This article is an online version of a poster presented at the 25th WAAVP International Conference, Liverpool, 16-20 August 2015.
ABSTRACT
Antiparasitic brands for cattle, sheep, swine, poultry, dogs and cats from 157 different multinational and local Animal Health companies in 12 Spanish-speaking countries were recorded and analyzed in 2012 and in 2015 in the corresponding corporate websites or veterinary vademecums. The number of brands recorded in 2012 and 2015 was 1764 and 2019, respectively. From the brands recorded in 2015 most are approved for use on cattle (1175), followed by sheep (770), dogs (651), swine (575), cats (334) and poultry (161). For production animals ivermectin was the active ingredient used in the largest number of brands (368) followed by cypermethrin (189), levamisol (152), albendazole (149) and fenbendazole (136). For dogs and cats, the active ingredient used in most brands was praziquantel (178) followed by pyrantel (embonate or pamoate; 136), permethrin (77), ivermectin (65), and cypermethrin (63).
INTRODUCTION
For decades, approved parasiticides in most countries have been listed together with their major features in classic printed vademecums, often with restricted access. Acquiring a global picture of parasiticidal products used in larger regions required laboriously extracting information. Nowadays, some of these vademecums are also available online, and most AH companies display their products and their major features in their own corporate websites as well. In addition, many regulatory bodies now maintain databases listing the registered products and their features. This makes it easier to collect information and to analyze specific regional characteristics.
This paper presents the results of a survey on parasiticidal products for production animals and pets marketed in Spanish-speaking countries between 2012 and 2015, with emphasis on active ingredients and delivery forms as well as on major peculiarities when compared with the antiparasitics available in the UK, the USA and Australia.
MATERIALS & METHODS
A total of 157 Animal Health companies (6 multinationals*, the rest local companies) in 12 countries were selected for the review (Table 1). Only those companies that marketed at least three parasiticidal brands were selected.
Only ectoparasiticides, anthelmintics and endectocides for use on livestock (cattle, sheep, swine, poultry), dogs or cats were considered. Within the same company, if the same formulation was marketed under different trade names only one brand was considered. Only brands containing at least one parasiticidal active ingredient were considered. Those containing only “natural products” or repellents (e.g. plant extracts, limonene, geraniol, etc.) were not included in the survey.
A total of 2019 different brands were recorded in 2015, most of them approved for use on several target animal species.
* Bayer, Novartis-Elanco, Merial, Merck AH, Pfizer-Zoetis, Virbac
RESULTS & DISCUSSION
Many of the 157 companies surveyed are active in more than one country of the region, either with own affiliates or through other local distributors. For this reason many of the products reviewed are available in more than one country, but sometimes not under the same trade name. This means that different brands in various countries may be exactly the same product, manufactured by the same company but marketed under different trade names. However, the manufacturer is usually not disclosed in most countries, which makes it impossible to identify such multi-branded products.
Out of the 2019 brands 1479 contain a single parasiticidal a.i., 416 brands contain two different a.i., 108 brands three a.i. and 16 brands four a.i. Mixtures of more than two a.i. are particularly abundant among livestock drenches and products for pets (tablets, oral pastes, and spot-ons). Figure 1 summarizes the number of brands approved for each major target animal species.
The largest number of brands is approved for use on cattle (1175), followed by sheep (770) and dogs (651). Most brands are indicated for use on more than one target animal, those for livestock often also for dogs, horses and/or for off-line use on animal premises.
Livestock Brands
Chemical Classes & Active Ingredients used in Livestock Brands
A total of 61 different parasiticidal a.i. are used in the 1413 brands approved for livestock. Benzimidazoles (432 brands) is the most frequently used chemical class, followed by macrocyclic lactones (424), synthetic pyrethroids (213), organophosphates (180), imidazothiazoles (152), salicylanilides (92), and amidines (52).
The most used a.i. is ivermectin (365 brands), followed by cypermethrin (187) and levamisole (152). Figure 2 shows the active ingredients most used on livestock. Ivermectin is the dominant macrocyclic lactone: other compounds of this chemical class play only a secondary role: abamectin (22 brands), doramectin (20), eprinomectin (8), and moxidectin (6).
Delivery forms and active ingredients used in livestock brands.
Injection (mainly sc) is the most frequent delivery form. All injectables are used as anthelmintics, but those containing macrocyclic lactones are increasingly used for the control of ticks on cattle.
Among the injectables, ivermectin (301 brands) is the overwhelming market leader, followed by levamisole (95), closantel (37), clorsulon (33, always in mixture with ivermectin), ricobendazole (25), doramectin (20), nitroxynil (16) and abamectin (12).
