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Dose-dependent relationships in potential prescribing cascades: a cohort study using community pharmacy dispensing
Ruveyda Gündogan-Yilmaz1, Sadaf Wahedi1, Johanna H M Driessen2,3
1Department of Clinical Pharmacy, OLVG, Amsterdam, The Netherlands.
International Journal of Clinical Pharmacy
|February 17, 2026
Summary
Medication dose significantly impacts prescribing cascades, where one drug triggers another. Higher doses of index medications like ACE inhibitors, statins, antidepressants, and DCCBs increased the risk of these cascades, highlighting the importance of dose awareness in clinical practice.
Area of Science:
- Pharmacovigilance and Drug Safety
- Clinical Pharmacology
- Medication Error Research
Background:
- Prescribing cascades occur when a new drug is prescribed to manage adverse drug reactions (ADRs) from an initial medication.
- Evidence for a dose-dependent relationship in many prescribing cascades is limited, despite dose reduction being a common strategy for managing ADRs.
Purpose of the Study:
- To investigate the dose-dependent relationship in potential prescribing cascades for various index medications where this link was previously unknown.
- To analyze the association between medication dosage and the initiation of subsequent drugs in a cascade.
Main Methods:
- A cohort study utilized prescription sequence symmetry analysis in over 600 Dutch pharmacies (2015-2020).
- Eighteen potential prescribing cascades involving ACE inhibitors (ACEIs), statins, antidepressants, and dihydropyridine calcium channel blockers (DCCBs) were assessed.
- Index medication doses were classified as low (<0.50 DDD), medium (0.50-1.50 DDD), and high (>1.50 DDD) using WHO Defined Daily Doses (DDD).
Main Results:
- Twelve of 18 potential prescribing cascades exhibited a dose-dependent relationship.
- Angiotensin-converting enzyme inhibitor (ACEI) related cascades showed increasing adjusted sequence ratios (aSRs) with higher doses, particularly for ACEI-induced cough.
- Dose-dependent relationships were also observed for statins, antidepressants, and DCCBs, but not for proton pump inhibitors, diuretics, or NSAIDs.
Conclusions:
- Medication dosage is a significant factor in the development of potential prescribing cascades.
- Healthcare professionals should consider the role of dose in prescribing cascade development.
- Further research is needed to confirm findings and support clinical recommendations, as this study design does not allow for causal inference.
Keywords:
Drug prescriptionsDrug-related adverse reactionsPharmacoepidemiologyPolypharmacyPrescribing cascadesMore Related Videos
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