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

Every year, millions of people take nitrofurantoin to treat a simple urinary tract infection. It works fast, it’s cheap, and for most people, it’s safe. But for a significant number of others, this common antibiotic can trigger a life-threatening reaction they never knew they were at risk for: hemolytic anemia caused by an undiagnosed genetic condition called G6PD deficiency.

What Is Nitrofurantoin, and Why Is It So Common?

Nitrofurantoin, sold under brand names like Macrobid and Furadantin, has been around since the 1940s. It’s not a flashy drug. It doesn’t cure pneumonia or sepsis. But for uncomplicated bladder infections - the kind that make you pee constantly and burn when you go - it’s one of the most effective options. Unlike many antibiotics, bacteria haven’t developed strong resistance to it. About 10-15% of E. coli strains are resistant, compared to 20-25% for trimethoprim-sulfamethoxazole, another go-to UTI drug.

It’s also targeted. Nitrofurantoin doesn’t flood your whole body. It concentrates in your urine, where it kills the bacteria causing the infection. That’s why it’s often the first choice for doctors treating healthy adults with no kidney problems. In the U.S. alone, about 5.5 million prescriptions are filled each year.

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. Think of it like a shield. When your body breaks down toxins, produces energy, or fights infection, it creates reactive molecules called free radicals. G6PD helps neutralize them so your red blood cells don’t get damaged.

But if you’re born with G6PD deficiency - and about 400 million people worldwide are - that shield is weak or missing. You might never know it… until something like nitrofurantoin comes along.

Nitrofurantoin doesn’t just kill bacteria. In your body, it turns into reactive, oxidizing compounds. In people with normal G6PD, those compounds are handled easily. In someone with G6PD deficiency, the red blood cells can’t defend themselves. The hemoglobin inside them starts to clump and break down. The cells burst. That’s hemolysis. And when enough red blood cells are destroyed at once, you get acute hemolytic anemia.

How Dangerous Is This Reaction?

It’s not rare. 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. Most happened within 24 to 72 hours of starting the drug.

Symptoms come on fast: sudden fever, chills, dark urine (like cola), extreme fatigue, yellowing skin or eyes, rapid heartbeat, and dizziness. In severe cases, people collapse from low blood pressure. One case report described a patient whose hemoglobin dropped from 14 g/dL to 7.2 g/dL in under 72 hours - a drop that would send most people straight to the ER.

What’s scary is how quickly it can be missed. Many doctors don’t think to ask about ancestry or family history. They just see a UTI and reach for the most common, cheapest antibiotic. And here’s the problem: if you’re of African, Mediterranean, Middle Eastern, or Southeast Asian descent, your chance of having G6PD deficiency is much higher - up to 14% in some groups. Yet screening isn’t routine.

Who’s Most at Risk?

It’s not just adults. Infants exposed to nitrofurantoin through breast milk have developed hemolytic anemia. Pregnant women with undiagnosed G6PD deficiency who took the drug also had serious reactions. In fact, eight documented cases involved pregnant patients.

And here’s the twist: even if you’ve taken nitrofurantoin before without issues, that doesn’t mean you’re safe. G6PD deficiency can be mild. You might only react under stress - like an infection, certain foods (fava beans), or a new drug. A person could take nitrofurantoin safely at 25, then have a crisis at 45 after a viral illness weakens their system further.

What Do Experts Say About Screening?

The American Society of Hematology, the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the European Medicines Agency all agree: avoid nitrofurantoin in patients with known G6PD deficiency.

But here’s the gap: the FDA label only says, “Hemolytic anemia has been reported in G6PD-deficient individuals.” It doesn’t require testing. No mandatory screen. No checklist. No alert in most electronic health records.

A 2022 survey of 350 primary care doctors found only 32% routinely check for G6PD deficiency before prescribing nitrofurantoin. That means nearly 7 out of 10 patients are being put at risk without anyone asking.

Meanwhile, G6PD testing costs $35-$50. A hospital stay for hemolytic anemia? That averages $8,500-$12,000. You’re spending less to prevent a crisis than you’d pay to treat one.

What Are the Alternatives?

If you have G6PD deficiency - or you’re from a high-risk population - there are safer options.

• Fosfomycin: A single-dose antibiotic, often used as first-line for UTIs in G6PD-deficient patients. It’s not affected by the same oxidative pathways.
• Pivmecillinam: Available in many countries, not yet approved in the U.S., but widely used in Europe with low hemolytic risk.
• Cephalexin: A first-generation cephalosporin. While some cephalosporins can cause immune-mediated hemolysis, this one doesn’t trigger oxidative damage.
• Trimethoprim-sulfamethoxazole: Higher resistance rates, but generally safe for G6PD-deficient patients - unless they have a history of sulfa allergy.

For patients with kidney problems, options shrink. Nitrofurantoin is already off the table if your eGFR is below 60. But so are many other drugs. That’s why knowing your G6PD status matters even more - it helps doctors pick the right drug without guessing.

What Should You Do?

If you’ve ever been told you have anemia, jaundice as a baby, or a family history of blood disorders - especially if you’re of African, Mediterranean, Middle Eastern, or Southeast Asian descent - ask your doctor for a simple G6PD blood test. It’s a quick finger-prick or venous draw. Results come back in hours.

If you’re prescribed nitrofurantoin and you don’t know your status, ask: “Is this safe for someone with G6PD deficiency?” Don’t be afraid to push back. Your life might depend on it.

If you’ve already taken nitrofurantoin and developed symptoms like dark urine, fatigue, or yellowing skin within a few days - stop the drug immediately and get medical help. Hemolytic anemia from nitrofurantoin is treatable if caught early. Most patients recover fully within 48 hours after stopping the drug and getting fluids.

The Bigger Picture

Nitrofurantoin isn’t going away. It’s too effective against resistant UTIs. But the medical world is slowly waking up. Point-of-care G6PD tests are being developed - imagine a test you can do in the doctor’s office while you wait. The NIH is running a trial to see if universal screening before prescribing nitrofurantoin saves money and lives. Early results are promising.

Right now, we’re treating UTIs like they’re all the same. But they’re not. One size doesn’t fit all - especially when genetics play a role. The future of antibiotics isn’t just about resistance. It’s about matching the right drug to the right person.

Don’t wait for a crisis to find out you’re at risk. Ask. Test. Know. It’s simple. And it could save your life.