Clinical Review & Education

JAMA Dermatology Clinical Evidence Synopsis

Evaluation of Ivermectin vs Permethrin for Treating Scabies—

Summary of a Cochrane Review
Stefanie Rosumeck, MA; Alexander Nast, MD; Corinna Dressler, MSc, PhD

CLINICAL QUESTION Is the use of ivermectin in patients infested with scabies associated with
improved clinical and safety outcomes compared with permethrin?

BOTTOM LINE Both ivermectin and permethrin treatment were associated with high
clearance rates. There is low-certainty evidence that ivermectin was associated with slightly
lower rates of complete clearance after 1 week compared with permethrin, 5%, cream
(relative risk [RR], 0.65; 95% CI, 0.54-0.78). After 2 weeks, there was no difference in
efficacy (RR, 0.91; 95% CI, 0.76-1.08; low-certainty evidence), or in the number of
participants with adverse events (week 4: RR, 1.30; 95% CI, 0.35-4.83; low-certainty
evidence).

Introduction Systemic ivermectin treatment may be preferred if proper ap-

Scabies is an intensely itchy parasitic infestation of the skin. It oc-
curs worldwide but is particularly problematic in areas of poor sani-
tation, overcrowding, and social disruption. Permethrin and iver-
mectin have become the key interventions for scabies.1,2 This Clinical
Evidence Synopsis summarizes a Cochrane review3 assessing the ef-
ficacy and safety of permethrin and ivermectin for treating pa-
tients infested with scabies.
Summary of Findings
Oral ivermectin treatment at a standard dose of 200 μg/kg may be
associated with slightly lower rates of complete clearance of sca-
bies after 1 week compared with permethrin, 5%, cream (whole-
body application; relative risk [RR], 0.65; 95% CI, 0.54-0.78; low-
certainty evidence; Table 1), but may also be associated with little
or no difference in rates of complete clearance by week 2 (RR, 0.91;
95% CI, 0.76-1.08; low-certainty evidence) or week 4 (RR, 1.00; 95%
CI, 0.86-1.16; high-certainty evidence). There was little or no differ-
ence in rates of complete clearance between oral ivermectin and
1 application of permethrin lotion after 1 week (moderate-certainty
evidence) and 2 weeks (low-certainty evidence, Table 1).
After 4 weeks, ivermectin may be associated with a slightly larger
proportion of participants with at least 1 adverse event (AE) (RR, 1.30;
95% CI, 0.35-4.83; low-certainty evidence, Table 2). Studies with
repeated applications of either treatment did not report more AEs.
However, AEs were rarely and poorly reported. For systemic iver-
mectin, headache and nausea were relevant and likely related
findings, whereas for permethrin, erythema, burning, and pruritus
were noted.
Discussion
Permethrin and ivermectin were both associated with high clear-
ance rates in the treatment of scabies. Highly relevant differences
could not be seen. The choice of 1 of these treatments can be guided
by considerations such as practicability, availability, drug licensing,
and costs, depending on the individual setting.
plication of permethrin to the whole body cannot be ensured, or if
very large groups of patients need to be treated. The need for a single
vs a repeated application cannot be properly answered based on the
available evidence. For most patients, a 1-time treatment is suffi-
cient. When deciding on the necessity for a repeated treatment, fac-
tors such as the extent of the disease, the number of contact per-
sons affected, the likelihood of correct application, the immune
status of the patient, and the clinical response seen during fol-
low-up visits should be taken into consideration.
Limitations
Many included trials were poorly reported and had a moderate risk
of bias. Applicability to Western countries and external validity is lim-
ited owing to studies being conducted in regions with high preva-
lence rates and in resource-poor countries. The identified single-
Evidence Profile
No. of randomized clinical trials: 15
Study years: 1996-2016 (published)
Literature search: Up to April 25, 2017
No. of patients: 1896 (women: 45.22%, 11 studies reported)
Age: 2-80 years (14 studies reported)
Setting: Outpatient clinics or departments of medical colleges or
hospitals
Countries: India (n=10), Pakistan (n=2), Egypt (n=2), Mexico (n=1)
Comparison: Oral ivermectin vs topical permethrin; oral ivermec-
tin vs topical ivermectin; topical ivermectin vs topical permethrin;
oral ivermectin vs oral ivermectin in different doses
Primary outcome: Complete clearance (ie, cure or improvement,
as defined in each study)
Secondary outcomes: Number of people retreated; number of
people with at least 1 adverse event (AE); number of people with-
drawn from study owing to AEs

jamadermatology.com (Reprinted) JAMA Dermatology Published online April 24, 2019 E1

