BACKGROUND: Prescribing cascades occur in clinical practice when a medication causes an adverse drug reaction (ADR), which is addressed by prescribing additional medication. AIM: The aim was to provide proof-of-concept for pharmacy-led interventions to reverse or prevent prescribing cascades. METHOD: Two community pharmacies each tested two approaches. To reverse prescribing cascades, ten cascades were selected from literature. Dispensing records were screened to identify patients with these cascades. To prevent prescribing cascades, patients who started medications associated with five of these cascades were telephoned one month after their first dispensing to discuss ADRs. Pharmacists assessed the need to intervene together with prescribers. Primary outcome was the proportion of patients with a treatment change initiated. Secondary outcomes were time investment, potential cost-savings, and pharmacists' experiences. RESULTS: To reverse prescribing cascades, 24 patients were included. For eight the prescriber was consulted, resulting in the reversal of three cascades. Forty-four patients were included to prevent prescribing cascades. Six of them experienced an ADR that could lead to a prescribing cascade. For two patients interventions were conducted to prevent this. The estimated time investment to identify patients possibly in need of intervention was 4.5 h for the reversing approach and 4.8 h for the preventing approach, while follow-up actions required 1.8 h and 0.5 h, respectively. Both approaches could be cost-saving. Pharmacists considered both approaches relevant but identified a knowledge gap on how to intervene for some cascades. CONCLUSION: Pharmacy-led interventions may reverse and prevent prescribing cascades, but more efficient screening methods and tools are needed before further implementation.