A topical formulation having significant parasiticidal activity effective against endoparasites and/or ectoparasites such as heartworms, mites, fleas, ticks, flies is provided, which can be safe to use and avoids the many common deleterious side effects of conventional topical formulations. The topical formulations comprise a combination of a macrocyclic lactone, a neo-nicotinoid and optionally, an insect growth regulator. The topical formulation can be packaged together or packaged so that the macrocyclic lactone and the neo-nicotinoid are stored separately prior to administering the topical insecticide formulation to the animal.