Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

Lufenuron
Lufenuron (Program®) is a chitin synthase inhibitor of the
benzoylphenyl urea class.
From: Small Animal Clinical Pharmacology (Second Edition), ����

Related terms:

Dermatitis, Lymphocyte, Sarcoma, Cat, Dog, Felid, Pig, Sheep, Ruminant, Canine

Lufenuron
Mark G. Papich DVM, MS, DACVCP, in
Saunders Handbook of Veterinary Drugs (Fourth Edition), ����

Indications and clinical uses

Lufenuron is used to control flea infestations by preventing hatching of
eggs. It has been used as part of flea control, often with other drugs that
kill adult fleas. Lufenuron has been combined with milbemycin in
formulations for small animals, and additional details may be found in the
section on milbemycin. There are clinical reports of the use of lufenuron
for treating dermatophyte infections in small animals—particularly cats—
at high doses of 80-100 mg/kg orally. However, endorsement of this use
has diminished, and dermatologists have disputed the efficacy and have
observed a high incidence of recurrence. In horses, lufenuron was not
absorbed orally and is not effective for treating fungal infections. It does
not have any in vitro effect on Aspergillus fumigatus or Coccidioides
immitis.

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B�������������������

Lufenuron
Mark G. Papich DVM, MS, DACVCP, in
Papich Handbook of Veterinary Drugs (Fifth Edition), ����

Indications and Clinical Uses

Lufenuron is used to control flea infestations by preventing hatching of
eggs. It has been used as part of flea control, often with other drugs that
kill adult fleas. Lufenuron has been combined with milbemycin in
formulations for small animals, and additional details may be found in the
section on milbemycin.

There are isolated clinical reports of the use of lufenuron for treating

1 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

dermatophyte infections in small animals, particularly cats, at high

dosages of 80–100 mg/kg PO. However, endorsement of this use has
diminished, and dermatologists have observed a high incidence of
recurrence and disputed the reports of efficacy. In horses, lufenuron was
not absorbed orally and is not effective for treating fungal infections. It
does not have any in vitro effect on Aspergillus fumigatus or Coccidioides
immitis.

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B�������������������

PARASITICIDES IN DERMATOLOGY
Robert Kennis DVM, DACVD, in Small Animal Dermatology Secrets,
����

7. How is lufenuron different from other IGRs?

Lufenuron is classified as an insect development inhibitor (IDI).
Lufenuron's mechanism of action is interference with chitin synthesis,
polymerization, and deposition. It is administered orally with food or may
be injected into cats. Lufenuron is taken up by the female flea as she
consumes a blood meal. The lufenuron disrupts the ability of the larva to
emerge from the egg, thereby halting reproduction. Lufenuron is excreted
unchanged in the flea feces. If a larva consumes the feces with lufenuron,
it prevents a normal pupa from developing. Ultimately, the net effect is
environmental control. Lufenuron must be given orally monthly or
injected every 6 months in cats to be effective. Also, the flea must feed for
lufenuron to work. Other IGRs can be applied to the pet or to the
environment and will work without the flea feeding first.

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B�������������������

Recent Research on Dermatophytosis*

Karen A. Moriello, Douglas J. DeBoer, in
Consultations in Feline Internal Medicine (Fifth Edition), ����

Lufenuron
Lufenuron is a benzoylphenylurea drug that disrupts chitin synthesis and
is used for flea control. Chitin is a critical component of the outer cell wall
of fungi, and drugs that disrupt chitin synthesis also may have antifungal
activity. In 2000, a retrospective study suggested lufenuron treatment was
associated strongly with recovery in a large number of dogs and cats with
a variety of fungal infections, including dermatophyte infections.30

Since that report, the use of lufenuron has been a widely debated topic in
the lay and veterinary literature and has been the focus of numerous
anecdotal and published reports.15,31-33 Two reports exist of controlled
blinded studies that evaluate the efficacy of lufenuron to prevent or alter

