The Antimicrobials Working Party from the European Medicines Agency (EMA) has published an important reflection paper on off-label use and the application of the cascade system for antibiotic therapy in animals.
The document refers to a number of statutory provisions, provides a list of the most common reasons for off-label use and application of the cascade system, and highlights the possible risks. FAMHP would like to give you some information about this document and ask you to express your opinion about the Belgian situation in connection with off-label use and the cascade system.
The package leaflet and the SPC (Summary of Product Characteristics) form the scientific basis for proper use of a medicinal product. In that sense, the package leaflet succinctly summarises the approved authorisation dossier. Every use of a medicinal product that deviates from what is stated or recommended in the package leaflet, must be able to be justified or explained by the veterinarian.
The key reasons why veterinarians use medicinal products off label or via the cascade system is the unavailability of a substance or preparation for treating a specific condition in a particular species or category of animal. The legislation permits veterinarians to use the cascade system by way of exception, in a limited number of animals and to prevent unnecessary deaths.
However, the basic principle for any medicinal intervention by a veterinarian should always be complying with the package leaflet. Every treatment in the context of the cascade system should comply with the statutory conditions, and for off-label use, good veterinary practice must prevail. Using a medicinal product “off label” means balancing the possible risks for the animal, the user and the environment against the hoped-for effect.
A correct diagnosis, a good estimate of the weight of the animals to be treated, and checking the quality of the drinking water or the composition of the feed are very important. Where an incorrect diagnosis is made or the weight is estimated inaccurately, unintentional off-label use often occurs. This is clearly stated in the reflection paper: “There is no justification for intentional under-dosing”.
Practical cases teach us that with oral treatment of (usually large) groups of animals, whether deliberately or not, medicinal products are often used off label and under-dosing occurs. This is an important cause of increasing germ resistance. Resistant germs (or genes) can be transferred from animals to humans and vice versa through direct contact, the environment or the food chain. Measures such as age separation and compartmentalisation are often necessary to reduce antibiotic treatments on a farm.
In pets, the application via the cascade system of medicinal products for human use, and often of medicinal products that are only authorised for use in humans, requires extremely careful assessment and a well-founded risk-benefit analysis.
The FAMHP would like to have a closer look at the Belgian situation. The reasons for off-label use of antibiotics are not entirely clear, and nor are the motivations behind the application of the cascade system in pets and livestock or the extent to which this occurs. From the initial analysis of registrations in SANITEL-MED for antibiotic treatment of livestock (pigs, poultry, veal calves), it appears that the need for the cascade system through the “importing” of veterinary medicinal products not authorised in Belgium or the use of human medicinal products is extremely limited or non-existent. However, there is less information about off-label use of medicinal products authorised for use in Belgium for veterinary use or application of the cascade system in small pets.
The FAMHP would particularly appreciate comments about off-label use or the cascade system, whether in general or specific to this document. Such comments would provide us with additional information about the practical situation regarding local unavailability of suitable medicinal products for veterinary use, packaging or pharmaceutical forms for the treatment of specific conditions in particular species or categories of animals. You can send your comments to firstname.lastname@example.org.