Is there a benefit to switching to ivermectin (antiparasitic medication) for treatment when permethrin (pyrethroid insecticide) is ineffective?

From the Guidelines

Switching to oral ivermectin can be beneficial when topical permethrin treatment fails for conditions like scabies or certain parasitic infestations. The typical ivermectin dosage is 200 micrograms per kilogram of body weight, taken as a single oral dose and often repeated after 7-14 days, as recommended by the 2015 sexually transmitted diseases treatment guidelines 1. For an average adult weighing 70kg, this equals about 14mg. Ivermectin works through a different mechanism than permethrin - it paralyzes parasites by binding to glutamate-gated chloride channels in their nerve and muscle cells, while permethrin disrupts sodium channels. This different mode of action makes ivermectin effective against permethrin-resistant parasites.

Key Considerations

• Ivermectin offers advantages of better systemic distribution throughout the body, reaching areas that topical treatments cannot, and improved compliance since it requires only one or two oral doses rather than full-body application of creams.
• However, ivermectin should be used with caution in pregnant women, children weighing less than 15kg, and patients with certain neurological conditions, as noted in the 2015 guidelines 1.
• Common side effects may include headache, dizziness, muscle pain, and gastrointestinal disturbances, which are usually mild and transient.
• It's also important to consider the potential for resistance to permethrin, as reported in the 2010 Pediatrics study on head lice 1, which may necessitate the use of alternative treatments like ivermectin.

Dosage and Administration

• The recommended dosage of ivermectin is 200 micrograms per kilogram of body weight, taken as a single oral dose and often repeated after 7-14 days 1.
• Ivermectin should be taken with food because bioavailability is increased, in turn increasing penetration of the drug into the epidermis, as noted in the 2015 guidelines 1.

From the FDA Drug Label

The safety and pharmacokinetic properties of ivermectin were further assessed in a multiple-dose clinical pharmacokinetic study involving healthy volunteers. Ivermectin is active against various life-cycle stages of many but not all nematodes. Efficacy, as measured by cure rate, was defined as the absence of larvae in at least two follow-up stool examinations 3 to 4 weeks post-therapy.

There is no direct information in the provided drug label that supports the benefit of switching to ivermectin when permethrin is ineffective. No conclusion can be drawn regarding the benefit of switching to ivermectin in this scenario, as the label does not directly address this question 2.

From the Research

Benefits of Switching to Ivermectin

• There are several studies that compare the efficacy of ivermectin and permethrin in the treatment of scabies 3, 4, 5, 6, 7.
• The results of these studies suggest that oral ivermectin and topical permethrin are equally efficacious in the treatment of scabies 3, 4, 6.
• A study found that a single dose of ivermectin provided a cure rate of 70%, which increased to 95% with two doses at a two-week interval, while a single application of permethrin was effective in 97.8% of patients 5.
• Another study found that two doses of ivermectin were as effective as a single application of permethrin, and that permethrin-treated patients recovered earlier 5.
• Topical ivermectin has also been shown to be effective in the treatment of scabies, with a cure rate of 63.1% at the 2-week follow-up and 84.2% at the 4-week follow-up after repeating the treatment 7.
• The studies also suggest that ivermectin is well tolerated and has few side effects, making it a useful alternative to permethrin for patients who are intolerant to topical treatments 3, 4, 6.

Comparison of Efficacy

• A comparative study found that oral ivermectin and topical permethrin cream had similar cure rates at the end of 4 weeks, with 94.7% of patients in the permethrin group and 90% of patients in the ivermectin group achieving cure 6.
• Another study found that two applications of topical ivermectin were as effective as two applications of permethrin 2.5% cream at the 2-week follow-up, and that ivermectin was as effective as permethrin 2.5% cream at the 4-week follow-up after repeating the treatment 7.
• The Cochrane review found that oral ivermectin may lead to slightly lower rates of complete clearance after one week compared to permethrin 5% cream, but that there may be little or no difference in complete clearance rates after two weeks or four weeks 4.

Safety and Tolerability

• The studies suggest that ivermectin is well tolerated and has few side effects, making it a useful alternative to permethrin for patients who are intolerant to topical treatments 3, 4, 6.
• A study found that there was no difference in the number of participants with at least one adverse event between the ivermectin and permethrin groups, and that adverse events were rare and of mild intensity 4.
• Another study found that ivermectin was well tolerated, with no serious adverse events reported 6.