Critical analysis of digitalis glycosides: declining use but increasing poison-center exposure cases for digitoxin

Belonging to one of the oldest drug classes in cardiovascular-medicine, the scientific interest in Na^+/K⁺-ATPase inhibitors (NKA-inhibitors, digitalis glycosides) has increased once again after the publication of the recent DIGIT-HF study. This analysis and scoping review aim to assess long-term prescribing trends of NKA-inhibitors and poison center data to investigate the discrepancy between declining use and increasing poison center reports involving digitoxin in Germany.

By using prescription data (defined daily dose, DDD) and poison center records between 1990 and 2023 in Germany we conducted a pharmacological, pharmacoeconomic and toxicological analysis of the four NKA-inhibitors digitoxin, digoxin, acetyldigoxin and metildigoxin. For identifying trend changes and prescribing trends, we used joinpoint regression and DDD-half-time analyses.

The DDD of NKA-inhibitors declined substantially over our investigated timeframe. Reported exposure cases involving digitoxin, recorded by the GIZ-Nord poison center, showed a significant and continuous increase. Population-adjusted exposure cases increased by 4.65% per year. Exposure-adjusted exposure cases per 1 mio. DDD increased by 11.80% per year. The data for reported cases involving digoxin showed large year-to-year variability and no significant increase in reported case numbers. The PRISM DDD-half-time analysis showed big differences between the four substances, with digitoxin exhibiting the longest DDD-half-time despite the absence of supportive evidence in the form of clinical trials, suggesting a dissociation between evidence and real-world prescriptions.

Prescription volumes decrease but digitoxin is associated with steadily increasing reports of exposure cases from poison center data. This indicates discrepancies between prescribing trends and real-world exposure patterns and highlights the importance for patient selection and careful monitoring, especially in elderly patients.