Pharmacotherapy in pigeons and cage and aviary birds:
A difficult task, both for the general practice veterinarian and for the manufacturers of medicines for this minor species.
Veterinarian Guy Werquin
The costs of research and development to meet the increasing number of requirements for quality, safety and efficacy of veterinary medicines are causing a gradual reduction in the supply of authorised medicines for species and therapeutic indications of lesser economic importance. It is becoming increasingly difficult, especially for minor species such as pigeons and cage and aviary birds, to obtain suitable medicines within the legal provisions.
An authorised medicine: guarantee of safety and efficacy
To guarantee the efficacy and safety, industrially prepared medicines must have a Marketing Authorisation (MA). The MA is granted by the competent authorities after a panel of European experts has assessed the dossier submitted by the applicant (the company). This dossier contains all the data and studies that are required to carry out a risk analysis and on which the therapeutic indications, methods of administration and optimal follow-up are based.
The dossier is not limited to an evaluation of the active ingredient; the quality of the primary packaging and the stability during storage and use are also evaluated. For instance, the stability of the pharmaceutical form and packaging of medicines is evaluated at various ambient temperatures and humidity levels.
The main points of this risk analysis are summarised in an evaluation report for the public (EPAR or European Public Assessment Report). The data that guarantee the proper use of the medicine are included in the “Summary of Product Characteristics” or SPC. This document constitutes the reference for the user on which to base his/her therapeutic choice.
Furthermore, the Marketing Authorisation Holder is obliged to register all side effects of his authorised medicines via a pharmacovigilance system and to report them to the authorities via PSURs (Periodic Safety Update Report) at predefined intervals. In the case of antimicrobial agents, for example, the extent to which antimicrobial resistance undermines the efficacy of products already on the market will be assessed. If this is the case, the recommended dosages may have to be increased.
In short, the effectiveness, quality and safety of authorised medicines are strictly monitored, not only during the pre-registration process, but also continuously afterwards during the use of the medicines in practice.
What about the minor species and minor indications (MUMS)
Veterinarians need to treat animals from many different species, which results in a very fragmented market. This requires large investments to extend the licences of veterinary medicinal products granted for one species to others. Furthermore, the prices of veterinary medicinal products are usually considerably lower than those of medicinal products for humans. The scale of the veterinary pharmaceutical industry is only a fraction of the scale of the pharmaceutical industry for human medicines. As a result, few companies are willing to invest in medicines for minor species such as pigeons or cage and aviary birds, which means that the number of authorised medicines is very limited. In Belgium, barely 17 medicines have been authorised for non-food-producing pigeons, of which only about five can be used for food-producing pigeons.
| Table 1: Overview of the registered medicines for food-producing pigeons and non-food-producing pigeons in Belgium |
| A) for food-producing pigeons |
| AMOXICURE® – Oropharma – amoxicillin – Waiting time Meat: 60 h
COLOMBOVAC PMV® – Zoetis COLUMBA® – Pharmagal Bio – paramyxovirus (Co) NOBILIS PARAMYXO P201® – Intervet Int via MSD AH – paramyxovirus (Co) PHARMAVAC PHA® – Pharmagal Bio
|
| B) for non-food-producing pigeons |
| AMOXICURE® – Oropharma – amoxicillin
AVICAS® – Oropharma – febantel COLUMBA® – Pharmagal Bio – paramyxovirus (Co) COXI PLUS® – Oropharma – sulphamides EUTHOXIN 500 mg/ml® – Chanelle MERANOX 25mg/ml® – Avimedical NOBILIS PARAMYXO P201® – Intervet Int via MSD AH – paramyxovirus (Co) ORNICURE 150 mg/g® – Oropharma – doxycycline PHARMAVAC PHA® – Pharmagal Bio R-12® – Acme – nicarbazin RELEASE 300 mg/ml inj opl® – WDT SPARTRIX compr® – Elanco – carnidazole T61® – Intervet – Embutramide Mebezonium Iodide THERAPRIM pot® – Oropharma – trimethoprim THERAPRIM sachet® – Oropharma – trimethoprim TRICHO PLUS® – Oropharma – ronidazole TRICHOCURE® – Oropharma – ronidazole
|
(Source: FAMHP veterinary medicinal product database)
Oropharma, the pharmaceutical company that was founded some thirty years ago by Professor Patrick De Backer, holds the registration for about half of the medicines for pigeons and cage and aviary birds authorised in Belgium. The company, which is part of the Versele-Laga Group, market leader in nutrition and care products for birds, has invested heavily in recent years to keep its registration dossiers in line with the increasingly strict standards that scientific studies, production methods and stability tests must meet.
