Hartz Companion - Animal Introducing Etofenprox: A Broad-Spectrum, Comprehensive Ectoparasiticide

Albert Ahn, DVMVice President of Corporate Communications

and Consumer RelationsThe Hartz Mountain Corporation

Comprehensive ectoparasite controlremains a top priority for pet owners andthe veterinary medical community.According to the American Pet ProductManufacturers Association (APPMA), thenumber of cats being treated with flea andtick products increased 15% between 2002and 2004.1 That means an estimated 36million cats are currently being treated forfleas and ticks, and the majority of petowners use topical applications.1

Cat owners want a product that issafe, effective, easy to use, and affordable,and they want one that is able to protectagainst fleas, ticks, and mosquitoes.While many cat owners turn to theirveterinarian for prescription ectoparasitecontrol products, others prefer to purchaseover-the-counter products. Hartz ispleased to announce the introduction of Hartz® UltraGuard plus™ Drops for Cats. This easy-to-use topicalformulation provides protection against

ALSO IN THIS ISSUE:

Ask the Vet ................................ 7

adulticidal activity of a flea preventive iscrucial to prevent FAD.

Anemia is a common sequela of fleainfestation, particularly for young puppiesand kittens, and can be life threatening incats. C. felis are hearty feeders capable ofconsuming up to 15 times their bodyweight in blood daily.3 Seventy-two femalefleas can consume 1 ml of blood in a day.4

Substantial flea infestations can result insevere clinical signs associated withanemia, and severe anemia can be fatal.

In addition to inducing skininflammation and causing blood loss, fleasare linked to several other health threats.This ectoparasite can serve as a vector forthe transmission of Rickettsia typhi (the

J U N E 2 0 0 6 V O L U M E 4 , N U M B E R 2

adult and immature fleas, deer ticks, andmosquitoes. The active ingredients inHartz® UltraGuard plus™ Drops for Cats are etofenprox and (S)-methoprene.

ECTOPARASITES AND DISEASEFleas

The cat flea, Ctenocephalides felis (Figure 1), is the most common speciesaffecting dogs and cats.2 C. felis is notmerely a nuisance; it poses many healthrisks to the feline population. Flea allergydermatitis (FAD) accounts for at least half of all dermatologic problems seen by veterinarians.3 When fleas feed on a host,saliva is transferred. Flea saliva containsproteolytic enzymes and histamine-likesubstances, which cause the inflammatoryand pruritic signs associated with FAD.3

Cats with FAD can present with self-excoriations, moist and miliary dermatitis,alopecia, papules, and eosinophilicgranuloma complex lesions.3 Rapid

Introducing Etofenprox:A Broad-Spectrum, Comprehensive Ectoparasiticide

A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALSA NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS

2 HARTZ® COMPANION ANIMALSM • JUNE 2006 • VOL. 4, NO. 2

Consulting EditorsAlbert Ahn, DVM

Vice President of CorporateCommunications and ConsumerRelationsThe Hartz Mountain Corporation

Bruce TrumanSenior DirectorAnimal Health and NutritionThe Hartz Mountain Corporation

Associate EditorsJill A. Richardson, DVM

DirectorConsumer RelationsThe Hartz Mountain Corporation

David LevyAssistant ManagerAnimal Health and NutritionThe Hartz Mountain Corporation

HARTZ® COMPANION ANIMALSM

is produced for The Hartz Mountain Corporation by Veterinary Learning Systems, 780 Township Line Rd.,Yardley, PA 19067.

Copyright © 2006 The Hartz Mountain Corporation. All rights reserved.

Hartz® and other marks are owned byThe Hartz Mountain Corporation.

Printed in U.S.A. No part of thispublication may be reproduced in anyform without the express writtenpermission of the publisher.

For more information on The HartzMountain Corporation, visitwww.hartz.com.

J U N E 2 0 0 6 V O L U M E 4 , N U M B E R 2

A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS

causative agent of murine typhus),Rickettsia felis (rickettsiosis), Bartonellahenselae (cat scratch fever), and Dipylidiumcaninum (tapeworm),4 all of which pose azoonotic risk. Fleas can also transmitMycoplasma haemophilus (formerly calledHemobartonella felis), the agent responsiblefor feline infectious anemia.

The potential impact of fleas on humansextends beyond the aforementionedinfectious agents. Papular urticaria is anannoying rash that humans develop as aresult of flea bite hypersensitivity;children tend to be affected more thanadults.5 Home flea infestations can also be frustrating and costly to eliminate.

