I've always used Heartguard Plus and Ruckus has had no bad reactions to it. However, it really depends on the dog. For example, I started off using Frontline for flea and tick prevention and we have to do it year round because it normally doesn't get cold enough where we are to kill everything off (except maybe this winter....polar vortex or whatever we're calling it). Ruckus would run around in circles like crazy right after I gave it to him and then he'd crash and act lethargic. I switched to Advantix and haven't had any issues with it at all.