In January 2022, EU Regulation 2019/6, the new European legislation on veterinary medicinal products, will come into force. This new regulation will also require additional efforts from the pharmaceutical industry. Apart from the huge investments involved in marketing or retaining medicines for minor species, other factors mean that the industry is actually unable to achieve sufficient return on investment with medicines for pigeons and cage and aviary birds.
Recent surveys (Goossens 2018) show that pigeon fanciers also obtain medicines through channels other than the veterinarian or pharmacist. This often involves non-registered medicines, the efficacy, safety and stability of which have not been proven. Since this is considered an illegal practice, there are few concrete figures available about this phenomenon, but there are reports about it on various websites and forums for pigeon fanciers. Furthermore, in Belgium as well as in other countries, medicines are also purchased from abroad via the Internet. This could be dangerous for the health of the pigeons, as the exact composition of these products is often unknown (Scullion and Scullion, 2002). Moreover, the purchase of medicines via the Internet, also for personal use, is prohibited when they require a medical prescription in Belgium, are not licensed or are bound to special rules. This, for instance, applies to anti-microbial agents, psychotropic substances, narcotics and hormones. The penalties for violating this legislation are fines and seizure of the goods.
One of the objectives of the new European legislation is to take stronger action against illegal online sales of veterinary medicinal products, including a general ban on offering prescription medicines online.
Veterinarians themselves sometimes also resort to the unlawful off-label use of veterinary medicines registered for other species when, for example, a licensed therapeutic alternative is available in Belgium.
This article therefore takes a closer look at the exceptional circumstances that allow a veterinarian to use a medicine for other animal species and/or indications than those included in the official SPC.
The cascade system: possibilities and conditions
Due to the limited supply of licensed medicines for pigeons, veterinarians are sometimes forced to administer medicines outside the stipulations of the SPC. This is legally possible within the cascade or waterfall system (Royal Decree of 14 Dec 2006, Articles 230 and 231). The waterfall system offers the attending veterinarian the possibility of deviating from the strict use of medicines registered in our country. Thus, on the one hand it is possible to use a medicine for another animal species or for a different disorder, while on the other hand, a veterinarian can also prescribe a veterinary medicine that is authorised in another European Member State, a medicine for human use and even a magistral preparation.
- Veterinary medicines authorised in another European Member State. To be able to use these medicines, the veterinarian must place the order with a licensed wholesaler-distributor or a pharmacist.
- Medicines for human use. To be able to use these medicines, the veterinarian must place the order with a pharmacist.
Whether, within the cascade system, the veterinarian chooses a veterinary medicine for a different indication or a different target animal or a medicine for human use or a medicine prepared extempore, the veterinarian always bears full responsibility for this therapeutic choice.
With a view to animal welfare, the veterinarian may only use the waterfall system under strict conditions. Economic motives should not play a role in this! The following three conditions must always be met:
- No therapeutic alternative is available in Belgium for the relevant species or disorder.
- The treatment is absolutely necessary to avoid unacceptable suffering.
- It is an exceptional situation.
Doxycycline medicines registered for poultry or pigs often appear to be cheaper than medicines specifically registered for pigeons or cage and aviary birds. As a veterinarian, can I treat pigeons with doxycycline preparations registered for other animal species, such as Soludox, Doxx-sol, Alti-Dox, Doxy-veto C or Doxylin?
One of the explicit conditions for applying the cascade system is that there is no therapeutic alternative available in Belgium for the relevant species or disorder. In Belgium, the Oropharma medicine Ornicure is registered specifically for use in pigeons and cage and aviary birds. It is therefore not allowed to use other doxycycline preparations registered for other animal species for pigeons or cage and aviary birds.
For the same reasons it is not allowed to use other amoxycillin preparations registered for poultry (like Dokamox, Moxapulvis, Suramox, Amoxycylline Kela, etc.) instead of Amoxicure (Oropharma) for pigeons.
The same applies to trimethoprim: the availability of Theraprim, in Belgium specifically authorised for pigeons and cage and aviary birds, prevents the use of other trimethoprim preparations such as Cosumix, Emdotrim, Metaxolin or Trimazin for pigeons or cage and aviary birds via the cascade system.
Is the veterinarian allowed to fractionate medicines and what are the requirements?
When applying the cascade system, especially when medicines licensed for other species are used, the packaging size is often not adapted to the species for which one wants to use the medicine off-label.
