It's not unheard of. I've seen it on a couple of very allergy prone goldens I work on.

From ask the vet.com:

Fipronil (the chemical ingredients in Frontline Plus) has been shown in studies to be neurotoxic to dogs and rats and affects the reproduction of rats. There have also been some disturbing reports of carcinogenicity (cancer causing) in the rat studies (however it must be stated that rats in these studies were given large amounts of fipronil and not the usual dose rate that is given to dogs/cats in flea prevention). It is classed as a Possible Human Carcinogen based on the studies done on rats. Constant exposure is the worry and there was a warning issued in 1996 regarding the Frontline spray product to all pet groomers and veterinarians who would be exposed at a far greater level than the public as there is a greater chance of inhalation and absorption of the product through the skin at increasing doses with these professions. The most common side effect seen with Frontline Plus application is skin irritation at the point of application. However there have been reports of animals that are allergic to Fipronil, and these animals will react violently to the product.

I have noticed some of my dogs being sensitive to Fronline - the weird itchy thing you described. I quit using Frontline (which I loved btw) and nobody is itching now. My itchy guys were my 'collie-types' I just assumed it had something to do with the whole mdr1 mutation issue. I guess maybe not, then.

The list of stuff which shows a negative reaction besides Ivermectin on the mdr1 gene is found http://www.vetmed.wsu.edu/depts-VCPL/drugs.aspx

It causes burn like spots if I apply it to Strider. Cassie doesn't seem 'too bothered' by it......except....

I've used it on my dogs since it came out, mmmm I want to say late 80's(?), and have always noted a drop in energy level for a couple of days after about 24 hours from application. Vets tell me I'm nuts. And I say nuts to them.

Itching though? Nope, no help there.


Ignorance can only be excused for so long, then it becomes malice.
Randy

I see a drop in energy for a day or so when I apply any flea medication to my animals, the vet poop-pooed me too but I know what I see.

I can't used revolution on Nico or on any of the cats, it leaves red burning bald marks on their necks.

Frontline seems to be the most gentle, but it no longer works for us, so now I am using comfortis and advantage.

Capstar is great for flea emergencies and I do not see a drop in energy from it, but it is way to expensive to use all that often.