Using specials medications

Have you ever wanted a pharmacological agent that is not licensed, or in a different formulation? This can be achieved in some scenarios.

The aims of this article are to discuss what specials are, how they can be used on the prescribing cascade, what their similarities and differences are from licensed veterinary products and provide some examples of where they might be used.

What are specials?

Specials are compounded medications. Many people may be reticent of their use due to the poor and variable reputation they have obtained historically in other countries, notably North America.

However, production of specials medications in the UK is highly regulated and manufacturers must be approved and licensed by the VMD. This provides much better quality control than in other jurisdictions, or when compared with formulating your own products from chemical grade materials. In some situations, they have the potential to provide a superior product, rather than using alternative, unlicensed products – for example, crushing enteric-coated human tablets to facilitate dosing may significantly reduce the efficacy of these drugs, as well as exposing workers to potential health risks due to the aerosolisation of material.

Equally, specials may provide access to medicines no longer available in human medicine, where their occasional use in minor species would prevent investment from pharmaceutical industry – for example, cisapride was withdrawn from the human market due to its association with cardiac dysrhythmias. However, cisapride remains a highly effective and safe prokinetic agent, commonly recommended for rabbits with ileus, and may have indications in a horse that would be unavailable without the use of specials manufacturers.

Specials medications do not offer the same level of assurance as licensed veterinary medical products regarding safety data and recommendations for dosing. Where specials are used, it becomes the responsibility of the veterinary surgeon to use agents and dosages based on evidence-based medicine, as specials companies cannot provide information on the dose that should be used. However, this can have the advantage of using dosages based on up-to-date studies, rather than how products were licensed historically.

Specials companies can only provide products directly to veterinary surgeons. They are not available through wholesalers, online pharmacies and clients cannot obtain them directly.

Working with specials

Specials companies are likely to produce products that will be a targeted formulation suitable for the species being treated. This may be a stable paste or transdermal drug that replaces traditional tablet formulations.

As a veterinary surgeon, you will need to obtain informed consent for the use of these drugs and provide client information leaflets for the product you are prescribing. Many of these leaflets are available for download on the BSAVA¹ (for members only) and BEVA² websites. Appropriate dosages for use are available in the published literature and through species-specific formulary apps provided on membership to the BSAVA³ and BEVA⁴.

Prescribing cascade

The prescribing cascade is designed to help and allow veterinary surgeons to prescribe medications that may not be licensed for a specific condition in a particular species, if the situation requires it.

There is a proposal to simplify the cascade for non-food-producing animals into a three-step process that will combine steps one to three (see below), although this is dependent on the final version of the EU Veterinary Medicines Regulations being debated in Brussels.

The cascade provides veterinary surgeons with a stepwise system to access medicines, when a veterinary medicinal product is not licensed for that species, for the treatment of a particular condition. Where no such medicine exists, the following steps should be adhered to sequentially:

1. A drug should be used that is licensed for another condition in the target species.
2. A drug should be used that is licensed for another species.
3. A drug should be used that is a human medicinal product or a veterinary medicinal product that can be imported from a EU member state.
4. If there is still no suitable product, specials medications may be used.

When are specials not appropriate?

Food-producing animals may only be treated under the cascade with medicines that contain pharmacologically active substances listed in the Table of Allowed Substances in Commission Regulation EU No 37/2010⁵, in the interest of food safety. This means, for food-producing animals, specials medications are unlikely to be suitable.

If horses are treated with medications not listed in 37/2010 or 133/2013 (The Essentials lists), they should be signed out of the food chain, as they would be if phenylbutazone had been administered. Specials medications should not be used in place of licensed products based on cost.

Practical examples

A horse with weight loss

A six-year-old Warmblood gelding presented with weight loss and ventral oedema. Worm egg count was negative and there were no specific abnormalities on blood work, other than hypoalbuminaemia.

Transabdominal ultrasonography revealed thickened small and large intestinal walls. The top differential diagnoses were infiltrative bowel disease and intestinal lymphoma. The horse was treated with prednisolone granules for four weeks and there was an improvement in demeanour and ventral oedema. However, the horse remained thin, albumin stayed low and the intestinal wall remained thickened.

At this stage, the decision was made to try a more potent oral steroid (dexamethasone) in combination with oral azathioprine. Azathioprine tablets licensed for use in people were used on the prescribing cascade. Intravenous dexamethasone licensed in horses was used orally on the prescribing cascade, as the clients were unable to inject the horse. The horse avidly consumed the azathioprine tablets, but would not consume the dexamethasone in food, nor tolerate the drug being syringed into its mouth; even when the drug could be syringed, much of the liquid ended up on the floor. In the end, the horse had to be euthanised and was confirmed to have eosinophilic enterocolitis.