An understanding of the biology offleas provides insight into how theseparasites rapidly infest their environmentand provides the key to their eradication.Under ideal temperature and humidityconditions, one mating female flea canproduce more than 20,000 adults andmore than 160,000 preadult fleas in 2months.4 Because of the remarkablereproductive capacity of C. felis, aneffective insecticide against this pest mustinclude a “birth control” component.

Female fleas lay eggs on the host anddeposit them in the environment. Thesmooth, oval eggs are not sticky, so eggslaid on the host quickly fall to the ground.Under ideal conditions, fleas usually hatchwithin 36 hours to 10 days. The emerginglarvae feed on debris and adult flea feces.After two molts, the final larval stagespins a cocoon from which the adult flea

emerges. The entire life cycle typicallyoccurs in 3 to 4 weeks. The majority ofthe flea’s life cycle takes place in theenvironment, not on the host. It istherefore imperative to address both thepet and the environment for a successfulflea eradication plan.4

TicksThe importance of tick prevention

extends beyond the aestheticallydispleasing nature of the ectoparasite(Figure 2). A proactive approach topreventing tick bites is important toreduce the number of protozoal, bacterial,and viral pathogens transmitted by thesevectors. Tick-borne diseases such asborreliosis (Lyme disease), ehrlichiosis,rickettsiosis (Rocky Mountain spottedfever), babesiosis, and viral encephalitishave many health implications for bothhumans and animals.6

MosquitoesThe mosquito (Figure 3) is another

ectoparasite that serves as a vector forinfectious diseases in both humans andanimals. Mosquitoes are responsible for the transmission of heartworm disease(HWD). Although cats are lesssusceptible to HWD than dogs, cats candevelop more severe clinical signs. It isalso harder to diagnose HWD in catsthan in dogs; in fact, because cats oftenare not microfilaremic and have low wormburdens and less-specific clinical signsthan dogs, feline HWD remainsunderdiagnosed.

Many owners may not be aware of theheartworm risk their cats face. Althoughstudies have shown that cats that spendtime outdoors are predisposed toheartworm infection, a surprising one-third of affected cats are reported to livestrictly indoors.7

The clinical signs associated withfeline heartworm infection are distressingto patients and their owners. The deathor migration of adult worms can result inacute dyspnea, tachycardia, shock, coughor hemoptysis, dementia, blindness,seizures, and death.7 The grave prognosis

and lack of safe and effective treatmentoptions for feline HWD warrant effectivemosquito prevention and prophylaxis.

West Nile virus (WNV) is a newlyemerging disease that poses risk for bothhumans and animals. WNV is also spreadby the bites of infected mosquitoes. As ofFebruary 2006, there have been reports ofbirds, mammals, or mosquitoes being

Figure 1. The cat flea,Ctenocephalides felis.

infected with WNV in every state exceptAlaska and Hawaii.

Cats have tested positive for WNV,8

and a recent study evaluated the risksposed by WNV to experimentallyinfected dogs and cats. All of the testanimals exposed to mosquitoes wereconfirmed to be carriers of WNV. In thislaboratory-controlled study, the fourcanine subjects developed low andtransient virus levels, but the four felinesubjects developed titers higher thanthose seen in the dogs. Three of four catsdeveloped mild lethargy and spikes inbody temperature.9 Interestingly, thestudy also showed that ingestion ofinfected prey animals (mice) can induceviremia, suggesting that prey animals canserve as an important reservoir ofinfection to predators.9

PARASITICIDESMany agents have been developed

to help eradicate parasitic insectsdetrimental to humans, animals, andcrops. Pharmacologic advances haveyielded products that are safe and availableas user-friendly topical applications.

(S)-Methoprene(S)-Methoprene (Figure 4) is a

synthetic juvenile insect hormone analogthat prevents the completion of the flealife cycle and thus diminishes the numberof emerging adults.10 During the flea’slarval stages, juvenile hormone ( JH) in the

hemolymph (i.e., insect blood) is found in high concentrations. This regulatoryhormone prevents metamorphosis, andthe flea remains in the larval stage.11

A synthetic JH analog tricks the insect into a persistent immature phase, whichresults in death. Further research led tothe development of JH mimetics, whichfall into two categories: the terpenoidsand nonterpenoids. (S)-Methoprene, aterpenoid compound, was found to be amore effective insecticide than naturallyoccurring JH.11

Until the early 1980s, (S)-methoprenewas the only approved insect growthregulator (IGR). It was initially administered orally to cattle to helpcontrol the surrounding fly population.Treated cattle subsequently producedfeces containing concentrations of (S)-methoprene that were beneficial incontrolling developing fly larvae. Since

then, the safety and efficacy of (S)-methoprene has been upheld innumerous studies.11–13 The World HealthOrganization has approved adding (S)-methoprene to drinking water tocontrol mosquito populations and, in1999, classified methoprene as “unlikely to present acute hazard in normal use.”12

This statement remains undisputed.Methoprene is a selective, stable, andpotent larvicide. Its selective mode oftoxicity to insects is based on interferencewith metamorphosis; there is no clearlydefined analogous mechanism by which itcan exert a harmful impact on mammals.

