Dermatologic Therapy, Vol. 29, 2016, 5863 C 2015 Wiley Periodicals, Inc.

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DERMATOLOGIC THERAPY
ISSN 1396-0296

ORIGINAL PAPERS

Clinical efficacy and safety of

topical versus oral ivermectin in
treatment of uncomplicated
scabies
Hesham M. Ahmad, Eman S. Abdel-Azim,
& Rasha T. Abdel-Aziz
Department of Dermatology and Venereology, Faculty of Medicine, Minia
University, Egypt

ABSTRACT: Many medications are available for scabies treatment including oral and topical
ivermectin. However, studies comparing these two forms as a scabies treatment are few. This study
compares efficacy and safety of topical versus oral ivermectin as scabies treatment. The study
included 62 confirmed uncomplicated scabies patients, divided into: Group I (32 patients, received
topical ivermectin) and Group II (30 patients, received oral ivermectin). Patients were assessed,
clinically and by KOH smear at 1, 2 and 4 weeks. Treatment was repeated after one week in patients
with persistent infection. Adverse events were recorded. Most patients (87.5% and 73.5% in group I
and group II respectively) were symptom free after a single treatment. A second treatment was
required in 4 patients of group I and 8 patients of group II. However, 2 weeks after treatment
symptoms and signs completely resolved in all cases with no recurrence at 4 weeks. This study
suggests that both topical and oral ivermectin are safe and equally effective in treatment of
uncomplicated scabies. Single treatment, whether topical or oral, is associated with high cure rate in
a week post treatment. However, repeating treatment after one week may be required to achieve
100% cure.

KEYWORDS: oral ivermectin, scabies, topical ivermectin

Introduction time (24). The female parasite invades the epi-

Scabies is an ectoparasitic infestation caused by
Sarcoptes scabiei var. hominis (1). It is a very
common disease worldwide; with 300 million
people suffer from scabies infestation at any one
Address correspondence and reprint requests to: Hesham M.
Ahmad, MD, Department of Dermatology and Venereology,
Minia University Hospital, Minia 61111, Egypt, or e-mail:
heshammoneer@yahoo.com.
Authors have no conflict of interest to disclose
dermis and lays eggs in the stratum corneum.
This leads to an immune response that clinically
results in a characteristic skin rash and pruritus
(57). Diagnosis is usually clinical, but definitive
diagnosis relies on identification of mites or its
products (eggs, empty eggs, and scybala) by
microscopy. However, failure to find a mite is
common and does not rule out scabies (2,4).
Several medications are available to treat sca-
bies, but whether oral or topical treatment is

58

more advantageous regarding efficacy, tolerance
or convenience remains unknown (79). Topical
treatments include permethrin, lindane, benzyl
benzoate, esdepalletrine (bioallethrin), crotami-
ton, and precipitated sulfur. Topical scabicides
have neurotoxic effects on mites and larvae (2,4).
Ivermectin is a member of macrocyclic lac-
tones, named avermectins, which proved active
against a variety of nematode and arthropod
parasites. The drug causes paralysis in suscepti-
ble parasites (10); it interrupts the gamma-
aminobutyric acid-induced neurotransmission of
many parasites (including mites) (2,4). Ivermec-
tin is effective in treatment of scabies, however
only few studies have explored the difference
between oral and topical forms of the drug in
treatment of this disease (11).
The aim of this work was to compare the ther-
apeutic efficacy and safety of topical 1% iver-
mectin solution versus oral ivermectin (200 lg/
kg/dose) in patients with clinically and labora-
tory diagnosed scabies.
Patients & methods
The study included 62 patients (26 males and 36
females), clinically and laboratory diagnosed to
have uncomplicated scabies, of those attending
the outpatient clinic at Department of Dermatol-
ogy, Minia University Hospital, Minia, Egypt. All
patients signed an informed consent and the
study was approved by the Internal Review Board.
Patients were randomized into two groups, Group
I (32 patients) and Group II (30 patients) who
received topical and oral ivermectin respectively.
In order to balance the group sizes the restricted
randomization method adaptive biased-coin
randomization was used (12).
Inclusion criteria
Patients included in the study are those with
uncomplicated scabies, aged 5 years or more,
weighting more than 15 kg, not pregnant or lac-
tating at the time of diagnosis.
Exclusion criteria
The following patients were not included in the
study: patients with crusted (Norwegian) sca-
bies, young children under age of 5 years or
weighing <15 kg, pregnant and lactating women
as well as scabies patients with history of epilep-
tic fits, immunodeficiency, secondary cutaneous
infection or eczematization, and coexisting skin
Clinical efficacy and safety
disease that could interfere with treatment eval-
uation. In addition, patients with history of
recent anti-scabetic treatment as well as those
with known hypersensitivity to ivermectin were
not included in the study.
Clinical assessment
Clinical assessment was done by one researcher
(author number 3) to standardize clinical evalua-
tion. At initial visit, complete cutaneous examina-
tion and body weight measurement were carried
out. Clinical diagnosis was based on the presence
of at least 3 out of 4 criteria: nocturnal pruritus,
family history of similar illness, clinical demon-
stration of burrows and presence of scabies
lesions at classical sites. Meanwhile, laboratory
diagnosis was based on demonstration of mites
and/or mite products (eggs, larva or fecal pellets)
in scrapings from skin lesions (burrows or scabetic
papules from classical sites: finger webs, flexural
aspect of wrist, or penile shaft) using light micros-
copy after incubation in 15% KOH. The severity of
scabies was assessed by subjective assessment of
pruritus and objective counting of the number of
skin lesions and this was expressed as a 4-point
scale as previously described (13) as follows: Score
0 5 no pruritus, no skin lesions; Score 1 5 mild
pruritus, 10 lesions; Score 2 5 moderate pruritus,
1149 lesions; Score 35 marked pruritus, 50
lesions.
Antiscabetic treatment
Patients included in Group I received a single top-
ical application of 1% ivermectin solution to entire
body (below neck) at night. Whereas patients
included in Group II received an oral ivermectin
(200 lg/kg/dose) after food as previously recom-
mended (2). Treatment was repeated after one
week only in patients with persistent symptoms
and/or signs of infection. Treatment of contacts
and proper hygienic measures were stressed on.
Follow up and Treatment outcome
Patients were assessed, clinically and by KOH
smear, at 1, 2, and 4 weeks after starting treat-
ment, the last being the study end-point. At each
visit the intensity of scabies-related pruritus,
changes in lesion counts and presence or
absence of the parasite and/or its products by
microscopy were assessed. Adverse events,
whether cutaneous (e.g., topical irritation or der-
matitis) or systemic (e.g., headache, dizziness,
diarrhea, vomiting, muscle pain) were recorded.
59
Ahmad et al.

Table 1. Pruritus scores before and after treatment with topical and oral ivermectin

Pruritus scores before, during and after treatment in Groups I & II

Group I Group II
Topical ivermectin Oral ivermectin
(n 5 32 cases) (n 5 30 cases)
Number of Number of p value**
cases with Mean score 6 SD cases with Mean score 6 SD (Group I versus
different scores (Median; range) different scores (Median; range) Group II)
Before treatment Score 0 5 0 2.5 6 0.50 Score 0 5 0 2.6 6 0.62 0.27
(2; 23) (3; 13) (Insignificant)
Score 1 5 0 Score 1 5 2
Score 2 5 17 Score 2 5 8
Score 3 5 15 Score 3 5 20
One week after Score 0 5 29 0.09 6 0.29 Score 0 5 23 0.5 6 1.00 0.29
first treatment (0; 01) (0; 03) (Insignificant)
Score 1 5 3 Score 1 5 2
Score 2 5 0 Score 2 5 2
Score 3 5 0 Score 3 5 3
2 and 4 weeks Score 0 5 32 0.0 6 0.0 Score 0 5 30 0.0 6 0.0 N/A
after treatment Score 1 5 0 Score 1 5 0
Score 2 5 0 Score 2 5 0
Score 3 5 0 Score 3 5 0

* 5 Mean 6 SD.
** 5 p-value calculated by MannWhitney Rank Sum test.