In this instance, the veterinarian may “fractionate” the medicine: this means that the presentation of a medicine is changed or divided because there is no primary packaging size for the duration of the treatment. Fractionation is only permitted if the following requirements are met:
– There is no adequate primary packaging size, licensed and on the market in Belgium for the duration of the treatment.
– Only fractionation from larger to smaller packaging sizes is allowed.
– The physical properties and pharmaceutical form of the medicinal product must not be changed:
-
- dissolving tablets is not permitted
- removing tablets from blisters and putting them in other boxes is not allowed. You may, however, provide blisters if you include a copy of the information leaflet.
- mixing medicines with other substances is prohibited: it is therefore not allowed to dilute medicines or mix them with other medicines.
– The fractionated medicine dispensed should state the name, batch number and expiry date of the original medicine.
– When a medicine is fractionated, a copy of the original packaging leaflet must always be provided.
Is a veterinarian allowed to administer enrofloxacin to pigeons and to fractionate an enrofloxacin solution such as Enroshort 1 litre packaging into 100 ml bottles himself?
Since enrofloxacin is not registered for pigeons, the veterinarian can use an enrofloxacin preparation licensed for another animal species via the cascade system.
However, a packaging size of 100 ml of enrofloxacin is licensed in Belgium (Baytril 100 ml). So, instead of fractionating, the veterinarian should prescribe or dispense the 100 ml packaging of BAYTRIL 100 mg/ml solution unchanged.
Some pigeon veterinarians use self-composed “mixes”, often combining several medicines. Is this legally permitted?
Mixing two or more substances together is not considered fractioning. This is considered a magistral preparation and only pharmacists are entitled to prepare them (De Backer and Croubels, 2017). It requires a prescription from a physician, dentist or veterinarian.
The packaging of magistral preparations must also compulsorily state several things:
- the quantitative and qualitative composition of the active ingredients in the preparation (unless the prescriber specifies not to state this)
- the date, expiry date and directions for use of the preparation
- the conditions for storage, if specified
- the family name and given name of the prescriber
- the family name and given name of the person responsible for the animals
- the serial number on the prescription.
The labelling is only legally correct when all these details are correctly stated on the packaging.
TAKE HOME MESSAGE
Authorised medicines registered for a specific animal species and indication are subject to strict evaluation by the government and offer the best guarantees of effectiveness and safety. The European legislation on pharmaceuticals first of all obliges veterinarians to use the medicines specifically authorised for the target species, even if it concerns minor species such as pigeons or cage and aviary birds for which the supply of authorised medicines is limited.
The off-label use of veterinary medicines intended for another animal species or indication or a medicine for human use or another medicine prepared extempore is only legally permitted in exceptional cases and under specific conditions. If a veterinarian chooses to do so within the provisions of the cascade system, that veterinarian always bears full responsibility for this therapeutic choice.
References
AMCRA opinion ‘Maatregelen richting een verantwoord antibioticagebruik bij reisduiven’ (Measures towards responsible use of antibiotics in homing pigeons). AMCRA, Centre of Expertise on Antimicrobial Consumption and Resistance in Animals, 2019. https://www.amcra.be/swfiles/files/Antibioticaproblematiek%20duiven_finaal_NL_325.pdf
De Backer, P., Croubels, S., 2017. Cursus wetgeving geneesmiddelendepot en voorschriftenleer (Course in pharmaceutical legislation and prescribing.). Faculty of Veterinary Medicine, Ghent University, Belgium.
FASFC Circular letter about introducing pigeons into the food chain. 15/06/2015. https://www.favv-afsca.be/professionelen/dierlijkeproductie/dieren/omzendbrieven/_documents/2015_06_15_NL_circ-ob_duiven_v1.pdf
FOLIA VETERINARIA, Pigeons and available medicines in Belgium. 2 October 2017, www.vetcompendium.com
Goossens Lauren-Tess. Gebruik en misbruik van antimicrobiële middelen bij de sportduif. Part of the Master thesis submitted for the degree of Master of Veterinary Medicine, Academic Year: 2017 – 2018. https://libstore.ugent.be/fulltxt/RUG01/002/481/276/RUG01-002481276_2018_0001_AC.pdf
Royal Decree on medicines for human and veterinary use – Part 2: Medicines for veterinary use (Articles 141 to 285) and annexes. 14 December 2006, The cascade system. Articles 230 and 231.
Scullion, M.G., Scullion, F.T., 2002. Investigation of diseases in young racing pigeons. In: World Association of Wildlife Veterinarians Wildlife Sessions. 73-75.
Regulation (Eu) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC