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Ticks on the animal prior to administration or from new infestations after product administration are killed within 48 hours.
For fleas, the onset of efficacy is within 12 to 24 hours of attachment for five weeks after product administration. Fleas on the animal prior to administration are killed within 8 hours. The veterinary medicinal product kills newly emerged fleas on the dog before they can lay eggs and therefore it prevents environmental flea contamination in areas to which the dog has access.
Sarolaner is an acaricide and insecticide belonging to the isoxazoline family. The primary target of action of sarolaner in insects and acarines is functional blockade of ligand-gated chloride channels (GABA-receptors and glutamate-receptors). Sarolaner blocks GABA- and glutamate-gated chloride channels in the central nervous system of insects and acarines. Sarolaner is active against adult fleas (Ctenocephalides felis and Ctenocephalides canis) as well as several tick species such as Dermacentor reticulatus, Ixodes hexagonus, Ixodes ricinus and Rhipicephalus sanguineus.
Moxidectin is a second generation macrocyclic lactone of the milbemycin family. Its principal mode of action is interfering with neuromuscular transmission at the level of the glutamate-gated chloride channels and, to a lesser extent, of GABA (gamma amino butyric acid)-gated channels. This interference leads to the opening of the chloride channels on the postsynaptic junction to allow the inflow of chloride ions. This results in flaccid paralysis and eventual death of parasites exposed to the drug. Moxidectin is active against adults of Toxocara canis, L4 larvae and immature stages (L5) of Ancylostoma caninum, L4 of Dirofilaria immitis and immature stages (L5) of Angiostrongylus vasorum.
Pyrantel is a nicotinic acetylcholine (ACh) channel receptor (nAChR) agonist. Pyrantel mimics the agonist effects of ACh through high affinity binding to subtype specific ionophoric nAChRs in nematodes, while not binding at muscarinic mAChRs. Following receptor binding, the channel opens to allow the influx of cations resulting in a depolarization and excitatory effects on nematode muscle, ultimately leading to spastic paralysis of the worm and death. Pyrantel is active against immature stages (L5) and adults of Toxocara canis, adults of Ancylostoma caninum, Toxascaris leonina and Uncinaria stenocephala.
In this fixed combination, moxidectin and pyrantel provide complementary anthelmintic efficacy through distinct mechanisms of action. In particular, both active substances contribute to the overall efficacy against the gastrointestinal nematodes Ancylostoma caninum and Toxocara canis.
No adverse reactions were observed in 8-weeks old healthy puppies administered with up to 5 times the maximum recommended dose for 7 consecutive monthly administrations.
In a laboratory study, the product was well tolerated in dogs with a deficient multidrug-resistance-protein 1 (MDR1 -/-) following single oral administration at 3 times the recommended dose. After a single administration of 5 times the maximum recommended dose to this sensitive dog breed, transient ataxia and/or muscle fasciculation were observed.
Macrocyclic lactones including moxidectin have been shown to be substrates for p-glycoprotein. Therefore, during treatment with the veterinary medicinal product, other products that can inhibit p-glycoprotein (e.g. cyclosporine, ketoconazole, spinosad, verapamil) should only be used concomitantly according to the benefit-risk assessment of the responsible veterinarian.