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Imidacloprid for Removal and Control of Fleas on Dogs

Imidacloprid chews, topical solutions, and collars have been shown to treat flea infestations in dogs.

Emily SorahPharmD, RPh, DICVP, FSVHP, FACVP

Dr. Sorah received her Doctor of Pharmacy degree from East Tennessee State University Bill Gatton College of Pharmacy in 2014. She then completed the clinical veterinary pharmacy residency program at NC State College of Veterinary Medicine before accepting a staff pharmacist position. Dr. Sorah now serves as Director of Clinical Pharmacy Services at NC State College of Veterinary Medicine. She also serves as an adjunct professor, teaching veterinary pharmacology at Campbell University School of Pharmacy and UNC Eshelman School of Pharmacy.

Marissa Allinder RPh, PharmD, FSVHP

Dr. Allinder received her Doctor of Pharmacy degree from the Medical University of South Carolina College of Pharmacy in 2020. She subsequently began a clinical veterinary pharmacy residency at the NC State College of Veterinary Medicine.

Bailey SlaterRPh, PharmD, FSVHP

Dr. Slater earned her Doctor of Pharmacy degree from the University of Kansas School of Pharmacy in 2020. She is currently completing a clinical veterinary pharmacy residency at the NC State College of Veterinary Medicine.

Imidacloprid for Removal and Control of Fleas on Dogs

Imidacloprid is a neonicotinoid insecticide, approved for use in the United States by the Environmental Protection Agency in 1994.1 It is available as a topical formulation and was approved by the Food and Drug Administration as an oral chewable formulation in 2015.2 Imidacloprid is indicated for the treatment of fleas (adult and larval stages) on dogs and cats; it is often combined with other therapies to treat intestinal parasites, repel ticks, and prevent heartworm infection (TABLE 1). Although several options are also available for cats, the focus of this article is imidacloprid efficacy for the control of fleas on dogs.


One study involving 32 dogs compared the kill speeds of nitenpyram, selamectin, imidacloprid, and fipronil.3 Each treatment group comprised 8 dogs, and each dog was experimentally infested with 100 fleas. Efficacy at 8 hours after treatment was 100% for nitenpyram, 95.7% for imidacloprid, 74.4% for selamectin, and 46.5% for fipronil.

Another study compared the efficacy of topical fipronil and imidacloprid when used on 23 dogs in flea-infested homes.4 Treatments were administered once monthly for 3 months, and flea counts were assessed for the animals and the residences. After treatments, flea counts on the animals were reduced by 99.5% (imidacloprid) and 96.5% (fipronil).


Imidacloprid acts on the nicotinic acetylcholine receptors at the postsynaptic membranes in the flea, blocking acetylcholine and eventually leading to central nervous system impairment and death. The mechanism of action of imidacloprid is unique, differing from that of other insecticides (e.g., organophosphates, insect growth regulators) in that insect receptors are more sensitive than mammalian receptors to imidacloprid.5 This property was originally thought to make imidacloprid more advantageous than other commonly used agricultural insecticides on the market at the time, thereby limiting toxicity and negative effects on other organisms;6 however, we now know that this class of insecticides could have significant environmental effects.


When administered orally, imidacloprid is absorbed rapidly and nearly completely from the dog’s gastrointestinal tract and reaches effective concentration after about 1.3 hours.7 It is distributed throughout the tissues but does not accumulate in the tissues. Its penetration of the blood–brain barrier is poor, which leads to a more favorable safety profile. It is metabolized by the liver to an active metabolite and is eliminated in the urine (70% to 80%) and feces (20% to 30%); terminal half-life is about 2.2 hours.5

When applied topically to dogs, imidacloprid is distributed across the skin by translocation and can be found in hair follicles, shed hair, and sebum.7 In dogs, systemic absorption of topical preparations seems to be minimal to none.


For active flea infestations, initial treatment with imidacloprid may be oral or topical. However, its use as monotherapy does not completely prevent infection with other parasites (e.g., heartworms and intestinal parasites).3 Patients should be evaluated to ensure that they are receiving complete parasite prevention regimens with or without imidacloprid augmentation.

When topical formulations of imidacloprid are used, the veterinarian should consult individual product labels to be able to counsel clients on accurate restrictions, such as shampooing and water immersion, before and after application of these products (TABLE 2).


Adverse Effects of Imidacloprid

Topical administration of imidacloprid is generally considered to be well tolerated. However, adverse effects may include irritation of the skin at the application site and, in rare cases, pruritus, lethargy, reduced appetite, and hyperactivity.5

Oral administration of imidacloprid at labeled doses is also considered to be well tolerated. Reported adverse effects associated with oral administration include vomiting, decreased appetite, lethargy, diarrhea or soft feces, and difficulty walking. Imidacloprid has also been associated with gallbladder mucocele formation, specifically in Shetland sheepdogs.8 In 2015, Gookin et al. found that among Shetland sheepdogs, those with gallbladder mucoceles were 9.3 times more likely than controls to have reportedly received imidacloprid.