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Idaho State University User on 04/25/2019

 Clinical Review & Education JAMA Dermatology Clinical Evidence Synopsis

Table 1. Number of Patients With Complete Clearance With Ivermectin, 200 μg/kg, or Permethrin, 5%, Creama

Events/Total, No. (%)

Ivermectin Permethrin Weight, Risk Ratio Certainty of the
Source (1-3 doses) (1-3 applications) %b (95% CI)b Evidence
After 1 week of
treatment
Bachewar et al, 15/34 (44) 23/34 (68) 13.1 0.65 (0.42-1.02)
2009
Meenakshi 32/70 (46) 52/70 (74) 22.7 0.62 (0.46-0.82)
et al, 2014
a
Rohatgi et al, 28/50 (56) 34/50 (68) 21.0 0.82 (0.60-1.12) For full citations and study
2013 characteristics see the Cochrane
Sharma et al, 26/80 (33) 27/40 (68) 16.2 0.48 (0.33-0.71) Review.3 Details of the diagnostic
2011 criteria can be found in the
Usha et al, 4/40 (10) 14/45 (31) 3.1 0.32 (0.12-0.90) Cochrane Review, Appendix 4. The
2000 definition and diagnosis of complete
Wankhade 29/50 (58) 39/50 (78) 23.8 0.74 (0.56-0.98) clearance can also be found in the
et al, 2016 Cochrane Review.3
b
Total 134/324 (41) 189/289 (65) 100 0.65 (0.54-0.78)c Lowd Mantel-Haenszel, random effects
After 2 weeks of model.
c
treatment Heterogeneity: χ 52 = 7.65 (P = .18);
Bachewar et al, 27/34 (79) 27/34 (79) 21.7 1.00 (0.79-1.27) I2 = 35%. Test for overall effect:
2009 z = 4.52 (P < .001).
Mushtaq et al, 24/44 (55) 20/42 (48) 12.0 1.15 (0.76-1.74) d
Downgraded for serious risk of bias
2010 (moderate) and serious imprecision
Rohatgi et al, 45/50 (90) 46/50 (92) 31.1 0.98 (0.86-1.11) (confidence interval crosses
2013 minimal clinically important
Sharma et al, 57/80 (71) 33/40 (83) 24.9 0.86 (0.71-1.05) difference threshold: statistically
2011 significant difference of uncertain
Usha et al, 14/40 (35) 31/45 (69) 10.3 0.51 (0.32-0.81) clinical importance).
2009 e
Heterogeneity: χ 42 = 10.23,
Total 167/248 (67) 157/211 (74) 100 0.91 (0.76-1.08)e Lowf (P = .04); I2 = 61%. Test for overall
After 4 weeks of effect: z = 1.08 (P = .28).
treatment f
Downgraded for serious risk of bias
Sharma et al, 36/40 (90) 36/40 (90) 100 1.00 (0.86-1.16) High (moderate) and for serious
2011 inconsistency (I2 = 61%, P = .04).

Table 2. Safety Outcomes for Ivermectin, 200 μg/kg, vs Permethrin, 5%, Creama

Events/Total, No. (%)

