Update on pharmacotherapy of head lice: Practical considerations

Summer is winding down and school is back in session.

For pediatric clinicians, this means an increase in telephone calls and office visits for head lice infestations. New to the discussion of head lice is the recent update of management guidelines from the American Academy of Pediatrics.

An update from the Academy’s last report published in 2002, treatment issues discussed in this report include medications labeled and not labeled by the FDA for the treatment of head lice infestation. Non-pharmacotherapies are also discussed. The report states that use of a permethrin or pyrethrin product continues to be recommended as initial therapy, unless resistance is shown or strongly suspected. If treatment with a permethrin or pyrethrin product is not successful, malathion can be then used. The report states that other products may also have a role in select children.

Several literature and treatment reviews have been published in recent years on head lice infestation. While the authors of these reviews have recommended some products over others, little evidence for superior product efficacy from controlled, comparative trials exists. Complicating these comparisons is the development of resistance by head lice to some of the pharmacotherapeutic agents. Resistance by head lice, while documented by some studies, has not been standardized, and this complicates the comparison of different studies and the clinical application of suspected or known resistance patterns.

Initial therapy

Recommendations for initial therapy of head lice infestation continue to be permethrin 1% (a pyrethroid) or a pyrethrin-based product.

Permethrin 1% is available as the product Nix and is also available as generic products.

Pyrethrin-based products include A-200, Pronto, RID and generic products. These agents continue to be recommended initially because they are effective, available over-the-counter, relatively inexpensive, and safe. Permethrin may have an advantage over pyrethrin-based products as it may have some residual and ovicidal activity. However, most experts recommend retreatment on day 9 or on day 7 and additionally on day 13-15. Pyrethrin-based products do not have ovicidal activity and retreatment is necessary to kill nymphs. Complicating the use of permethrin or pyrethrin is resistance to these agents by head lice, which has been documented in several published studies.

Second-line therapy

As few data from controlled comparative trials are available, recommendations for alternative treatments when initial therapy with permethrin or pyrethrin fails is based upon patient age, resistance patterns and medication cost.

Prior to concluding that a child failed therapy with permethrin or pyrethrin, however, it is important that clinicians assess other factors, mainly proper product use (see below).

For children older than 24 months who failed initial therapy, the AAP guidelines state that malathion (Ovide) can be used. Authors of other topic reviews also recommend malathion for permethrin/pyrethrin treatment failures. Although malathion requires a prescription and is more expensive (approximately $100-$150), cure rates in clinical studies using malathion have been high. A significant consideration for malathion’s high efficacy rate is the lack of documented resistance by head lice in the United States. Malathion also has considerable ovicidal activity. Package labeling for malathion states that a second treatment application is necessary if live lice are found 7-9 days after initial use. Directions for malathion include application to dry hair and left in place for 8-12 hours. One published controlled trial found, however, that malathion was highly effective when applied for 20 minutes only. In this study, malathion was significantly more effective than permethrin 1%.

Several products containing malathion have been introduced and withdrawn from the U.S. market over past years and the current product has been commercially available for about 10 years. Malathion has been available longer in the United Kingdom and European countries, and resistant head lice have been noted in these countries, so it may only be a matter of time before malathion-resistant head lice are found in the United States.

Complicating the use of malathion is its flammable potential, as it contains 78% isopropyl alcohol. Thus, it is important to follow product application directions carefully, and not to apply malathion near an operating hair dryer or similar source of heat. Malathion is labeled for use in children 6 years of age and older, and its labeling includes a contraindication for use in infants less than 24 months of age, due to the potential for increased systemic absorption. Malathion is a weak organophosphate cholinesterase inhibitor. For children less than 24 months of age who failed initial therapy, the AAP’s report states that benzyl alcohol 5% (Ulesfia) can be used. This prescription-only product is relatively new, introduced last year. It is labeled for use in infants and children 6 months of age and older. Clinical studies of benzyl alcohol 5% show that cure rates are not especially high (approximately 75%), and its use can be expensive, especially for children with longer hairstyles.

