Veterinary Dermatology 2005, 16, 334 337

Blackwell Publishing, Ltd.

Brief communication

Efficacy of topical administration of eprinomectin for treatment of

ear mite infestation in six rabbits
BULENT ULUTAS*, HUSEYIN VOYVODA*, GOKSEL BAYRAMLI* and TULIN
KARAGENC
*Department of Internal Medicine, Faculty of Veterinary Medicine, University of Adnan Menderes, PK
17 09016, Aydin, Turkey
Department of Parasitology, Faculty of Veterinary Medicine, University of Adnan Menderes, PK 17 09016,
Aydin, Turkey
(Received 5 January 2005; accepted 31 May 2005)

Abstract Six rabbits naturally infested with Psoroptes cuniculi were treated topically on the skin at the base of
the neck with 0.5 mg kg1 of 0.5% pour-on eprinomectin for cattle, twice at 14-day intervals. Efficacy of the drug
was based on the disappearance of clinical signs and the absence of live mites for a period of 6 weeks. Clinical
improvement was seen within 3 days of the first application; however, complete recovery of clinical signs and
elimination of mites in 5/6 rabbits did not occur until the end of the study. No adverse reactions attributable to
eprinomectin treatment were observed during the observation period. Results of this trial indicated that
eprinomectin was partially effective in the treatment of psoroptic mange in rabbits.

Psoroptes cuniculi is a common worldwide parasite of

rabbits that causes infestation primarily in the ears.
Ear mange in rabbits caused by P. cuniculi mites is of
importance with respect to general animal health and
hygiene, and economic concerns. The infestation can
cause considerable weight loss, less favourable feed
conversion rates, vestibular dysfunction, and meningitis, which is frequently fatal when complicated by the
secondary bacterial pathogens. Heavy infestations in
laboratory rabbits may alter immune function, and
pruritus may produce behavioural changes that could
affect a variety of studies, including those dependent
upon adequate feed intake.1
Treatment of ear mange in rabbits is traditionally
achieved by using a number of different preparations
(pyrethroids, organophosphates, amitraz, flowers of
sulphur, benzyl benzoate solutions, and herbal preparations) that are applied on the pinna and/or canal of
the ear, and down the side of the head and neck as well.
A current trend in the treatment of ear mite infestations involves the use of systemically acting macrocyclic lactones that have long persistent action and are
easily administered. Topical administration of eprinomectin with a single dose of 0.5 mg kg1 was found
to be effective for treatment of infestations of Chorioptes bovis and Sarcoptes bovis in cattle.2 In another
study,3 topical administration of eprinomectin
0.5 mg kg1 led to a complete resolution of caprine
Correspondence: B. Ulutas, Adnan Menderes University, Faculty of
Veterinary Medicine, Department of Internal Medicine, PK 17 09016
Isikli/Aydin, Turkey. E-mail: bulutas@adu.edu.tr
334

demodectic mange. To the best of the authors knowledge, no publications are available on the efficacy of
topical administration of eprinomectin in rabbits with
ear mite infestations. When large numbers of animals
are involved the topical formulation of eprinomectin
may be a convenient and economical alternative. The
purpose of the study reported here was therefore to
evaluate the efficacy of topical eprinomectin administration at the standard cattle dose rate of 0.5 mg kg1 in
rabbits naturally infested with P. cuniculi.
Six New Zealand White rabbits of both sexes (two
females and four males) from the laboratory animal
unit, Adnan Menderes University, Turkey, were presented because of severe pruritus, and clinical findings
including light brown, thick, crustly, foul smelling
exudate within the external ear canal and pinnae
(Fig. 1a,b). Rabbits were between 2 and 4 years of age
and weighed between 3 and 3.6 kg. Clinical examination was consistent with psoroptic mange. Psoroptes
cuniculi infestation was confirmed by direct observation
of viable mites in all animals with the aid of an otoscope
and by microscopic examination of scab materials
from the ears under low power magnification (4).
On the day of presentation, all rabbits received a
physical examination. The severity of infestation in
each ear was scored semiquantitatively. Briefly, small
skin lesions, only identifiable with an otoscope, were
recorded with one cross; skin lesions involving 1/4 of
the auricle with two crosses; skin lesions involving 1/3
1/2 of the auricle with three crosses; and a completely
occluded auricle with crusts and puss with four crosses.
Rabbits were then hospitalized in separate cages differ 2005 European Society of Veterinary Dermatology

Eprinomectin for treatment of ear mange

335

Figure 1. Clinical aspects of the rabbit severely infested with Psoroptes cuniculi before and after eprinomectin treatment (rabbit no: 2). (a)
Clinical view of the ears before eprinomectin treatment. (b) Crust formation on the auricle. (c) Clinical view of the ears 14 days after the first
eprinomectin treatment. (d) Clinical view of the ears at the end of the study.

