Mepifilina in Spain: Accessible evidence, guideline positioning, utilization and proportionate reassessment

Mepifilina (mepyramine-acefyllinate) is a long-authorized legacy combination medicine in Spain for bronchoconstriction associated with acute/chronic bronchitis and remains reimbursed by the Spanish National Health System (SNS). We triangulated publicly accessible clinical evidence, GINA/GOLD/NICE/GEMA/GesEPOC mentions and pharmacological-class positioning, aggregate SNS dispensing/expenditure for ATC5 R03DA12, and regulatory auditability. A secondary, exploratory, non-validated Evidence-Practice Structural Misalignment (EPSM) rubric was used only as a transparency aid. Three randomized trials were identified (1994-2002; n=214); none evaluated the licensed indication, two were at high risk of bias, and certainty was very low. No guideline explicitly mentioned mepifilina; xanthines/theophylline had limited, later-line or conditional roles. During 2022-2024, SNS dispensing totaled 6.30 million packages (€27.87 million), with no public historical evaluation report available. Aggregate, non-clinical data do not permit inference on indication, duration, prescribing appropriateness, benefit or real-world safety. Findings support prioritizing proportionate reassessment; they do not establish clinical ineffectiveness, excess harm, inappropriate prescribing, overuse or withdrawal.