THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP Educational Director, VeterinaryPartner.com

June 24, 2008: According to the FDA's enter for Veterinary Medicine (CVM), dogs receiving the drug Comfortis (spinosad) concurrently with high, extra-label doses of ivermectin are having adverse reactions in some cases. The regulatory agency warned that it has received adverse reaction reports that are consistent with ivermectin toxicity. Ivermectin is the main medication in many heartworm preventives. CVM advises veterinarians that extra-label doses of ivermectin in conjunction with comfortis may cause adverse reactions. The safety warning also comes from Elanco Animal Health, which manufactures Comfortis, a monthly oral, chewable tablet used for the prevention and treatment of flea infestations on dogs. The company is addressing the issue: see http://elms.xh1.lilly.com/10788_03_tech_Bulletin.pdf for more information.

Brand Name: Comfortis

Available in 140 mg, 240 mg, 560 mg, 810 mg, and 1620 mg chewable tablets

Background

Historically, flea control was a labor-intensive process involving sprays, dips, foggers, yard sprays, powders and more. As technology progressed, products became safer and more convenient and culminated in a whole “next generation” of products starting with Program® in 1995, and Advantage® and Frontline® not long after. For the first time, flea control could be performed once a month in the simple form of a chewable tablet or smear of topical oil. These products were extremely effective and still are but there was still room for improvement.

The topical products require time to spread over the fur and skin oil of the pet, typically needing a day or even two depending on the amount of skin oil present. The flea is killed when it moves through the toxin-treated hair. After a couple of days, all the fleas that were on the pet at the time of the product application are dead but new fleas will have arrived from the environment and they will not be dead for another day or so. The relative slow kill of the topicals means that it is normal to see some fleas on the pet even if the product is working perfectly.

After 20 days from the initial product application, the flea kill becomes even slower. In the time it takes for fleas to be killed by the product, they are still biting the pet and possibly laying eggs. The eggs will be of questionable viability after treatment with the product, but the public was not comfortable seeing fleas on a pet using the topical product.

What the public really wanted was a product that killed fleas fast, so fast that even with a heavy flea emergence from the environment, fleas would not be seen on the pet. The first ultra-fast flea product on the market was Capstar®, a tablet that began killing fleas in 30 minutes and could clear every flea on a pet’s body in a matter of hours. The problem was that this pill did not have residual activity. It could be given daily if needed but it would be expensive to do so. If only there could be a pill that worked as fast but lasted the whole month…

To fill the need for an ultra-fast flea killing tablet that lasts an entire month, in late 2007 Eli Lilly and Company released Comfortis®, with active ingredient spinosad, for small animal use. The pill is for dogs only and comes in a six-month supply. Prior to its use as a small animal product, spinosad had been used globally in agriculture throughout the 1990s. It is a biological product, produced by the bacterium Saccharopolyspora spinosa and has been classified by the USDA as an organic substance approved for use on organic produce. In 1999, Dow Agrosciences received the Presidential Green Chemistry Award from the Environmental Protection Agency for the development of spinosad for pest control. Oral spinosad, the Eli Lilly product, is classified as a drug and not an insecticide for regulatory purposes.

How this Medication is Used

Spinosad is given once a month to kill fleas. It does not kill other internal or external parasites. It is for dogs 14 weeks of age or older. The product is best given on a full stomach, and it’s beef-flavored so as to be accepted by the pet as a treat.

Spinosad is a prescription drug. It is not available without a valid doctor-patient relationship or at retail outlets.

Side Effects

During initial testing, 12% of dogs vomited after taking spinosad the first time with an additional 5% showing reduced appetite and another 5% having diarrhea. These numbers dropped with subsequent uses of the medication. Obviously, if a pet seems to be intolerant to the medication, another flea control product should be selected.

Interactions with other Drugs

Spinosad works by activating nicotinic acetylcholine receptors in the flea nervous system, causing an overload of the flea nervous system. The flea seizes to death. Spinosad is felt to be safe in conjunction with all other flea control products and heartworm preventives. There is one interaction that bears mentioning: spinosad can increase the risk of ivermectin side effects when ivermectin is used at the high doses required to treat skin parasites such as demodectic mange.  Low doses of ivermectin used in heartworm prevention are not problematic for this interaction.

It should be mentioned that numerous non-FDA approved ivermectin doses have been circulated on the Internet allowing people to save money by using large animal formulations of ivermectin rather than those manufactured for dogs and cats. This practice rarely involves ivermectin doses comparable to those in the small animal products, it certainly involves doses that could be toxic to ivermectin-sensitive individuals, and most certainly involves doses that could be toxic if combined with spinosad. See more details on circumstances leading to ivermectin toxicity.

Concerns and Cautions

See the June 24, 2008, ivermectin notice at the beginning of article.

Comfortis® tablets are beef flavored but contain pork protein. They should not be a problem for dogs with beef allergy but could be a problem for a dog with a pork allergy, rare as that might be.

Spinosad is best not used in pregnant or nursing females. During initial testing, spinosad was given to pregnant and nursing mother dogs at doses slightly above the recommended dose. Problems observed included loss of litter during pregnancy, poor weight gain of puppies, and vomiting. Problems did not occur after puppies reached age 14 weeks.

Spinosad should not be used in puppies under age 14 weeks.

Initial testing included use in dogs with pre-existing seizure disorders with doses higher what are recommended. Some of these dogs broke with seizures. It is unknown whether or not this was caused by the product. For this reason, dogs with seizure disorders should probably use a different flea control product.

SPINOSAD IS NOT APPROVED OR RECOMMENDED FOR USE IN CATS.

It is our policy not to give dosing information over the Internet.

Date Published: 4/17/2008 3:28:00 PM
Date Reviewed/Revised: 06/24/2008