Trifexis should be given with a meal to ensure maximum effectiveness. The package insert states that "Trifexis should be administered with food. If a dose is missed and it is within one day of the next scheduled dose, administer the missed dose with food. If a dose is missed and more than one day has passed since the last scheduled dose, administer the missed dose as soon as possible and return to the regular schedule. Do not administer two doses at once."