Off-Label Use

Definition

In drug therapy, “off-label use” refers to deviations from the officially approved specifications in the drug information leaflet of approved drugs that are ready for use. Frequently, this concerns the areas of application (indications). However, other changes also fall under the definition, for example with regard to the dose, duration of therapy, patient groups, gender, dosage form or age limits. The legal responsibility for an off-label use is assumed by the medical professionals, i.e. usually the physicians and not the pharmaceutical companies. The law does not prohibit off-label use, provided due diligence is exercised and accepted scientific rules are followed. Off-label use of medicines is also very common in pharmacies and it is also practiced by patients themselves. Patients should always be informed about this practice in advance by the professionals. With regard to marketing authorizations, there are considerable differences between countries. What is “on-label” in one country may be off-label in another. If preparations or active ingredients are used that are not registered as medicines, on the other hand, they are not referred to as off-label use. This applies, for example, to extemporaneous preparations, experimental therapies, or clinical trials.

Examples

Off-label use occurs very frequently in practice. The following list shows only a small selection of typical examples:

Off-label use is part of everyday life in medicine and pharmacy. Common it is, for example, in pediatrics, gynecology, psychiatry, oncology, intensive care, geriatrics and dermatology.

Reasons for off-label use

There are many reasons why a drug may be administered contrary to official guidelines. For example, when there is no approved drug on the market for a condition. The professional information may be too restrictive for legal, regulatory, or commercial reasons and may even contradict current scientific knowledge. Clinical studies, which form the basis for the formulation of indications, as well as registration, are expensive and time-consuming. Often the financing is not worthwhile for the companies, also because patents have expired and generics are available. For rare diseases or special patient groups, there is often no approval. In some cases, testing is not even possible for ethical reasons. In the case of incurable or acutely life-threatening diseases, regulatory requirements play a subordinate role. Off-label use is also considered for economic reasons, for example, if a non-approved drug is cheaper than a registered one. However, this practice is critically discussed in the literature.

Problems and solutions

Off-label use can be problematic when there are insufficient efficacy and safety data. In such a case, it is also referred to as experimental therapy. In principle, off-label treatment should be based on scientific evidence. Careless off-label use can lead to adverse effects. Because the legal responsibility lies with the healthcare professional, he or she exposes himself or herself to a certain risk when prescribing or dispensing. The reimbursement of the medications may be refused by the health insurers. Before dispensing, an application for a cost approval can be submitted. This is particularly relevant for high-priced therapies. The coverage is regulated by the Health Insurance Ordinance (KVV). Patients can be confused when they receive medications whose package inserts do not contain information for the disease being treated. Another disadvantage is the lack of documentation (patient information).Patients should be informed accordingly and their consent should be obtained in advance (“informed consent”). The procedure should be documented. In addition, it would be desirable for a corresponding note to be made on doctors’ prescriptions. Pharmaceutical companies can get into legal trouble if they advertise the off-label use of their drugs. This is because advertising is prohibited in this area, and even information can be legally very tricky. In the past, companies have had to pay enormous sums due to lawsuits and in out-of-court settlements due to infringements. As a result, they have become very careful and cautious, which in turn makes it difficult to provide information to professionals and patients. This overcautiousness required by law may result in inadequate reporting of meaningful off-label use.