Monitoring the safety of off-label medicine use.(Pharmacovigilance Focus)

Medicine labels contain important information on the conditions of use. These conditions typically include the indication, dosage, frequency of administration, and route of administration. Other important conditions of use can include the age range of patients, duration of treatment, and contraindications to use of the medicine. Deviations from the conditions of use set forth in the label constitute off-label use.

In the USA, off-label use is legal. While the Food and Drug Administration (FDA) regulates the marketing of medicines, it does not regulate prescribing practices. In one study (1), approximately 21 per cent of drug use in office-based practice was for off-label use. Off-label use may occur for a variety of reasons. For example, there are some diseases for which no adequate, labelled treatment exists. In these situations, prescribers use medicines for off-label indications. In the case of medicines for children, many drugs have never been studied in children, so there has been extensive off-label use in children, although there are ongoing efforts to correct this situation. In some cases, there may be a reasonable body of published evidence to support off-label use. In other cases, such use is speculative. However, off-label use may become part of accepted practice, and may be part of professional society guidelines.

Because off-label use is common, there is a public health imperative to monitor the safety of medicines when used off-label. First and foremost, monitoring the safety of medicines in off-label settings is necessary to gain information on the usage of medicines in these settings. While formal study of medication safety would be optimal in these settings, such studies are often not available. Thus, safety monitoring plays a critical role. Data derived from monitoring safety in an off-label setting can also potentially be relevant to the safety of the medicine when used according to the label. In addition, data derived in the off-label setting may serve as a stimulus for more formal study.

There are many specific concerns that need to be addressed when monitoring the safety of medicines in an off-label setting. Many factors that could affect the safety of the medicine could be different in the off-label compared to the on-label setting. These factors include the age of patients, range of co-morbidities, use of concomitant medication, drug-disease interactions and differences in pharmacokinetics and pharmacodynamics.

Despite the importance of monitoring the safety of medicines in an off-label setting, there are many challenges that this situation presents. First, spontaneous reports do not always contain the indication for use or other details that would allow one ...