Practical Parasitology
The Flea-Infested Pet: Overview of Current Products

May/June 2017   •   (Volume 7, Number 3)

Cherie M. Pucheu-Haston, DVM, PhD, DACVD
Louisiana State University School of Veterinary Medicine

Dealing with flea-infested pets has never been easier—or more complicated. At this time, at least 20 active ingredients are commonly used in prescription flea control products in the United States, with numerous other ingredients appearing in various over-the-counter products. Despite this wealth of options, providing practical and effective suggestions for flea control to clients can still be a frustrating and overwhelming experience. This article provides an overview of some of the clinically relevant features of currently available flea control agents (Table 1). A subsequent article will discuss how to use client and patient information to help select an optimal treatment control program.

PYRETHRIN AND PYRETHROIDS

These are the oldest flea control products currently in common use. Both pyrethrin and pyrethroids work by disrupting insect nerve sodium channels.1 They are active against adult fleas but have no efficacy against immature stages. Pyrethrin is derived from the chrysanthemum plant.2 It is generally very safe when applied properly, even in young cats.1 Pyrethrin has a very quick “knock-down” effect but minimal residual activity. It is readily removed by water exposure. Pyrethrin products are often formulated to include a synergist, such as piperonyl butoxide. These synergists are typically well tolerated in dogs and cats when used at label doses. However, pyrethrins and many synergists may be highly toxic to other pet species, such as fish and amphibians.2,3

Pyrethroids are synthetic pyrethrins. Compared with pyrethrin, these products have a slightly slower onset of action but significantly better residual and repellent effects. Examples of this class include permethrin and cyphenothrin. Pyrethroids are often combined with other agents to take advantage of the pyrethroids’ repellent effects and efficacy against ticks. Examples of these products include K9 Advantix (bayerdvm.com), Certifect, Vectra 3D (vectrapet.com), and Activyl Tick Plus (us.activyl.com). As a general rule, pyrethroids have relatively poor resistance to water exposure.

Unfortunately, most pyrethroids are extremely toxic to cats.1 Notable exceptions include flumethrin and etofenprox, which appear to be well tolerated by most cats. Signs of pyrethroid intoxication include depression, coma, seizures, hypersalivation, muscle twitching or tremors, and hyperthermia. Severe or untreated intoxication may be fatal.4 Many cases of pyrethroid intoxication come from mistaken or intentional application of dog-only flea control formulations. However, a few cases of toxicity have been reported in cats that came into contact with treated dogs soon after application.5 For this reason, client education is critical when dispensing pyrethroid-containing products to households that include cats. Alternatively, these products may be avoided completely for dogs that live with cats or as environmental treatments in homes with cats.4

Resistance to pyrethrins and pyrethroids has been reported in both colonized flea strains and wild-caught fleas.6,7 Resistance may be associated with mutations in a gene coding for neural sodium channels.8 These mutations, which are commonly referred to as kdr (knockdown resistance) or super kdr mutations, are widely distributed throughout flea colonies and in field-collected fleas.9 As a result, the effectiveness of this class of compounds may be reduced in some areas, especially when they are not combined with other therapeutic agents.

NEONICOTINOIDS

This class of agents acts by binding to insect acetylcholine receptor sites.1 This induces inhibition of insect nervous system function, with subsequent paralysis and death.

Imidacloprid

This product has a rapid onset of action.10,11 It primarily targets adult fleas, and it is often combined with an insect growth regulator to provide efficacy against immature flea stages.1 Imidacloprid is available as a spot-on product, either by itself or in combination with permethrin (K9 Advantix), flumethrin (Seresto collar; seresto.com), or moxidectin (Advantage Multi; bayerdvm.com). Imidacloprid is generally very well tolerated by most individuals. Products containing imidacloprid alone (or imidacloprid/insect growth regulator alone) can be applied up to once weekly for aggressive flea control.1 In my experience, imidacloprid has poor water resistance and must be reapplied after bathing or water immersion. The imidacloprid/flumethrin collar appears to replenish the product on the pet, making this product better suited for patients that are bathed or swim regularly.12 However, this does shorten the expected lifespan of the collar. The efficacy of the collar is generally very good, which represents a substantial improvement over most older flea collars (typically containing organophosphates), which demonstrated low efficacy.13,14

