Sign in to continue reading this article

Not registered? Create an account for free to read full articles on

To access full articles on, please sign in below.

Busy? Sign in Faster. Sign into with your social media account.

Sponsored by Virbac


Flea prevention and control has historically centered on topical or spot-on protocols, including these common products1

  • Fipronil 
    • Phenylpyrazole parasitic. 
    • GABA-gated chloride channel antagonist.
    • Prevents uptake of chloride ions leading to excessive neuronal stimulation and insect death.
  • Methoprene
    • Insect growth regulator (IGR).
    • Mimics insect juvenile growth hormone.
    • Concentrates in flea ovaries leading to non-viable eggs.
  • Selamectin 
    • Avermectin antiparasitic. 
    • GABA-agonist. 
    • Binds to glutamate-gated chloride channels in muscle and nerve cells of invertebrates. 
    • Causes paralysis leading to death. 
  • Imidacloprid 
    • Binds to postsynaptic nicotinic acetylcholine receptors.
    • Results in the inhibition of cholinergic transmission. 
    • Paralyzes insect leading to death.
  • Dinotefuran 
    • Similar mechanism of action to imidacloprid.
    • Binds to postsynaptic nicotinic acetylcholine receptors.
    • Paralyzes insect leading to death.

Although these products can be effective when used properly, owner reluctance or inability to comply remain common realities that most general practitioners must address. Owner reluctance may stem from their concerns regarding use of topical products and potential exposure to others in the household or the pet’s resistance to the application process. Concerns that the products may become ineffective when the animal is bathed or swims are likely unfounded.  

These issues, paired with owner desire for enhanced convenience, have fueled a growing trend toward oral flea control options. 

New Options for Historic Problems 

In the mid 1990’s, lufenuron, an oral flea control product, became commercially available and revolutionized treatment of flea infestations, as the prior approach involved sprays and foggers. Shortly thereafter, milbemycin oxime with lufenuron (SENTINEL® FLAVOR TABS ®) was originally approved by the FDA,2 and label indications include:

  • Prevention of heartworm disease caused by Dirofilaria immitis
  • Prevention and control of flea populations.
  • Control of adult hookworms (Ancylostoma caninum).
  • Removal and control of roundworms (Toxocara canins, Toxascaris leonina) and whipworms (Trichuris vulpis).

Responsible for flea control in these products is lufenuron, a chitin synthesis inhibitor that not only prevents eggs from hatching, but also can prevent the maggot-like larvae from developing.* 

Another oral flea control product, spinosad, is a macrocyclic lactone with activity at the nicotinic acetylcholine receptors causing involuntary muscle contractions, paralysis and death of fleas.

Within the past 5 years, there have been several new entrants into the flea control market, including fluralaner, afoxolaner, and sarolaner. These new products are isoxazoline acaricides, which inhibit GABA and glutamate-receptors at the neuromuscular junction of insects, and acarines, causing uncontrolled neuromuscular activity leading to the death of the organism. These drugs have specific efficacy against adult fleas.

Flea Life Cycle: Key Points3

  • Adult fleas comprise 5% of the total flea population
  • An adult flea can lay thousands of eggs in a lifetime
    • Eggs represent approximately 50% of the total flea population
  • Flea larvae migrate away from light, into carpet and cracks in flooring 
    • Persistent in the environment
    • Represent approximately 35% of flea population 
  • Development of pupae highly environmentally dependent
    • Warm, humid conditions foster development
    • Cool, dry conditions hinder development 
  • Once adult fleas emerge, feeding begins within a few hours
    • Mating and egg-laying occurs within 24 hours

Time to Update Flea Control Protocols

The traditional approach to flea prevention and control has been to use just one product. As topical flea control products become increasingly replaced by oral products, however, a key component of flea control protocol has fallen by the wayside: the IGR. Whereas the use of a single product can work if the product is administered consistently and correctly, the newer oral flea control products are missing IGRs, thus missing the opportunity to eliminate fleas at more than one point in the life cycle. Replacing the IGR back into these newer protocols may offer a greater likelihood of complete flea control. Not only will patients be healthier, it should result in greater client satisfaction.

Addressing the individualized needs of a patient and owner are paramount when choosing a protocol. A potential multiple oral drug protocol might look like this*: 

  • Milbemycin oxime + lufenuron
    • Monthly heartworm prevention
    • IGR-based flea control
  • Isoxazoline acaricide 
    • Monthly or every 3 months (depending on product used)
    • Flea and tick adulticide 

Depending on clinician and owner preferences, other combination protocols can be used. It is important to remember that although these products have well-established safety profiles, there are no studies documenting the safety of the concurrent use of these products. 

Essential Aspects of Environmental Management

  • Vacuuming of carpets and baseboards 
  • Hot water washing of bedding and other fabrics
  • Sanitation 
  • Rodent control
  • Environmental insecticides (if warranted)

In Summary

Varying mechanisms of action between products can be used in combination by clinicians to eliminate fleas at multiple points in the insect’s life cycle; with an ideal protocol including both an adulticide and an IGR.  When combined with appropriate environmental management, flea prevention and control can be optimized.

*Important Safety Information for SENTINEL FLAVOR TABS: Dogs should be tested for heartworm prior to use. In a small percentage of treated dogs, digestive, neurologic, and skin side effects may occur. Click here for complete product information. For technical questions, please contact Veterinary Technical Product Support at 1-800-338-3659, or visit

*Important Safety Information for SENTINEL® SPECTRUM® (milbemycin oxime/lufenuron/praziquantel): Dogs should be tested for heartworm prior to use. Mild hypersensitivity reactions have been noted in some dogs carrying a high number of circulating microfilariae. Treatment with fewer than 6 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention. Click here for complete product information. For technical questions, please contact Veterinary Technical Product Support at 1-800-338-3659, or visit

SENTINEL® and FLAVOR TABS® are registered trademarks of Virbac Corporation.

References Show
  1. Plumb’s Veterinary Drugs. Accessed Apr 19, 2017.
  2. NADA 141-084 SENTINEL® FLAVOR TABS® Tablets Label. Accessed Apr 19, 2017. 
  3. Biology, treatment, and control of flea and tick infestations. Blagburn BL, Dryden MW. Vet Clin North Am Small Anim Pract. 39:1173-1200, 2009.

Suggested Reading

  • Greene CE, Weese JS, Caplin JP. Environment factors in infectious disease. in Greene, CE: Infectious Disease of the Dog and Cat. Fourth edition. St. Louis, MO: Elsevier Saunders, 2012: 1097-1100. 
  • Companion Animal Parasite Council. 4/22/17

Material from Clinician’s Brief may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.

Up Next