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231 DISC

Veterinary Dermatology 2001, 12, 8992

Ecacy of 1.25% amitraz solution in the treatment of


generalized demodicosis (eight cases) and sarcoptic
mange (ve cases) in dogs
CHRISTOPHE HUGNET,* CHRISTINE BRUCHON-HUGNET,* HERVE
ROYER* and GILLES BOURDOISEAU{
*Docteur veterinaire, Clinique veterinaire des Lavandes, 26160 La Begude de Mazenc, France
{Professeur, Departement de Sante Publique, Unite de parasitologie, Ecole Nationale Veterinaire de Lyon, BP
83, 69280 Marcy l'Etoile, France
(Received 23 February 2000; accepted 15 June 2000)

Abstract Eight dogs with generalized demodicosis and ve with sarcoptic mange were treated with 1.25%
amitraz solution applied weekly and associated with an antidote treatment (atipamezol, 0.1 mg kg71 IM once:
and yohimbine 0.1 mg kg71 once daily for 3 days, orally). Results of skin scrapings were used to determine
whether therapy should be continued or stopped. The median number of treatments for demodicosis and
sarcoptic mange was three (range 25) and two (range 13), respectively. Some side-eects were observed but
all were stopped with antidote treatment; no failure or relapses occurred at 636 months after treatment.
Keywords: amitraz, atipamezol, demodicosis, sarcoptic mange, yohimbine.

INTRODUCTION
Canine demodicosis is a parasitic disease due to an
excessive proliferation of Demodex canis within the
hair follicles. The generalized form is considered to be
one of the most severe canine skin diseases and is one
of the most frustrating to treat. Sarcoptic mange is
due to the multiplication of Sarcoptes scabiei var.
canis and the prognosis is usually good.
Over the last few years, several new products have
become available for the treatment of these mite
infestations1: systemic macrocyclic lactone endectocides (ivermectin,26 milbemycin oxime,710 moxidectin11) and amitraz.12,13
All endectocides were found to be eective in up to
85% or more of dogs with generalized demodicosis1
and to 100% of dogs with sarcoptic mange.14 However,
ivermectin is potentially toxic and lethal idiosyncratic
toxicity has been reported in Collies and several other
breeds.15 None of these products is authorized in
France for the treatment of demodicosis (except milbemycin-oxine: Inteceptor1 14 bd Richelieu, BP430,
92845 Rueil-Malmaison, France) or sarcoptic mange.
Amitraz is an acaricid from the formamidine
family; in France, amitraz solution (Ectodex,
Hoechst Roussel Vet, Pantin, France) is approved
since 1995 for use at a nal dilution strength of 250
500 p.p.m. every 57 days.16,17 Several reports stated
that biweekly treatment with amitraz was almost

Correspondence: Professor G. Bourdoiseau, Departement de Sante


Publique, Unite de parasitologie, Ecole Nationale Veterinaire de
Lyon, BP 83, 69280 Marcy l'Etoile, France.
# 2001 Blackwell Science Ltd

100% eective in resolving generalized demodicosis


and sarcoptic mange.1214,16 But, in some cases of
demodicosis, dogs do not respond to this approved
treatment and the following options are available:
increase the frequency of treatments to weekly or daily
(but it is not always possible), or increase the
concentration of amitraz. Unfortunately, the use of
highly concentrated amitraz solution is associated with
severe, and sometimes fatal, poisoning in dogs18:
clinical signs of toxicosis included sedation, bradycardia, polyuria, hypothermia and hyperglycemia. Some
studies have demonstrated the ecacy of certain
antidotes: atipamezol (Antisedan, Pzer, Orsay,
France) an injectable a2-antagonist, or yohimbine
(Yohimbine Houde, Hoechst Houde, Paris, France)
only available in France in an oral formulation.19,20
Atipamezol is marketed in France for the
reversal of anaesthesia induced by a2-agonists
such as xylazine or medetomidine. Therefore, the
administration of specic antidotes appears as a
possible solution when using a highly concentrated amitraz solution.
The purpose of this study was to evaluate the
ecacy of weekly dips of 1.25% amitraz solution in
association with antidotes (atipamezol and yohimbine) in the treatment of canine demodicosis and
sarcoptic mange.
METHODS
Signalment of animals
Eight privately owned dogs (numbers 18) with
generalized demodicosis and with or without super89

Ahed
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231 DISC
90

C. Hugnet et al.

cial pyoderma were included in this study (Table 1).