(S)-Methoprene has been used formore than 20 years to fight infestationsof mosquitoes, flies, ants, fleas, and other insects. It prevents flea eggs from hatching, which is an importantcomponent of a flea-prevention program.

EtofenproxEtofenprox (also called ethophenprox)

is a very effective insecticide with a widemargin of safety in mammals. Themechanism of action of this compound issimilar to that of the pyrethroid class ofpesticides.14

Etofenprox shares structural similaritywith type I ester pyrethroids (Figure 5),but it has a unique ether composition,which gives it a much higher medianlethal dose (LD50). This structuraldifference is what differentiatesetofenprox from pyrethroids and providesit with a high level of safety for warm-blooded animals. Because of its unique

Figure 2. Ticks are capable oftransmitting a variety of illnesses to petsand humans.

Figure 3. Mosquitoes are responsiblefor transmitting heartworms and WestNile virus.

C CH3CH3

O

CH3

O

CH3

CH2 CH2 CH2 CH CH2

CH3

H3C

C

H

C

H

H

C

C C

O

CH CH3

Empirical Formula: C19H34O3

Figure 4. Chemical structure of (S)-methoprene.

HARTZ® COMPANION ANIMALSM • JUNE 2006 • VOL. 4, NO. 2 3

ether (as opposed to ester) structure andmolecular composition, it imparts a ratoral LD50 of more than 42,880 mg/kgand a mouse oral LD50 of more than107,200 mg/kg.

Etofenprox is an important chemical in the fight against ectoparasites affectinganimals and humans and is also widelyused to protect crops from insect pests.It is effective against an array of pests,including ants, cockroaches, wasps,hornets, and beetles.15 The British Army has deemed etofenprox a safe andeffective additive to nets and screens used in controlling arthropod vectors of disease.16 The World HealthOrganization classified etofenprox asunlikely to present an acute hazard innormal use.14

Studies have been conducted toevaluate the metabolism and toxicity ofetofenprox. The agent is primarilyexcreted in feces and to a lesser extent inurine. There was no evidence to suggestthat etofenprox is genotoxic orcarcinogenic.14

Hartz® UltraGuard plus™

Drops for CatsThe synergistic combination of

(S )-methoprene and etofenprox providesa scientifically proven and effectiveproduct for controlling the primaryectoparasites that threaten cats and theircaregivers. Hartz® UltraGuard plus™Drops for Cats is an innovative product

containing 40% etofenproxand 3.6% (S)-methoprene.15

Both of these EPA-registered products provideprotection against adult andimmature fleas, deer ticks,and mosquitoes.

Selective toxicity—theability to kill the offendingpest without causing harmto the species beingprotected—is a desiredfeature of ectoparasiticideproducts. The combinationof ingredients in Hartz®

UltraGuard plus™ Dropsfor Cats achieves this goal. Hartz®

UltraGuard plus™ Drops for Cats hasbeen subjected to multiple efficacy, safety,and toxicology tests. Hartz® UltraGuardplus™ Drops for Cats received EPAregistration for use on pets in 2004. It isin the Level 4 Toxicity Category, thelowest possible toxicity ranking. No“Danger,” “Warning,” or “Caution”statement is required on the label, and nospecial safety precautions (e.g., wearingeye protection or gloves as required byother flea and tick products) are requiredwhen applying the product on cats.

The product was evaluated in cats at one, three, and five times therecommended dosages. Test subjects were evaluated for clinical signs of illness,changes in appetite or body weight,and clinical pathology test results. Nosystemic adverse effects were observed.Even at five times the recommended dose in cats, only mild skin changes,similar to those associated with anytopical pesticide, were seen. Tests showed no adverse effects if Hartz®

UltraGuard plusTM Drops for Catscontacts the eyes.15

Efficacy studies showed that 98% of adult fleas were killed 2 weeks aftertopical application and a 95% or greaterreduction in flea egg hatch was notedafter 4 weeks. The IGR and fleaadulticide combination provides fast andlong-lasting protection against C. felis.Hartz® UltraGuard plusTM Drops for

Cats has been shown to kill and repelCulex spp and Aedes spp mosquitoes,15

and 90% of deer ticks were killed in 4weeks.

