THERAPY

A comparative study of oral ivermectin

and topical permethrin cream in the
treatment of scabies
V. Usha, DNB, and T. V. Gopalakrishnan Nair, MD Kerala, India

Background: The conventional antiscabietics have poor compliance. Ivermectin, an oral antiparasitic
drug, has been shown to be an effective scabicide and could be a useful substitute.

Objective: This study compares the efficacy of oral ivermectin with topical permethrin cream in the
treatment of scabies.

Methods: Eighty-five consecutive patients were randomized into 2 groups. Forty patients and their
family contacts received 200g/kg body weight of ivermectin, and another 45 patients and their
family contacts received a single overnight topical application of 1% permethrin cream. Patients were
followed up at intervals of 1, 2, 4, and 8 weeks.

Results: A single dose of ivermectin provided a cure rate of 70%, which increased to 95% with 2
doses at a 2-week interval. A single application of permethrin was effective in 97.8% of patients.
One (2.2%) patient responded to 2 applications at a 2-week interval. Permethrin-treated patients
recovered earlier.

Conclusion: A single application of permethrin is superior to a single dose of ivermectin. Two

doses of ivermectin is as effective as a single application of permethrin. The temporal dissociation
in clinical response suggests that ivermectin may not be effective against all the stages in the life
cycle of the parasite. (J Am Acad Dermatol 2000;42:236-40.)

S
cabies is a re-emerging infection of the new Inc. 0190-9622/2000/$12.00+0 16/1/101934
millennium, especially with the pandemic of
HIV infection.1-4 It is still a major public
health
problem in developing countries5.
Available antiscabietics are mainly topical and
require prolonged and repeated application.
Resistance to some of these drugs has been
report- ed.6 Accidental ingestion, especially by
children, may be fatal. Currently, topical 1%
permethrin cream is considered as the drug of
choice in the management of scabies,7
although recurrence4 and allergic side effects8
have been documented. Permethrin is costly
and is applied all over the body for at least 8
hours. This causes poor compliance in patients
and family contacts, making community control
of scabies difficult.5
Ivermectin is a novel antiparasitic agent effective
against a variety of endoparasites and ectoparasites

From the Department of Dermatology and Venereology,

Medical College and Hospitals,Trivandrum.
Reprint requests: V. Usha, B-10, New Faculty Block, SCT
Quarters, Poonthy Road, Kumarapuram,Trivandrum, 695011,
India.
Copyright©2000 by the American Academy of Dermatology,
(endectocide)9. With a single oral dose,
ivermectin is effective against intestinal
nematodes9 and appears to be a promising
treatment for head lice infestations, which are
common coinfections in developing coun- tries. It
is not yet approved by the US Food and Drug
Administration for the treatment of human
scabies.
Initial reports have highlighted the utility of
oral ivermectin in the treatment of scabies.10-13
Hence it was considered worthwhile to
generate more data regarding the human use
of ivermectin in the treat- ment of scabies,
comparing the result with the currently
available first-line treatment of scabies,
236
permethrin.
The aim of the study was to compare the
efficacy of asingle oral dose of 200 g/kg body
weight of iver- mectin with topical 1%
permethrin cream in the treatment of patients
with scabies and their family contacts and to
know the utility of the drugs in the prevention of
recurrence over a period of 2 months.
METHODS
Subject selection
The study included consecutive patients
with scabies and their family contacts older than
5 years of age who were attending the
Dermatology
J AM ACAD DERMATOL Usha and Gopalakrishnan Nair
VOLUME 42, NUMBER 2, PART 1

Table I. Baseline characteristics of the patients

Clinical parameters
Ivermectin Permethrin P value

Age distribution (y) Sex distribution, M/F (%) Duration21.28±

(wk) Nocturnal
13.44 pruritus (%) 22.4±
Family12.6
history (%) Secondary
.05272
infection (%)
Severity of lesions, mild/moderate/severe (%) Severity of pruritus
65/35 (%) 77.3/26.7 .40527
Microscopy (%) 6.4± 5.84 6.9± 7.1 .50165
95 97.8 .48847
82.5 55.6 .00774
25 20 .58075
27.5/60/12.5 40/51.1/8.9 .46458
71.8± 9.7 70.2± 8.4 .45234
72.5 68.9 .20302
Outpatient Department of the Medical College, instructions
Trivandrum, India, from August 1996 to December
1997. Patients who had received any antiscabietic
treatment in the previous1 month, pregnant and
lac- tating women, and patients with serious
central ner- vous system, hepatic, cardiac, or renal
disease were excluded from the study. Informed
consent was obtained from all patients who
participated in the study. The entire project was
presented to the hos- pital ethical committee,
and formal sanction was obtained for the study.

