Drug combinations have long been used in treating disease. The principle that combinations of chemotherapeutic agents benefit animals by maintaining drug efficacy in the presence of resistance has been repeatedly demonstrated from insecticide, pesticide, and antibacterial use.
Anthelmintics are commonly used in combination, and this practice can confer therapeutic advantages. For example, two drugs with differing mechanisms of action may be more effective when used together, thereby lowering the required therapeutic dose and possibly decreasing toxicity. Alternatively, antagonistic effects could occur if drug combination results in alteration in the constituent drugs' pharmacokinetic or pharmacodynamic profiles. These concepts should be borne in mind when using combination anthelmintic therapies.
According to the World Association for the Advancement of Veterinary Parasitology guidelines, there are three main reasons to use fixed-dose combinations of anthelmintics:
To cover the desired breadth of spectrum. For example, the combination ivermectin (nematicidal) and praziquantel (taeniacide) is recommended for broad-spectrum helminth control in horses. Derquantel (spiroindole) has been approved for use in some countries as a combination anthelmintic product with abamectin (macrocyclic lactone). The combination exhibits ≥ 95% efficacy against a greatly increased spectrum of parasite species.
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.
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 drugs when used alone, has revealed no issues of special concern with the routine use of such products.
