Advice

Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in March 2014. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Summary

Oral ivermectin appears to be effective for treating people with classical or crusted scabies. However, differences in treatment regimens and the length of follow-up make interpreting comparisons with topical treatments difficult. Transient exacerbation of pruritus may occur at the beginning of treatment.

Regulatory status: unlicensed

The topic was prioritised because there was a high volume of requests from the NHS for information on this topic and there is uncertainty about the evidence-base for using ivermectin in scabies.

Effectiveness

  • In classical scabies, most RCTs used a single oral dose of ivermectin 200 micrograms/kg

    • Ivermectin was superior to placebo (1 RCT, n=55).

    • Ivermectin was superior to benzyl benzoate in 1 RCT (n=58), not statistically significantly different in 3 RCTs (total n=176) and inferior in 1 RCT (n=162).

    • Ivermectin was inferior to permethrin in 3 RCTs (total n=339) and not statistically significantly different in 3 RCTs (4 comparisons: total n=479).

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

  • In crusted scabies, uncontrolled trials and case series used multiple doses of oral ivermectin and/or ivermectin in combination with topical therapy (see table 4).

Safety

  • The European summary of product characteristics for ivermectin states that safety in children weighing less than 15 kg has not been established.

  • A report in 1997 suggested that ivermectin was associated with an increased risk of death among a group of elderly people with scabies in a long-term care facility, but the validity of this report has been questioned.

  • Ivermectin has been used globally in the treatment of onchocerciasis (river blindness) – serious adverse effects have been rare, even with repeated doses.

Patient factors

  • Ivermectin is an oral tablet where other treatments for scabies are topical.

  • Ivermectin is taken as a single dose, which may need to be repeated (especially in crusted scabies).

  • The European summary of product characteristics states that transient exacerbation of pruritus may occur at the beginning of treatment, but no frequency for this is given.

Resource implications

  • Ivermectin is unlicensed in the UK and can be supplied from 'special order' manufacturers or specialist importing companies. No costs could be obtained from standard published sources.*

  • Permethrin 5% cream is £6.96 for 30 g, malathion 0.5% aqueous liquid (Derbac-M) is £2.37 for 50 ml and £5.93 for 200 ml, and 25% benzyl benzoate emulsion is £2.50 for 500 ml.

* informal sources suggest that the cost is around £160 for 20×3 mg tablets.

Key points

Ivermectin is an anthelmintic used to treat infections caused by various parasites. Oral ivermectin has been used to treat crusted scabies (also known as hyperkeratotic, Norwegian or atypical scabies) that does not respond to topical treatment alone. It has also been used to treat other forms of 'difficult-to-treat' scabies (for example, if a topical treatment cannot be used or has not worked).

Ivermectin is unlicensed in the UK. It is available on a named-patient basis from 'special order' manufacturers or specialist importing companies.

The European summary of product characteristics for ivermectin 3 mg tablets (Stromectol) (Merck Sharp & Dohme: personal communication December 2013) states that the recommended dose for scabies is a single oral dose of ivermectin 200 micrograms/kg body weight. For classical scabies, recovery is considered definite only after 4 weeks have elapsed since treatment. Persistence of pruritus or scraping lesions does not justify a second treatment before this date. Administration of a second dose within 2 weeks after the initial dose should only be considered when new specific lesions occur or when parasitological examination is positive. For crusted scabies, a second dose within 8–15 days of the initial dose of ivermectin and/or concomitant topical therapy may be necessary.

A Cochrane systematic review that included 7 randomised controlled trials (RCTs) of oral ivermectin compared with placebo or topical treatments available in the UK was identified, along with 4 additional RCTs of oral ivermectin that were published after the Cochrane review. All of these trials assessed the efficacy and safety of oral ivermectin (mostly as a single oral dose of ivermectin 200 micrograms/kg) for the treatment of classical or uncomplicated scabies.

Oral ivermectin was superior to placebo in 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.

No RCTs comparing oral ivermectin with malathion were identified.

Adverse events reported in people receiving oral ivermectin in RCTs for classical or uncomplicated scabies included aggravation of symptoms (including pruritus), irritation, headache, nausea, pustular rash, cellulitis, abdominal pain and mild diarrhoea. The trials were too small to assess serious but rare potential adverse effects.

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

This evidence summary includes the results of 5 uncontrolled trials and case series with 4 or more participants with crusted scabies that reported cure rates or treatment failures. Multiple doses of oral ivermectin and/or ivermectin in combination with topical therapy were frequently administered in these studies, and treatment failure rates varied widely (see table 4 for details). More robust studies are needed to further evaluate the safety and efficacy of ivermectin for the treatment of crusted scabies.

Because ivermectin is unlicensed in the UK, no costs could be obtained from standard published sources. No data were identified that reported the extent to which ivermectin is currently being used to treat scabies in the UK.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.