2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 334337

336

B. Ulutas et al.

ent from their original ones to avoid any skin or fur

contact throughout the study period, in an isolated
room with adequate heat and ventilation different from
the original housing. The domestic environment and
the equipment of the handlers were also treated with an
appropriate acaricidal spray (Duowin, Tum Ilac,
Istanbul, Turkey) to prevent a possible re-infestation
from these sources. Commercial rabbit pellet, alfalfa
and water were available ad libitum.
Two days after hospitalization, rabbits were given
eprinomectin 0.5%, weight/volume solution (Ivomec
Eprinex pour-on for cattle and deer, Merial, Manukau City, New Zealand) at the standard cattle dose
rate of 0.5 mg kg1.4 Because eprinomectin has not
been approved for use in rabbits, the department signed
a consent form to use this drug. Enrofloxacin 5%
(Baytril, Bayer, Istanbul, Turkey) was administrated to
treat or prevent bacterial pathogenic agents at a dose
rate of 15 mg kg1 subcutaneously once daily for the
first 7 days of treatment. A vitamin complex (Bavitsole
9, Bayer) was also administrated subcutaneously once
for the first day of treatment. On day 14, rabbits were
given a second dose of eprinomectin. Parting the hair
to expose the skin, eprinomectin was applied directly
with an automated pipette at the base of the neck, cranial to the scapulae, thereby eliminating any need to
manipulate the affected ears.
The general health of all rabbits was monitored
daily for a period of 6 weeks; detailed clinical observations were made approximately 4 and 24 h after each
eprinomectin application. At each weekly clinical
examination, debris of the external ear canal including
pinnae from both ears of each rabbit was examined
for the presence of live P. cuniculi, on the basis of
movement by an otoscope. The absence of mites on
direct /otoscopic examination of the ear canal was
confirmed by microscopic examination of aural debris
from each ear on each examination week. Beginning
on the first day of treatment, and each week thereafter,
the lesions in the ears of all animals were also scored
as detailed earlier.
On the day of presentation and prior to the first eprinomectin application, all rabbits had live P. cuniculi mites
and clinical signs consistent with P. cuniculi infestation: head shaking, pruritus/ear scratching, trauma or
alopecia of the pinnae, and erythema, ulceration, and
debris in the ear canals. Additionally, in two rabbits
lesions associated with P. cuniculi were observed on the
eyelids and/or forehead. The severity of infestation in
ears varied from 2+ to 4+. Three ears with sensitive ear
canals in two rabbits (rabbit no. 2 and 5) did not tolerate the use of an otoscope. On microscopic examination of scab materials from each ear, all development
stages of P. cuniculi were observed.
All rabbits had a perceptible reduction in the severity
of pruritis 3 days after the first administration of eprinomectin. Decrease in the frequency of shaking of the
head and increase in appetite were noticed; the crusts
in heavily infested ears began to fall off and erythematous, erosive and ulcerative areas were noted. Recovery

