Overview for healthcare professionals

Ivermectin is an anthelmintic that acts against infections caused by parasitic worms (helminths). It also appears to be effective against other endoparasites and ectoparasites. Oral ivermectin has been used to treat crusted scabies that does not respond to topical treatment alone (British National Formulary 2014). It has also been used to treat other forms of 'difficult-to-treat' scabies (for example, if a topical treatment can't be used or hasn't worked). There are also reports in the literature about using oral ivermectin to treat outbreaks of scabies in mass care settings, such as nursing homes.

Regulatory status of ivermectin

Ivermectin is unlicensed in the UK.

Oral ivermectin is licensed in the USA for the treatment of strongyloidiasis and onchocerciasis parasitic infections, and in France for the treatment of strongyloidiasis and scabies. It is available on a named-patient basis in the UK from 'special order' manufacturers or specialist importing companies (British National Formulary 2014).

In line with the guidance from the General Medical Council (GMC), it is the responsibility of the prescriber to determine the clinical need of the patient and the suitability of using ivermectin.

Evidence statements

For the treatment of classical or uncomplicated scabies

  • Most randomised controlled trials (RCTs) used a single oral dose of ivermectin 200 micrograms/kg.

  • Ivermectin was superior to placebo (1 RCT).

  • Ivermectin was superior to benzyl benzoate in 1 RCT, not statistically significantly different in 3 RCTs and inferior in 1 RCT.

  • Ivermectin was inferior to permethrin in 3 RCTs and not statistically significantly different in 3 RCTs (4 comparisons, 2 from the same trial).

  • Treatment failure rates with ivermectin varied widely in these RCTs, from 7% to 70% (see tables 1, 2 and 3 for details).

  • Differences in treatment regimens and the length of follow-up may explain some of the heterogeneity in the results of the different studies.

  • Adverse events reported in people receiving oral ivermectin include aggravation of symptoms (including pruritus), irritation, headache, nausea, pustular rash, cellulitis, abdominal pain, and mild diarrhoea.

For the treatment of crusted scabies

  • No RCTs that assessed oral ivermectin for the treatment of crusted scabies were identified. Five uncontrolled trials and case series with 4 or more participants with crusted scabies that reported cure rates or treatment failures were identified.

  • Multiple doses of oral ivermectin and/or ivermectin in combination with topical therapy were frequently administered to cure scabies in the studies identified.

  • Treatment failure rates varied widely (see table 4 for details).

Summary of the evidence

This section gives a brief summary of the main evidence. A more thorough analysis is given in the Evidence review section.

Efficacy

Classical or uncomplicated scabies

A Cochrane systematic review has evaluated topical and systemic drugs for treating scabies. The review included 1 RCT that compared oral ivermectin with placebo, 5 RCTs that compared oral ivermectin with benzyl benzoate and 2 RCTs that compared oral ivermectin with permethrin. Since the publication of the Cochrane systematic review, 4 RCTs comparing oral ivermectin with permethrin have been published.

The primary outcome of the Cochrane systematic review was treatment failure, defined as the persistence of original lesions, the appearance of new lesions or confirmation of a live mite. Treatment failure has been calculated for the 4 additional RCTs identified.

Table 1 shows the results of the only RCT that compared oral ivermectin with placebo. Ivermectin was superior to placebo at 1 week.

Table 1 Treatment failure in trials of oral ivermectin compared with placebo

Trial

Ivermectin

Placebo

Analysis

Macotela-Ruíz and Peña-González (1993) a

200 micrograms/kg ivermectin vs. placebo, follow-up at 7 days

6/29 (21%)

22/26 (85%)

RR 0.24

(95% CI 0.12 to 0.51)

Statistically significant difference in favour of ivermectin

Abbreviations: CI, confidence interval; RR, risk ratio (or relative risk).

a Results extracted from the Cochrane systematic review.

Five RCTs compared oral ivermectin with topical benzyl benzoate. Ivermectin was superior to benzyl benzoate in 1 trial at 4 weeks, not statistically significantly different in 3 trials (at 1, 3 and 4 weeks) and inferior in 1 trial (at 2 weeks). Differences in treatment regimens and the length of follow-up may explain some of the heterogeneity in the results (see table 2).

Table 2 Treatment failure in trials of oral ivermectin compared with topical benzyl benzoate

Trial

Ivermectin

Benzyl benzoate

Analysis

Glaziou et al. (1993) a

100 micrograms/kg ivermectin vs. 10% benzyl benzoate 2×12 h, follow-up at 30 days

7/23 (30%)

11/21 (52%)

RR 0.58

(95% CI 0.28 to 1.22)

No statistically significant difference

Nnoruka and Agu (2001) a

200 micrograms/kg ivermectin vs. 25% benzyl benzoate 72 h, follow-up at 30 days

2/29 (7%)

15/29 (52%)

RR 0.13

(95% CI 0.03 to 0.53)

Statistically significant difference in favour of ivermectin

Brooks and Grace (2002) a

200 micrograms/kg ivermectin vs. 10% benzyl benzoate overnight, follow-up at 3 weeks

19/43 (44%)

18/37 (49%)

