When the Law Changes Therapy: Interrupted Time-Series Analysis of the Regulatory Impact on Intravenous Analgesic...

Tramadol is a centrally acting weak opioid widely used for moderate postoperative pain in orthopaedic surgery, so its regulatory status is directly relevant to hospital pharmacists. In November 2022 the Italian Ministry of Health reclassified tramadol as a controlled substance under Section A of Presidential Decree 309/1990. Its effect on surgical-hospital prescribing has not been systematically described. We quantified the change in consumption and expenditure of intravenous (IV) tramadol and of the IV non-steroidal anti-inflammatory drugs (NSAIDs) used as alternatives in 2 Italian orthopaedic IRCCS hospitals.

Retrospective 2-centre drug-utilisation study (Hospital A: 9100 procedures/year; Hospital B: 13 500/year) covering January 2021 to December 2024. Monthly dispensing and cost of IV tramadol, ketorolac, ketoprofen lysine and ibuprofen were extracted from the pharmaceutical management system. Use was expressed as Defined Daily Doses (DDDs) per 100 procedures. Pre- and post-policy periods were compared with a single-group interrupted time-series analysis using segmented linear regression with calendar-month indicators and Newey-West standard errors.

Mean annual IV tramadol dispensing fell from 953 to 259 units at Hospital A (-72.8%) and from 2011 to 617 at Hospital B (-69.3%). Segmented regression showed immediate level changes for IV tramadol of β₂ = -1.45 at Hospital A (P < .001) and -2.60 at Hospital B (P < .001); expressed relative to the model-predicted pre-policy level at the intervention, these correspond to immediate reductions of approximately 57% and 63%. For IV ketorolac, level changes were +2.41 (P = .012) and +12.68 (P < .001). Aggregate IV-analgesic expenditure per 100 procedures rose from €18.96 to €25.99 at Hospital A (+37%) and from €47.20 to €412.73 at Hospital B (+774%); this between-centre difference was driven by Hospital B's high-cost ready-to-use IV ibuprofen bag, which accounted for about 93% of total post-policy expenditure and 99% of the increase at that centre.

The reclassification coincided with a marked reduction in IV tramadol use and a parallel rise in IV NSAID use. The rise in pharmacy expenditure was driven less by the regulatory shift than by the local formulary choice that accompanied it.