• off-label;
  • drug use;
  • general practice;
  • epidemiology;
  • medical registration



The aim of this study is to quantify the extent of ill-founded off-label drug prescriptions in Dutch general practice. The study is based upon information on both the prescription itself and the patient's medical history.


In total, 48 combinations of drugs and off-label indications were selected from a list of 477 known off-label combinations. These 48 combinations were considered as ill-founded since pharmacotherapeutic handbooks or clinical practice guidelines did not provide evidence for their efficacy and safety. They were considered to be relevant for investigation in general practice. We used a nationally representative information network of 85 general practices in the Netherlands. By using information on the patients' diagnoses and medication in the period before and after the prescription, we were able to exclude non-conclusively off-label prescriptions.


Twenty-one of the selected 48 off-label combinations did not occur in Dutch general practice. The drugs with the highest proportion of ill-founded off-label prescriptions were betahistine (26.7%), celecoxib (16.3%) and etoricoxib (12.5%). In total, 18.2% of the prescriptions, which were initially assessed as ill-founded off-label, were re-evaluated as on-label, after considering the patient's medical history.


Ill-founded off-label prescribing in Dutch general practice is limited for 48 relevant combinations of drugs and off-label indications. In order to overcome limitations in registration databases, it is useful to look at as much information as possible—for example, co-medication and co-morbidity—when determining off-label prescribing. Studying ill-founded off-label prescribing should be performed on a day-to-day basis, especially for recently introduced drugs. Copyright © 2008 John Wiley & Sons, Ltd.