Ivermectin Permethrin Weight, Risk Ratio Certainty of the
Source (1-3 doses) (1-3 applications) %b (95% CI)b Evidence
Patients with at least 1 adverse event,
within 2 weeks after treatment
initiation
Bachewar et al, 2009 0/27 (0) 0/28 (0) - Not Moderatec
estimable
Patients with at least 1 adverse event,
within 4 weeks after treatment
initiation
Chhaiya et al, 2012 2/100 (2.0) 1/99 (1.0) 19.3 1.98
(0.18-21.49)
Mushtaq et al, 2010 8/44 (18.2) 1/42 (2.4) 23.3 7.64
(1.00-58.46) a
For full citations and study
Sharma et al, 2011 6/79 (7.6) 5/38 (13.2) 38.0 0.58 characteristics see the Cochrane
(0.19-1.77)
Review.3
Wankhade et al, 2016 1/50 (2.0) 2/50 (4.0) 19.4 0.50 b
(0.05-5.34) Mantel-Haenszel, random effects
model.
Total 17/273 (6.2) 9/229 (3.9) 100 1.30 Lowe
c
(0.35-4.83)d Downgraded for serious risk of bias
Withdrawal due to adverse event, within (moderate).
4 weeks after treatment initiation d
Heterogeneity: χ 32 = 5.79 (P = .12);
Manjhi et al, 2014 0/60 (0) 0/60 (0) - Not I2 = 48%. Test for overall effect:
estimable z = 0.39 (P = .70).
Usha et al, 2000 0/40 (0) 0/45 (0) - Not e
Downgraded for serious risk of bias
estimable
(moderate) and serious imprecision
Wankhade et al, 2016 0/50 (0) 0/50 (0) - Not (CI crosses minimal clinically
estimable
important difference threshold:
Total 0/150 (0) 0/155 (0) - Not Moderatec statistically significant difference of
estimable uncertain clinical importance).

E2 JAMA Dermatology Published online April 24, 2019 (Reprinted) jamadermatology.com

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Idaho State University User on 04/25/2019

 JAMA Dermatology Clinical Evidence Synopsis Clinical Review & Education

center studies were heterogeneous and included predominately following systemic ivermectin treatment were found to be supe-
small numbers of participants. rior to topical permethrin treatment.

Comparison of Findings With Current Literature Areas in Need of Future Study

The present results are similar to a published comprehensive sys-
tematic review considering several scabies treatments4 and cur-
rent guidelines.5 Of interest is also a larger study by Romani et al,6
who randomized 3 island communities to either permethrin for only
affected patients and their contacts, permethrin for all island inhab-
itants, or ivermectin for all inhabitants. After 12 months, outcomes
Public health questions like mass drug interventions for preven-
tion and treatment of scabies should be further investigated. Resis-
tance toward permethrin continues to be a matter of debate, but
studies are lacking. Further studies with clear and strict treatment
regimens, a larger sample size, and better documentation and clas-
sification of AEs are needed.

ARTICLE INFORMATION
Author Affiliations: Division of Evidence-Based
Medicine, Department of Dermatology,
Venereology, and Allergology, Charité–
Universitätsmedizin Berlin, Freie Universität Berlin,
Humboldt-Universität zu Berlin, Berlin Institute of
Health, Berlin, Germany.
Corresponding Author: Alexander Nast, MD,
Division of Evidence-Based Medicine, Department
of Dermatology, Venereology, and Allergology,
Charité–Universitätsmedizin Berlin, Freie
Universität Berlin, Humboldt-Universität zu Berlin,
Berlin Institute of Health, Charitéplatz 1, 10117
Berlin, Germany (alexander.nast@charite.de).
Published Online: April 24, 2019.
doi:10.1001/jamadermatol.2019.0279
Conflict of Interest Disclosures: None reported.
REFERENCES
1. Banerji A; Canadian Paediatric Society, First
Nations, Inuit and Métis Health Committee.
Scabies. Paediatr Child Health. 2015;20(7):395-402.
doi:10.1093/pch/22.7.395
2. Robert Koch Institut. RKI Guide Scabies.
http://www.rki.de/DE/Content/Infekt/EpidBull/
Merkblaetter/Ratgeber_Skabies.html. Accessed
May 25, 2017.
3. Rosumeck S, Nast A, Dressler C. Ivermectin and
permethrin for treating scabies. Cochrane Database
Syst Rev. 2018;4:CD012994.
4. Dressler C, Rosumeck S, Sunderkötter C, Werner
RN, Nast A. The treatment of scabies. Dtsch Arztebl
Int. 2016;113(45):757-762.
5. Salavastru CM, Chosidow O, Boffa MJ, Janier M,
Tiplica GS. European guideline for the management
of scabies. J Eur Acad Dermatol Venereol. 2017;31
(8):1248-1253. doi:10.1111/jdv.14351
6. Romani L, Whitfeld MJ, Koroivueta J, et al. Mass
drug administration for scabies control in a
population with endemic disease. N Engl J Med.
2015;373(24):2305-2313. doi:10.1056/
NEJMoa1500987

jamadermatology.com (Reprinted) JAMA Dermatology Published online April 24, 2019 E3

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Idaho State University User on 04/25/2019