Diagnosis and intervention

The diagnosis of scabies was made by the
demon- stration of eggs, larva, mites, or fecal
pellets by light microscopy or by the presence of at
least 3 of the following clinical criteria confirmed
independently by 2 consultants: (1) demonstration
of burrow, (2) pres- ence of scabietic lesions at the
classical sites, (3) noc- turnal pruritus, and (4)
family history of similar illness. A detailed
systemic and dermatologic examina- tion was
made, and weight was recorded to deter- mine
the dose of the drug. The intensity of pruritus
was recorded with the visual analogue scale
and graded as mild, moderate, or severe. The
severity of
skin lesions was also graded.
Scrapings from skin lesions were taken from
mul- tiple sites for demonstration of mites or
their prod- ucts. Secondary infection, if present,
was treated with a 7-day course of erythromycin
250 mg 4 times daily. Treatment of scabies was
started after control of inflammation.
Once the diagnosis was confirmed by satisfying
the above-mentioned criteria, the patients were
random- ly allocated to one of 2 groups. One
group, including the family contacts, were given
ivermectin (Mectizan- Merck Sharp and Dohme) as
a supervised single oral dose of 200 g/kg body
weight. The other group and their family contacts
were given 1% permethrin cream (Permite-
Croslands, a division of Ranbaxy) as a single
overnight topical application. Standard
238 Usha and Gopalakrishnan Nair J AM ACAD DERMATOL
FEBRUARY 2000
were given about the mode of application,
general measures, importance of treating the
family contacts, and prevention of fomite
transmission by washing all infested clothes and
bedding with soap and water and drying them in
the sun. They were advised not to apply any
other medications for this disease during the
study period.
Both drugs were given free of cost to all
the patients and their family contacts.
Children below 5 years of age and pregnant
women in the family con- tacts in both
groups were treated with 12.5% to 25% benzyl
benzoate emulsion, which was supplied free of
cost by the hospital.

Evaluation
All the patients were followed up at regular
inter- vals of 1, 2, 4, and 8 weeks and were
thoroughly examined clinically. Microscopy of
skin lesions, if present, was repeated.
Treatment was considered to be effective if, at
the end of 2 weeks, there was improvement
in pruritus assessed by the visual ana- logue
scale, clinical improvement in skin lesions with
no new lesions, and absence of mites or their
prod- ucts on microscopy. Improvement was
graded as mild, if there was less than 50%
reduction in the number of lesions and
pruritus, as moderate if there was more than
50% reduction, and as good if there was
complete clearance.
Treatment was considered to be a failure if
at the end of 2 weeks, there was no
improvement in pruri- tus and skin lesions,
appearance of new lesions, or presence of mites
or their products on microscopy. In case of
treatment failure, another dose of the same
treatment was repeated. If the repeat treat-
ment also failed, at the end of a further 2
weeks of follow-up (fourth week after
randomization) the treatment was crossed
over to the other group.

