{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:27:34Z","timestamp":1781173654901,"version":"3.54.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012752","name":"Elanco Animal Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012752","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Elanco Animal Health, United Kingdom"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The combination of lotilaner, moxidectin, praziquantel, and pyrantel pamoate (Credelio Quattro) is a novel systemic endectocide that provides month-long effectiveness in dogs after a single oral treatment. The safety of Credelio Quattro flavored chewable tablets was investigated when administered orally at the upper end of the recommended dosage range (20\u201341\u00a0mg\/kg lotilaner, 0.02\u20130.04\u00a0mg\/kg moxidectin, 5\u201310\u00a0mg\/kg praziquantel, and 5\u201310\u00a0mg\/kg pyrantel) and multiples thereof when administered long term.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study was randomized and blinded, with parallel groups beginning in healthy 8-week-old Beagle dogs and continuing until they reached adulthood. A total of 32 dogs were randomized among four groups (8 dogs\/group) to nontreated controls or to treated groups at target doses of 1\u00d7, 3\u00d7, or 5\u00d7 the maximum dose. Treatment was administered on nine occasions to dogs in a fed state every 4 weeks, with the control group receiving placebo tablets. Assessment of safety was based on regular health observations, complete physical\/neurological examinations, food consumption, clinical pathology evaluations (hematology, clinical chemistry, and urinalysis), body weight, and macroscopic and microscopic examinations of collected tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Credelio Quattro did not induce any serious treatment-related adverse effects based on health observations, physical\/neurological examinations, food consumption, clinical pathology, body weight, or macroscopic and microscopic examinations. The only non-serious treatment-related effects of Credelio Quattro were a dose-dependent increase in the frequency of discolored feces, diarrhea, and vomiting (including hypersalivation associated with vomiting in two of the 5\u00d7 dogs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that Credelio Quattro exhibits a wide safety margin when administered monthly to puppies and dogs at the maximum recommended commercial dose, with only transient gastrointestinal symptoms similar to other oral antiparasitic products observed. Therefore, Credelio Quattro may be safely administered to dogs each month in accordance with the approved label.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-025-07201-3","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:05:07Z","timestamp":1765811107000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-term safety of Credelio Quattro\u2122 (lotilaner, moxidectin, praziquantel, and pyrantel chewable tablets), a novel orally administered combination endectocide for dogs"],"prefix":"10.1186","volume":"19","author":[{"given":"Kari L.","family":"Riggs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Wiseman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"7201_CR1","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1186\/s13071-017-2468-y","volume":"10","author":"EA Kuntz","year":"2017","unstructured":"Kuntz EA, Kammanadiminti S. Safety evaluation of lotilaner in dogs after oral administration as flavoured chewable tablets (Credelio\u2122). Parasit Vectors. 2017;10:538.","journal-title":"Parasit Vectors"},{"key":"7201_CR2","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1186\/s13071-018-2969-3","volume":"11","author":"EA Kuntz","year":"2018","unstructured":"Kuntz EA, Kammanadiminti S. Safety of lotilaner flavoured chewable tablets (Credelio\u2122) after oral administration in cats. Parasit Vectors. 2018;11:409.","journal-title":"Parasit Vectors"},{"key":"7201_CR3","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1186\/s13071-021-04760-z","volume":"14","author":"KL Riggs","year":"2021","unstructured":"Riggs KL, Wiseman S. Long-term and acute safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio\u00ae Plus) in juvenile and adult dogs. 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The study was reviewed and approved by CRL\u2019s Institutional Animal Care and Use Committee. This manuscript was prepared in compliance with the ARRIVE Guidelines Checklist for animal in vivo experiments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"These studies were funded by Elanco Animal Health. All authors are employees of Elanco Animal Health.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36"}}