Nitrofurantoin and G6PD Deficiency: What You Need to Know About Hemolytic Anemia Risk

When you get a urinary tract infection (UTI), your doctor might reach for nitrofurantoin. It’s cheap, effective, and widely prescribed-over 5.5 million prescriptions in the U.S. alone each year. But for some people, this common antibiotic can trigger a dangerous, even life-threatening reaction: hemolytic anemia. And the biggest risk factor? A hidden genetic condition called G6PD deficiency.

What is G6PD deficiency, and why does it matter?

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme your red blood cells need to protect themselves from oxidative stress. If you’re deficient in this enzyme, your red blood cells can’t handle certain drugs, infections, or even fava beans. When exposed to oxidizing agents like nitrofurantoin, those cells break down too fast-leading to hemolytic anemia.

This isn’t rare. Around 400 million people worldwide have G6PD deficiency, according to the World Health Organization. It’s most common in people of African, Mediterranean, Middle Eastern, and Southeast Asian descent. In Black African and African American populations, up to 14% are affected. In Mediterranean groups, it’s 4-7%. Yet, most people don’t know they have it until they take a drug like nitrofurantoin and suddenly feel terrible.

How nitrofurantoin triggers hemolysis

Nitrofurantoin works by creating reactive compounds in your urine that kill bacteria. But those same compounds don’t just target bacteria-they can also damage red blood cells. In healthy people, antioxidants like glutathione neutralize the damage. But in someone with G6PD deficiency, glutathione levels crash. Without it, hemoglobin inside red blood cells starts to clump, forming Heinz bodies. The spleen then destroys these damaged cells, leading to rapid anemia.

Symptoms show up fast-usually within 24 to 72 hours of starting the drug. You might feel dizzy, have dark urine, jaundice (yellow skin or eyes), rapid heartbeat, or shortness of breath. In severe cases, you could develop fever, confusion, low blood pressure, or kidney damage. A 2023 case report in the National Center for Biotechnology Information described a patient whose hemoglobin dropped from 13.2 g/dL to 7.1 g/dL in just 48 hours after taking nitrofurantoin. He was hospitalized but recovered fully after stopping the drug and getting IV fluids.

The data doesn’t lie: it’s a real and documented danger

A 2022 review of medical literature found 42 confirmed or highly probable cases of nitrofurantoin-induced hemolytic anemia in G6PD-deficient patients. Ten of those cases ended in death. Another 24 cases were confirmed G6PD-deficient, with 4 highly probable. Eight of those cases involved pregnant women-some because they were taking nitrofurantoin themselves, others because the drug crossed the placenta. Three cases involved infants, two from maternal exposure during pregnancy.

The Clinical Pharmacogenetics Implementation Consortium (CPIC), which sets drug safety guidelines based on genetics, says nitrofurantoin should be avoided entirely in G6PD-deficient patients who’ve had chronic hemolytic anemia. For others with G6PD deficiency but no prior complications, it’s still considered high-risk and should be used only if no alternatives exist.

Why isn’t everyone tested before taking it?

Here’s the problem: the FDA label for nitrofurantoin says it can cause hemolytic anemia in G6PD-deficient people-but it doesn’t require doctors to test for it first. Many clinicians don’t screen. A 2022 survey of 350 primary care doctors showed only 32% routinely check G6PD status before prescribing nitrofurantoin.

Why? Cost, convenience, and lack of awareness. A G6PD test costs $35-$50. A hospital stay for hemolytic anemia? $8,500-$12,000. Yet, most doctors don’t think to ask about ancestry or family history. They assume their patient is “low risk.” But in Melbourne, Sydney, Toronto, or Los Angeles, you’re likely to see patients from high-prevalence backgrounds. Ignoring that is dangerous.

What are the safer alternatives?

If you have G6PD deficiency-or if your doctor suspects you might-there are better options for treating UTIs:

• Fosfomycin (Monurol): A single-dose antibiotic, safe in G6PD deficiency, and effective against common UTI bugs like E. coli.
• Cephalexin: A first-generation cephalosporin with minimal oxidative risk.
• Amoxicillin-clavulanate: Often used for uncomplicated UTIs, especially if resistance is a concern.
• Pivmecillinam: Used in Europe and Canada, not available in the U.S., but has a strong safety profile in G6PD-deficient patients.

Trimethoprim-sulfamethoxazole (TMP-SMX) is another common UTI drug-but it’s also an oxidizing agent and can trigger hemolysis in G6PD-deficient people. So it’s not a safe alternative either.

Who should get tested before taking nitrofurantoin?

You should consider a G6PD test before taking nitrofurantoin if you:

• Are of African, Mediterranean, Middle Eastern, or Southeast Asian descent
• Have a family history of anemia, jaundice, or blood transfusions
• Have had unexplained anemia after taking antibiotics or antimalarials
• Are pregnant and from a high-risk ethnic group
• Have had dark urine or fatigue after taking medications like sulfonamides or primaquine

Even if you’ve never had symptoms, you could still be G6PD-deficient. Half to 60% of people with the condition don’t know it until they have a hemolytic crisis. Testing is simple-a finger prick or blood draw. Results come back in hours.

What if you’re already taking nitrofurantoin?

If you start feeling unwell-dark urine, yellowing skin, extreme fatigue, or rapid heartbeat-stop the medication immediately. Call your doctor. Don’t wait. Hemolysis can escalate quickly. In most cases, stopping the drug and staying hydrated is enough. Blood transfusions are rarely needed unless the anemia is severe.

Recovery usually happens within 3-5 days. One patient in a 2023 study saw his hemoglobin rebound from 7.1 g/dL to 12.5 g/dL in under a week after stopping nitrofurantoin and getting IV fluids. No transfusion. Just time and care.

What’s changing in 2025?

There’s growing pressure to make G6PD screening standard before prescribing nitrofurantoin. The NIH is running a multi-center trial (NCT04567891) to see if routine testing saves money and lives. Early results suggest it does. Point-of-care G6PD tests are now available in some clinics-results in 15 minutes. Insurance coverage is slowly improving.

Meanwhile, electronic health records are starting to add alerts. If you’re flagged as African, Middle Eastern, or Southeast Asian descent, your doctor’s system might now pop up a warning: “Avoid nitrofurantoin-consider G6PD testing.” That’s progress.

But until universal screening becomes law, the responsibility falls on you. If you’re from a high-risk group, ask your doctor: “Could I have G6PD deficiency? Should I get tested before taking this antibiotic?”

Nitrofurantoin isn’t going away. It’s still one of the best tools we have against resistant UTIs. But it’s not safe for everyone. Knowing your status isn’t just smart-it could save your life.