Why Product Information Should not be Set in Stone: Lessons from a Decade of Linezolid Therapeutic Drug Monitoring: An Opinion Paper

Abstract

WHAT IS 'PRODUCT INFORMATION'?The "product information" (PI) for a medicine contains the documents providing officially approved information for health care professionals and patients. The regulatory agencies for drugs (eg, the European Medicines Agency, the Food and Drug Administration, Therapeutic Goods of Australia) provide guidance and templates to give marketing authorization applicants practical advice on how to develop the PI for human medicines. A summary of the product characteristics, labelling, and package leaflets is included.The information in a PI document is written by the pharmaceutical company responsible for the medicine and approved by regulatory agencies. It provides objective information regarding the quality, safety, and effectiveness of the medicine, as demonstrated in the data provided by the pharmaceutical company. This information is intended to assist physicians, pharmacists, and other health care professionals in prescribing and dispensing medicines. In addition, health professionals in their consultations with patients can use this information so that patients are better informed about their medicines.A list of information that should be contained in the PI is highlighted in the box below. CAN A PHARMACEUTICAL COMPANY ALTER THE PI AFTER A MEDICINE IS MARKETED?As discussed above, the information in a PI document is written by the pharmaceutical company responsible for the medicine, based on the results of phase I-III registration trials. However, it is widely recognized that pharmacological and clinical data (efficacy/safety) may change when a drug is administered in real-world clinical practice. This is in large part because most complex patients, such as the elderly, patients with comorbidities receiving polypharmacy, patients with impairment of the excretory organs, or those undergoing renal replacement therapy are usually excluded from phase I-III clinical trials. In real life, these patients generally have access to the medicine in question, generating novel pharmacokinetic/pharmacodynamic (PK/PD) data when appropriate research is undertaken with the potential to reverse the key concepts provided in the PI. In addition, regulatory agencies require phase I studies aimed at characterizing the pharmacokinetics and safety of a new drug, which is conducted in healthy volunteers and typically after a single-dose administration. This is poorly representative of real-life scenarios in clinical practice and is an additional limitation to the applicability of the PI to all patients receiving a drug.In general, researchers who are independent of the pharmaceutical company that marketed the drug generate most of the data pertaining to a drug in real-life settings. It is presently unclear who should undertake periodic revisions of the PI, taking into consideration new evidence reported in the literature. If new data are generated during patent coverage, the pharmaceutical company responsible for the marketing of the medicine is expected to submit amended versions of the PI to regulatory agenci...