When a small animal needs a drug treatment, there is usually a licensed (authorised) medicine available, although it might be licensed for other species or indications. However, there are some circumstances when there is no suitable licensed product to fulfil a clinical need. To solve such a problem, it might be possible to use an unlicensed ‘special’ formulation. These specials are unlike licensed medicines because they are not assessed for safety or efficacy by a regulatory body. Here we outline the facts and practical information relevant to prescribing special formulations.
A special (also known as an extemporaneous preparation) is:
- a prescribed medicine that has been made to order by a vet, a pharmacist or a person holding an appropriate manufacturer’s authorisation (a specials manufacturer) (VMD 2015a);
- a medicine marketed under the Small Animal Exemption Scheme (which are available over the counter) but used outside its recommended use.
A special might be needed when a vet considers that the route of administration, strength, or formulation of the licensed medicine is inappropriate, or because there is no available licensed form of the optimal treatment. The following situations are examples.
- A different strength or formulation is needed.
- The animal is allergic to an ingredient in the licensed formulation.
- The animal refuses to take the licensed formulation.
- The animal’s owner has difficulty administering the licensed formulation (e.g. because of a disability).
- A chronic infection persists despite treatment with a licensed product.
- Use of a licensed product could affect the efficacy of the drug (e.g. when it involves crushing enteric-coated human tablets) or exposes people to potential health risks (e.g. use of tablets or capsules containing cytotoxics).
- Several drugs need to be combined in the same capsule to avoid pestering the animal with multiple tablets or capsules.
- No licensed product exists.
- A licensed product cannot be obtained in a reasonable time (e.g. because supply is interrupted). The VMD publishes a list of known supply issues online.
- Cost alone is not a reason to prescribe a special apart from exceptional cases in which animal welfare would otherwise be compromised. If such a situation arises, vets should keep a record to justify their decision (BEVA 2107)
Examples of special formulations
- Thiamazole (methimazole) transdermal gel applied to the pinna is an alternative formulation for cats that will not take the licensed oral forms (BSAVA 2017; Plumb’s 2017; Boretti et al. 2014). Reported drawbacks include difficulty maintaining constant blood concentrations, occasional inflammation and erythema of the pinna after prolonged treatment (Boretti et al 2014), and higher cost and shorter shelf life compared with oral therapy (Plumb’s 2017).
- Tramadol (not licensed for use in animals) is available in smaller dose tablets than licensed for humans.
- Trilostane in liquid form allows for more accurate dose titration than is possible with licensed capsules.
- Doxycycline paste is an alternative to tablets for an uncooperative cat. It has been suggested that oral doxycycline monohydrate (which is used in paste formulations) may have less potential to cause oesophagitis than the hyclate salt (used in most tablets formulations) because the former is less acidic and slower to dissolve in neutral solutions (Carlborg 1983). Nevertheless each dose of doxycycline should be followed by a swallow of water or food, whichever salt is used (Plumb’s 2017).
- The prokinetic drug cisapride was withdrawn from the human market in the UK many years ago because of cardiac side effects (Pharmaceutical Journal 2000). It is still recommended for dogs, cats, rabbits and horses but there is no licensed product, so it is only available as a special (BSAVA 2017; Plumb’s Veterinary Drugs 2017).
- A re-formulated product (e.g. a gelatine capsule filled to contain a different dose than that available in a licensed capsule product) is an extemporaneous preparation.
The use of veterinary specials is regulated by the Veterinary Medicines Regulations (VMR) 2013 and guidance from the Veterinary Medicines Directorate (VMD) on using the prescribing cascade (HM government 2013; VMD 2015a). Use of a special is only legally allowed when the following steps in the prescribing cascade have been considered first:
- use of a suitable authorised alternative. A special should not contain the same active ingredient, at the same dose, in the same form, as an available authorised medicine;
- a veterinary medicine authorised in the UK for use in another animal species, or for a different condition in the same species;
- a medicine authorised in the UK for human use;
- a veterinary medicine not authorised in the UK, but authorised in another member state for use in any animal species in accordance with the Special Import Scheme. [The VMR allows for medicines from outside the EU to be imported in exceptional circumstances using a special import certificate (SIC) on a named animal basis] (VMD 2015a, VMD 2016).
A vet needs to consider each option and make a clinical decision about whether the available choices are suitable before moving onto the next step in the cascade. Also, vets must keep up to date with what animal and human medicines become available, in case a new licensed product can replace a medicine previously provided as a special.
A veterinary prescription is needed to use a special under the cascade; this may be written, or oral if the prescriber also supplies or administers the medicine. Only vets registered with the RCVS may prescribe medicines under the cascade. Because there is no marketing authorisation holder to take responsibility for the safety of a special and to give dosage recommendations, product liability lies with the prescriber (VMD 2015a).
When a special is needed, the RCVS recommends that vets first contact a manufacturer holding a ‘Specials Manufacturing Authorisation’ that permits them to manufacture such a product (RCVS 2017). Such companies are required to comply with Good Manufacturing Practice and supply a Product Quality Statement with every product. Also, they may already have experience of preparing the product in question, and will have the necessary equipment to prepare it and check its quality. They may also be able to provide information from pharmacokinetic and clinical studies of the formulation. It is a good idea to contact specials manufacturers and ask if a product is available, and to check whether the medication will be appropriate for the animal (such as what additives it will contain, shelf life after opening, method of administration etc.). Prices can vary between manufacturers so it is a good idea to compare costs first. Some companies offer a more cost-effective deal if larger amounts are ordered. Some specials companies will formulate a medicine using an active ingredient supplied by the vet.It makes sense to use the same product specification and supplier, if possible, to ensure consistency and bioequivalence when dispensing a repeat supply.
