An anthelmintic's pharmacokinetics, rate of metabolism and excretion, and safety profile determine the length of withdrawal time; this period can vary between species and also be affected by route of administration and dose. Most anthelmintics have withholding periods if milk or meat from treated animals is intended for human consumption; specific requirements for each must be observed.
Of the benzimidazoles, thiabendazole is absorbed and excreted quickly; fenbendazole, oxfendazole, and albendazole are absorbed and excreted over a longer period, which necessitates withholding periods of 3–14 days before slaughtering for meat and 3–5 days before milking for human consumption. Other members of the group have withholding periods between these extremes; however, withholding periods are longer for bolus formulations.
Flubendazole, a benzimidazole anthelmintic compound, is the approved drug commonly used for helminth parasite control in poultry. It is administered in medicated feed every 24 hours for 7 consecutive days. Treated birds may be slaughtered for human consumption between 1 and 7 days from the last treatment. Flubendazole has no adverse effect on egg laying or hatchability, and eggs are safe for human consumption (no withholding time is required) if the treatment is supplied at the correct dosage. Although other anthelmintic drugs are not approved for use in poultry, their extralabel use is rather common in some countries. Ivermectin is used mainly to control internal and external parasites in chicks and hens.
Although levamisole and morantel are rapidly excreted, withholding periods for meat are approximately 30–40 days in cattle and pigs. Frequently, there is no, or only a short, withholding period for milk. However, in some countries, levamisole cannot be used in lactating animals when milk is intended for human consumption.
Ivermectin and doramectin are excreted in milk and are not recommended when milk is intended for human consumption. In keeping with the long period of activity of macrocyclic lactones, ivermectin, abamectin, doramectin, and moxidectin have lengthy withholding periods before slaughter (typically between a few weeks and a few months), which vary with formulations and local regulations.
Long-acting formulations of ivermectin and moxidectin have much longer withdrawal times. Residual concentrations of moxidectin in milk after topical administration are below threshold limits, resulting in no milk withholding period in many countries. Because long milk withdrawal times may be required, extralabel use of macrocyclic lactone compounds should be avoided in dairy animal species producing milk for human consumption, eg, ivermectin should not be used in goats.
The macrocyclic lactone molecule's chemical structure can be manipulated to change the milk partitioning coefficients in lactating dairy animals. This property led to the development of eprinomectin, of which only 0.1% of the total dose is eliminated in milk, resulting in no withholding period for milk worldwide.
Monepantel has a withdrawal period of 7–14 days for meat and is not authorized for use in lactating animals producing milk for human consumption.
In combination with abamectin, derquantel has a withholding period of 14 days for meat and is not authorized for use in lactating animals producing milk for human consumption.
A relation between the rate of metabolism and activity against immature parasites also exists with certain fasciolicides. Closantel, rafoxanide, and nitroxynil bind more strongly to blood proteins than does oxyclozanide, and therefore these drugs remain in the blood for longer periods. Although this greater persistence is associated with greater activity against immature liver flukes, the withholding period for slaughter is also longer: 21–77 days for closantel, rafoxanide, and nitroxynil, compared with 3–14 days for oxyclozanide. In sheep, however, residual tissue concentrations of closantel are extremely low: 7–21 times lower than corresponding plasma concentrations. Sheep may be slaughtered for human consumption 28 days after closantel treatment, whereas that period extends to 77 days in cattle.
In dairy cattle, approximately 1% of closantel is excreted with milk each day. In this species, the calculated withdrawal time for closantel in milk is between 39 and 43 days postadministration. Moreover, closantel residual concentrations in milk subproducts, such as cheese, are higher than those measured in the milk used for its production. For these reasons, use of this anthelmintic in dairy animals is forbidden. Nitroxynil also cannot be administered to lactating animals when milk is intended for human consumption, whereas oxyclozanide has a withdrawal time of only 60–108 hours.
Because synthetic anthelmintics continue to be the most important tool for internal parasite control in poultry, caution is required to avoid drug residue–induced adverse effects.
Key Points
Withdrawal periods for milk and meat should be strictly observed after anthelmintic administration, and extralabel use is not recommended.