Two were mixed-breed dogs and seven were purebred dogs representing ve breeds. Median age at the
time treatment was initiated was 2 years (range 4
months12 years). A physical examination and
multiple skin scrapings were performed. The diagnosis was established by microscopic examination of
the samples demonstrating many adult and larval
forms of Demodex canis. The disease was considered
generalized when over 50% of the skin surface was
involved or when the four feet were aected.
Five dogs with sarcoptic mange (numbers 913)
were also included in this study (Table 2). The
diagnosis was established by a complete physical
examination and a microscopical examination of the
samples obtained by multiple skin scrapings, demonstrating adults, larval forms or eggs of Sarcoptes
scabiei. All dogs were pure-bred representing ve
breeds; the median age was 3 years (range 4 months
10 years).
Treatment
Each dog was treated for secondary pyoderma with
antibacterial topical and oral products (chlorhexidine
2% shampoo: Douxo (Sepval-Sogeval, Laval,
France), and cephalosporins or uoroquinolones,
respectively) and then on the same morning, with
1.25% amitraz solution (Taktic, Virbac, Carros,
France: 10 mL of Taktic diluted in 90 mL of water)
applied with a surgical sponge (E-Z scrub 160, BectonDickinson, Rungis, France). Fresh solution was
reconstituted for each dip and all treatments were
performed by the veterinarian or his assistant in the
clinic. To minimize human exposure to the solution
protective clothing and gloves were worn, and treatments were administered in a well-ventilated area. The
dogs' eyes were protected by the administration of a
protective ocular gel (Ocrygel, TVM, Lempdes,

France). Dogs with long hair coats (numbers 7 and


12) were clipped prior to the rst treatment.
After this dip, the 13 dogs received injectable
solution of atipamezol (0.1 mg kg71) and then oral
presentation of yohimbine (0.1 mg kg71 once a day
for 3 days). The rst oral administration occurred 3
h after the dip and was administered at home by
the owner.
All dogs were observed by the veterinarian for 8 h
after the dip, then, if they remained clinically normal,
follow-up information was obtained by telephone.
Outcome
The patients were given a physical examination and
the skin scraped on a weekly basis. Results of
microscopic examination of skin scrapings were
compared with those obtained at the previous
examination. For the cases of sarcoptic mange, the
treatment was considered successful and stopped if
the dog had complete resolution of signs and if no
mites were seen in skin scrapings. For demodicosis,
the dogs were given another dip in amitraz solution 7
days after the last negative skin scraping. The dog
was considered cured if it was clinically normal and
skin scrapings negative 6 months (or more) after the
last dip.
RESULTS
The results are presented in Tables 1 and 2. For the
demodicosis cases, 5 dogs (numbers 1, 2, 3, 4 and 7)
had been previously treated unsuccessfully with
multiple amitraz dips (0.05% solution of amitraz)
every 5 days and were not cured after 3 months of
treatment; two relapses were observed 3 months after
the end of the treatment for the dogs numbers 5 and 8.
One dog (number 3) with adult-onset demodicosis had

