artemisinin-based therapies - Safe for all G6PD classes. First-line for malaria.

Here’s the tricky part: some drugs have warnings on their labels, but those warnings are outdated or based on weak evidence. For example, sulfonylureas like glyburide (used for diabetes) carry G6PD warnings in 92% of global package inserts-even though only 17 cases of hemolysis have ever been documented since 1965. Don’t assume every warning is backed by strong data. But don’t ignore the big ones either.

Testing Is Not Optional-It’s Essential

Many people live their whole lives unaware they have G6PD deficiency until they get sick from a medication. That’s why testing matters. The standard test is a simple blood draw that measures enzyme activity. Results are reported in units per gram of hemoglobin (U/g Hb). According to WHO classification:

• Below 1.7 U/g Hb = Class I or II (severe deficiency)
• 1.7-12.0 U/g Hb = Class III (moderate deficiency)
• Above 12.0 U/g Hb = Normal

But here’s the catch: if you’ve had a recent hemolytic episode, your test will show falsely normal results. Why? Because your body has just destroyed the oldest, most deficient red blood cells. The new ones are still healthy. That’s why you need to wait at least three months after a crisis before testing. Otherwise, you might be told you’re fine-when you’re not.

There’s a faster option now: the STANDARD G6PD Test System, approved by the FDA in January 2024. It gives accurate results in 8 minutes using a finger prick. This is a game-changer for emergency rooms and clinics in malaria-endemic areas. No more waiting days for lab results while a patient gets sicker.

What About Women? You’re Not Just a Carrier

For years, people thought G6PD deficiency only affected men. After all, it’s an X-linked disorder. But women can have it too. Because of X-chromosome inactivation (where one X chromosome is randomly turned off in each cell), some women express the defective gene in enough red blood cells to be at risk. A 2020 Lancet Haematology study found that 15% of women with G6PD deficiency had hemolytic episodes after taking oxidative drugs.

That means if your mother or maternal uncle had the condition, you should get tested-even if you’ve never had symptoms. Don’t assume you’re safe just because you’re female.

Safe Alternatives for Common Conditions

Living with G6PD deficiency doesn’t mean you can’t be treated. It just means you need smarter options.

For malaria prevention: Use atovaquone-proguanil (Malarone) instead of primaquine. A 2021 study of 1,245 travelers found 95% avoided hemolysis using Malarone. Artemisinin-based combination therapies (ACTs) are safe for treatment.

For infections: Avoid sulfa drugs and nitrofurantoin. Use amoxicillin, cefdinir, or azithromycin instead. These are safe and effective.

For pain or fever: Acetaminophen (paracetamol) is safe. Avoid high-dose aspirin. Ibuprofen is generally safe in standard doses, but check with your doctor if you’re unsure.

For diabetes: Metformin and insulin are safe. Avoid glyburide unless absolutely necessary-and even then, only after testing.

For methemoglobinemia: Instead of methylene blue, use ascorbic acid (vitamin C). It’s slower but safe.

What to Do If You’re Diagnosed

Getting diagnosed isn’t the end-it’s the start of a safer life. Here’s your action plan:

1. Get a formal diagnosis with a quantitative enzyme test.
2. Carry a medical alert card or bracelet that says “G6PD Deficiency.”
3. Keep a printed list of unsafe medications and share it with every doctor, dentist, and pharmacist.
4. Ask: “Is this drug on the G6PD avoidance list?” before accepting any new prescription.
5. For malaria-prone travel: Get tested before departure and use Malarone.
6. Inform your family-especially male relatives and daughters-so they can get tested too.

One woman from Perth shared her story: after her son had a hemolytic crisis from an antibiotic, she created a G6PD-safe medication list and posted it on her phone. “Now I show it to every nurse before they give him anything,” she said. “I used to feel helpless. Now I feel in control.”

The Bigger Picture: Why This Matters

G6PD deficiency affects 400 million people worldwide. Yet in the U.S., only 12 states require newborn screening. In Australia, there’s no national policy. That means thousands of people are walking around unaware. In countries like Saudi Arabia, where universal screening was introduced, hospital admissions for hemolytic crises dropped by 78% in ten years.

The Global Fund has invested $127 million to expand testing in 32 African countries. The WHO now lists 12 new medications with G6PD warnings. And research is moving forward-NIH is testing a recombinant G6PD enzyme therapy that could one day replace the need for avoidance altogether.

But until then, prevention is everything. The most effective treatment for G6PD deficiency isn’t a drug. It’s knowledge.

What If You’ve Already Had a Hemolytic Episode?

If you’ve had one, you’re at higher risk for another. But that doesn’t mean you’re doomed. The key is to prevent future triggers. After a crisis, your body needs time to recover. New red blood cells are made over 7-10 days. During that time, avoid any known triggers-even if you feel better. Your doctor should monitor your hemoglobin and reticulocyte count until you’re stable.

And don’t assume you’re safe just because you didn’t react to a drug before. Your sensitivity can change. Your enzyme levels can drop after illness, infection, or stress. Always assume you’re at risk unless proven otherwise by testing.

The goal isn’t perfection-it’s awareness. With the right knowledge, you can take any medication safely. You just need to ask the right questions before you take it.