Hartz® UltraGuard plusTM Drops forCats is labeled for external use on cats 12 weeks of age or older. This topicalproduct is applied between the cat’sshoulder blades once a month.10 As withany product, pet owners should contacttheir veterinarian before using on cats thatare geriatric, sick, pregnant, or nursing.After application, the cat should not bebathed for at least 24 hours, and catswithin the same household should not be permitted to groom each other untilthe product is completely dry.17 Hartz®

along with many experts, including the Companion Animal Parasite Council (CAPC), recommends the use of ectoparasite products on a year-round basis.18

With the advent of clinically-proven, effective, and easy-to-useectoparasiticides, there is no reasonableexcuse for pets and their owners to sufferthe consequences of these pests. Greaterattention drawn to the various vector-borne diseases carried by fleas, ticks, andmosquitoes will likely result in improvedcompliance by pet owners. The use ofectoparasiticides helps to ensure thehealthy and happy lifestyles of pets andtheir caregivers.

C

O

H3C

CH3

CH2

O CH2

CH2 CH3

O

Empirical Formula: C25H28O3

Figure 5. Chemical structure of etofenprox.

Benefits of Hartz® UltraGuard plus™

Drops for Cats

■ Kills deer ticks that may transmitLyme disease for up to 1 month

■ Kills and repels mosquitoes that maytransmit heartworm disease

■ Kills fleas that may cause flea allergydermatitis, flea bite anemia, andtapeworm infestation

■ Kills flea eggs for up to 1 month

■ Quick acting

■ Long lasting

4 HARTZ® COMPANION ANIMALSM • JUNE 2006 • VOL. 4, NO. 2

We HaveSolutions.

Your Clients have Flea & Tick Questions.

www.fleaandticksolutions.com

REFERENCES1. APPMA: 2005–2006 APPMA National Pet Owners

Survey. Greenwich, CT, American Pet ProductManufacturers Association, pp 96-97, tables 22A and 23.

2. Keil K, Wellington J, Ciszewski D: Efficacy ofimidacloprid in controlling flea allergy dermatitis incats. Proc 2nd Int Flea Control Symp:15, 2001.

3. Keil K, Wellington J, Ciszewski D: Efficacy ofadvantage in controlling flea allergy dermatitis incats. Proc 3rd Int Flea Control Symp:6, 2002.

4. Scott DW, Miller WH, Griffin CE: Muller andKirk’s Small Animal Dermatology. Philadelphia, WBSaunders, 2001, pp 490–508.

5. Stibich AS, Schwartz RA, Chaffer C: PapularUrticaria. Available at www.emedicine.com/DERM/topic911.htm; accessed April 2006.

6. Otranto D, Paolo Lia R, Cantacessi C, et al:Efficacy of a combination of imidacloprid10%/permethrin 50% versus fipronil 10%/(S)-methoprene 12%, against ticks in naturally infecteddogs. Vet Parasitol 130:293–304, 2005.

7. Atkins CE, Ryan WG: CVT update: Diagnosis

and prevention of heartworm disease in cats. Kirks’sCurrent Veterinary Therapy XIII Small AnimalPractice. Philadelphia, WB Saunders, 2000, pp782–787.

8. Centers for Disease Control and Prevention: WestNile Virus Questions and Answers. www.cdc.gov/ncidod/dvbid/westnile/qa/transmission.htm;accessed April 2006.

9. Austgen LE, Bowen RA, Bunning ML, et al:Experimental infection of cats and dogs with WestNile virus. Emerging Infectious Diseases (serialonline) 2004 Jan (date cited). Available fromwww.cdc.gov/ncidod/EID/vol10no1/02-0616.htm;accessed April 2006.

10. Young DR, Jeannin PC, Boeckh A: Efficacyof fipronil/(S)-methoprene combination spot-on for dogs against shed eggs, emerging andexisting adult cat fleas (Ctenocephalides felis,Bouche). Vet Parasitol 125:397–407, 2004.

11. Garg RC, Donahue WA: Pharmacologicprofile of methoprene, an insect growthregulator, in cattle, dogs, and cats. JAVMA194(3):410–412, 1989.

12. Pesticide Residues in Food 2001: Toxological

Evaluations, Methoprene and (S)-Methoprene.Available at www.inchem.org/documents/jmpr/jmpmono/2001pr01.htm; accessed April2006.