Table 1. Cases of demodicosis and results


Dog
number

Breed

Sex

Age when
treatment initiated

1
2
3
4
5
6
7
8

WHWT
Doberman
mixed breed
German Shepherd
Doberman
Boxer
Collie
Boxer cross

M
M
F
F
M
F
M
M

2 years
8 months
12 years
11 months
9 months
4 months
5 months
1 years

Associated
disease

Number
of dips
4
3
5
3
4
2
3
3

Side-eects
erythema
scaling
erythema
erythema

*hyperadrenocorticism
Table 2. Cases of sarcoptic mange and results
Dog
number

Breed

Sex

Age when
treatment initiated

9
10
11
12
13

English Setter
Epagneul breton
Fox Terrier
Collie
Poodle

M
M
M
M
F

4 months
10 years
2 years
2 years
1 years

*iatrogenic Cushing's syndrome


# 2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 8992

Associated
disease
*

Number
of dips
1
3
1
2
2

Side-eects
vomiting
erythema
erythema
pruritus

231 DISC
Ecacy of amitraz solution in treatment of demodicosis and sarcoptic mange
hyperadrenocorticism and was concurrently treated
with Mitotane (RousselUclaf, Paris, France); all
seven other dogs had juvenile-onset demodicosis.
The median number of dips was three (range 25),
i.e. the median duration of treatment was 21 days
(range 1435 days). All dogs were cured: the adult
mites and the immature forms of Demodex disappeared quickly. No relapse was observed 636
months after the last dip in all dogs and no relapse
was observed for 12 months or more in six dogs.
For the cases of sarcoptic mange, the median number
of dips was 2 (range 13), i.e. the median duration of
treatment was 14 days (range 721 days). All dogs were
cured, no relapse was observed 636 months after the
last dip and for 12 months or more in four dogs. One
dog suered of iatrogenic hyperadrenocorticism due to
multiple topical and oral administration of glucocorticoids by the owner. This medication was stopped at the
time of the rst dip.
Side-eects were noted by the owners and reported
to the veterinarian. Generalized erythema was
observed after each dip for ve dogs but disappeared
in 48 h, one dog had scaling for three days after the
second dip and one puppy vomited 30 min after the
dip. One owner developed a headache in his car while
bringing his pet home. All owners reported an
unpleasant odour for 26 days after each dip.
DISCUSSION
Amitraz is approved in France for use as a topical dip
for treating canine demodicosis. This approved
product is a liquid concentrate containing 5%
amitraz that is applied as a 250500 p.p.m. amitraz
solution to the entire body every week, or as 1250
p.p.m. for half-body daily applications. These applications were reported to be eective and safe for the
treatment of generalized demodicosis. Response to
treatment is monitored by repeating multiple skin
scrapings every two to four weeks. As long as mites
are found, treatment is continued.
Unlicensed protocols with amitraz solution have
been developed involving more concentrated solutions of the drug applied more frequently, but not all
dogs with generalized demodicosis are cured. Several
unapproved protocols for these persistent cases have
been described.13,17
One study9 used milbemycin oxime which was
administered orally to dogs once daily at 0.53.8 mg
kg71 body weight. The overall cure rate was 53.3%.
Milbemycin oxime has the advantage of being
relatively safe and easy to give. However, this drug
is expensive.
Oral ivermectin used at 0.6 mg kg71 body weight
once daily was found to be eective in dogs with
chronic demodicosis.35 Although all dogs clinically
resolved with this treatment, and ivermectin is easy to
administer and less expensive than milbemycin
oxime, this unapproved use of ivermectin is asso-

91

ciated with adverse reactions including neurological


manifestations and death.
Moxidectin is also eective for generalized demodicosis but some cases of intoxication can cause
various abnormal neurological manifestations.21
In this study, the authors found that 1.25%
amitraz solution applied weekly was 100% eective
in curing dogs which had demodicosis previously
refractory to multiple amitraz treatments. Seven of
the eight dogs with generalized demodicosis resolved
after two to four dips and one with ve dips.
With sarcoptic mange, one to two dips were
necessary, and three dips for the dog which suered
hyperadrenocorticism. For both diseases, Cushing's
syndrome was the factor associated with the need for
an additional dip. When compared to using milbemycin oxime or ivermectin for treating the refractory
cases of generalized canine demodicosis, topical
weekly treatments with amitraz associated with
antidote treatment were less dangerous and less
time-consuming.
Amitraz is a a2-agonist whose toxic eects are lifethreatening: decrease of rectal temperature, modications of heart rate and cardiac disorders are usually
responsible for death of amitraz-poisoned animals.
Atipamezol controlled all toxic eects of amitraz
within 20 min after the intramuscular administration.1820 The duration of action of atipamezol is
limited at 24 h; consequently dogs should be treated
immediately with atipamezol, then at subsequently
with yohimbine.
Although canine generalized demodicosis and
sarcoptic mange remain diseases that are not easily
treated, the prognosis for dogs with these disorders
has dramatically improved in the past few years.
Although the administration of dips with a highly
concentrated solution of amitraz associated with an
antidote should not be a rst option treatment, this
unlicensed protocol is an alternative which may lead
to permanent cure without relapse or failure.