Other products

Several other products have been offered as potential alternative therapies, although most are not FDA-labeled for treatment of head lice, and fewer efficacy data are available.

Perhaps most promising is ivermectin. Ivermectin has been shown in one study to demonstrate some efficacy in treating head lice, at a dose of 200 mcg/kg (repeated in 10 days). A new controlled study, however, compared a higher dose of ivermectin (400 mcg/kg orally, repeated in 7 days) to malathion in children ≥2 years of age (with a weight of ≥15 kg).

More subjects receiving ivermectin (95.2%) were free of live lice at day 15 as compared to subjects receiving malathion (85%, p<0.05). Despite FDA-labeling for head lice, lindane has no current role for the treatment of head lice, due to resistance and its potential for toxicity. Although they have been recommended by some, few efficacy and safety data support the use of crotamiton or trimethoprim-sulfamethoxazole for treating head lice infestation.

Resistance

As discussed above, increasing resistance by head lice to many current pharmacotherapies complicates effective treatment in children. Numerous studies have documented resistance by head lice to permethrin, pyrethrins, and other agents. Several different mechanisms of resistance to current medications are believed to be important. However, determination of resistance is not standardized or widely available, and other than anecdotal reports, assessing for head lice resistance in a community can be difficult for a health care provider. Before concluding that reported medication treatment failure is due to resistance, it is important to assess for other potential, and perhaps more practically likely, reasons.

Other considerations of treatment failure

Prior to concluding that a child failed treatment with one of the pharmacotherapies discussed above because of resistance, clinicians should consider addressing the following:

1. Was the product used correctly? Product directions differ by length of application time, application to wet or dry hair, and other factors. Permethrin should not be applied after use of a hair conditioner or conditioning shampoo. Was an additional application of the product used at 7-10 days used?
2. Was the child re-infested? Were recommendations for preventing re-infestation given or followed?
3. Is a diagnosis of head lice accurate? One study found that just over 50% of samples of “head lice” submitted by clinicians, teachers, or lay public were actually live lice or viable eggs. Accurate diagnosis is also important to limit over-use of head lice products, potentially contributing to increased resistance.

If the clinician determines that a child was treated properly and continues to be actively infested, then resistance to the agent used is perhaps likely.

Practical considerations

For treatment of initial infection, use of permethrin 1% or a pyrethrin-based product continue to be recommended as first-line therapy. These OTC products are available generically, are relatively inexpensive, and they can be used in children as young as 2 months of age. Safety and animal studies have shown that these products are safe, with very little absorption. Adverse effects reported are minor, such as local erythema. Serious systemic adverse effects have not been reported. Malathion and benzyl alcohol 5% can be considered for permethrin or pyrethrin treatment failures. Malathion may be more likely to be effective, as reported cure rates are higher. Malathion (Ovide) is labeled for use at age 6 years and older, although experts state it can also be used at age 24 months and older. Benzyl alcohol 5% (Ulesfia) is labeled for use at 6 months of age and older. Both of these products can be expensive to use ($150 or more), depending upon insurance plan coverage. Ovide must not be used near heat sources, as it is flammable. Resistance has not been documented to either of these products in the United States.

Whatever head lice product is used, appropriate use is important, and product directions should be closely followed. Clinicians should counsel caregivers on this, and verify appropriate product use prior to assessing treatment failure. Resistance by head lice to some agents has been documented, but prevalence patterns may not be known and determination of resistance can be difficult and has not been standardized. Clinicians should consider other factors before concluding that treatment failure is due to resistance.

For more information:

• AAP. Pediatrics. 2010;126:392-403.
• Diamantis SA. Dermatologic Ther. 2009;22:273-8.
• Jones KN. Clin Infect Dis. 2003;36:1355-60.
• Meinking TL. Pediatric Dermatol. 2004;21:670-4.
• Chosidow O. NEJM. 2010;362:896-905.