End point
The complete disappearance of clinical signs
and symptoms and no appearance of new lesions
at the
 J AM ACAD DERMATOL
VOLUME 42, NUMBER 2, PART 1
Fig 1. Pie chart showing the response to ivermectin and permethrin.
Fig 2. Time course of good response to therapy with ivermectin and permethrin.
end of 2 months after the last dose was taken as
the end point.
RESULTS
A total of 85 patients were studied, of which 40
were in the ivermectin group and 45 in the
perme- thrin group. There was no significant
difference between the study groups in any of
the clinical para- meters except that the family
history of scabies was present more in the
ivermectin group than in the permethrin group,
and the difference was statistical- ly significant
(Table I).
Of the 175 family contacts (exclusive of
patients) in
the ivermectin group, 102 were symptomatic. Of the
179 family contacts in the permethrin group, 73
were symptomatic. There was no significant
differences in the severity of symptoms in the
family contacts in either group. There were no
pregnant women in the families of the index
patients in either group.
On follow-up, with a single dose, by the first
week 20 patients (50%) in the ivermectin group
Usha and Gopalakrishnan Nair
patients (84.3%) in the permethrin group had
symp- tom improvement. By the second week,
28 patients (70% ) in the ivermectin group and
44 patients (97.8% ) in the permethrin group had
symptom improvement, and the nonresponders
(12 and 1, respectively) received a repeat
therapy. By the fourth week, 38 (95%) patients
had symptom improvement with ivermectin,
whereas all the patients were cured with
permethrin. Two (5%) patients did not respond to
2 doses of ivermectin. They were crossed over to
the permethrin group and were cured after a single
application (Fig 1). Complete clearance of lesions
(graded as good improvement) occured earlier in
permethrin-treated patients (Fig 2).All the s
patient
were completely cured at the end of 8 weeks.
There
was no recurrence of scabies at the end of 2
DISCUSSION
and 35
240 Usha and Gopalakrishnan Nair J AM ACAD DERMATOL
FEBRUARY 2000
In this study a single application of
permethrin was superior to a single oral dose of
ivermectin by 2
J AM ACAD DERMATOL Usha and Gopalakrishnan Nair
VOLUME 42, NUMBER 2, PART 1

Table II. Effect of single-dose ivermectin

Serial No. No. of patients Response Comment

Studies in immunocompetent patients with low-dose ivermectin of<200g/kg

1 2 Poor Inadequate dose15
2 7 Poor No benefit when compared with control subject1s4
3 23 70% Ivermectin better than BB, but no statistically significant
differen1c6e
Studies in immunocompetent patients with 200g/kg ivermectin
4 29 79% Ivermectin wasmore effective than placeb1o0
5 11 100% Ivermectin was very effectiv1e0
6 152 100% Eradication of scabies in a communit1y7
7 47 100% Eradication of scabies in a hospita1l8
Studies in immunosuppressed patients
8 11 73% Three patients needed repeat dose1s0
9 2 100% Concomitant use of salicylic acid; rapid response in 5-6 day1s9
10 2 100% Simultaneous use of malathion2
11 1 100% Effective in an HTLV-I carrie3r

HTLV-I,HumanT-lymphotropic virus type I;BB,benzyl benzoate.

weeks (P < .001). Permethrin acts by disrupting the thick egg shell.
sodium channel current, resulting in delayed
repolar- ization, paralysis, and death of the parasite.8
Sodium channels are ubiquitous, and therefore
permethrin acts at all stages of the life cycle of
the parasite. Furthermore, topical application
ensures maximum concentration of the drug in the
skin. These factors could account for the superior
efficacy of a single top- ical application of
permethrin. This study also con- curs with the
excellent cure rates (90%-100% ) observed in the
initial studies with permethrin7. Although the
drug was introduced in India in April 1995, it is
infrequently used because of its high cost. The
good compliance observed in the study reflects the
high literacy prevalent in the state of Kerala.
The lack of efficacy of a single dose of
ivermectin in some patients may be due to the lack
of ovicidal action of ivermectin. No definite data
regarding the dose or parasiticidal effect of
ivermectin in the various stages of the mite is
available. Probably ivermectin acts only at certain
stages of the life cycle of the parasite, as is reported
in the case of onchocerciasis and strongy-
loidiasis.9 Ivermectin acts by binding selectively and
with high affinity to glutamate (or -amino butyric
acid) gated chloride ion channels, which occur in
invertebrate nerve and muscle cells. This leads to an
increase in the permeability of the cell membrane to
chloride ions with hyperpolarization of the cell,
result- ing in paralysis and death of the parasite.9
Ivermectin, because of its specific site of action,
may not be effective against the younger stages of
the parasite inside the egg because the nervous
sys- tem has not yet developed. Furthermore,
ivermectin may not adequately penetrate the
242 Usha and Gopalakrishnan Nair J AM ACAD DERMATOL
FEBRUARY 2000
Table III. Efficacy of 2 doses of oral
ivermectin administered 2 weeks apart
Serial No. of
No. patients Response Comment