continued and by day 7 the rabbits were bright and

more alert. Alopecia, crusting, and pruritus diminished; however, live psoroptic mites were visualized on
otoscopic examination, and by microscopic examination of the samples. Erythema and/or ulceration in two
rabbits and debris in the ear canals of all rabbits were
present. The rabbits continued to improve, and by day
14 severity of the ear lesions decreased markedly (Fig. 1c)
but live P. cuniculi mites were found microscopically on
otoscopic examination of aural debris. One week after
the second eprinomectin application, on day 21, the
rabbits still had active lesions, and live mites in five
rabbits were seen microscopically and on otoscopic examination. At the end of the study, on day 42, five of the six
rabbits had live mites and ear lesions scoring between
1+ and 2+ (Fig. 1d), while one was free of clinical signs
and live mites. No general adverse reactions and/or no
hair and/or skin changes on the topical eprinomectin
application sites were observed.
This study indicated that eprinomectin was partially
effective in the treatment of rabbits naturally infested
with P. cuniculi. Eprinomectin, doramectin and ivermectin show some similar structural features as well
as an apparent common mode of action and efficacy
against the most important parasites of animals.4 Therefore,
the result of the present study can be compared with
those of ivermectin and doramectin. Ivermectin diluted
in mineral oil, applied directly on the ear, has been found
to be effective in rabbits with psoroptic mange in only
one study5. In contrast, several studies showed that
subcutaneous administration of ivermectin5,6 and
doramectin7 led to complete clinical and parasitological recovery in psoroptic rabbits. Therefore, topical
eprinomectin formulation (0.5 mg kg1) used in this
study appeared to be less effective than the 1% injectable ivermectin5,6 and doramectin7 formulation (0.2 mg kg1).
As previously described,4 pharmacokinetic differences
between these three avermectins and /or route of administration can explain certain differences in efficacy.
Alternatively, it has been suggested that strain differences in the sensitivity of P. cuniculi to ivermectin
are widespread8 and a resistant strain may have been
used in the present study. The result of this treatment
trial also was not in agreement with that obtained
by McTier et al.9 who found that selamectin, a macrocyclic lactone differing in chemical structure from
eprinomectin, led to complete clinical and parasitological recovery in rabbits naturally infested with
P. cuniculi.
The dosage and frequency of administration of the
pour-on eprinomectin used in this treatment trial
markedly decreased the severity of clinical signs; however, a complete control of mites and lesions in five
of six rabbits did not occur during the observation
period. Although pour-on eprinomectin has been
shown to be efficacious on sarcoptic mange in cattle,2
chorioptic mange in cattle2 and demodectic mange in
goats,3 no results have previously been reported concerning its therapeutic efficacy on psoroptic mange
in rabbits or other species. Therefore, the results of the

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Eprinomectin for treatment of ear mange

present study could not be compared. However, apart
from dosage, the low success rate may be related to
the factors that determine efficacy of macrocyclic
lactones. The effectiveness of a macrocyclic lactone
depends upon the formulation of the dosage form,
route of administration, bioavailability, pharmacokinetic
behaviour and metabolism pattern.4,10 The influence of
these factors varies according to differences in the
chemical structure of the drugs and in the species of
animal.4,10 The partial success obtained in this study
could be due to poor systemic availability, short
half-life, insufficient dose, or a combination of some
of these factors. Previous investigations also revealed
pharmacokinetic differences with the similar standard dose rate of 0.5 mg kg1 between cattle and goats10
and insufficiency of the cattle standard dose for goats.10
Because of the partial control of the disease, we can
assume that there is a reasonable degree of systemic
absorption and/or cutaneous dispersion. It is possible
that an increased frequency of administration or a
higher dosage may be more effective.
Although detailed toxicity studies in rabbits have
not been reported, eprinomectin has been shown to be
safe in cattle when applied topically at 1, 3 and 5 times
the recommended dose at 7-day intervals for 3 weeks.4
In the present study, topical administration of eprinomectin at the standard cattle dose rate of 0.5 mg kg1
did not result in any adverse reaction.
In conclusion, the results of this study indicate that
eprinomectin, given topically twice at 14-day intervals
at the cattle dose rate of 0.5 mg kg1, is partially effective in the treatment of rabbits naturally infested with
P. cuniculi. Because of the small number of animals in
this study and the lack of a control group, further
investigation is necessary using a larger number of ani-

337

mals and comparing the efficacy of eprinomectin to

other treatments and to a control.

