The principle that combinations of chemotherapeutic agents benefit animals by maintaining drug efficacy in the presence of resistance has been repeatedly demonstrated for diverse pathogens and builds on knowledge gained from insecticide, pesticide, and herbicide use. Also, combinations of anthelmintics are being used more and more. According to the recent guidelines of the World Association for the Advancement of Veterinary Parasitology, there are three main reasons to use fixed-dose combinations of anthelmintics:
1) To cover the desired breadth of spectrum. For example, derquantel (spiroindole class) has been approved for use in some countries as a combination anthelmintic product with abamectin (macrocyclic lactone class). The combination exhibits ≥95% efficacy against a significantly increased spectrum of parasite species.
2) To minimize (delay) the development and spread of resistance to new and existing anthelmintic classes. Mathematical simulation studies have demonstrated that the full benefit of combination anthelmintic product therapy is realized when initial resistance-allele frequencies are low, and that the likelihood of resistance occurring to a combination anthelmintic product will increase with increasing resistance-allele frequency to its individual constituent actives.
3) To overcome existing species-specific resistance profiles. The wide use of anthelmintic combinations, often necessitated by the very high frequency of resistance to one or more available constituent actives when used alone, has revealed no issues of special concern with the routine use of such products.
Three primary areas of concern are apparent with fixed-dose commercial anthelmintic combination products, viz, drug-drug interactions (safety and efficacy implications of pharmacokinetics and pharmacodynamics), common mechanisms of resistance, and best-practice management to ensure appropriate use for sustainability of parasite control with the products.