2 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

the course of experimentally induced M. canis infections in cats.32,33 Two

oral doses (30 or 133 mg/kg) of lufenuron were evaluated; after 2 months
of pretreatment, the kittens were challenged with infective M. canis
spores. In this study, neither dose of lufenuron prevented infection nor
altered the course of infection; however, the challenge was markedly
larger than what would occur under field exposure.33

In a follow-up study, two groups of cats were pretreated with either oral
or injectable lufenuron before exposure to a subclinically infected cat.32
Cats received four doses of lufenuron at monthly intervals (100 to 133 mg/
kg PO or 40 mg SQ) before exposure to the infected cat, and monthly
treatments thereafter for an additional 5 months. In this study, lufenuron
did not prevent infection in either treatment group. In addition, infections
in the control and two treatment groups resolved at about the same time.
What was noticed in this study was that infections were established more
slowly in the lufenuron-treated groups when compared with the control
group. In a clinical field study involving 100 cats in two catteries with
naturally occurring dermatophytosis, cats were divided randomly into
two treatment groups.15 Both groups were treated topically with
enilconazole once weekly, but one group received griseofulvin (25 mg/kg
PO q24h) and the other lufenuron (60 mg/kg). Although the investigators
reported a decrease in fungal culture counts over 90 days and resolution
of clinical signs, cures were not reported.15 At this time, we do not
recommend lufenuron for the treatment or prevention of dermatophytosis.

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B����������������

Antiparasitic drugs
Randy C. Lynn, Robert A. Duquette, in
Georgis' Parasitology for Veterinarians (Eleventh Edition), ����

Lufenuron.
Lufenuron is an IGR or insect development inhibitor that works by
inhibiting chitin biosynthesis (Fig. 6.1) (Insecticide Resistance Action
Committee [IRAC], 2017). Lufenuron is available in an injectable
formulation (Program 6-Month Injectable for Cats) that is designed to
allow application every 6 months for control of fleas. Adverse reactions
after injection include pain on injection, injection site lumps/granulomas,
vomiting, listlessness, lethargy, and anorexia. The drug is highly lipophilic,
resides in the fat tissues of the pet, and redistributes into the
bloodstream. Adult fleas ingest lufenuron when they feed, and the drug is
passed transovarially to the flea egg. Most flea eggs exposed to lufenuron
fail to hatch, and the few flea larvae that do hatch die during their first
molt. The action on the immature flea is thought to be owing to
disruption of chitin synthesis and deposition. Lufenuron is a convenient
and effective agent for flea control in pets. It is known to be safe in pets of
all ages, as well as in breeding dogs and cats.

3 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

Concurrent use of lufenuron and nitenpyram was discussed in the

Nitenpyram section. Lufenuron is also available in combination with
milbemycin oxime (Sentinel Flavor Tabs), as well as with milbemycin
oxime and praziquantel (Sentinel Spectrum) for control of fleas and
internal parasites in dogs; see the combination products in the
Anthelmintics section of this chapter for more information (pg 331 and
332).

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B�������������������

Arthropods
Dwight D. Bowman MS, PhD, in
Georgis' Parasitology for Veterinarians (Eleventh Edition), ����

Treatment of infestations with Ctenocephalides.

Dogs and cats have enjoyed the possibility of living a flea-free existence
for the past 25 years since the 1994 launch of lufenuron as a direct-to-pet
flea product with remarkable efficacy. The current pharmacopeia for flea
control contains some molecules that have been developed as FDA-
approved products that are internalized by the pet or molecules in EPA-
approved products that are topically distributed on the surface of the pet
(see Chapter 6). Veterinarians and the public have come to expect these
products to work very well, so the bar has been set very high, and the
products do deliver.