Nitenpyram

This agent is available as a nonflavored oral tablet (Capstar). It has a very rapid onset of activity against adult fleas but a short duration of action (approximately 24 to 48 hours).1 Because of the speed of onset, it is well suited for rapid decontamination of animals before or after hospitalization or boarding or after trips to areas such as dog parks. The short duration of action makes it poorly suited for use as a primary flea control agent, but it can be used as often as daily if desired.1 For this reason, it is sometimes used daily for a short period to get a “head start” on flea depopulation in heavily contaminated environments. It has no larvicidal or ovicidal properties.1

Dinotefuran

This agent is primarily active against adult fleas.1 It is available in a spot-on formulation in combination with an insect growth regulator either with (Vectra 3D) or without (Vectra) permethrin. It is labeled for application once monthly. This agent has moderate to good resistance to water, although it is suggested that the pet not be bathed or allowed to swim for several hours after application.15 Nonetheless, it is probably not ideal for a dog that swims or is bathed very frequently.

Spinosad/Spinetoram

These two products are closely related. Spinosad is a naturally occurring mixture of spinosyns A and D, which are produced by Saccharopolyspora spinosa, a soil-dwelling actinomycete bacterium.16 It is available as a flavored (pork) tablet. It should be given with food.16 The same formulation (Comfortis; comfortis.com) is used in cats and dogs, although the feline version reflects the need for a higher dose per body weight than in dogs (50 mg/kg vs 30 mg/kg, respectively). It is labeled for once-monthly administration.

The major side effect in both species is vomiting, which can be treatment limiting in some individuals.16 Spinosad should be administered with caution (or avoided entirely) in dogs with preexisting seizure disorders because seizures have been associated with administration of this drug in these dogs.16 However, this effect has not been reported in cats. Spinosad should not be given with extralabel doses of ivermectin because coadministration has been associated with seizures, ataxia, twitching, and other neurologic signs.16

Spinetoram is a semisynthetic insecticide produced by chemical modification of the naturally occurring spinosyns J and L.17 It is labeled for use in cats only (Cheristin; cheristin4cats.com).18 It is provided as a spot-on formulation, which may be easier for some clients to administer than oral tablets. It is normally well tolerated, although it may be associated with vomiting in some cats. Application-site dermatitis has been reported, although this is less common than with the older formulation.18,19

ISOXAZOLINES

These products selectively inhibit insect gamma-aminobutyric acid (GABA)- and glutamate-gated chloride channels. This induces hyperexcitation and uncontrolled central nervous system activity, resulting in death of the insect.1 There are currently three agents in this category: afoxolaner, fluralaner, and sarolaner. Because the agents are very similar in many respects, they will be discussed together.

Afoxolaner (NexGard; nexgardfordogs.com), fluralaner (Bravecto; us.bravecto.com), and sarolaner (Simparica; simparica.com) are all available as flavored chewable oral tablets labeled for dogs only; fluralaner is also available in a topical formulation for both cats and dogs.20–22 Afoxolaner and sarolaner are given monthly, whereas fluralaner is given every 3 months.20–22 Because these tablets are flavored with food-based ingredients (soy or pork), they are not suitable for administration during food allergy elimination diet trials, and they may or may not be tolerated by food-allergic individuals. However, because of fluralaner’s extended duration of action, it may be given at the beginning of an elimination diet, with efficacy expected to continue through the 10- to 12-week duration of the trial.

Afoxolaner and sarolaner may be given with or without food, but the bioavailability of fluralaner is best when the agent is given with food.20

All 3 agents have very good efficacy against adult fleas and may also have clinically significant inhibition of flea reproduction. They are also efficacious against many species of ticks, including Ixodes scapularis, Dermacentor variabilis, Rhipicephalus sanguineus, and Amblyomma americanum.20–22 However, fluralaner must be given every 2 months for maximal efficacy against A americanum.20 Sarolaner also has efficacy against A maculatum.22

All of the agents appear to have very good efficacy against canine demodicosis.23–25 Evidence shows that they are also effective against Sarcoptes, although whether this is reliable enough to permit diagnostic therapy remains to be seen.26–28 Sarolaner has also been demonstrated to be efficacious against Otodectes species.25

Overall, the 3 agents are well tolerated, with vomiting being the most common adverse effect.20–22 Afoxolaner should be given with caution in animals with preexisting seizure disorders, as breakthrough seizures have been reported.21 Seizures, ataxia, and trembling have been reported with sarolaner and with topical (but not oral) fluralaner in dogs.20,22 Similar reactions have not been reported in cats with topical fluralaner.

