Veterinary medicinal products (VMPs) must be administered in accordance with the prescribing cascade, as set out in The Veterinary Medicines Regulations (VMR) 2013. The current law starts from the principle that all VMPs must be authorized, and that use of an unauthorized medicine, or use of an authorized medicine in an unauthorized way, is an offence. However, the law recognizes that there are circumstances where the benefits of treatment of animals with unauthorized medicines outweigh the risks, particularly where there are not veterinary authorized medicines for a condition or for a species. As a result, the legislators have given veterinary surgeons an exemption from the legal requirement to use an authorized VMP for the species and condition that they are treating. This exemption is known as the prescribing cascade.

'Off-label’ use of medicines

‘Off-label’ use is the use of medicines outside the terms of their marketing authorization (MA). It may include medicines authorized outside the UK or NI that are used in accordance with an import certificate issued by the VMD. A veterinary surgeon, with detailed knowledge of the medical history and clinical status of a patient, may reasonably prescribe a medicine ‘off-label’ in accordance with the prescribing cascade. Authorized medicines have been scientifically assessed against statutory criteria of safety, quality and efficacy when used in accordance with the authorized recommendations on the product literature. Use of an unauthorized medicine provides none of these safeguards and may, therefore, pose potential risks that the authorization process seeks to minimize. Note that the use of an ESPA medicine not in accordance with the product’s labelling would be classed as use under the cascade and considered an extemporaneous preparation.

Medicines may be used ‘off-label’ for a variety of reasons, including:

• No authorized product is suitable for the condition or specific subpopulation being treated
• Need to alter the duration of therapy, dosage, route of administration, etc., to treat the specific condition presented
• An authorized product has proved ineffective in the circumstances of a particular case (all cases of suspected lack of efficacy of authorized veterinary medicines should be reported to the VMD).

Responsibility for the use of a medicine ‘off-label’ lies solely with the prescribing veterinary surgeon. They should inform the owner of the reason why a medicine is to be used ‘off-label’ and record this reason in the patient’s clinical notes. When electing to use a medicine ‘off-label’ always:

• Discuss all therapeutic options with the owner
• Use the cascade to determine your choice of medicine
• Obtain signed informed consent if an unauthorized product is to be used, ensuring that all potential problems are explained to the client
• Administer unauthorized medicines against a patient-specific prescription. Do not administer to a group of animals if at all possible.

An ‘off-label’ medicine must show a comparative clinical advantage to the authorized product in the specific circumstances presented (where applicable). Medicines may be used ‘off-label’ in the following ways (this is not an exhaustive list):

• Authorized product at an unauthorized dose
• Authorized product for an unauthorized indication
• Authorized product used outwith the authorized age range
• Authorized product administered by an unauthorized route
• Authorized product used to treat an animal in an unauthorized physiological state, e.g. pregnancy (i.e. an unauthorized indication)
• Product authorized for use in humans or a different animal species to that being treated.

Adverse effects may or may not be specific for a species, and idiosyncratic reactions are always a possibility. If no adverse effects are listed, consider data from different species. When using novel or unfamiliar drugs, consider pharmaceutical and pharmacological interactions. In some species, and with some diseases, the ability to metabolize/excrete a drug may be impaired/enhanced. Use the lowest dose that might be effective and the safest route of administration. Ensure that you are aware of the clinical signs that may suggest toxicity. Information on ‘off-label’ use may be available from a wide variety of sources (Appendix of Useful Websites).

Marketing authorizations

Following the exit of the United Kingdom (UK) from the European Union (EU) there are now three MAs for veterinary medicines in  the UK. The options that veterinary surgeons must consider under the prescribing cascade depend on whether they are working in Great Britain (GB) or Northern Ireland (NI). The Northern Ireland Protocol requires that the use of veterinary medicines in Northern Ireland be compliant with the regulations of the European veterinary medicines regulatory system. In practice, for the cascade this means that where no suitable NI-authorized veterinary medicine is available, veterinary surgeons in NI should consider using an EU authorized veterinary medicine before using an alternative medicine authorized elsewhere in the world.

The three types of authorization are:

• UK MA – a product with a UK MA has been approved for marketing in England, Wales, Scotland and Northern Ireland. These MAs were issued pre-2021 and retain a UK-wide authorization
• GB MA – a product with a GB MA has been approved for marketing in England, Wales and Scotland. These authorizations have been assessed and issued by the VMD against the requirements set out within the UK VMR 2013, as amended
• NI MA – a product with an NI MA has been approved for marketing in Northern Ireland. There are four different routes to obtain an NI MA:
  • – A national authorization (valid in NI only)
  • – A centralized authorization issued by the European Commission (valid in all EU member states, including NI)
  • – A mutual recognition procedure (valid in select EU member states where the product is already authorized on a national basis in one of them)
  • – A decentralized procedure (valid in select EU member states).

Compliance with the cascade

The cascade differs depending on whether the prescribing veterinary surgeon is based in Great Britain or Northern Ireland.

Veterinary surgeons in Great Britain: The steps, in descending order of suitability, are:

• Veterinary medicine with an MA valid in GB or UK wide for the indicated species and condition
• Veterinary medicine with an MA valid in NI for the indicated species and condition
• Veterinary medicine with an MA valid in GB, NI or UK wide for a different species or condition
• Human medicine with an MA valid in GB, NI or UK wide OR an authorized veterinary medicine from outside the UK. In the case of a food-producing animal, the medicine must be authorized in a food-producing species
• Extemporaneous preparation prepared by a veterinary surgeon, pharmacist or person holding an appropriate Manufacturer’s Authorization, located in the UK
• In exceptional circumstances, a human medicine may be imported from outside of the UK.

NOTE: For products not authorized in GB or UK wide, a Special Import Certificate from the VMD is required.

Veterinary surgeons in Northern Ireland: The steps, in descending order of suitability, are:

• Veterinary medicine with an MA valid in NI or UK wide for the indicated species and condition
• Veterinary medicine with an MA valid in NI or UK wide for a different species or condition
• Human medicine with an MA valid in NI or UK wide or a veterinary medicine with an MA valid in an EU member state. In the case of a food-producing animal, the medicine must be authorized in a food-producing species
• Extemporaneous preparation prepared by a veterinary surgeon, pharmacist or person holding an appropriate Manufacturer’s Authorization, located in the UK
• In exceptional circumstances, a veterinary medicine with an MA in GB or outside the EU may be imported, or a human medicine from outside NI may be imported.

NOTE: For products not authorized in NI or UK wide, a Special Import Certificate from the VMD is required.