Quinolones and risk of haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency: a nationwide retrospective active-comparator cohort study.

BACKGROUND

Quinolone product information and avoidance lists continue to caution against use in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency despite limited comparative epidemiologic evidence. We evaluated whether oral quinolone dispensations were associated with haemolysis-related outcomes compared with an active antibiotic comparator.

METHODS

We conducted a nationwide retrospective active-comparator cohort study using Clalit Health Services data from 2010 to 2023. Patients with at least one ICD-coded diagnosis of G6PD deficiency who received an outpatient oral quinolone or penicillin dispensation were included. The primary outcome was a haemolysis-related diagnosis code recorded within 30 days. Jaundice and laboratory markers were secondary outcomes. Models were adjusted for age, sex and Charlson comorbidity index. Additional analyses evaluated patients aged 18 years or younger, patients exposed to both antibiotic classes and individual quinolone agents.

RESULTS

The cohort included 465 083 dispensations among 64 861 patients (65 906 quinolone and 399 177 penicillin episodes). Haemolysis-related codes were recorded after 52 quinolone episodes (0.079%) and 198 penicillin episodes (0.050%); the adjusted odds ratio (aOR) was 1.29 [95% confidence interval (CI) 0.92-1.77; P = 0.12]. Among patients aged 18 years or younger, events occurred after 5/8865 quinolone and 91/160 423 penicillin episodes (aOR 1.02, 95% CI 0.36-2.26, P = 0.970). In the within-patient subcohort, episode-level event rates were 0.065% after quinolones and 0.061% after penicillins (aOR 0.95, 95% CI 0.65-1.37, P = 0.785). Laboratory outcomes did not show a coherent pattern of increased haemolysis after quinolones.

CONCLUSIONS

In this large outpatient cohort, oral quinolone dispensations were not associated with a detectable major increase in coded haemolysis compared with penicillins. The findings do not exclude small risks or increased susceptibility in patients with severe G6PD deficiency, very young children, active infection-related oxidative stress or concurrent oxidant exposures.