Esafoxolaner is the (S)-enantiomer of afoxolaner and belongs to the isoxazoline class, which is active against arthropods. Esafoxolaner acts as an antagonist at ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA). Isoxazolines, among the chloride channel modulators, bind to a distinct and unique target site within the insect GABACls, thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes. Prolonged esafoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of arthropods. The selective toxicity of esafoxolaner between arthropods and mammals may be inferred by the differential sensitivity of the arthropods’ GABA receptors versus mammalian GABA receptors. Fleas and ticks are eliminated within 24 and 48 hours respectively after treatment, except for R. sanguineus and I. hexagonus.

Esafoxolaner kills fleas before egg production and therefore prevents the risk of household contamination. It has activity against mites (N. cati, O. cynotis) causing notoedric or ear mange.

Eprinomectin is a member of the macrocyclic lactone class of endectocides. Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve or muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarisation of the nerve or muscle cell, resulting in paralysis and death of the parasite. The spectrum of efficacy of eprinomectin has been shown to cover gastrointestinal and extraintestinal nematodes and is also considered to have activity against mites (N. cati, O cynotis).

Praziquantel is a synthetic isoquinoline-pyrazine derivative with activity against tapeworms. Praziquantel is rapidly absorbed via the surface of the parasites and affects membrane permeability in cestodes, influencing divalent cation fluxes, particularly calcium ion homeostasis, which is thought to contribute to the rapid muscle contraction and vacuolisation. This results in severe damage to the parasite integument, contraction and paralysis, disruption of metabolism and finally leads to the death and expulsion of the parasite.

Esafoxolaner is systemically absorbed from the topical application site, reaching a maximum concentration in plasma between 4 and 14 days after application. Esafoxolaner is slowly eliminated from plasma (t1/2 = 21.7 ± 2.8 days following single administration) and excreted in faeces and urine. Eprinomectin is systemically absorbed from the topical application site, reaching a maximum concentration in plasma between 1 and 2 day(s) after application. Eprinomectin is slowly eliminated from plasma (t1/2 = 5.4 +/- 2.7 days following single administration) and excreted in faeces.

Praziquantel is systemically absorbed from the topical application site, reaching a maximum concentration in plasma between 4 and 8 hours after application. Praziquantel is slowly eliminated from plasma (t1/2 = 4.3 +/- 1.9 days following single administration) and excreted in urine.

The pharmacokinetic profiles of praziquantel and eprinomectin are not affected by co-administration.

While no accumulation could be observed after repeated administration for praziquantel, accumulation was observed from the 2nd to the 5th monthly administration for esafoxolaner (ratios of 3.24 for Cmax and of 3.09 for AUC) and for eprinomectin (ratios of 1.59 for Cmax and of 1.87 for AUC). Refer to 'Special precautions for use' for safe use after repeated treatment.