The U.S. Food and Drug Administration (FDA) Nov. 19 approved Navigator for treating equine protozoal myeloencephalitis (EPM). This drug has been under development for more than six years.IDEXX Laboratories of Westbrook, Maine, received approval for the 32% nitazoxanide antiprotozoal oral paste designed to kill the single-celled protozoan parasite Sarcocystis neurona, which causes EPM. (Read more on EPM at www.TheHorse.com/epm.)Navigator is the second FDA-approved EPM treatment to hit the equine market; Bayer's Marquis was the first to be launched (The Horse of August 2001).The treatment regimen lasts 28 days, and it begins with five days of half-strength doses. This provides "a more gradual kill" of the parasite to allow intestinal microflora to adjust to the drug, and minimize the transient neurological worsening sometimes seen with extreme immune system stimulation (by numerous dead parasites), said Dorsey Kordick, PhD, of IDEXX. The horse should receive one dose daily, just before receiving his grain. Navigator's cost to veterinarians should be comparable to other EPM treatments, she said.Efficacy and Safety StudiesTo be considered a success in two nitazoxanide field studies, a horse with EPM (positive on a cerebrospinal fluid, or CSF, test) had to show at least one grade level of improvement in his neurologic signs and/or test negative for EPM on CSF after treatment. In the first study of 49 acutely affected horses, which had not received prior EPM treatments, 28 (57%) improved, and seven (14%) were negative on CSF eight weeks after the treatment period.A second field study of 416 horses included those with chronic clinical signs and horses which were previously treated for EPM. Of the 416, 250 were evaluated for efficacy. There was an 81% success rate, and 20% tested negative on CSF after treatment. Of note, 44% returned to normal function.The first field study lasted eight months, while the second took place over 28 months. Kordick said, "We had a longer interval in many cases between pre-treatment and post-treatment exams in the second study, and therefore the horse had longer to recover."John Hunt, DVM, of Heritage Farm, a veterinary practice in Carthage, Ind., has treated more than 50 horses with nitazoxanide during field studies and pilot development studies. "My experience with nitazoxanide has been very positive with at least 70% of my cases returning to their previous levels of performance," he said.Adverse ReactionsIn safety trials in the first field study, 27% of horse owners reported one or more suspicious adverse reactions. The most commonly experienced adverse effects were fever, reduced appetite, and lethargy/depression. Some of the horses experienced stocking up when kept in a stall without turnout. "Once we started to suggest hand-walking or turnout, we didn't see this as much," said Kordick. Other, less-reported side effects included worsening of neurologic signs, anorexia, diarrhea, stiffness, and colic.Four horses in the first field study were euthanized for reasons deemed unrelated to the treatment. In the second field study of 416 horses, adverse effects were comparable to those in the first study, although the FDA said five horses which died or were euthanized might have been attributable to the nitazoxanide treatment. Kordick explained each of these five horses' situations-a probable Potomac horse fever case, a nosocomial (acquired in a hospital) salmonellosis case, a gastric ulcer in a young colt, a pneumonia case, and a laminitic stallion which had abrupt changes in his feeding regimen and whose semen collection was continued against the recommendation of the treating veterinarian.As with some antibiotics, administration of Navigator can disrupt the normal microbial flora of the gastrointestinal tract and lead to enterocolitis and even death.Hunt said his patients have displayed minimal side effects and speculates that many of the adverse events that occurred during the studies were due to larger-than-desired amounts of nitazoxanide reaching the hindgut."Veterinarians forever have had concerns about putting antimicrobials into the gastrointestinal tract," said Hunt. "If we enhance absorption of nitazoxanide in the foregut, much less will reach the hindgut to produce changes in the microflora." If absorption is increased, more of the medication is reaching the central nervous system and thus, the insulting parasite, S. neurona.Hunt believes that his patients have benefited from the administration of fat (4 oz. of corn oil) given with Navigator treatment. "Nitazoxanide is fat-soluble and my conjecture is that if nitazoxanide is administered with a significant amount of fat, then its absorption is going to be enhanced, and we know that high fat in the diet slows the rate of passage through the small bowel (providing more time for absorption)."Hunt also recommends Saccharomyces cerevisiae yeast culture supplementation to his clients with horses undergoing nitazoxanide treatment. He said, "It provides bacteria in the hindgut with readily available nutrients so they are better able to withstand the antimicrobial entering the hindgut.Dosing and Monitoring"Nitazoxanide is excreted in feces, urine, and sweat,"Kordick said. "Don't be alarmed if you see pale yellow, discolored urine and sweat in some cases, as it is an indication that the drug is being absorbed."IDEXX performed studies at five and 10 times the standard dose to predict problems in case of an overdose. Since nitazoxanide is a potent antimicrobial drug, chronic overdosing could be problematic, causing loose stools, decreased appetite, and lethargy. Therefore, accurate dose calculations are essential.Navigator will not be labeled for breeding animals, although the nine pregnant mares in the second field trial delivered full-term, healthy foals.