# Safety of Credelio Quattro™ (lotilaner, moxidectin, praziquantel, and pyrantel chewable tablets) in dogs infected with adult heartworms (Dirofilaria immitis)

## TL;DR

This study shows that Credelio Quattro is safe for dogs with heartworm infections, even at higher doses, and reduces microfilaria without causing serious side effects.

## Contribution

The study provides new safety data for Credelio Quattro in dogs with pre-existing heartworm infections.

## Key findings

- Credelio Quattro was well tolerated in dogs with heartworms, with only minor side effects like emesis and diarrhea.
- The drug significantly reduced microfilaria counts without causing adverse reactions or affecting adult heartworms.
- No signs of avermectin toxicity or hypersensitivity were observed in any group.

## Abstract

Credelio Quattro (lotilaner, moxidectin, praziquantel, and pyrantel chewable tablets) is a novel endectocide for monthly oral administration in dogs. The safety of Credelio Quattro was investigated in dogs with pre-existing patent heartworm (Dirofilaria immitis) infections. Heartworm preventive products are tested in heartworm-positive dogs as rapid microfilarial and adult worm death can lead to serious clinical reactions, including death.

This was a gender-stratified, randomized, placebo-controlled, blinded, parallel group design study. Prior to study, dogs were surgically implanted with 10 male and 10 female adult D. immitis worms (Georgia III isolate). After confirming a patent infection, dogs were randomized into three groups (placebo control, 1×, or 3× the maximum recommended labeled dose of Credelio Quattro) consisting of eight dogs each. Treatment was administered on three consecutive monthly occasions. The assessment of safety was based on body weight, physical examinations, clinical observations on the days of dosing, general health observations, microfilariae (MF) counts, and D. immitis antigen testing. On the last day of study, the heart, lungs, and pleural and peritoneal cavities were examined for adult D. immitis worms.

Credelio Quattro was well tolerated. Emesis occurred in the 3× group only. Diarrhea was observed in all groups at various times throughout the study. Owing to the timing of events relative to dosing, emesis and diarrhea were possibly related to treatment; however, all dogs recovered quickly and without treatment. No signs of avermectin toxicity or hypersensitivity reactions were observed in any dog. Compared with control, Credelio Quattro reduced the concentration of circulating MF on study day 1 by 38.8% for the 1× group and significantly reduced MF by 73.3% for the 3× group. MF reduction remained significant for both groups at all subsequent time points.

Credelio Quattro, when administered at 1× and 3× the maximum recommended label dose, was well tolerated following three consecutive monthly administrations to heartworm-positive dogs. Although Credelio Quattro caused a rapid reduction in microfilaria counts, no adverse effects related to microfilaria reduction were observed, and there was no effect on adult worms in this study.