Treatment was considered effective if at the
end of 4 weeks of follow up, there was marked to
excellent improvement in scabies-related pruri-
tus (Score 0) with no lesions and absence of
mites and their products on microscopy. Treat-
ment was considered to be a failure if at the
end of 4 weeks there is no improvement or just
mild to moderate improvement in scabies-
related pruritus (Score 13), appearance of new
lesions or persistence of mites and their prod-
ucts on microscopy.
Statistical analysis
R
Data were analyzed using Excel for WindowsV.
Data were expressed in the form of Mean 6 Stan-
dard Deviation (SD) as well as median and range.
Comparison between the two groups of patients
was done using the MannWhitney Rank Sum test
using the following web site (http://elegans.som.
vcu.edu). All p values were two-tailed and p value
was considered significant when it is 0.05.
Results
The age of patients included in the study ranged
from 5 to 75 years (mean and SD: 21.8 6 15). All
patients included in the study were confirmed to
have scabies (uncomplicated) based on the clini-
cal and laboratory diagnostic criteria mentioned
in Materials and Methods section. Tables 13
show score of pruritus and lesion counts for all
cases included in the study.
Clinical response
At 1 week after first treatment it was noticed that
87.5% (n 5 28) and 73.5% (n 5 22) of patients
were symptoms- and clinical signs-free in group
I and group II respectively (p < 0.001 compared
to baseline for both groups). However, the differ-
ence in cure rates between the two groups was
not statistically significant (p 5 0.29). Because of
persistent symptoms and/or clinical lesions, a
second treatment was required in 4 (12.5%)
patients of group I and 8 (26.6%) patients of
group II. This increased the cure rates to 100%,
so that at 2 weeks after first treatment all symp-
toms and signs completely resolved in all cases
with no symptoms or signs of disease recurrence
at the fourth week of follow up (p < 0.001 com-
pared to baseline for both groups).
Subjective evaluation
Pruritus was a constant symptom among all
patients before treatment. However, after

60
 Clinical efficacy and safety

Table 2. Lesion counts scores before and after treatment with topical and oral ivermectin.

Scores of lesions counts before, during and after treatment in Groups I & II
Group I Group II
Topical ivermectin (n532 cases) Oral ivermectin (n530 cases)
Number of Number of p-value**
cases with Mean score 6 SD cases with Mean score 6 SD (Group I versus
different scores (Median; range) different scores (Median; range) Group II)
Before treatment Score 0 5 0 1.5 6 0.55 Score 0 5 0 1.7 6 0.53 0.49
(2; 13) (2; 13) (Insignificant)
Score 1 5 14 Score 1 5 10
Score 2 5 17 Score 2 5 19
Score 3 5 1 Score 3 5 1
One week after Score 0 5 28 0.12 6 0.33 Score 0 5 22 0.36 6 0.66 0.29
first treatment (0; 01) (0; 02) (Insignificant)
Score 1 5 4 Score 1 5 5
Score 2 5 0 Score 2 5 3
Score 3 5 0 Score 3 5 0
2 and 4 weeks Score 0 5 32 0.0 6 0.0 Score 0 5 30 0.0 6 0.0 N/A
after treatment Score 1 5 0 Score 1 5 0
Score 2 5 0 Score 2 5 0
Score 3 5 0 Score 3 5 0

* 5 Mean 6 SD.
** 5 p-value calculated by MannWhitney Rank Sum test.

treatment it was observed that pruritus disap-
peared more quickly in patients of group I
receiving topical ivermectin than those of group
II receiving oral ivermectin. At one week after
treatment, pruritus disappeared in 90.6% (n 5 29)
and 76.6% (n 5 23) of patients and pruritus score
changed from a mean of 2.4 6 0.5 and 2.6 6 0.6
to a mean of 0.09 6 0.2 and 0.5 6 1 in group I
and II, respectively (p < 0.001 for both groups).
When pruritus scores of the two groups were
statistically compared at one week after treat-
ment, the scores were not significantly different
(p 5 0.29). After the second treatment of persis-
tent cases in both groups, pruritus completely
disappeared (p < 0.001 compared to baseline for
both groups; Tables 13).
Objective evaluation
KOH smear test was negative in all patients after
one week of treatment and was still negative at 2
and 4 weeks after treatment. However, in some
patients (4 in group I and 8 in group II) symp-
toms and/or signs of infection were still present
at first week of follow up despite negative KOH
smear.
Clinically, the number of scabies lesions
showed highly significant decrease after treat-
ment in both groups (p < 0.001 for both groups).
After 1 week of treatment, the score of lesion
counts changed from a mean of 1.5 6 0.5 and
1.7 6 0.5 to a mean of 0.1 6 0.3 and 0.3 6 0.6 in
group I and II, respectively (Tables 13). How-
ever, the difference between the two groups was
statistically insignificant (p 5 0.27). With further
follow up, lesions completely disappeared in all
patients after 2 weeks of treatment with no
recurrences at 4-weeks end point (p < 0.001 com-
pared to baseline for both groups).
Tolerance and side effects
Both topical and oral ivermectin treatments were
well tolerated. Adverse events, whether cutane-
ous (e.g., topical irritation or dermatitis) or sys-
temic (e.g., headache, dizziness, diarrhea,
vomiting, muscle pain) were mild and rare
among both groups. Furthermore, none of the
patients stopped treatment because of side
effects.
Discussion
Scabies represents a major health problem in
many communities (1). Several medications are
available to treat scabies including oral and topi-
cal ivermectin and many studies have compared
the efficacy of either topical or oral ivermectin