ACKNOWLEDGEMENTS
The authors would like to thank Dr S. Keroack for
her assistance in translation.

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231 DISC
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C. Hugnet et al.

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Resume Huit chiens sourant de demodecie generalisee, et cinq de gale sarcoptique ont ete traites par l'application
hebdomadaire d'une solution a 1.25% d'amitraze, en association avec un antidote (atipamezole, 0.1 mg kg71 IM une
administration: et yohimbine 0.1 mg kg71 une fois par jour pendant 3 jours per os). Les raclages cutanes etaient
utilises pour determiner si le traitement devait etre poursuivi ou arrete. Le nombre moyen de traitement pour la
demodecie et la gale sarcoptique etait respectivement de trois (25) et de deux (13). Des eets secondaires ont ete
observes, mais ils ont retrocede avec un traitement antidote; aucun echec ou rechute n'est apparu 636 mois apres le
traitement. [Hugnet, C., Bruchon-Hugnet, C., Royer H., Bourdoiseau G. Ecacy of 1.25% amitraz solution in the
treatment of generalized demodicosis (8 cases) and sarcoptic mange (5 cases) in dogs. (Ecacite d'une solution a
1.25% d'amitraze pour le traitement de la demodecie generalisee (8 cas) et de la gale sarcoptique (5 cas) chez le
chien.) Veterinary Dermatology 2001; 12: 8992.]
Resumen Ocho perros con demodicosis generalizada y cinco con sarna sarcoptica fueron tratados con una solucion
del 1.25% de amitraz semanalmente, asociada a un tratamiento ant doto (atipamezol, 0.1 mg kg1 IM una toma y
yohimbina 0.1 mg kg1 una vez al d a durante 3 d as, oralmente). Los resultados de los raspados cutaneos fueron
utilizados para determinar si la terapia deber a continuarse o retirarse. El numero mediano de tratamientos para
demodicosis y para sarna sarcoptica fue tres (rango 25) y dos (rango 13), respectivamente. Algunos efectos
colaterales fueron observados pero todos fueron controlados con tratamiento ant doto; no se produjeron fracasos ni
recidivas a los 636 meses despues del tratamiento. [Hugnet, C., Bruchon-Hugnet, C., Royer H., Bourdoiseau G.
Ecacy of 1.25% amitraz solution in the treatment of generalized demodicosis (8 cases) and sarcoptic mange (5
cases) in dogs. (Ecacia de una solucion de 1.25% de amitraz en el tratamiento de la demodicosis generalizada (ocho
casos) y la sarna sarcoptica (cinco casos) en perros.) Veterinary Dermatology 2001; 12: 8992.]
Zusammenfassung Acht Hunde mit generalisierter Demodikose und funf mit Sarcoptesraude wurden wochentlich
mit 1.25% Amitrazlosung verbunden mit einem Antidot (eine einmalige intramuskulare Injektion von 0.1 mg kg1
Atipamezol und Yohimbine 0.1 mg kg1 einmal taglich fur drei Tage oral) behandelt. Je nach Resultat der
Hautgeschabsel wurde die Therapie fortgesetzt oder beendet. Fur Demodikose wurden durchschnittlich drei
(zwischen 2 und 5) und fur Sarcoptesraude zwei (zwischen 1 und 3) Behandlungen benotigt. Einige Nebenwirkungen
traten auf, verschwanden jedoch nach der Therapie mit dem Antidot, weder Behandlungsmisserfolge noch Rezidive
wurden nach 636 Monaten gesehen. [Hugnet, C., Bruchon-Hugnet, C., Royer H., Bourdoiseau G. Ecacy of
1.25% amitraz solution in the treatment of generalized demodicosis (8 cases) and sarcoptic mange (5 cases) in dogs.
(Wirksamkeit von 1.25%-iger Amitrazlosung bei der Behandlung der generalisierten Demodikose (acht Falle) und
Sarcoptesraude (funf Falle) beim Hund.) Veterinary Dermatology 2001; 12: 8992.]
# 2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 8992