What's new for head lice treatment?

Several years have elapsed since this column reviewed pharmacotherapies for head lice (Pediculus humanus capitus) infestation, a common pediatric malady when school is in session. A new prescription product to treat head lice became available in 2009. Concerns over treatment failure with current products due to drug resistance continue.

As a brief review, several pediculicides are available to clinicians and parents to treat head lice infestation.

Pyrethrin-based products (eg, RID, A-200, generic) are available over-the-counter and are natural agents derived from the chrysanthemum plant. Permethrin-based products (eg, Nix, generic) are synthetic and are described as pyrethroids ("like pyrethrin"). These products are also available over-the-counter to parents and caregivers in a 1% concentration. Permethrin-based products are labeled for use in children and infants as young as 2 months of age, while pyrethrin-based products are labeled for use at ages 2 years and older. Permethrin may have residual activity for up to two weeks after application, although many recommend that a second treatment be applied seven to 10 days. Permethrin is also available as a 5% product (Elimite, Acticin), but is labeled only for the treatment of scabies and is available only by prescription. Several other agents are available only by prescription, including malathion 0.5% (Ovide) and a new product, benzyl alcohol 5% (Ulesfia, Sciele). Other agents are available by prescription, for which fewer efficacy data are available, and all of these medications are not specifically labeled for use to treat head lice infestation. These include ivermectin, trimethoprim-sulfamethoxazole (TMP-SMX) and crotamiton. Lindane is a prescription product with very limited applicability, as it exhibits the potential for significant central nervous system toxicity and its efficacy is likely to be low.

Benzyl alcohol 5%: A new product

This year, the FDA approved labeling of benzyl alcohol 5% lotion for use in the treatment of head lice infestation in infants and children 6 months of age and older. Benzyl alcohol acts by asphyxiating lice.

Clinical studies evaluating benzyl alcohol efficacy have not been published but are described in the product's labeling. Two RCT trials were conducted in infants and children 6 months of age in which benzyl alcohol was compared with product vehicle only. At 14 days post-treatment (two treatments separated by seven days), about 75% of 127 trial participants receiving active drug were free of live lice, compared with 4.8% to 26.2% of trial participants receiving vehicle only. Ulesfia lotion is applied to dry hair and left in place for 10 minutes, and rinsed. As this product has no ovicidal activity, a second treatment seven days later is necessary. The most common adverse effects reported in these clinical trials were pruritus and erythema. Ulesfia is available as an 8-ounce bottle, and product labeling lists that three to four bottles are necessary per treatment for children with long hair (16-22 inches), and four to six bottles per treatment for children with longer hair (greater than 22 inches). Cost of Ulesfia is approximately $30 for an 8-ounce bottle.

Resistance: A growing concern

Resistance by head lice to the above medications is frequently cited in the literature as a cause of treatment failure. Resistance to pyrethroids and pyrethrin has been documented in the literature and mechanisms may include enzymatic drug inactivation or genetic changes in drug target site ("knock-down resistance," or kdr).

Use of products containing higher concentrations of permethrin (eg, permethrin 5%, Elimite) will be no more clinically effective than OTC products containing permethrin 1% in lice with genetic target site mutations.

Wide geographic variability in resistance patterns are possible, and with little standardized testing for resistance, it can be difficult to predict potential clinical effects of resistance in a community. Recently published clinical studies have documented cure rates of less than 50% with permethrin in some geographic areas. Resistance of head lice to malathion has been documented outside the United States, but resistance has not been documented here. Differences in malathion product formulation may be additionally important, as malathion products available in the United States have been shown to kill lice resistant to malathion products available in the United Kingdom. Some experts predict that as malathion has been commercially available for fewer years in the United States, with time and continued use, resistance by head lice to malathion is likely to develop here as well.

Home remedies

With resistance to many OTC products a potential reason for treatment failure, many parents and caregivers have resorted to various home remedies to kill head lice.

Although anecdotal evidence for these therapies' efficacy has been discussed in the literature, few data from controlled clinical studies exist.