RR 0.91

(95% CI 0.57 to 1.46)

No statistically significant difference

Bachewar et al. (2009) a

200 micrograms/kg ivermectin vs. 25% benzyl benzoate overnight × 2, follow-up at 1 week

14/27 (52%)

6/25 (24%)

RR 2.16

(95% CI 0.98 to 4.74)

No statistically significant difference

Ly et al. (2009) a

150–200 micrograms/kg ivermectin vs. 12.5% benzyl benzoate 1 or 2 overnights, follow-up at 14 days

38/54 (70%)

38/108 (35%)

RR 2.00

(95% CI 1.47 to 2.72)

Statistically significant difference in favour of benzyl benzoate

Abbreviations: CI, confidence interval; h, hours; RR, risk ratio (or relative risk).

a Results extracted from the Cochrane systematic review

The Cochrane systematic review included 2 RCTs that compared oral ivermectin with topical permethrin. Both trials found that ivermectin was inferior to permethrin at 1 or 2 weeks. Four other RCTs were published after the Cochrane review, 1 of which compared 2 dosing strategies of ivermectin. In these 4 trials, ivermectin was found to be inferior to permethrin in 1 RCT at 1 week, and not statistically significantly different in 3 RCTs (4 comparisons, 2 from the same trial) at 2 or 4 weeks. Differences in the length of follow-up may explain some of the heterogeneity in the results (see table 3).

Table 3 Treatment failure in trials of oral ivermectin compared with topical permethrin

Trial

Ivermectin

Permethrin

Analysis

Usha and Gopalakrishnan Nair (2000) a

200 micrograms/kg ivermectin vs. 5% permethrin overnight, follow-up at 2 weeks

12/40 (30%)

1/45 (2%)

RR 13.50

(95% CI 1.84 to 99.26)

Statistically significant difference in favour of permethrin

Bachewar et al. (2009) a

200 micrograms/kg ivermectin vs. 5% permethrin overnight, follow-up at 1 week

14/27 (52%)

5/28 (18%)

RR 2.90

(95% CI 1.21 to 6.96)

Statistically significant difference in favour of permethrin

Sharma and Singal (2011)

200 micrograms/kg ivermectin vs. 5% permethrin overnight, follow-up at 4 weeks

4/40 (10%)

2/38 (5%)

p=0.769 for treatment failure

No statistically significant difference

Sharma and Singal (2011)

2 doses of 200 micrograms/kg ivermectin 2 weeks apart vs. 5% permethrin overnight, follow-up at 4 weeks

4/39 (10%)

2/38 (5%)

p=0.769 for treatment failure

No statistically significant difference

Chhaiya et al. (2012)

200 micrograms/kg ivermectin vs. 5% permethrin >8 h, follow-up at 1 week

70/100 (70%)

25/99 (25%)

p<0.05 for clinical cure

Statistically significant difference in favour of permethrinb

Goldust et al. (2012)

200 micrograms/kg ivermectin vs. 5% permethrin 2×12 h 1 week apart, follow-up at 2 weeks

17/121 (14%)

9/121 (7%)

p=0.42 for clinical cure

No statistically significant difference

Saqib et al. (2012)

200 micrograms/kg ivermectin vs. 5% permethrin 10–12 h, follow-up at 2 weeks

20/60 (33%)

20/60

(33%)

p=1.0 for clinical cure

No statistically significant difference

Abbreviations: CI, confidence interval; h, hours; p, p value; RR, risk ratio (or relative risk).

a Results extracted from the Cochrane systematic review.

b In this trial clinical cure was assessed weekly. If there were no signs of cure the treatment was repeated. By the third week there was no statically significant difference between ivermectin and permethrin.

No RCTs comparing oral ivermectin with malathion were identified.

Crusted scabies (also known as hyperkeratotic, Norwegian or atypical scabies)

No RCTs of oral ivermectin for the treatment of crusted scabies were identified.

Uncontrolled trials and case series with 4 or more participants with crusted scabies that reported cure rates or treatment failures are summarised in table 4.

Table 4 Ivermectin for crusted scabies

Trial

Population

Intervention

Treatment failure rate

Huffam and Currie (1998)

20 people with crusted scabies refractory to initial treatment

1 to 3 doses of ivermectin, 14 days apart; 3 treatments with 5% permethrin overnight during 1 week plus keratolytic therapy with 10% urea and 5% lactic acid

12/20 (60%)

Larralde et al. (1999)

2 people with Down's syndrome and crusted scabies refractory to topical 5% permethrin

1 dose of 200 micrograms/kg ivermectin

2/2 (100%)

2 doses of 200 micrograms/kg ivermectin 2 to 3 weeks apart

0/2 (0%)

2 HIV-positive people with crusted scabies

2 doses of 200 micrograms/kg ivermectin 1 week apart

0/2 (0%)

Alberici et al. (2000)

8 HIV-positive people with crusted scabies

1 dose of 200 micrograms/kg ivermectin

1/1 (100%)

Topical 15% benzyl benzoate solution applied twice daily for 3 days

3/3 (100%)

