OBJECTIVES: Numerous prescription products have become available OTC in recent years and there are several reasons why this number is likely to increase significantly in the future. To date, there have been simulation models, but no empirical assessment of the impact of the Rx-to-OTC switch of loratadine. Previous simulation models have shown the Rx-to-OTC switch of loratadine to be cost-effective. The purpose of this research is to empirically assess the overall impact of the Rx-to-OTC switch of loratadine as well as the specific impact of different pharmacy benefit structures on prescription drug utilization and cost in a variety of plan sponsors. METHODS: Data from a national pharmacy benefit management organization covering 27 million lives throughout the US were used. The analysis included a comparison of the difference in prescription utilization and cost for the 12-months after a change in prescription benefits for second-generation antihistamines (SGA) due to OTC loratadine compared to 12-months before for plan sponsors that instituted no change, moved SGA to the 3rd-tier and restricted SGA benefits through prior authorization requirement. Change in utilization and cost of medications for allergic rhinitis (AR), asthma, respiratory infections and all classes combined was examined. Multivariate regression analysis was used to control for differences across study groups. RESULTS: There was a substantial decrease in utilization and cost of all prescription drugs and combinations of drug classes. AR patients facing restricted prescription benefits for SGA did not appear to increase utilization of other AR medications or other medications used to treat comorbid conditions such as asthma, sinusitis and otitis media. CONCLUSIONS: Utilization and cost decreased substantially for all types of medications and all pharmacy benefit structures. Future studies need to examine the impact of the Rx-to-OTC switch of loratadine and resultant prescription benefit policies on medical utilization and OTC antihistamine utilization.