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•We introduced restrictive interventions for some antibiotics in ambulatory care.•The change in antibiotic consumption before and after the interventions was evaluated by interrupted time series method.•Consumption of restrictive antibiotics decreased more than that of non-restrictive antibiotics.•Restrictive interventions had a significantly greater impact on consumption 3 years post-intervention than after 12 years.•The combination of restrictive and regulative interventions had an important impact on the costs of antibiotics.