1 dose of 200 micrograms/kg ivermectin plus topical 15% benzyl benzoate solution applied twice daily for 3 days

0/4 (0%)

Paasch and Haustein (2000)

12 people with crusted scabies from 3 residences for the elderly

1 or 2 doses of 12 mg ivermectin (second dose after 8 days) 

0/12 (0%)

Nofal (2009)

8 people with crusted scabies

1 dose of 200 micrograms/kg oral ivermectin

6/8 (75%)

2 doses of 200 micrograms/kg oral ivermectin 2 weeks apart

2/6 (33%)

3 doses of 200 micrograms/kg oral ivermectin 2 weeks apart plus topical therapy with permethrin 5% and salicylic acid 5%

0/2 (0%)

Safety

Adverse events reported in people receiving oral ivermectin in RCTs for classical or uncomplicated scabies include aggravation of symptoms (including pruritus), irritation, headache, nausea, pustular rash, cellulitis, abdominal pain and mild diarrhoea. The adverse events reported in individual trials are summarised in tables 5, 6 and 7.

Table 5 Safety in trials of oral ivermectin compared with placebo

Trial

Ivermectin

Placebo

Analysis

Macotela-Ruíz and Peña-González (1993) a

200 micrograms/kg ivermectin vs. placebo, follow-up at 7 days

None recorded

None recorded

a Results extracted from the Cochrane systematic review.

Table 6 Safety in trials of oral ivermectin compared with topical benzyl benzoate

Trial

Ivermectin

Benzyl benzoate

Analysis

Glaziou et al. (1993) a

100 micrograms/kg ivermectin vs. 10% benzyl benzoate 2×12 h, follow-up at 30 days

None reported

Mild increase in pruritus: 5/21 (24%)

Not reported

Nnoruka and Agu (2001) a

200 micrograms/kg ivermectin vs. 25% benzyl benzoate 72 h, follow-up at 30 days

None reported

Pruritus and irritation: 7/29 (24%)

Not reported

Brooks and Grace (2002) a

200 micrograms/kg ivermectin vs. 10% benzyl benzoate overnight, follow-up at 3 weeks

Pustular rash: 3/43 (7%)

Cellulitis: 1/43 (2%)

Burning or stinging: 6/37 (16%)

Dermatitis: 6/37 (16%)

Not reported

Bachewar et al. (2009) a

200 micrograms/kg ivermectin vs. 25% benzyl benzoate overnight × 2, follow-up at 1 week

None reported

None reported

Ly et al. (2009) a

150–200 micrograms/kg ivermectin vs. 12.5% benzyl benzoate 1 or 2 overnights, follow-up at 14 days

Abdominal pain: 5/65 (8%)

Mild diarrhoea: 2/65 (3%)

Irritant dermatitis: 30/116 (26%)

Not reported

Abbreviations: h, hours

a Results extracted from the Cochrane systematic review.

Table 7 Safety in trials of oral ivermectin compared with topical permethrin

Trial

Ivermectin

Permethrin

Analysis

Usha and Gopalakrishnan Nair (2000) a

200 micrograms/kg ivermectin vs. 5% permethrin overnight, follow-up at 2 weeks

Aggravation of symptoms:

3/43 (7%)

None recorded

Not reported

Bachewar et al. (2009) a

200 micrograms/kg ivermectin vs. 5% permethrin overnight, follow-up at 1 week

None recorded

None recorded

Sharma and Singal (2011)

1 or 2 doses of 200 micrograms/kg ivermectin vs. 5% permethrin overnight, follow-up at 4 weeks

Headache:

4/80 (5%)

Nausea: 2/80 (3%)

Transient burning sensation: 3/40 (7.5%)

Pruritus: 2/40 (5%)

Not reported

Chhaiya et al. (2012)

200 micrograms/kg ivermectin vs. 5% permethrin >8 h, follow-up at 1 week

Headache:

1/100 (1%)

Increase in pruritus: 1/100 (1%)

Mild burning sensation: 1/99 (1%)

Not reported

Goldust et al. (2012)

200 micrograms/kg ivermectin vs. 5% permethrin 2×12 h 1 week apart, follow-up at 2 weeks

Irritation: 3/121 (2%)

Irritation: 6/121

(5%)

Not reported

Saqib et al. (2012)

200 micrograms/kg ivermectin vs. 5% permethrin 10–12 h, follow-up at 2 weeks

None reported

None reported

Abbreviations: h, hours.

a Results extracted from the Cochrane systematic review.

Three of the studies on the use of ivermectin for crusted scabies reported either no side effects or that no adverse effects were observed (Huffam and Currie 1998, Larralde et al. 1999 and Alberici et al. 2000). Nofal (2009) reported that no major adverse effects occurred. One person complained of gastric upset and 2 people experienced a transient increase in pruritus. Paasch and Haustein (2000) reported that one-third of people experienced an increase in pruritus for 2 days and haematomas developed in 2 people with an increase in prothrombin time.

Cost effectiveness and cost

Because ivermectin is unlicensed in the UK, no costs could be obtained from standard published sources. Informal sources suggest that the cost is around £160 for 20×3 mg tablets. No cost-effectiveness studies were identified.