The oral formulations of all agents are expected to be waterproof. Topical fluralaner is expected to be very water resistant after 3 days.20,*

MISCELLANEOUS ACTIVE INGREDIENTS

Selamectin

This agent is an avermectin, similar to ivermectin.1,29 It activates insect glutamate-gated chloride channels, which causes paralysis and eventual death of the fleas. It is marketed as a spot-on product for both cats and dogs. It is primarily used for its heartworm preventive and flea control properties but also has label claims against Otodectes, Dermacentor, and Sarcoptes species in dogs and Otodectes, Toxocara, and Ancylostoma species in cats.29 It inhibits development of immature flea stages.30 Unlike some other avermectins, selamectin can be administered to ivermectin-sensitive dogs (although salivation and ataxia have been reported with extralabel dose administration in these breeds).29 Selamectin is systemically absorbed and is essentially waterproof after 2 hours.

Fipronil

This agent belongs to the phenylpyrazole class.1 Like the isoxazolines, it acts by blocking GABA- and glutamate-gated chloride channels, causing hyperexcitation and death. It is available as both a spray and a spot-on. Fipronil is available in numerous formulations, many of which include other agents (such as permethrin or amitraz). It is labeled for once-monthly use. Fipronil kills adult fleas and is typically formulated with an insect growth regulator. Some reports suggest that this agent may be losing efficacy, at least against certain strains of fleas.31 Fipronil is somewhat water resistant but may not hold up if the patient requires frequent bathing or swims frequently.

Indoxacarb

This agent belongs to the oxadiazine pesticide class. It is considered a pro-insecticide because it requires activation by insect enzymes to become effective.1 Once activated, it blocks sodium channels, resulting in flea paralysis and death. Indoxacarb has good water resistance but may not be sufficient in patients that require very frequent bathing or swim frequently. Indoxacarb is available as a spot-on formulation, both on its own (Activyl) and with permethrin (Activyl Tick Plus). This product is normally well tolerated, but there have been anecdotal reports of seizures, neurologic signs, and occasional application-site dermatitis (of varying severity) in both cats and dogs.

Insect Growth/Development Regulators

Two classes of insect growth/development regulators have been registered for use as flea control products: juvenile hormone analogs (methoprene, pyriproxyfen) and chitin synthesis inhibitors (lufenuron).1 These agents have no adulticidal effects but prevent the development or maturation of immature flea stages. They are not well suited for use as sole flea control products but are commonly added to formulation of agents with adulticidal therapy to provide broad, multi–life stage control.

CONCLUSIONS

Today’s veterinary practitioner has more choices than ever before when it comes to flea control. Nonetheless, there is still no single product that is ideal for use under all circumstances. Effective formulation of a flea control program requires a thorough understanding of the available products and of the individual client and patient situation. In the next article, I will discuss key factors that will allow the practitioner to select the right product for the patient.

*Correction: The original version of this article incorrectly stated the time to water resistance of topical fluralaner as 3 hours. Updated 5/17/17.

