Adverse reactions to antibiotics and Glucose-6-Phosphate Dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that protects red blood cells from damage caused by oxidative stress. People with G6PD deficiency have less of this protection. Most of the time they feel well, but certain medications, infections or eating fava beans can cause red blood cells to break down suddenly. This is called acute hemolytic anemia. G6PD deficiency affects about 5% of people worldwide, which makes it one of the most common inherited conditions. This article explains who is affected, which medications matter, how G6PD deficiency is diagnosed and how genetic testing can help.

What happens during a G6PD-related reaction?

When red blood cells break down faster than the body can replace them, symptoms usually appear within one to three days of the trigger:

• Tiredness, weakness and shortness of breath
• Pale skin or yellowing of the skin and eyes (jaundice)
• Dark, tea-coloured urine
• A fast heartbeat and, sometimes, fever

These reactions can be serious, especially in children, and need urgent medical care. Most people recover once the trigger is removed. G6PD deficiency is also a common cause of jaundice in newborns, which needs to be monitored and treated to prevent complications.

Who is affected by G6PD deficiency?

The G6PD gene is on the X chromosome. Men have one X chromosome, so a single variant copy causes G6PD deficiency. Women have two X chromosomes, so most women with one variant copy have enough enzyme activity. However, because one X chromosome is randomly switched off in each cell, some women with one variant copy have low activity and can have reactions as severe as men's. A genetic test alone cannot predict which women are affected, so women with one variant copy need an enzyme activity test.

G6PD deficiency is most common in people of African, Mediterranean, Middle Eastern, South Asian and Southeast Asian ancestry, and in some groups it affects 30% of people or more. It is common in these regions because carrying a G6PD variant protects against severe malaria. More than 200 G6PD variants are known, and different variants are common in different populations. For example, G6PD A− is common in people of African ancestry, G6PD Mediterranean in people of Mediterranean, Middle Eastern and South Asian ancestry, and G6PD Kaiping and Canton in people of Chinese and Southeast Asian ancestry.

Which medications are risky with G6PD deficiency?

Many medications have been listed as unsafe in G6PD deficiency, often based on old case reports. In 2022, the Clinical Pharmacogenetics Implementation Consortium (CPIC) reviewed the evidence and sorted these medications by risk:

Risk	Examples	What it means
High	Rasburicase and pegloticase (uric acid medications), primaquine at standard doses and tafenoquine (malaria), dapsone, methylene blue	Avoid in G6PD deficiency
Medium	Nitrofurantoin (urinary tract infections), primaquine once weekly	Use with caution and monitoring
Low to no risk	Sulfamethoxazole (in Septra and Bactrim), low-dose aspirin, acetaminophen	Can be used normally

The full list is on the CPIC website. Higher doses, several medications at once and infection can all increase the risk, so always tell your doctor and pharmacist if you have G6PD deficiency.

Can antibiotics cause reactions in G6PD deficiency?

Most commonly used antibiotics are safe in G6PD deficiency. CPIC found that sulfamethoxazole, the sulfa antibiotic in Septra and Bactrim, can be used normally regardless of G6PD status, and there is little evidence that other common antibiotics cause hemolysis. Nitrofurantoin, used for urinary tract infections, should be used with caution. Dapsone, used for some infections and skin conditions, should be avoided.

Not every reaction to an antibiotic is related to G6PD. A rash, hives or swelling after an antibiotic is usually an allergy or another type of drug reaction. The infection itself can also trigger hemolysis in G6PD deficiency, which can make it hard to tell whether the illness or the medication caused the problem. If you developed jaundice, dark urine or anemia after an antibiotic or an infection, ask your doctor whether a G6PD test is right for you.

What else can trigger a reaction?

• Fava beans. Eating fava (broad) beans can cause severe hemolysis, called favism, especially in children. People with G6PD deficiency should avoid them. Other beans and legumes are safe.
• Infections, such as pneumonia, hepatitis or gastrointestinal infections.
• Some chemicals, such as naphthalene in mothballs, and henna applied to the skin of babies.

Some websites list other foods, such as blueberries or bitter melon, but CPIC could not find reliable evidence that foods other than fava beans cause reactions. Very high doses of vitamin C given by intravenous infusion should be avoided.

How is G6PD deficiency diagnosed?

There are two types of tests, and they work best together:

• An enzyme activity test measures how much G6PD is working in red blood cells. It is the standard test and the only way to know the enzyme level in women with one variant copy. It can give a falsely normal result during or soon after a hemolytic episode or a blood transfusion, because young red blood cells and transfused cells have more enzyme.
• A genetic test looks for G6PD variants. Its result does not change with recent hemolysis or transfusion, and it is reliable in men. However, each test checks only certain variants, so a negative result does not rule out G6PD deficiency, especially if your ancestry is linked to a variant the test does not include.

Does Pillcheck test for G6PD?

Yes. A Pillcheck test reports seven G6PD variants: Mediterranean, Kaiping, Malaga, Aveiro, Iowa, Nashville and Santiago de Cuba. The A− variant, which is the most common in people of African ancestry, will be added in the report update planned for December 2026. Until then, a Pillcheck result without a G6PD variant does not rule out G6PD deficiency, especially in people of African ancestry. Women who carry one variant copy, and anyone with symptoms or a history of hemolysis, should also have an enzyme activity test.

Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results together with all your medications and gives you recommendations to discuss with your doctor.

Summary

• G6PD deficiency affects about 5% of people worldwide and can cause sudden anemia after certain medications, fava beans or infections.
• Men with one variant copy are affected. Some women with one variant copy are also affected and need an enzyme activity test.
• High-risk medications include rasburicase, pegloticase, primaquine, tafenoquine, dapsone and methylene blue. Nitrofurantoin should be used with caution.
• Most common antibiotics, including sulfamethoxazole, are safe in G6PD deficiency.
• Genetic and enzyme tests work best together. A negative genetic result does not rule out G6PD deficiency.

Frequently asked questions

Can I take sulfa antibiotics if I have G6PD deficiency?

Yes, in most cases. CPIC classifies sulfamethoxazole as low to no risk, so it can be used normally. Some drug labels still include a caution, so tell your doctor and pharmacist about your G6PD status.

Can women have G6PD deficiency?

Yes. Women with two variant copies are deficient, and some women with one variant copy have low enzyme activity. An enzyme activity test is needed to know for sure.

Should I avoid all beans?

No. Only fava (broad) beans are a proven trigger. Other beans and legumes are safe.

I had a reaction to an antibiotic. Should I be tested for G6PD?

If the reaction was a rash, hives or swelling, it is more likely an allergy. If you had jaundice, dark urine or anemia, ask your doctor about a G6PD enzyme test.

References

Gammal RS, Pirmohamed M, Somogyi AA, et al. Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Clin Pharmacol Ther. 2023;113(5):973-985.

Luzzatto L, Ally M, Notaro R. Glucose-6-phosphate dehydrogenase deficiency. Blood. 2020;136(11):1225-1240.

Italian G6PD Deficiency Association. G6PD deficiency information and drug lists.