Specials manufacturers can only provide products directly to vets. Specials are not available through wholesalers or online pharmacies, and clients cannot obtain them directly. Specials manufacturers are allowed to advertise the services they provide but not the specific products that can be manufactured. They can provide information on the different types of dosage forms that are available and, on a vet’s request, may provide a list of active substances, formulations with prices and placebo samples (VMD 2015b). The VMD’s website has lists of veterinary-only specials manufacturers and combined human and veterinary specials manufacturers.
A pharmacist may dispense specials they have prepared against a prescription from a vet (VMD 2015a). In general, it is not common practice for community pharmacists in the UK to make specials; hospital pharmacies are more likely to do so. The pharmacy at the Royal Dick Hospital for Small Animals produces some specials (for example, tylosin capsules, budesonide capsules and external creams) and can prepare bespoke formulations; it also stocks certain specials.
The British Equine Veterinary Association (BEVA) has a product database to help its members get difficult-to-source medicines (BEVA 2107). There is no such source for small-animal practitioners.
Examples of specials manufacturers
- BCM Specials: manufactures a wide range of products.
- Bova: manufactures a doxycycline paste and a sucralfate paste for cats, sterile formulations such as injectables and ophthalmics, and a large range of equine formulations.
- Nova Labs: manufactures a wide range of products and stocks items such as azathioprine 10mg capsules.
- Rosemont: specialises in liquid dosage forms and has a wide range of products available such as clopidogrel and mirtazapine oral solution.
- Summit Veterinary Pharmaceuticals: manufactures products such as cisapride 2.5mg tablets, gabapentin 50mg tablets and methimazole transdermal gel.
- The Specials Laboratory: manufactures a wide range of products.
Veterinary specials can be held in stock in a practice but stock levels should be justified by clinical needs under the cascade, and take into account shelf life (VMD 2015a). Specials often have a short shelf-life (for example, 28 days after opening for liquids).
There are specific requirements for vets who administer or supply medicines, including specials, under the cascade. These records must be kept for 5 years and made available upon request from a duly authorised person. The records that must be retained are listed in the VMR (VMD 2015a).
Vets are not legally obliged to report an adverse effect that they think might be due to a special, but the VMD encourages reporting through the adverse event reporting scheme.
It is not a legal requirement under the VMR to obtain informed consent from the owner of an animal to be treated under the cascade. However, the RCVS Code of Professional Conduct considers it good practice for vets to obtain the owner’s consent, in writing, for the animal to be treated under the cascade. The owner should be made aware of the intended use of a special and be given a clear indication of potential adverse effects (VMD 2015a). Unlike licensed medicines, there will be no summary of product characteristics, data sheet or patient information leaflet for a special – the onus to provide information is on the prescriber (see the box below for more details). The British Small Animal Veterinary Association (BSAVA) has produced client information leaflets on many unlicensed medicines. The BEVA has produced a client information sheet on specials.
Whenever a medicine, including a special, is prescribed under the cascade, the person supplying the medicine is legally required to supply written information* about the medicine. This should include, at least, the following:
- name and address of the pharmacy, veterinary surgery or approved premises supplying the medicine
- name of the vet who has prescribed the product
- name and address of the animal owner
- identification (including the species) of the animal or group of animals
- date of supply
- expiry date of the product, if applicable
- name or description of the product, which should include at least the name and quantity of active ingredients
- dosage and administration instructions
- any special storage precautions
- any necessary warnings for the user, target species, administration or disposal of the product
- the withdrawal period, if relevant
- the words “Keep out of reach of children” and “For animal treatment only”.
*The VMR state that the product must be labelled with this information, but it is reasonable for the supplier to place some of the required information on a separate sheet (personal communication, VMD). It is not necessary to supply the information if the vet who prescribed the medicine both supplies the product and administers it to the animal in person. (HM government 2013b; Veterinary Prescriber 2014)
Veterinary specials are unlicensed medicines prescribed under the cascade that are specially formulated for use in individual patients. They can solve a variety of problems to do with administering medicines to animals. There are many specials-manufacturing companies that supply specials, either from stock or produced as a one-off product. However, there is no comprehensive list of what is available to help small-animal vets source specials. Responsibility for safety lies with the vet. If a special is supplied to the owner to administer, it is the responsibility of the vet to supply information to ensure safe and effective use. Also, because specials often have a short shelf-life it is important to note the expiry date and use them according to the manufacturer’s advice.
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Goal of activity: Update knowledge; help clinical decision-making.
Authors/disclosures: Veterinary Prescriber editorial team/no conflict of interest.
Specific learning objectives: to improve knowledge and understanding of Specials.
How we produced this module
Our modules start with a detailed outline and electronic literature search. We commission a collaborating author, who is a specialist in the module topic, to write a draft module. The collaborating author on this module was Helen Barnett. The draft is circulated unsigned to a wide range of commentators, include practising first-opinion vets, other topic specialists, the companies that market any mentioned drugs and other organisations and individuals, as appropriate. They can raise points about the interpretation of evidence, ask questions that are important to clinical practice, and present alternative viewpoints. There is a rigorous editing and checking process and the result is a module that is evidence-based, impartial and relevant to clinical practice. The final module is unsigned because it is the result of collaboration.
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