4CPS-115 Dose-dependent relationships in prescribing cascades: a cohort study

<h3>Background and Importance</h3> Prescribing cascades occur when new medications are introduced to treat adverse drug reactions (ADRs) caused by an initial (index) medication. This could lead to polypharmacy and increased healthcare costs. While dose reduction is often suggested as a strategy to mitigate prescribing cascades, the extent to which the dosage of an index medication affects the development of these cascades remains unknown. <h3>Aim and Objectives</h3> This study aimed to investigate the dose-dependence of prescribing cascades across a range of index medications. <h3>Material and Methods</h3> We conducted a retrospective cohort study using prescription sequence symmetry analysis (PSSA) with dispensing data from over 600 pharmacies. The relationship between different doses of index medications and 18 prescribing cascades was examined, including Angiotensin-Converting Enzyme inhibitors (ACEIs), statins, proton pump inhibitors (PPIs) and diuretics. Doses were classified using the World Health Organization’s defined daily dose (DDD) into low (&lt;0.50 DDD), medium (≥0.50 and ≤1.50 DDD), and high (&gt;1.50 DDD) dose groups. Adjusted sequence ratios (aSRs) were calculated, with an aSR &gt;1 indicating a prescribing cascade. Dose-dependence was confirmed when aSRs increased with higher doses and the 95% confidence intervals (CIs) between dose groups did not overlap. <h3>Results</h3> Of the 18 cascades analysed, 12 showed a dose-dependent relationship. All seven ACEI-related cascades displayed dose-dependence. For example, the aSR for ACEI-induced cough followed by antitussives increased from 2.09 (95% CI: 1.95–2.23) in the low-dose group to 2.75 (95% CI: 2.67–2.83) in the high-dose group. Similarly, for ACEI-induced cough followed by inhaled adrenergics, the aSR rose from 0.86 (95% CI: 0.71–1.00) in the low-dose group to 1.51 (95% CI: 1.44–1.59) in the high-dose group. Statins exhibited dose-dependence in three of six cascades. No dose-dependent relationship was observed for cascades involving PPIs (1 cascade), diuretics (1 cascade). <h3>Conclusion and Relevance</h3> These findings highlight the importance of dosage in managing prescribing cascades, particularly for ACEIs and possibly statins. Hospital pharmacists should remain vigilant for ADRs at higher doses and consider dose reduction as a strategy to reverse or prevent prescribing cascades. Further research is necessary to assess the effectiveness of dose adjustments in preventing ADRs and prescribing cascades. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest