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Flea and Tick Control


New Flea and Tick Products hit the Market

What’s new in the world of conventional flea and tick treatments?

News item by Mary Straus, published in the Whole Dog Journal, December 2011

Lately, it seems like new flea and tick control products have been popping up left and right. I suspect this is due to some of the original patents running out. When a patent expires, other companies can create generic versions of the same product, usually for less money. This inspires the original companies to create new products that they can patent anew. In some cases, new products are introduced because fleas and ticks may be developing resistance to the older products, lowering their efficacy. Most new products, including all those introduced this year, are just new combinations of older ingredients. Here’s a rundown on these new options.

Advantage II and K9 Advantix II

Bayer introduced Advantage II and K9 Advantix II in January 2011. The added ingredient in these new topical products is pyriproxyfen (Nylar), an insect growth regulator that inhibits the development of eggs and larvae, helping to break the flea life cycle. Other insect growth regulators used in flea control products include lufenuron (Program and Sentinel) and S-methoprene (see Certifect below). Pyriproxyfen was used in Bio Spot flea control products in the past, but was replaced with S-methoprene around 2007. These new products are also marketed under the name Advantage Plus and K9 Advantix Plus. Pyriproxyfen is also used on cats.

Other ingredients in Advantage products include imidacloprid, used to control fleas, and permethrin (K9 Advantix only), used to kill ticks as well as adult fleas. Permethrin is highly toxic to cats, and products containing permethrin are unsafe to use on dogs in households that include cats, particularly if the dog and cat share sleeping areas or the cat grooms the dog.

As with many flea and tick control ingredients, permethrin may also be more likely to cause problems for small dogs, according to the EPA’s Review of 2008 Incident Reports for Pet Spot-on Pesticides (click on View Document). Shih Tzu, Bichon Frise, Chihuahua, Yorkshire Terrier, Maltese, and Pomeranian are breeds that appear to be overrepresented in adverse incidents. Bayer also makes Advantage Multi, which combines imidacloprid with moxidectin, also found in ProHeart 6, used for heartworm prevention.

Also in January, Elanco (a division of Eli Lilly) introduced Trifexis, a new oral product that combines spinosad (Comfortis), used to kill fleas, with milbemycin oxime (found in Interceptor and Sentinel), used to prevent heartworm infection and intestinal parasites. Comfortis is a newer flea-control product introduced in November 2007 that appears to be more effective than either Advantage or Frontline (likely due to fleas developing resistance to these older products), but it may also have more side effects, such as vomiting, particularly when the medication is first used. Spinosad should not be combined with the very high doses of ivermectin (Heartgard) or milbemycin oxime (Interceptor) used to treat demodectic and sarcoptic mange, as it increases their neurological effects, but should be safe when used along with the normal heartworm preventive dosage found in this new product, though I would use with caution in dogs who have or may have the MDR1 mutation that causes sensitivity to certain drugs (see Dogs with a Drug Problem for more information). Spinosad is not recommended for dogs with seizure disorders.

Unlike most flea and tick control products, Comfortis and Trifexis are administered orally rather than topically, via a pill that is given once a month. Neither product is recommended for dogs weighing less than 5 pounds. Comfortis is not recommended for puppies under the age of 14 weeks, and Trifexis warns that younger puppies may experience a higher rate of vomiting. These products are not approved for cats, but a similar product to Comfortis called Assurity, with a partially synthetic analog of spinosad, is marketed for cats. Comfortis and Trifexis are also marketed under the names Vethical AcuGuard and ComboGuard by VCA clinics.

UPDATE: There have been a number of reports of serious adverse effects caused by Trifexis. It's unclear what is causing the problems, but investigation found that one of the active ingredients, milbemycin oxime, is being imported from China (see Green Country vet refuses to carry Trifexis). Also see Owners blame 700 dog deaths on Trifexis and additional documents discovered by use of a Freedom of Information request.

Certifect

In July, Merial introduced Certifect, likely as a result of their patent on Frontline products expiring. Certifect contains fipronil (the active ingredient in Frontline, used to kill fleas and ticks, and to help control sarcoptic mange) and S-methoprene (Precor, an insect growth regulator also found in Frontline Plus). Certifect adds amitraz, one of the most effective, but also more toxic, methods of tick control. Amitraz is also used in the Preventic tick collar, and in Mitaban, used to treat demodectic mange.

Amitraz should not be used on dogs with diabetes or heart problems, and older amitraz products warn against using them on puppies less than four months of age and very small dogs. Amitraz, a monoamine oxidase inhibitor (MAOI), can also be dangerous when combined with certain other drugs, including antidepressants (such as those used to treat separation anxiety), Anipryl (used for canine cognitive dysfunction and Cushing’s disease), and DL-Phenylalanine (DLPA), used to treat chronic pain in dogs. Amitraz was one of the ingredients used in Promeris, a flea and tick control product that was discontinued in the spring of 2011, likely due to studies indicating it might trigger pemphigus folicaeus, but there is no indication that this was linked to amitraz (see Promeris Discontinued below for more information). While Frontline and Frontline Plus are safe to use on cats, Certifect is not, as amitraz is toxic to cats.

Vectra

The only product using a new ingredient (rather than a new combination of older ingredients) is Vectra, introduced in 2007 and sold only through veterinarians. Vectra products (there are several) all include dinotefuran, a newer neonicotinoid-class insecticide that kills fleas on contact. Vectra also contains the insect growth regulator pyriproxyfen (see Advantage II above), and Vectra 3D adds permethrin to kill ticks (similar to K9 Advantix). Vectra is also marketed under the names FirstShield and SimpleGuard. Vectra products are made by Summit VetPharm, originally a subsidiary of the Hartz Mountain Corp. (Summit was sold to CEVA Animal Health in 2010).

General Advice

We’d advise caution in using any of these new products. Adding more chemicals and using more toxic ingredients may make these products more effective, but it also increases their potential for adverse effects. In some cases, such as when nothing else is effective for dogs with flea allergies or regular tick exposure, the benefit may be worth the risk, but we wouldn’t recommend switching if what you’re using now is working.

For those who want to try generic versions of older products, there are a few things to keep in mind. First, these products may not be identical to the original product. While the active ingredient is the same, other inert ingredients, such as those used to spread topical applications across the body, may differ. The generic product might not be as effective, or might cause problems for your dog that didn’t occur with the original product. Watch for any signs of adverse effects, or of products not working as well, whenever you try anything new.

Be careful where you buy your flea and tick products, particularly online, where many counterfeits are found. Be sure that the seller is trustworthy. One solution is to look for the Veterinary-Verified Internet Pharmacy Practice Sites (Vet-VIPPS) seal of approval (see When Buying Veterinary Drugs Online, Look for Accredited Sites).

Updates

FDA approves Bravecto (fluralaner), a chewable flea-tick preventive from Merck (May 2014)
Bravecto is the first oral flea and tick medication that lasts for up to 12 weeks. Bravecto kills fleas, as well as black-legged ticks (also called deer ticks), American dog ticks, and brown dog ticks, for 12 weeks following a single dose. It is also effective against the Lone Star tick for 8 weeks. Fluralaner, the active ingredient, is a new flea and tick treatment that is part of the isoxazoline group (similar to afoxolaner in Merial's NexGard, below). Common side effects in clinical trials included vomiting, decreased appetite, diarrhea, lethargy, polydipsia and flatulence. Bravecto is not approved for puppies less than six months of age, or dogs weighing less than 4.4 pounds (2 kg). Merck claims that Bravecto will only be sold by licensed veterinarians, though these products usually make it to online retailers through diversion. See the Product Insert for more information.

FDA approves Merial's NexGard, a chewable flea-tick preventive for dogs (September 2013)
NexGard is esigned to treat and prevent flea infestations and treat and control the American dog tick (Dermacentor variabilis) in dogs and puppies over the age of 8 weeks and weighing at least 4 pounds for one month. (It has since been approved to treat two additional species of ticks: the black-legged tick (Ixodes scapulars) and the Lone star tick (Amblyomma americium).) This prescription-only product contains the active ingredient afoxolaner, an isoxazoline-based compound with a new and distinct mode of action (see Bravecto above). Little is known about this new ingredient, but the product is designed for dogs only, so it may be dangerous to use around cats. The manufacturer also warns to use with caution in dogs with a history of seizures

FidoPharm launches PetArmorPro Advanced (April 2013)
FidoPharm, a subsidiary of Velcera, has released PetArmorPro Advanced, a topical parasite control product for dogs containing fipronil (same as Frontline) and permethrin to kill ticks (similar to K9 Advantix), which is not safe to use around cats, and should not be used on dogs younger than 8 weeks or weighing less than 4 pounds. It will be sold over the counter at Walmart. Velcera had to remove previous fipronil products from the market after it was determined that they infringed on the patent covering Merial’s Frontline Plus. Velcera was recently sold to Perrigo, the world’s largest manufacturer of OTC pharmaceutical products for the store brand market.

Bayer Health Care introduces Seresto (January 2013)
Seresto uses a collar to deliver a flea and tick preventive over 8 months. The collar is supposed to work the same way that a topical product would. Seresto contains imidacloprid (same as Advantage) and flumethrin (a pyrethroid, new in the U.S., that kills and repels ticks and is safe for cats). The pesticides are released from the collar gradually rather than all at once. Seresto will be sold for a suggested price of $70. Seresto has been used in the UK and other parts of Europe before being introduced in the U.S.

Merck Animal Health Announces ACTIVYL® AND ACTIVYL® TICK PLUS (June 2012)
Activyl and Activyl Tick Plus are new topical flea and tick control products that will be sold only by veterinarians. Both products contain indoxacarb, a newer flea-control ingredient, which is safe to use on cats as well as dogs. Activyl Tick Plus also contains permethrin to kill ticks (similar to K9 Advantix), which is not safe to use around cats, and should not be used on dogs younger than 8 weeks or weighing less than 4 pounds.
Update: I've heard one report of a dog with a severe skin reaction to Activyl (March 2013). A second report came in of skin sensitivity on the back where Activyl Tick Plus was applied persisting two weeks after application (May 2013). A third report said the dog's hair fell out in clumps after the third monthly application of Activyl Tick Plus (Sept 2013). Reactions could be linked to the inactive ingredients used to spread the medication over the body, rather than the active ingredients used to kill fleas and ticks.

VPL Launches Vet-Exclusive Parasiticides for Dogs, Cats (June 2012)
Ovitrol X-Tend Flea and Tick Shampoo and Spray both contain etofenprox, which kills adult fleas, and S-Methoprene (Precor), an insect growth regulator (see Certifect above for more information on this ingredient). The spray kills fleas and ticks on contact and claims to “protect against” them and mosquitoes for up to two weeks (the insect growth regulator lasts longer). Directions say to apply monthly, which means this product would not provide continuous protection.

Novartis introduces ParaStar Plus (May 2012)
ParaStar Plus is a new flea and tick product that combines fipronil (the active ingredient in Frontline) with cyphenothrin, which appears comparable to Sentry Fiprogard for dogs (see below). Cyphenothrin has been associated with a number of problems in dogs when used in earlier products, and is toxic to cats. Novartis also makes Sentinel (lufenuron, an insect growth inhibitor, plus milbemycin oxime for heartworms prevention) and CapStar (nytenpyrim), an oral neonicotinoid that kills fleas currently on pets but does not provide any lasting protection.

Virbac Animal Health launches Effitix (April 2012)
Effitix is a topical flea and tick product that uses a combination of fipronil (the active ingredient in Frontline, used to kill fleas and ticks) and permethrin (used to repel ticks, also found in K9 Advantix). The combination of ingredients may be more effective against ticks than either by itself. It also repels mosquitoes, kills lice, aids in the control of sarcoptic mites; and prevents and inhibits blood feeding by biting flies. Note that permethrin is highly toxic to cats (the company offers a fipronil-only product called Effipro for cats). Not for use on puppies under the age of 12 weeks.

Sergeant’s Rolls Out Fipronil-based OTC Flea and Tick Meds (February 2012)
The new treatments will be sold as Sentry Fiproguard Max in pet specialty stores and Pronyl OTC Max in grocery and mass retail stores. The treatments contain fipronil, which is the active ingredient in Frontline, in addition to cyphenothrin in the dog formula and etofenprox in the cat formula. Cyphenothrin is a pyrethroid insecticide used in other Sergeants flea products. It is toxic to cats and may also be toxic to small breeds of dogs, with Chihuahuas, Shih Tzus, Miniature Poodles, Pomeranians and Dachshunds accounting for 33 percent of reactions, according to the article Small Dogs Prove Susceptible to Flea Poison.
Also see 2 Flea Collar Makers Agree to Stop Using Propoxur: "Sergeant’s Pet Care Products Inc. and Wellmark International [makers of Adams Plus collar] have agreed to phase out the use of the chemical propoxur in pet flea collars. . . . Propoxur is a neurotoxin and known carcinogen that authorities say poses a risk to the brains and nervous systems of children. People who handle propoxur pet collars may ingest the chemical if they also touch their mouth, experts state."

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Novartis Drug Shortages Continue

Plant shutdowns make it hard to find certain veterinary medications

News item by Mary Straus, published in the Whole Dog Journal, September 2012

Novartis Animal Health suspended production at its Lincoln, Nebraska, plant in December 2011 following a series of warnings from the U.S. Food and Drug Administration (FDA) regarding manufacturing and quality control violations. At that time, the only veterinary drugs affected were the heartworm and flea products Interceptor, Program, and Sentinel. Novartis said it hoped to return to full production in January 2012.

Instead, further problems were discovered when Novartis warned veterinarians about possible tablet mix-ups in bottles of Clomicalm, used to treat separation anxiety. On January 5th, 2012, Novartis sent a letter to veterinarians informing them that it was suspending production and shipments of Clomicalm and Milbemite (used to treat ear mites) in addition to the products listed above.

Novartis resumed shipping already manufactured products in early February, but those have since run out, including supplies of Deramaxx, a non-steroidal anti-inflammatory drug (NSAID) whose production had been moved to the Nebraska facility shortly before the shutdown. (Update: Production of Deramaxx was resumed in March 2013.)

While substitutes for all of these products exist, it can be difficult for pet owners who rely on certain products that they know work well for their pets to suddenly have to make a change. The situation becomes even more stressful when using products such as Deramaxx, where it is unsafe to switch quickly from one to another without a washout period in between, or medications like Clomicalm that can take weeks to build up to effective levels in the blood (see Anxiety Medications for Dogs for more information).

Almost nine months after the initial announcement, the facility still has not resumed full production. Novartis says that it is now shipping the 5 mg strength of Clomicalm (the generic equivalent, clomipramine hydrochloride, is available in higher strengths elsewhere, including 1800petmeds.com). The company also states that it is at the testing pre-production stage for Sentinel, a combination of milbemycin oxime (heartworm preventive medication also found in Interceptor) and lufenuron (insect growth regulator used to control fleas, also found in Program), but they have not given an estimated date as to when this product will be available. Note that the Novartis veterinary products Atopica, Capstar, and Adequan are produced at other facilities and are therefore not an issue.