13. Pesticide Residues in Food—1984. Available atwww.inchem.org/documents/jmpr/jmpmono/v84pr31.htm; accessed April 2006.

14. 1993 FAO/WHO Joint Meeting on PesticideResidues: Etofenprox: Available at www.fao.org/ag/AGP/AGPP/Pesticid/JMPR/Download/93_rep/Report1993.pdf; accessed April 2006.

15. Data on file. The Hartz Mountain Corporation,Secaucus, NJ.

16. Croft AM, Baker D, von Bertele MJ: Anevidence-based vector control strategy formilitary deployments: The British armyexperience. Med Trop (Mars) 61(1):91–98, 2001.

17. Product Label: Hartz® UltraGuard plus™Drops for Cats. Secaucus, NJ, The HartzMountain Corporation, 2006.

18. Companion Animal Parasite Council:Controlling Internal and External Parasites inDogs and Cats: 2005 CAPC Guidelines. Availableat www.capcvet.org; accessed April 2006.

HARTZ® COMPANION ANIMALSM • JUNE 2006 • VOL. 4, NO. 2 5

ASK THE VETQA

Additional newsletters may be obtained by contacting us at [email protected] or by phone at 800-275-1414.

Albert Ahn, DVM, is Vice President of Corporate Communicationsand Consumer Relations at The Hartz Mountain Corporation.

WE WANT TO HEAR FROM YOU!• Have questions or comments? Call our Consumer Relations

Department at 800-275-1414 and ask to speak to a Hartzstaff veterinarian or email us at [email protected].

• To obtain a Hartz Veterinary Catalog of products, please call 800-275-1414 or email us [email protected].

Q

A

HARTZ® COMPANION ANIMALSM • JUNE 2006 • VOL. 4, NO. 2 7

QA

What type of insecticide does Hartz®

UltraGuard plus™ Drops for Cats contain?

Hartz® UltraGuard plus™ Drops for Cats is for use oncats and comes in two sizes; one for cats weighingup to 5 pounds and one for cats weighing 5 poundsand over. This product contains the active ingredientsetofenprox and (S)-methoprene.

Etofenprox is effective against fleas, ticks, andmosquitoes and is considered to be low in toxicity to mammals.

(S)-methoprene is a synthetic insect growthregulator or juvenile hormone mimetic and is further classified as a terpenoid. Juvenile hormonesmaintain the larval stage in the insect or preventmetamorphosis; when the level of juvenile hormonedrops, pupal and adult developmental stages begin.

What kind of safety profiles do etofenprox and (S)-methoprene have?

Etofenprox shares structural similarity with type I esterpyrethroids, but it has a unique ether composition,which gives it a much higher median lethal dose(LD50) (which is over 42,880 mg/kg in rats and over107,200 mg/kg in mice). The oral LD50 of etofenproxin dogs is more than 5,000 mg/kg.

Of the 17 pesticides approved for indoor fleacontrol, (S)-methoprene has the highest LD50 for oraland dermal doses in rabbits and rats. Because of theminimal absence of risk to humans, animals, or theenvironment, (S)-methoprene has been approved bythe World Health Organization for use in drinkingwater to control mosquitoes. In dogs, the acute oralLD50 is 5,000 to 10,000 mg/kg. (S)-Methoprene isnot irritating to the skin or eyes.

Q

A

A Hartz® representative visited mycollege last week and gave out samplesof this newsletter; could you tell me ifveterinary students are eligible forsubscriptions?

Yes, all students are welcome to sign up for freemembership for this newsletter and also for any otherHartz® publication. To do so, email your name andmailing address, along with the publication name, [email protected], or you can call 800-275-1414.

I went to the Hartz® booth at theWestern Veterinary Conference inFebruary and received a signed copy ofArden Moore’s Come, Sit, Stay. This bookis a fantastic addition to our waitingroom. I love this book and want to knowmore about the author.

Arden Moore held book signings for Hartz® at boththe 2005 and 2006 Western Veterinary Conferences.At this year’s convention, she signed more than 400copies of her two new books, Come, Sit, Stay and Tricksand Treats. Her words have inked the pages ofPrevention Magazine, Dog Fancy, Catnip, VeterinaryPractice News, and dozens of national and internationalpublications. Since 1999, she has written, co-authored,ghostwritten, and contributed to nearly 30 books onhuman health, dogs, cats, fitness, herbs, homeimprovements, and caregiving. To learn more aboutthis incredible writer, visit www.ardenmoore.com.

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