Contraindications for Imidacloprid

Use of imidacloprid is contraindicated in puppies younger than 7 weeks of age, dogs weighing less than 3 pounds, and kittens younger than 8 weeks of age. Pertinent clinical considerations should be made before use is recommended in animals that are debilitated, aged, pregnant, nursing, or receiving medication.9

Warnings for Imidacloprid

Clients should be mindful that permethrins can be toxic to cats. Combination products containing permethrins should not be used on cats, and caution should be taken with use of these products on dogs in households with cats to ensure that the cats are not exposed through grooming or rubbing.


According to the product label, the oral formulation of imidacloprid may be used concomitantly with other medications (i.e., corticosteroids and antibiotics).5,10 Because topically applied imidacloprid is not absorbed systemically, no significant drug–drug interactions have been associated with topical administration of imidacloprid.9

In some circumstances, it may be appropriate to treat dogs with more than one product to prevent fleas, ticks, heartworms, and intestinal parasites. Although duplicate therapy to provide full preventive coverage against fleas, ticks, and heartworms should be avoided, some products have been studied in combination and shown to be safe. One such study showed no dermal or systemic safety issues when imidacloprid topical solution was used along with an imidacloprid-containing collar.11 However, in the absence of other studies or evidence, use of products with the same active ingredient or mechanism of action should be avoided.


An often-overlooked aspect of parasite prevention is the effect that these insecticides can have on nontarget organisms, ecosystems, and the environment. Neonicotinoids such as imidacloprid can potentially enter the soil and water and negatively affect the environment. A particular concern expressed by the Environmental Protection Agency is that “imidacloprid is classified as very highly toxic to adult honeybees.”1   An association between agricultural use of neonicotinoid insecticides and honeybee failure and colony collapse has been documented.6 Residues have also been found in crop soil and in aquatic ecosystems, affecting their structure and function.6 Therefore, to minimize environmental risk when using these products for flea prevention and treatment, care should be taken to follow all directions on product labels.


Although imidacloprid is approved and indicated for the removal and control of fleas, it has often been used in an extra-label manner to treat other similar parasitic conditions.

Sarcoptic Mange

In a blinded, randomized controlled efficacy study, 29 dogs with Sarcoptes scabiei infestation received either an imidacloprid (10% w/v)/moxidectin (2.5% w/v) combination topically or selamectin topically.12 Dogs in each group received 2 treatments, 4 weeks apart. After day 22, no Sarcoptes mites were found on skin scrapings from any dogs in either treatment group. Clinical signs were nearly entirely resolved by 50 to 64 days after the initial treatment.


Another study evaluated efficacy of imidacloprid 10%/moxidectin 2.5% topical solution for treating cheyletiellosis (walking dandruff) in dogs.13 A total of 20 dogs with microscopy-confirmed cheyletiellosis received 2 treatments with the combination product, 4 weeks apart. On or after day 30 after the first treatment, clinical signs improved but mites were still visible; on or after day 60, no mites or eggs were detected.


In 2009, a blinded, randomized clinical trial compared efficacy of 2 products for treatment of demodicosis.14 A total of 50 dogs with demodicosis received either ivermectin daily or imidacloprid 10%/moxidectin 2.5% topical solution applied monthly, every 2 weeks, or weekly. Of the 50 dogs, 35 completed the trial through 4 months or 2 successive examinations with negative skin scrapings. The results showed that the imidacloprid combination product was not significantly more efficacious than ivermectin but that weekly application of imidacloprid was significantly more efficacious than monthly application. Newer agents, however, may prove to be more efficacious in the treatment of demodicosis when given at labeled dosing frequencies. In a recent (2019) study, 16 dogs with naturally acquired demodicosis were randomized to receive 1 treatment of topical fluralaner or 3 treatments of topical imidacloprid/moxidectin at 4-week intervals (or weekly for some with severe cases). Miticidal efficacy of fluralaner was 99.7% at day 28, >99.9% at day 56, and 100% at day 84, whereas efficacy of imidacloprid/moxidectin was 9.8% at day 28, 45.4% at day 56, and 0% at day 84.15


  • For immediate treatment of flea infestation, give imidacloprid soft chews once daily, as needed, based on weight. To prevent future infestations, use in conjunction with a preventive product.10
  • Apply topical solutions directly to the skin and allow them to dry thoroughly before the dog comes into contact with other pets or children. Dispose of packaging according to label recommendations.9
  • Imidacloprid collars provide up to 8 months of protection from fleas and ticks; however, consider replacing collars more frequently for dogs that are frequently immersed in water.9
  • Because permethrins are toxic to cats, avoid using permethrin-containing combination products in households with cats.
  • Although imidacloprid products are generally considered to be well-tolerated, they have the potential to exacerbate gallbladder mucocele formation in Shetland sheepdogs.8