In Canada, the situation is even more dire. Sandoz Canada, part of the generic pharmaceuticals division of Novartis, discontinued some medications and downsized production of others in response to FDA citations noting product reliability concerns and safety issues tied to the Sandoz plant in Boucherville, Quebec. A fire that broke out March 4, 2012 in the plant's boiler room made the problem even worse. Affected drugs include morphine, fentanyl, phenobarbital, diazepam, and more. Sandoz has indicated that no human drugs will be delivered to veterinarians before the end of 2012, and vets are struggling to find acceptable alternatives.

Update April 2013: Deramaxx and Sentinel Flavor Tabs are once again available. Unforunately, Interceptor has been discontinued. All of these drugs have been out of production since December 2011. Sentinel contains milbemycin oxime for heartworm prevention and control of intestinal parasites, along with lufenuron, an insect growth regulator that can help to control flea populations. Novartis also introduced Interceptor Spectrum in Australia, which is a combination of milbemycim oxime and praziquantel, for tapeworms. The same product is called Milbemax in other countries. Neither is available in the U.S. I spoke with Novartis in August 2013, and they have no plans to reintroduce Interceptor, or to introduce a milbemycin/praxiquantel product in the U.S. at this time.

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Promeris Discontinued

Relatively new flea/tick control product to be removed from market

News item by Mary Straus, published in the Whole Dog Journal, May 2011

Pfizer has announced plans to discontinue manufacture and sale of its flea and tick control product, ProMeris. Orders will continue to be filled until September 20, 2011.

ProMeris was introduced in the fall of 2007, and touted as the first topical product to use metaflumizone. Pfizer gained control of ProMeris when it acquired Wyeth/Fort Dodge Animal Health in 2009. Pfizer is also the maker of Revolution, used to control fleas and one species of ticks, along with heartworm, ear mites, and sarcoptic mange.

While no specific reasons were given, it’s likely that Pfizer’s decision was influenced by the March publication of a study in the journal Veterinary Dermatology that was done at North Carolina State University. The study concluded that ProMeris “has the potential of triggering a variant of PF” (pemphigus foliaceus, an autoimmune disorder of the skin that is discussed in Noses and Toes Gone Wrong). Lesions begin at the site of application, sometimes months after the initial application, and may later spread to other areas of the body. Immunosuppressive drugs are sometimes required for treatment. While most dogs achieve complete remission, lesions may recur in a few cases even without the further application of ProMeris. Labrador Retrievers and other large-breed dogs appear to have an increased risk for this adverse reaction. It’s important for vets to be aware of these findings, to avoid misdiagnosis.

Amitraz, one of the active ingredients in ProMeris, is a monoamine oxidase inhibitor (MAOI ). Other products that contain amitraz include Preventic collars and Mitaban. Products containing amitraz should never be used together.

Amitraz can be dangerous when combined with antidepressants, such as Prozac (fluoxetine), or with other MAOI inhibitors, such as Anipryl (l-deprenyl, selegiline). DL-Phenylalanine (DLPA), used to treat chronic pain in dogs, should also be avoided when using MAOI s, such as amitraz. Cats are at risk if they come into contact with topical products, and even owners who are taking MAOI s themselves may run into problems using these products on their dogs.

ProMeris had recently been approved for treatment of generalized demodicosis, also called demodectic mange or demodex (treatment is not needed for the localized form). Other treatments for generalized demodex include giving high doses of ivermectin (the active ingredient in Heartgard) daily or every other day for long periods, and weekly or biweekly dips with potentially toxic Mitaban. In comparison, ProMeris is far more convenient, requiring only topical application every two to four weeks, and many veterinarians are sorry to see it go for that reason. Owners of dogs who reacted badly to the drug, however, may be wondering why it’s not being pulled off the market immediately.

Update: In July 2011, Merial introduced Certifect, a product that adds amitraz to Frontline Plus and may also be useful for treating demodectic mange. See New Flea and Tick Products Hit the Market above for more information.

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If you have any questions or comments, you can contact me, but I have less time to answer questions than I used to, and it may be several days to a week before I can respond. My name is Mary Straus and you can email me at either or

   


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