Hydroxyzine, sucralfate pose adverse ototoxic reactions

Hydroxyzine and sucralfate seem to trigger ototoxic adverse drug reactions in patients, a recent study has found. These drugs should not be given with other well-confirmed ototoxic medications.

Drawing electronic health records from the South Korea National Health Insurance Service, the researchers conducted a longitudinal analysis of ototoxic drug reactions in 679,760 patients. The MetaNurse algorithm identified three target drugs for analysis: cimetidine, hydroxyzine, and sucralfate. Bilateral hearing loss was the primary outcome.

Multiple Cox regression analysis revealed that all three drug candidates were significantly associated with bilateral hearing loss. Hydroxyzine (adjusted hazard ratio [HR], 2.20, 95 percent confidence interval [CI], 1.05–4.60) and sucralfate (adjusted HR, 2.26, 95 percent CI, 1.18–4.33) more than doubled the risk of the ototoxic outcome.

In contrast, cimetidine had a weaker effect but was nevertheless significant (adjusted HR, 1.31, 95 percent CI, 1.03–1.68). Kaplan-Meier survival curves for a 12-year follow-up period confirmed that patients taking the tested drugs developed bilateral hearing loss more frequently.

However, external validation using the United States Food and Drug Administration Adverse Event Reporting System (2012–2018 data) could only confirm the significance of hydroxyzine and sucralfate for otologic adverse events.

“This study provides new insight into the potential risk of ototoxic adverse drug reactions with hydroxyzine and sucralfate,” the researchers said. “Further studies are needed to elucidate the underlying pathophysiological mechanisms mediating the drug-related ototoxicity identified for these three drugs.”