  • Mechanism of action: Imidacloprid works as an insecticide by acting on nicotinic acetylcholine receptors at the postsynaptic membrane in the flea, blocking acetylcholine and eventually leading to central nervous system impairment and death.
  • Indication: Imidacloprid may be used for treatment of an active flea infestation; however, it should not be used as monotherapy for flea prevention.3
  • Adverse effects: Adverse effects of both topical and oral administration are usually mild and transient.
    • Topical administration has been associated with skin irritation at the application site and, more rarely, pruritus, lethargy, reduced appetite, and hyperactivity.
    • Oral administration has been associated with vomiting, decreased appetite, lethargy, and diarrhea/soft stools.
  • Contraindications and warnings: Use of imidacloprid is contraindicated for puppies younger than 7 weeks, dogs weighing less than 3 pounds, and kittens younger than 8 weeks. Clients should be aware that combination products containing permethrins are toxic for cats.
  • Environmental effects: The neonicotinoid class of insecticides has been associated with negative effects on nontarget organisms and ecosystems including honeybee colonies, soil of treated crops, and aquatic environments. Veterinarians should be prepared to address clients’ concerns about potential negative environmental impacts and the importance of following administration and disposal instructions per packaging.

1. US Environmental Protection Agency. Imidacloprid: proposed interim registration review decision. Case number 7605. epa.gov/sites/production/files/2020-01/documents/imidacloprid_pid_signed_1.22.2020.pdf. Accessed January 2020.

2. Food and Drug Administration Center for Veterinary Medicine. animaldrugsatfda.fda.gov/adafda/views/#/home/previewsearch/141-435. Accessed November 2020.

3. Schenker R, Tinembart O, Humbert-Droz E, et al. Comparative speed of kill between nitenpyram, fipronil, imidacloprid, selamectin and cythioate against adult Ctenocephalides felis (Bouché) on cats and dogs. Vet Parasitol 2003;112(3):249–254. doi: 10.1016/s0304-4017(02)00425-9

4. Dryden MW, Denenberg TM, Bunch S, et al. Control of fleas on naturally infested dogs and cats and in private residences with topical spot applications of fipronil or imidacloprid. Vet Parasitol 2000;93(1):69–75. doi: 10.1016/s0304-4017(00)00318-6

5. Plumb DC. Imidacloprid, systemic. plumbsveterinarydrugs.com/#!/monograph/c4yrPefM0v. Accessed July 2020.

6. Sánchez-Bayo F, Goka K, Hayasaka D. Contamination of the aquatic environment with neonicotinoids and its implication for ecosystems. Front Environ Sci 2016;4:71. doi: 10.3389/fenvs.2016.00071

7. Wismer T, Means C. Toxicology of newer insecticides in small animals. Vet Clin North Am Small Anim Pract 2012;42(2):335–347. doi.org/10.1016/j.cvsm.2011.12.004

8. Gookin JL, Correa MT, Peters A, et al. Association of gallbladder mucocele histologic diagnosis with selected drug use in dogs: a matched case-control study. J Vet Intern Med 2015;29(6):1464–1472.

9. Advantage [package insert]. Shawnee Mission, KS: Bayer; 2013. bayer.cvpservice.com/product/basic/view/1040066. Accessed July 2020.

10. Advantus [package insert]. Shawnee Mission, KS: Bayer; 2016. bayer.cvpservice.com/product/basic/view/1040184. Accessed July 2020.

11. Krüdewagen EM, Remer C, Deuster K, et al. Chemical compatibility and safety of imidacloprid/flumethrin collar (Seresto®) concomitantly used with imidacloprid/moxidectin (Advocate®, Advantage® Multi) and emodepside/praziquantel (Profender®) spot-on formulations. Parasitol Res 2015;114(Suppl 1):S55-S80. doi: 10.1007/s00436-015-4514-z

12. Fourie, LJ, Heine J, Horak IG, et al. The efficacy of an imidacloprid/moxidectin combination against naturally acquired Sarcoptes scabiei infestations on dogs. Aust Vet J 2006;84(1-2):17–21. doi: 10.1111/j.1751-0813.2006.tb13117.x

13. Loft KE, Willesen JL. Efficacy of imidacloprid 10 per cent/moxidectin 2.5 per cent spot-on in the treatment of cheyletiellosis in dogs. Vet Rec 2007;160(15):528–529. doi: 10.1136/vr.160.15.528

14. Paterson TE, Halliwell RE, Fields PJ, et al. Treatment of canine-generalized demodicosis: a blind, randomized clinical trial comparing the efficacy of Advocate® (Bayer Animal Health) with ivermectin. Vet Dermatol 2009;20(5-6):447–455. doi: 10.1111/j.1365-3164.2009.00803.x

15. Fourie J, Meyer L, Thomas E. Efficacy of topically administered fluralaner or imidacloprid/moxidectin on dogs with generalised demodicosis. Parasit Vectors 2019 25;12(1):59. doi:10.1186/s13071-