Things changed again in 2014 when the first of two new FDA-approved
products of the isoxazoline class entered the market and were soon
followed by two more, providing four excellent new compounds for flea
control, that is, products containing afoxolaner, fluralaner, lotilaner, and
sarolaner. These products are formulated to be applied orally or topically
and have been developed now for both dogs and cats. After
administration, whether absorbed from the gastrointestinal tract or
through the skin, the products are distributed throughout the body and
kill arthropods, insects, and acarids that bite and take in blood. They work
mainly on the chloride channels that are gamma-aminobutyric acid
(GABA)-gated and a lesser extent glutamate-gated with a GABA-channel
target. These products are marvelous in their ability to kill fleas, sucking
lice, bugs, some diptera, ticks, and mites. For fleas, all four of the products
have great killing power, and can rapidly halt the flea cycle in a home
environment.

Other FDA-approved products for flea control include the drugs

lufenuron, nitenpyram, spinosad, and selamectin; the first three products
are administered orally, and the last, selamectin, is applied topically but
enters the bloodstream transdermally. All four products have been
approved for cats. Lufenuron, with no adulticide action, works by
inhibiting chitin synthesis and when a flea feeds on a treated dog or cat,
the drug makes its way into the flea and then into the larvae, which then

4 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

will fail to develop. This product persists in the body of the animal and is
used as a monthly flea preventive or as an injectable 6-month
formulation for cats. In treating dogs, lufenuron has been combined with
milbemycin oxime to provide flea control along with heartworm
prevention and treatment and control of internal nematode infections.
Nitenpyram is a neonicotinoid insecticide that undergoes rapid oral
absorption and rapidly spreads throughout the body of the dog and cat
after ingestion; it is known for its very rapid knock-down. Nitenpyram is
designed to be given daily as needed to kill adult fleas, and it is approved
to be used in conjunction with lufenuron for flea control within a given
environment. Spinosad kills adult fleas through activation of the nicotinic
acetylcholine receptors of the flea at a distinct binding site. Spinosad has
been formulated to kill adult fleas for a full month after oral treatment,
and for dogs, it has been combined with milbemycin oxime, when it
functions as a month-long flea adulticide along with the heartworm
prevention and internal parasite treatment and control provided by
milbemycin oxime. Selamectin is a specially formulated macrocyclic
lactone that is administered to animals for heartworm prevention and
flea control. This formulation of a macrocyclic lactone is absorbed and
then is redeposited in the dermal layer; it persists in the skin of the
animal for an extended period to provide flea control.

Products approved by the EPA for use on dogs and cats for flea control are
fipronil, imidacloprid, dinotefuran, flumethrin, indoxacarb, pyriproxyfen,
and methoprene; the products cyphenothrin and deltamethrin are for use
on dogs only. These EPA-approved products are not internalized by the
animal. Fipronil, active at the GABA-gated chloride channel, kills adult
fleas through contact and ingestion and has been formulated into topical
products that provide flea control for a full month. Imidacloprid binds to
the nicotinic acetylcholine receptor sites and appears in another set of
topical products designed for monthly application. Dinotefuran, another
neonicotinoid insecticide, has also been formulated for topical monthly
protection. These compounds are sometimes combined with an insect
growth regulator—methoprene or pyriproxyfen. These combination
products then kill adult fleas and have deleterious effects on the larvae
developing in the eggs and on developing larvae that do hatch. Fipronil
also has activity against ticks, and because imidacloprid and dinotefuran
do not, they have been mixed with permethrin products to provide tick
control for dogs. Fipronil has also been mixed with amitraz or
cyphenothrin to increase its activity against ticks. Two long-acting collars
are also available in the United States: one lasts 8 months and contains a
mixture of imidacloprid for flea prevention and flumethrin, a second-
generation pyrethroid, for tick control on dogs and cats; the other collar
for dogs contains a fourth-generation pyrethroid, deltamethrin, and
provides 6 months of protection against both fleas and ticks. Imidacloprid
has also been combined with topically applied and absorbed moxidectin
in a product that is designed for monthly application to dogs and cats for
flea prevention, heartworm prevention, and treatment and control of
various intestinal parasites. Indoxacarb is a proinsecticide that is rapidly

5 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

metabolized to an active moiety in the flea; it is available as a stand-alone

product for flea control on cats and is combined with permethrin to
control fleas and ticks on dogs.