REFERENCES
1. Baker DG. Natural pathogens of laboratory mice, rats,
and rabbits and their effects on research. Clinical Microbiology Reviews 1998; 11: 23166.
2. Barth D, Hair JA, Kunkle BN et al. Efficacy of eprinomectin against mange mites in cattle. American
Journal of Veterinary Research 1997; 58: 12579.
3. Strabel D, Schweizer G, Gansohr B et al. The use of avermectins in two goats with demodicosis. Schweizer Archiv
fr Tierheilkunde 2003; 145: 5857.
4. Shoop W, Soll M. Ivermectin, abamectin and eprinomectin. In: Vercruysse J, Rew RS eds. Macrocyclic Lactones and
Antiparasitic Therapy. Oxon: CABI Publishing, 2002: 129.
5. Wilkins CA, Conroy JA, Oishanney WJ et al. Treatment
of psoroptic mange with avermectins. American Journal
of Veterinary Research 1980; 41: 211214.
6. Bowman DD, Fogelson ML, Carbone LG. Effect of ivermectin on the control of ear mites (Psoroptes cuniculi) in
naturally infested rabbits. American Journal of Veterinary Research 1992; 53: 1059.
7. Bansod KV, Kolte SW, Maske DK et al. Treatment of
psoroptic mange in rabbits with doramectin. Indian
Veterinary Journal 2004; 81: 106.
8. Wright FC, Riner JC. Comparative efficacy of injection
routes and doses of ivermectin against Psoroptes in rabbits.
American Journal of Veterinary Research 1985; 46: 7524.
9. McTier TL, Hair JA, Walstrom DJ et al. Efficacy and safety
of topical administration of selamectin for treatment of
ear mite infestation in rabbits. Journal of the American
Veterinary Medical Association 2003; 223: 3224.
10. Dupuy J, Chartier C, Sutra JF et al. Eprinomectin in
dairy goats: dose influence on plasma levels and excretion in milk. Parasitology Research 2001; 87: 2948.

Rsum Six lapins infests naturellement par Psoroptes cuniculi ont t traits par voie locale par lapplication
sur la peau du cou de 0.5 mg kg1 dun pour-on deprinomectine pour bovins, deux fois 14 jours dintervalle.
Lefficacit du traitement a t value par la disparition des signes cliniques et labsence dacariens vivant pour
une priode de 6 semaines. Une amlioration clinique a t observe 3 jours aprs la premire application.
Cependant une gurison clinique et la disparition des acariens na pas t possible chez 5/6 lapins. Aucune raction
secondaire na t observe. Les rsultats de cette tude indiquent que lprinomectine est partiellement efficace
pour traiter la gale psoroptique du lapin.
Resumen Seis conejos infestados de forma natural con Psoroptes cuniculi fueron tratados mediante aplicacin
tpica en la piel de la base del cuello con 0.5 mg/kg de 0.5% eprinomectina de uso externo para ganado, dos veces
a 14 das de intervalo. La eficacia del tratamiento se bas en la desaparicin de signos clnicos y en la ausencia
de caros vivos durante un perodo de seis semanas. Observamos una mejora en los signos clnicos a los tres das
tras la aplicacin inicial; sin embargo una recuperacin total y la eliminacin de los caros en 5 de los 6 conejos
no fueron posibles hasta el final del estudio. No encontramos reacciones adversas atribuidas al tratamiento con
eprinomectina durante el perodo de observacin. Los resultados de esta prueba indican que la eprinomectina
fue parcialmente efectiva en el tratamiento de sarna sorptica en conejos.
Zusammenfassung Sechs Kaninchen mit natrlichem Psoroptes cuniculi Befall wurden zwei Mal in einem
Abstand von 14 Tagen topisch auf der Haut des Nackens mit 0.5 mg kg1 Pour-on Eprinomectin fr Rinder
behandelt. Die Beurteilung der Wirksamkeit des Arzneimittels basierte auf dem Verschwinden von klinischen
Symptomen and der Abwesenheit von lebenden Milben ber einen Zeitraum von sechs Wochen. Eine klinische
Verbesserung wurde innerhalb von drei Tagen nach der ersten Applikation gesehen; eine gnzliche Verbesserung
der klinischen Symptome und eine Elimination der Milben war allerdings bei 5 der 6 Kaninchen bis zum Ende
der Studie nicht mglich. Whrend der Studiendauer wurden keine auf Eprinomectin zurckzufhrenden
Nebenwirkungen beobachtet. Die Ergebnisse dieses Versuchs wiesen darauf hin, dass Eprinomectin teilweise
effektiv war zur Behandlung der Psoroptesrude beim Kaninchen.
2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 334337