One study published several years ago provides some useful information. Takano-Lee and colleagues evaluated six home remedies for their ability to kill head lice in an experimental study. Female lice from three geographic regions (one in the United States, two outside the United States) were evaluated. The home remedies tested included: mayonnaise, petroleum jelly, melted salted butter, white distilled vinegar, 70% isopropyl alcohol and olive oil. Deionized water was used as a control. Lice were placed onto cut human hair tufts, immersed into the home remedy treatments, and then placed into petri dishes. Louse survival at eight hours was evaluated, as this represents an approximate overnight treatment scenario. Egg laying and hatching were also evaluated for several days. Only lice treated with petroleum jelly exhibited a significantly reduced survival rate (38% survival, 15/40) as compared with water. In all groups, 28% to 43% of lice survived for 24 hours post-treatment. Isopropyl alcohol, mayonnaise, and petroleum jelly significantly reduced the number of eggs laid by female lice as compared with the water control, but the egg-hatching rate was not affected for any experimental treatment.

Lice were also separately submerged into deionized water for various time periods (six to 16 hours). Nearly all lice submersed for six hours were still biologically viable. Survival rates for lice submersed for eight to 16 hours were significantly reduced, although survival was 0% only at 16 hours. This study's major limitation is its experimental design, ie, it was not a clinical study. However, the testing of these remedies for time periods as long (or longer) as what would likely be used in practice, and the study's controlled evaluation methods, allow this study to provide useful information.

Conclusions

It seems reasonable to initiate treatment for head lice infestation with an OTC permethrin product.

Resistance to pyrethroids has been documented, but geographical differences in resistance patterns exist, and documentation of resistance may be difficult and is not widely standardized.

Before concluding that resistance is responsible for treatment failure in a specific child, clinicians should consider other potential reasons: 1) use of a conditioning shampoo or hair conditioner prior to use of lice treatment, as this may reduce the lice treatment product form adhering to hair; 2) reinfestation; 3) egg hatching after treatment, as no product is 100% ovicidal; 4) not following product instructions. If a child fails treatment and these factors have been considered, then pyrethroid-resistant lice may be present. Malathion should then be used, as resistance to this agent has not been documented in the United States, and it has high cure rates. Malathion is available only by prescription and is relatively expensive (approximately $150 generic), although it is likely to be included in major insurance plans. Malathion is labeled for use at ages 6 years and older, and labeling states it is contraindicated for use on infants. Directions for use of malathion include application for eight to 12 hours.

A published controlled trial evaluating a 20-minute malathion application time and comparison to permethrin 1% found malathion to be significantly more effective than permethrin when applied for this reduced time period. Ulesfia is a new prescription lice treatment available to clinicians for infants and children 6 months of age and older. Its efficacy and role have not been well defined and cure rates listed in the package insert are not especially high. Ulesfia can be expensive to use in children with long hair (up to $360). Other prescription products are also available (TMP-SMX, crotamiton, ivermectin), but they are not labeled for use to treat head lice. Lindane has a very limited role, if any, as it has significant potential for toxicity, and has lower cure rates. The use of home remedies should be discouraged, as they are not likely to be effective. The 2009 Red Book lists malathion or permethrin 1% as drugs of choice for head lice treatment, with pyrethrin-based products or ivermectin as alternative treatment choices.

For more information:

• Lebwohl M, et al. Therapy for head lice based on life cycle, resistance, and safety considerations. Pediatrics 2007;119:965-974.
• Meinking TL, et al. Efficacy of a reduced application time of Ovide Lotion (0.5% malathion) compared to Nix Crème Rinse (1% permethrin) for the treatment of head lice. Pediatric Derm. 2004;21:670-674.
• Takano-Lee M, et al. Home remedies to control head lice: assessment of home remedies to control human head louse, Pediculus humanus capitis. J Pediatr Nursing. 2004;19:393-398.
• Thomas DRh, et al. Surveillance of insecticide resistance in head lice using biochemical and molecular methods. Arch Dis Child. 2006;91:777-778.

Edward A. Bell, PharmD, BCPS is Professor of Pharmacy Practice at Drake University College of Pharmacy in Blank Children’s Hospital and Clinics in Des Moines, Iowa.