Environmental manipulation remains a major aid in controlling fleas, and

it does not necessarily require chemicals. A vacuum cleaner will markedly
reduce the numbers of eggs, larvae, pupae, and unfed adult fleas in an
environment (make certain to close and dispose of the bag after
vacuuming to prevent the fleas from escaping). Control efforts should
concentrate on places where the dog or cat habitually rests because this is
where eggs and flea feces, the provender of larvae, are most likely to be
deposited, and the development of adult fleas is likely to follow. If cage-
confined animals are kept in wire-bottom cages elevated at least 13
inches (33 cm) above the ground or floor, any fleas that develop
underneath the cage will not be able to jump high enough to get back
onto a host (Rothschild et al, 1973). This method has been used
successfully in a commercial beagle breeding establishment housing
several thousand dogs. Application of this latter environmental control
method is clearly limited to strictly confined animals.

Although the excellent products listed earlier often can bring heavy flea
infestations under control, it will sometimes be necessary to treat the
environment with insecticides or other mechanical methods. Steam
cleaning may be necessary, and it can sometimes help in larger areas. It
may be necessary to clean an area and remove all rugs, blankets, sand, or
sawdust where animals may have been resting. When in the outdoors,
treatment should concentrate in areas that are shaded and out of direct
sunlight. Yards and other buildings may be sprayed with cyfluthrin or
fenvalerate pyrethroids, but treatments need to be applied as per label
instructions.

Other available methods for the control of fleas differ widely in their
apparent effects on flea populations under various conditions. Several
traps are commercially available for the capture of adult fleas. Some of
these traps collect more than 85% of released fleas, whereas others collect
only slightly more than 10% (Dryden and Broce, 1993). Brewer’s yeast
failed as a repellent to fleas on dogs when fed as a dietary supplement at
the rate of 14 g/day (Baker and Farver, 1983). Ultrasonic flea collars also
do not repel fleas from dogs, at least under certain laboratory conditions
(Dryden et al, 1989).

It is important to remember that all insecticides are toxicants, and they

are safety tested only for certain animals. Thus fipronil, which is very,
very safe for dogs and cats, has been found to cause severe toxic reactions
in rabbits treated for flea control. It is actually against the law to apply
EPA-approved products except as stated on the label.

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B�������������������

Antiparasitic Drugs

6 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

Lindsay A. Starkey, Byron L. Blagburn, in

Greene's Infectious Diseases of the Dog and Cat (Fifth Edition), ����

Milbemycin Oxime
Milbemycin oxime is approved as a monthly oral tablet for dogs and cats.
This drug is also available in combination with other active ingredients,
lufenuron with or without praziquantel or spinosad, which can extend the
labeled indications to include flea immature stages +/- tapeworms or
adult fleas, respectively.1,15 Milbemycin oxime at a minimum target dose
of 0.5 mg/kg PO in dogs and 2 mg/kg PO in cats is indicated for the
prevention of heartworm disease, treatment of Ancylostoma spp. and
Toxocara spp. infections in dogs and cats, and T. leonina and T. vulpis
infection in dogs.1 Milbemycin oxime is safe for use in pregnant
animals1,15 and the oral formulation has been used extra-label for the
treatment of B. procyonis, C. vulpis, Demodex spp., D. immitis microfilaria,
Eucoleus spp., and Spirocerca lupi.2,5,8,9 Outside the United States,
milbemycin oxime has been combined with afoxolaner as a monthly
broad-spectrum parasite control product.35

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B�������������������

Flea Allergy Dermatitis

Craig E. Griffin, in
Saunders Manual of Small Animal Practice (Third Edition), ����

Treatment of Unaffected Pets

Treat unaffected animals in the same environment with adulticidal and/or
insect development inhibitor flea products that lack flea repellent effects.

