Medications and Acute Hemolysis in G6PD‐Deficient Patients – A Real‐World Study

Many drug labels contain precautions of use in G6PD‐deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or structural data. In this real‐world study, we aimed to examine if the administration of presumably risky medications for G6PD‐deficient patients was followed by hemolysis. The study is based on data from Clalit Health Services database that provides inclusive health care for more than half of the Israeli population (~ 4.7 million). Within the database, we identified all G6PD‐deficient patients by G6PD <6 U/g Hb. Within the G6PD‐deficient cohort, we identified all hospitalizations with a discharge diagnosis of hemolysis (January 1, 2010 to December 31, 2022), validated the cases, and identified the culprit event. For the rest of the G6PD‐deficient patients with no‐hemolysis, we recorded filled prescriptions of medications listed as presumably risky. We identified 31,962 G6PD‐deficient patients. Within the cohort, there were 71 cases of major hemolysis requiring hospitalization (0.2% of the cohort), of whom 51 (71.8%) had been caused by ingestion of fava beans, six (8.5%) were associated with an infection, and three (4.2%) suggested to be associated with medications (nitrofurantoin, phenazopyridine, and a “pain killer”). Within the 31,875 patients with no major hemolysis, nitrofurantoin has been prescribed safely to 1,366 G6PD‐deficient males and females; hundreds/thousands of G6PD‐deficient patients had been prescribed safely ciprofloxacin, glibenclamide, ofloxacin, phenazopyridine, sulfamethoxazole/cotrimoxazole, sulfasalazine, hydroxychloroquine, glimepiride, mesalazine, and sulfacetamide. In this real‐world study, we are showing that a list of medications, suspected previously as carrying risks for hemolysis in G6PD‐deficient patients, have been prescribed safely to G6PD‐deficient patients, providing reassurance to patients, prescribers, and regulators.