This horse may have benefited from a specials medication, formulated as a palatable liquid formulation of dexamethasone, administered either in food or as a palatable paste. No such formulation is available from specials manufacturers in the UK.

Chronic distal limb wound in a horse

A 12-year-old cob gelding presented with a wound that had initially been obscured in its feathers; the wound was only spotted when the hair became stained and the wound began to smell.

Once the hair had been clipped away, the wound required debridement and culture of some of the skin revealed a heavy growth of Staphylococcus aureus susceptible to ceftiofur, enrofloxacin and doxycycline. Ideally, an antimicrobial would be chosen that is not critically important (3rd and 4th generation cephalosporins and quinolones), which on this list would be doxycycline.

In addition, ceftiofur, which is licensed for use in the horse, is unavailable. Doxycycline is not licensed in the horse. Two formulations of doxycycline are available for use on the prescribing cascade – a liquid licensed for use in chickens and pigs, and tablets licensed for use in dogs. With both of these products, issues exist relating to palatability, oral and oesophageal ulceration and anorexia, which are thought to relate to the doxycycline salt (hyclate) used in both these products.

The liquid designed for use in chickens and pigs is designed for use in water and, as such, is watery in consistency, meaning when syringed into horses mouths, some drug falls out, making accurate dosing challenging, which has implications for the individual case, but also makes responsible antimicrobial use challenging.

An ideal form of doxycycline to administer to this horse would be a formulation made from a non-irritant salt, removing the risk of some of the side effects and allowing a palatable paste to be formulated.

No such product is available in the UK; however, specials manufacturing could provide access to such a product.

A foal with Rhodococcus equi

A 12-week-old Thoroughbred filly presented with signs consistent with Rhodococcus equi on a farm with a history of this disease. Transthoracic ultrasonography revealed multiple focal areas of surface consolidation on the pleural surface.

The American College of Veterinary Internal Medicine consensus statement⁶ recommends treatment of this condition with a macrolide (erythromycin, azithromycin or clarithromycin) and rifampin. None of these drugs are licensed in horses.

One of the challenges of treating this condition is macrolides are toxic if ingested by the mare, due to the effects on hind gut bacteria, resulting in fulminate colitis. Also, successful administration of oral medications to foals can be challenging. Tablets designed for treating humans are usually crushed up and syringed into the foal’s mouth. This can result in loss of drug, as well as being washed into water troughs and feed buckets, allowing inadvertent ingestion by the mare and environmental contamination with antibiotics, which may exacerbate multiple drug resistance.

Additionally, crushing antimicrobial tablets designed for treating humans poses significant health risks to the worker. As such, ideal treatment would be with a readily available and easily administered flavoured paste that is palatable, and, perhaps, contains both drugs, depending on the combination used. This should then improve the amount of drug ingested and reduce environmental contamination.

Again, specials manufacturing provides valuable opportunities to promote responsible medicine use in the future.

A cat with hyperthyroidism

A 14-year-old domestic shorthair cat presented with marked weight loss, tachycardia and a gallop rhythm, with a bad attitude. The clients did not wish to pursue surgery or radioactive iodine, but did wish to treat the cat. The cat’s demeanour meant administering the licensed products carbimazole and methimazole for this condition was impossible, particularly as these tablets should be administered whole.

The ideal solution for this animal would be a palatable product that could be administered on food, or a drug that could be administered transdermally, which a specials manufacturer could produce.

A dog with keratoconjunctivitis sicca

A three-year-old bloodhound presented with clinical signs consistent with keratoconjunctivitis sicca (KCS). No evidence existed of systemic illness and the dog had not received any drugs containing sulphonamides.

The animal was treated with ciclosporin for four weeks and no improvement was observed. Tacrolimus has been shown in peer-reviewed literature to be beneficial in the treatment of KCS refractory to ciclosporin. This product is licensed for human patients, for use on skin, meaning it is not an ocular preparation – it’s a product that could be produced by a specials manufacturer as a sterile, ready-to-use ophthalmic preparation available at an appropriate strength.

Summary

Specials medications, if appropriately regulated for quality, as they are in the UK, allow veterinary surgeons access to otherwise unavailable medicines.

The cascade is there to assist vets in deciding on the most appropriate treatments available to them, and to ensure animal welfare is paramount. Veterinary specials manufacturers specialise in formulations appropriate for the target species.