Immunocompetent patients (200g/kg)

1 33 100% Eradication of endemic
scabies in a
nursing home
when topical
scabicides
failed11
2 5 100% Very effectiv2e0
3 53 100% Utility in epidemic1s2
Immunosuppressed patients
4 6 100% Effective13
5 5 100% Effective20

The concentration achieved in the skin may

also be variable because ivermectin is orally
administered. These factors could also explain
the temporal delay in complete recovery
observed in the ivermectin group. One study
has shown that ivermectin is not ovicidal for
head lice.14 Because ivermectin has not been
proven to be ovicidal, a single dose of 200
g/kg body weight may be inadequate to
eradicate the different stages of the parasite,
and a higher dose or a second dose may be
required within 1 to 2 weeks for 100% cure.
However, the efficacy of a sin- gle dose of
ivermectin in the treatment of scabies, both in
immunocompetent and immunocompro-
mised patients has been observed to be 70%
to 100% by different authors (Table II).14-19
Response was poor in studies with less than
200 g/kg of iver-
J AM ACAD DERMATOL Usha and Gopalakrishnan Nair
VOLUME 42, NUMBER 2, PART 1

mectin,14-16 but 2 doses of ivermectin were appropriate schedule in the treatment of scabies.
found to be 100% effective (Table III).11-13,20 In
one report 2 doses of ivermectin given at a 4-
week interval were not effective in a terminally ill
patient with AIDS.21
In our study, by 4 weeks 2 doses of ivermectin
achieved a therapeutic response comparable with
that of permethrin, but there was a temporal
disso- ciation in the recovery pattern. By 8
weeks, there was no statistically significant
difference in cure rates (P = .21).
No major side effects were observed in either
group, except that in the permethrin group the
drug was applied inadvertently (as per the study
protocol) for a 10-month old baby by the parents.
Severe erythema developed in the baby
accompa- nied by oozing and itching all over
the body, which responded to symptomatic
measures. Each gram of Permite cream contains
50 mg of permethrin and 0.1% formaldehyde
solution as the preservative in a cream base. The
side effect observed in this child could be due to
any of the constituents. In the iver- mectin
group 3 patients had a mild improvement of
pruritus initially, but their condition was aggra-
vated 2 days later. This subsided spontaneously in
2 to 3 days. Similar findings have been observed
by others.20 This may be a hypersensitivity
reaction caused by destruction of the mite and
release of antigens.
Ivermectin is the mainstay of treatment in the
onchocerciasis control program, with about 19
mil- lion doses distributed over the world
without any major side effects.22 In the same
control program, 400 pregnant women
inadvertently received the drug in the first
trimester, but no significant increase in
teratogenicity was observed.23
The main limitation of the study was that iver-
mectin could not be given to children below 5
years of age (or <15 kg), and in developing
countries chil- dren form the majority of the
affected population. However, the availability of
an effective oral scabici- dal agent opens a new
era in the management of the oldest identified
disease of man, leaving hopes of even eradicating
the disease.24
A single application of permethrin is superior
to a single oral dose of ivermectin. Two doses of
iver- mectin taken at a 2-week interval are as
effective as a single application of permethrin.
Both drugs are effective in preventing recurrences
over a period of 2 months. The temporal
dissociation in clinical response suggests that
ivermectin may not be effec- tive against all stages
in the life cycle of the parasite. Therefore 2 doses
of ivermectin, 1 to 2 weeks apart, may be the
244 Usha and Gopalakrishnan Nair J AM ACAD DERMATOL
FEBRUARY 2000
We thank Professor C. R. Soman, Dr Barry stand. Dermatology end of year review. Lancet
Smith, Croslands, Merck Sharp and Dohme, and Dr 1996;348(Suppl II):3.
P. Sankara Sharma.

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