title: Adverse drug reaction labelling for atomoxetine, methylphenidate and modafinil: comparison of product information for oral formulations in Australia, Denmark and the United States.
abstract: Medical product information contains information about efficacy and safety for marketed pharmaceuticals. Three studies have compared safety labelling for different therapeutic categories in different countries and detected large variations in a number of reported adverse drug reactions (ADRs). The rapid increase in use of medications for treatment of ADHD symptoms has created concern due to lack of information about effects from long-term use. The aim of this study was to compare ADR information in product information (PI)/summary of product characteristics (SPC) for oral formulations of atomoxetine, methylphenidate and modafinil marketed by the same pharmaceutical companies in Australia, Denmark and the United States. Discrepancies in listed ADRs were defined as types of ADRs (system organ class) not listed in all countries. For ADRs where discrepancies were detected, we extracted information about study design (clinical trials, spontaneous report). Discrepancies in ADR labelling for the medications were found across the three countries. A total of 75 ADR categories were listed for atomoxetine and 80% of these were listed in all three countries. For methylphenidate, totally 101 ADR categories and for modafinil 115 ADR categories were listed. For both substances approximately 60% of listed ADRs were found in all three countries. Discrepancies were primarily detected for ADRs information based on clinical trials. For methylphenidate, many ADRs labelled in Australia and Denmark were not mentioned in PIs issued in the United States. In conclusion, information about possible ADRs associated with the use of a specific product should be made available worldwide, as the prescriber information about medicines' safety profile should not depend on the country in which the medication is licensed.
authors.affiliation: Institute of Public Health, Clinical Pharmacology, Faculty of Health Sciences, University of Southern Denmark, J.B. Winslows Vej 19, 2., DK - 5000 Odense C, Denmark. laagaard@health.sdu.dk
authors.forename: Lise
authors.initials: L
authors.lastname: Aagaard
authors.forename: Ebba Holme
authors.initials: EH
authors.lastname: Hansen
mesh_terms: D000284:Administration, Oral; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000069445:Atomoxetine Hydrochloride; D001315:Australia; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects; D003718:Denmark; D004345:Drug Industry; D004348:Drug Labeling; D006801:Humans; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects*; D000077408:Modafinil; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects*; D014481:United States
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D000077408:Modafinil