The relatively high number of doramectin injectables is also a peculiarity of the Latin American market: they are very rare in other large markets (USA, EU, Australia). The same applies to injectables containing generic levamisole, closantel, doramectin and ricobendazole, which are very popular in Latin America, whereas they are hardly marketed in the USA, Europe and Australia. Figure 3 shows the number of livestock brands for each major delivery form.
Intraruminal injectables (50 brands, all with benzimidazoles) for worm control on cattle are another peculiarity of Latin American countries. Many brands are often approved for oral administration (drench) too. To our knowledge such products are not marketed today in Europe, the USA or Australia.
All oral drenches (334 brands) are approved for worm control, mainly for cattle and sheep. Most brands contain benzimidazoles (298 brands), mainly albendazole (135), fenbendazole (82), triclabendazole (66) or oxfendazole (8). Other actives frequently used in drenches are closantel (34), levamisole (22), praziquantel (12) and rafoxanide (9). Macrocyclic lactones play a minor role within the oral drenches: ivermectin (19), moxidectin (4) and abamectin (2). Many oral drenches are combinations (62 brands), mostly of a nematicide (benzimidazoles, levamisole, ivermectin) with a flukicide (triclabendazole, closantel) and/or a cestodicide (praziquantel, rafoxanide). Rafoxanide is still used in several Latin American countries, although it has been mostly abandoned in the USA, Europe and Australia.
Topical concentrates for plunge dipping and/or spraying livestock are still very popular in Latin America, mostly for the control of ticks and biting flies in cattle, and for louse and mite control in sheep and swine. Cypermethrin is the most used a.i. (69 brands), followed by amitraz (50), ethion (14, mostly in combination with cypermethrin), diazinon (13), and trichlorfon (7).
Feed additives are used mainly as anthelmintics for swine (112 brands) and/or poultry (85), but a significant number of brands are also approved for use on cattle (50), sheep (38) and horses (27). They contain mainly fenbendazole (40), levamisole (25), ivermectin (24), piperazine (15), cyromazine (9), oxibendazole (9), and albendazole (8).
Most pour-ons (121 brands) are for use on cattle (115) against biting flies and ticks, often also on sheep (42), swine (39) and horses (19). Cypermethrin (67) is the dominant a.i. in pour-ons, often in combination with various organophosphates (29) or carbaryl (6), followed by ivermectin (13), eprinomectin (8), fipronil (8), permethrin (6), abamectin (5), fluazuron (4) and imidacloprid (3). To our knowledge, neither organophosphates nor fipronil are used in livestock pour-ons in Europe, the USA or Australia. The same applies to imidacloprid for Europe and the USA.
Dressings are very popular in Latin America for controlling and preventing screwworms and other cutaneous myiasis in livestock, horses, and pets. Most contain mixtures of more than one parasiticide, together with disinfectants, cicatrizants, antibiotics, and other constituents. Most used actives are cypermethrin (50), dichlorvos (44), chlorpyrifos (16), and trichlorfon (5).
Ivermectin (IVM).
The 1% IVM 1% injection (clones of Merial’s IVOMEC) is absolutely the most popular formulation at all, with 108 different brands, mostly approved for use on cattle, sheep, and swine. Interestingly, 30 brands containing >1% and <3% IVM are also available, as well as 49 more containing ≥3% IVM, most of them with IVM at 3.15% (clones of Merial’s IVOMEC GOLD). Such formulations with >1% IVM are not marketed in the USA, UK or Australia. Besides injectables, IVM is also offered as a feed additive (24 brands, mostly at 0.6%), drench (19, mostly at 0.08%), or pour-on (13, mostly at 0.5%). There are also 17 brands containing IVM approved for use on poultry in Latin America (mostly in feed additives or tablets), an indication not approved in Europe or the USA. Finally, there are numerous brands containing combinations of IVM with other a.i., e.g. with clorsulon (33 injectables), closantel (17 injectables or drenches), fenbendazole (10 drenches), triclabendazole (10 drenches), nitroxinil (5 injectables), and with various growth promoters (zeranol, methandienone, etc., 7 injectables). To our knowledge combinations of IVM with growth promoters are not marketed in Europe, the USA or Australia.
Dog and Cat Brands
Chemical Classes & Active Ingredients used in Dog & Cat Brands
A total of 64 different parasiticidal a.i. are used in the 686 brands approved for pets, out of which 651 for use on dogs and 333 for use on cats (300 for both dogs and cats). A total of 153 of these brands are also approved for use on livestock. Most brands (384) contain a single a.i., 197 brands contain two, 90 contain three, and 15 contain four actives.
Isoquinolines (179 brands) is the most frequently used chemical class on dogs and cats, followed by synthetic pyrethroids (174), benzimidazoles (158), tetrahydropyrimidines (155), organophosphates (92), and macrocyclic lactones ( 78).
The most used a.i. is praziquantel (178 brands), followed by pyrantel (136, various salts) and permethrin (77). Figure 4 shows the active ingredients most used on dogs and pets.