References

  1. Plumb DC. Plumb’s Veterinary Drug Handbook. Stockholm, WI: PharmaVet, 2015.
  2. Covallis, OR: National Pesticide Information Center, 2014: 1-4.
  3. Piperonyl butoxide. Covallis, OR: National Pesticide Information Center, 2000: 1-4.
  4. Wisner T. Feline toxins: recognition, diagnosis, treatment. In: Little SE, ed. August’s Consultations in Feline Internal Medicine. St. Louis, MO: Elsevier; 2016:798.
  5. Malik R, Ward MP, Seavers A, et al. Permethrin spot-on intoxication of cats Literature review and survey of veterinary practitioners in Australia. J Feline Med Surg 2010;12(1):5-14.
  6. Bossard RL, Dryden MW, Broce AB. Insecticide susceptibilities of cat fleas (Siphonaptera: Pulicidae) from several regions of the United States. J Med Entomol 2002;39(5):742-746.
  7. Lemke LA, Koehler PG, Patterson RS. Susceptibility of the cat flea (Siphonaptera: Pulicidae) to pyrethroids. J Econ Entomol 1989;82(3):839-841.
  8. Bass C, Schroeder I, Turberg A, et al. Identification of mutations associated with pyrethroid resistance in the para-type sodium channel of the cat flea, Ctenocephalides felis. Insect Biochem Mol Biol 2004;34:1305-1313.
  9. Rust MK, Vetter R, Denholm I, et al. Susceptibility of adult cat fleas (Siphonaptera: Pulicidae) to insecticides and status of insecticide resistance mutations at the Rdl and knockdown resistance loci. Parasitol Res 2015;114(1):7-18.
  10. Vo DT, Hsu WH, Abu-Basha EA, Martin RJ. Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals. J Vet Pharmacol Ther 2010;33(4):315-322.
  11. Arther RG, Cunningham J, Dorn H, et al. Efficacy of imidacloprid for removal and control of fleas (Ctenocephalides felis) on dogs. Am J Vet Res 1997;58(8):848-850.
  12. Stanneck D, Kruedewagen, EM, Fourie JJ, et al. Efficacy of an imidacloprid/flumethrin collar against fleas, ticks, mites and lice on dogs. Parasit Vectors 2012;5(1):102-108.
  13. Dryden MW, Smith V, Davis WL, et al. Evaluation and comparison of a flumethrin-imidacloprid collar and repeated monthly treatments of fipronil/(s)-methoprene to control flea, Ctenocephalides f. felis, infestations on cats for eight months. Parasit Vectors 2016;9(1):287.
  14. Dantas-Torres F, Capelli G, Giannelli A, et al. Efficacy of an imidacloprid/flumethrin collar against fleas, ticks and tick-borne pathogens in dogs. Parasit Vectors 2013;6(1):245.
  15. Vectra 3D product label. Lenexa, KS: Ceva Animal Health; 2013.
  16. Comfortis prescribing information. Indianapolis, IN: Elanco Animal Health; 2014.
  17. Sparks TC, Crouse GD, Dripps JE, et al. Neural network-based QSAR and insecticide discovery: spinetoram. J Comput Aided Mol Des 2008;22(6):393-401.
  18. Cheristin product label. Indianapolis, IN: Elanco Animal Health, 2014.
  19. Credille KM, Thompson LA, Young LM, et al. Evaluation of hair loss in cats occurring after treatment with a topical flea control product. Vet Dermatol 2013;24(6):602-605.
  20. Bravecto prescribing information. Madison, NJ: Merck Animal Health; 2016.
  21. NexGard prescribing information. Duluth, GA: Merial, Inc; 2015.
  22. Simparica prescribing information. Kalamazoo, MI: Zoetis, Inc; 2015.
  23. Beugnet F, Halos L, Larsen D, de Vos C. Efficacy of oral afoxolaner for the treatment of canine generalised demodicosis. Parasite 2016;23:14-21.
  24. Fourie JJ, Liebenberg JE, Horak IG, et al. Efficacy of orally administered fluralaner (BravectoTM) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs. Parasite Vectors 2015;8(1):187-193.
  25. Six RH, Becskei C, Mazaleski MM, et al. Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex and Otodectes cynotis. Vet Parasitol 2016;222:62-66.
  26. Beugnet F, de Vos C, Liebenberg J, et al. Efficacy of afoxolaner in a clinical field study in dogs naturally infested with Sarcoptes scabiei. Parasite 2016;23:26-37.
  27. Taenzler J, Liebenberg J, Roepke RKA, et al. Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs. Parasite Vectors 2016;9(1):392-396.
  28. Becskei C, De Bock F, Illambas J, et al. Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica), for the treatment of sarcoptic mange in dogs. Vet Parasitol 2016;222:56-61.
  29. Revolution prescribing information. Kalamazoo, MI: Zoetis, Inc., 2014.
  30. McTier TL, Shanks DJ, Jernigan AD, et al. Evaluation of the effects of selamectin against adult and immature stages of fleas (Ctenocephalides felis felis) on dogs and cats. Vet Parasitol 2000;91(3–4):201-212.
  31. Dryden MW, Payne PA, Smith V, et al. Evaluation of indoxacarb and fipronil (s)-methoprene topical spot-on formulations to control flea populations in naturally infested dogs and cats in private residences in Tampa FL. USA. Parasites Vectors 2013;6(1):366-372.

Cherie Pucheu-Haston, DVM, PhD, is an associate professor of veterinary dermatology and immunology at Louisiana State University School of Veterinary Medicine. She received her DVM from Louisiana State University and completed her residency at North Carolina State University (NCSU). She worked as a specialist in private practice for 7 years, then returned to NCSU to pursue a PhD in immunology. She is serving as the American co-chair of the International Committee on Allergic Diseases in Animals. Her interests include the immunology of allergic skin and pulmonary diseases, as well as the immune response to fungal infections.

 

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