Can drugs be prescribed outside the instructions written on the leaflet?

It may be surprising but yes: to treat a given condition, doctors may choose to prescribe a drug that was originally developed to treat another. Thus, it may happen that the pill we have been taking for years to manage anxiety is actually an anti-epileptic, or that the drug we have been prescribed as migraine prophylaxis was originally tested as a treatment for depression. These are the so-called off-label drugs ("off-label"): medicines used outside the conditions (e.g. pathologies, patient classes, dosages) for which they were authorized (1). A This is a rather common practice, especially in some areas. A 2006 study that analyzed a group of drugs that are very common in daily clinical practice showed that 21% of these was prescribed for indications other than those provided for in the package insert (2). In some categories of patients, then, this rate can be even higher: a research that investigated this practice in the pediatric field, for example, highlighted off-label prescriptions in 78.7% of children and adolescents admitted to hospitals for minors (3).

In Europe, as well as in the United States, it is the regulatory agencies that establish, on the basis of rigorous analyzes carried out to evaluate the level of efficacy, safety and quality of the product, which drugs can be sold (and therefore prescribed) in the context of specific pathologies (4). The legislation that regulates the use of off-label drugs establishes that the doctor must comply with the therapeutic indications and administration methods defined by the marketing authorization, as assessed in the various phases of drug experimentation (5). However, as also specified by the Italian Medicines Agency (AIFA), "the law allows a 'different' use of the drug if the attending physician, on the basis of the evidence documented in the literature and in the absence of better therapeutic alternatives, deems it necessary to administer a drug outside the authorized indications for use. The prescription of off-label drugs is therefore permitted and regulated from a regulatory point of view and represents an important opportunity that can lead to significant progress in the knowledge and treatment of some pathologies” (6).