• Regular use of the topical adulticides fipronil or imidacloprid or of

lufenuron helps prevent unaffected animals from contributing to
reintroduction of fleas into the home environment. Combination
products or combining IGR products will improve environmental
control of population levels and is an integrated pest control strategy.

• In cases in which topical treatments are not wanted by owners or pets

react, systemic products such as lufenuron or collars may be helpful.

• Use an approved flea collar with at least an IGR on cats that cannot be
treated with topical spot applications, dips, sprays, or foams.

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B����������������

Aspergillosis
Catherine Kohn, in Equine Infectious Diseases, ����

Chitin Synthesis Inhibitors

These newer antifungal drugs inhibit the synthesis of chitin, an important

7 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

component of the cell wall of many fungi but not of mammals. Chitin
synthase inhibitors have a narrow spectrum of antifungal action.116

Lufenuron, a nonspecific chitin synthase inhibitor, was administered by

the intrauterine route at a dose of 540 mg in 60 mL of sterile water in four
mares with mycotic endometritis.64 Based on empiric observations, the
authors concluded that lufenuron contributed to the recovery of these
mares. In contrast, lufenuron had no effect on the in vitro growth of
Aspergillus and Fusarium spp. isolated from the corneas of horses with
keratomycosis.117 In the same study, 21 healthy adult horses were given
lufenuron orally at dosages of 5 mg/kg q24h for 3 days, 20 mg/kg q24h for
3 days, or 60 mg/kg q24h for 1 day. Blood concentrations of lufenuron
were lower than the ineffective concentrations achieved in vitro.
Lufenuron was detected in blood samples from 20 of 21 horses. Currently,
minimal data support the efficacy of lufenuron in the treatment of fungal
diseases in horses.

Nikkomycin Z is a competitive inhibitor of chitin synthase. In experimental

models of fungal infection, this drug has poor antifungal activity against
many opportunistic fungi, including Aspergillus fumigatus.112 In vitro,
nikkomycin Z is synergistic with ITRA against Aspergillus flavus and A.
fumigatus.84,118 This drug has not been evaluated for use in horses.

Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/B�������������������

Systemic Mycoses
Robert G. Sherding, in
Saunders Manual of Small Animal Practice (Third Edition), ����

Chitin and Glucan Inhibitors

These drugs inhibit the synthesis of either chitin or beta-glucan, two
structural components of the cell walls of fungi that are not found in
mammalian cells.

• Chitin inhibitors such as the nikkomycins and lufenuron have a limited

spectrum, but they have been of interest for treatment of
coccidioidomycosis. However, Lufenuron (Program, Novartis), a chitin
synthesis inhibitor licensed for monthly flea control in dogs and cats,
has not been an effective antifungal agent for Coccidioides and other
systemic mycoses despite initial anecdotal reports of its use in dogs.

• Beta-glucan inhibitors include echinocandins and pneumocandins, for

example, caspofungin (Cancidas, Merck), micafungin, and
anidulafungin. These are potent broad-spectrum antifungal drugs
with activity against Aspergillus, Candida, and Pneumocystis carinii.
These agents are very costly and considered investigational only at
this time. Future indications for use of these drugs in dogs and cats
will need to be determined.

Read full chapter

8 of 9 06-04-2024, 16:55
Lufenuron - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/veterinary-science-and-veterin...

URL: https://www.sciencedirect.com/science/article/pii/B���������������X

Recommended publications

Veterinary Clinics of North America: Small

Animal Practice
Journal

Saunders Handbook of Veterinary Drugs

(Fourth Edition)
Book • ����

Clinical Veterinary Advisor: Birds and Exotic

Pets
Book • ����

Veterinary Clinics of North America: Exotic

Animal Practice
Journal

All content on this site: Copyright © ���� Elsevier B.V., its licensors, and contributors. All rights are
reserved, including those for text and data mining, AI training, and similar technologies. For all open
access content, the Creative Commons licensing terms apply.

9 of 9 06-04-2024, 16:55