Praziquantel is the dominating a.i. on pets, although it targets mainly tapeworms, which are not the most harmful pet parasites. But it is the only active used against tapeworms in pets and most pet anthelmintics contain praziquantel together with one among various nematicides. The vast use of cypermethrin on pets is peculiarity of the Latin American market: in the USA, UK and Australia permethrin is the dominant synthetic pyrethroid in pet products and cypermethrin is quite unusual.
Another peculiarity of Latin American pet parasiticides is the high number of imidacloprid generic brands recorded (about 50), which are very unusual in the USA, the UK and Australia.
Altogether, the market for parasiticides in Spanish-speaking countries is absolutely dominated by generics. At the time of the survey, out of the 686 brands recorded for use on pets only three brands containing patent-protected actives (afoxolaner, fluralaner, pyriprole) are available in Spain and a few Latin American countries.
Delivery forms and active ingredients used in pet brands.
Most delivery forms of brands approved for pets are pet-specific. However, most topical concentrates, dressings and injectables are also approved for use on livestock. Tablets (pills, capsules, etc.) for oral administration is the most frequent delivery form for dog and cat antiparasitics. They contain mainly anthelmintics and only a few (8 brands) are for ectoparasite control. Most tablets are approved for both dogs and cats (96), or only for dogs (65), only a few are only for cats (6). Most tablet brands are indicated against both roundworms and tapeworms (113) or only against roundworms (42), very few (10) only against tapeworms. The actives most used in tablets are praziquantel (123 brands), pyrantel (73, various salts), ivermectin (35), fenbendazole (29), febantel (25), albendazole (16), levamisole (15), oxantel (15), and mebendazole (13).
Figure 5 shows the number of brands recorded for each of the main delivery forms used on dogs and cats.
Among the oral liquids (suspensions, gels, pastes, etc.) for pets, most (88) are for both dogs and cats. A total of 78 brands and are indicated for both roundworm and tapeworm control, 49 brands only for roundworms. Pyrantel (various salts) is the most used a.i. (63 brands), followed by praziquantel (50), fenbendazole (28), albendazole (19), levamisole (12), febantel (11), ivermectin (11), and piperazine (various salts, 7). Oral suspensions and pastes for pets (often sold in pre-charged syringes) are rather popular in Latin America, in contrast with the USA and Europe, where they represent a minor fraction of all pet antiparasitics.
Topical ready-to-use sprays (aerosols, etc.) build the group of low-cost ectoparasiticides, together with topical concentrates (46 brands) for use on livestock that are also approved for use on pets. They are indicated for the control of fleas, ticks, mites, lice, mosquitoes and/or flies. Most used actives are permethrin (39 brands), cypermethrin (23), fipronil (15), carbaryl (16), tetramethrin (11), propoxur (11), amitraz (8), imidacloprid (8), chlorpyrifos (6) and dichlorvos (6).
Ready-to-use spot-ons represent premium flea and often tick control as well, mostly for once-a-month administration. Imidacloprid is the a.i. most used in spot-ons (50 brands), followed by permethrin (33) and fipronil (25). In addition to one or more adulticides, many spot-ons contain various IGRs such as methoprene (12), fenoxycarb (8) and pyriproxyfen (3). The predominance of imidacloprid over fipronil in generic spot-ons is another peculiarity of the Latin American market, in contrast with the USA, Europe and Australia where generic imidacloprid spot-ons are quite rare. The same applies to the use of fenoxycarb as an IGR in flea spot-ons.
INNOVATION
Between 2012 and 2015, local companies (66 out of 149) introduced a total of 234 new brands, compared with 22 new brands for the 6 multinationals surveyed. These new products are approved for use on cattle (133 brands), sheep (77), dogs (75), swine (50), cats (36), and poultry (15).
New products for livestock include 67 injectables, 34 drenches, 30 topical concentrates, 16 pour-ons, and 14 feed additives. New products for pets include 29 spot-ons, 23 oral tablets (pills, etc.), 17 topical sprays (aerosols, etc.), 9 oral liquids (pastes, gels, etc.), and 6 collars.
Figure 6 shows the actives most used in new products for livestock and pets.
CONCLUSIONS
The present survey indicates that the market for parasiticides in Spanish-speaking Latin America and Spain is highly competitive and innovative, but also strongly fragmented. Cattle products dominate the Latin American market, which is consistent with the importance of the cattle industry in most of these countries. Ivermectin is the dominating active ingredient
Generic active ingredients dominate the Spanish-speaking Animal Health market. Whereas multinationals are present in most of these countries, in the last years most new products have been introduced by local AH companies. These local companies do actually copy successful brands of multinationals after patent expiry. But they are also capable of identifying specific local needs and of consistently and quickly developing innovative formulations to satisfy those needs.