61
Ahmad et al.

versus other traditional anti scabies agents. How-

value**
<0.001

<0.001
ever, only few studies (11) have compared

p
topical versus oral ivermectin in treatment of
scabies. The aim of this work was to compare
After 2 & 4
the therapeutic efficacy and safety of topical ver-
weeks*
sus oral ivermectin in patients with uncompli-
cated scabies.
0.0

0.0
The results of this work confirm that both top-
ical and oral ivermectin are effective in treat-
value**
Lesion count (Score)

<0.001

<0.001 ment of uncomplicated scabies. The cure rates

p

were 87.5% and 73.5% after one week of a single

dose of either topical or oral ivermectin respec-
Table 3. Changes in scabies-related pruritus and lesion count score before and after treatment in group I and II

tively with no statistically significant difference

(Median; range)

between two groups (p 5 0.29). In those cases

After first
week*

with persistent symptoms and/or lesions a sec-

0.1 6 0.3

0.3 6 0.6

ond application or oral dose of ivermectin was

(0; 01)

(0; 02)

curative. Therefore, by the end of the study (4

weeks), the cure rate was 100% in both groups.
These results suggest that a single dose of either
(Median; range)

topical or oral ivermectin is effective in treat-

Treatment*

ment of uncomplicated scabies, may be with

Before

earlier response to treatment being observed

1.6 6 0.5

1.7 6 0.5
(2; 13)

(2; 13)

among those treated with topical than oral iver-

mectin. However, in some cases, a second dose
may be required after one week whether topical
or oral ivermectin was used in treatment. This
value**
<0.001

<0.001

may be explained on the basis that ivermectin is

p

not ovicidal (14) and hence a second dose may

be required within 1 or 2 weeks for 100% cure
rate.
After 2 & 4
weeks*

Previous studies had observed scabies cure

rates of 69.3% after one topical application (11)
0.0

0.0

and 100% after two topical applications of iver-

mectin lotion (11,15,16). Whereas treatment with
oral ivermectin, previous studies had observed
value**
<0.001

<0.001
Pruritus (Score)

cure rates ranging from 30% to 79.3% at the end

p

** 5 p-value calculated by MannWhitney Rank Sum test.

of the first week of single oral dose (11,14,17,18)

and cure rates of 63% to 100% at the end of the
week* (Median;

second week of two oral doses (11,17). Taken

After first

together these previous observations and ours

range)

suggest that repeating the treatment of scabies

0.1 6 0.2
(0; 01)

(0; 03)
0.5 6 1

with either topical or oral ivermectin is required

to achieve 100% cure.
The results of our study show earlier improve-
ment of pruritus scores following topical than
(Median; range)

oral ivermectin, although this was not statisti-

Treatment*
Before

cally significant. However, previous studies have

2.4 6 0.5

2.6 6 0.6

reported significantly lower scabies-related pruri-

(2; 23)

(3; 13)

tus scores following topical than oral ivermectin

* 5 Mean 6 SD.

(11,17). A larger group of patients may be

required to clarify this observation.
(Topical)

In this study, both topical and oral ivermectin

Group II
Group I

(Oral)

were well tolerated by all patients. None of the

patients stopped treatment because of side
effects. This, together with previous observations,

62

(11) suggests that both topical and oral ivermec-
tin have high safety profile in treatment of
scabies.
In conclusion: This study suggests that both
topical and oral ivermectin are safe and equally
effective in treatment of uncomplicated scabies,
probably with topical ivermectin providing faster
cure of scabies and its related pruritus. Single
treatment, whether topical or oral, is associated
with high cure rate in a week post treatment.
However, repeating either topical or oral iver-
mectin after one week may be required to
achieve 100% cure.
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