Head Lice Treatment: Perspective for Pharmacists

An estimated 6 to 12 million individuals in the United States develop head lice each year,¹ with most cases occurring in children ages 3 to 11.²

The burden of head lice may include pruritus, sleeplessness, absences from school, and secondary bacterial infections resulting from skin damage due to persistent scratching.^1,3

Head lice can cause substantial anxiety among school-aged children and commonly result in absenteeism from school and work. Costs related to head lice treatment may be as high as $1 billion annually.^4,5

Head Lice Life Cycle and Characteristics

Head lice are tan to grayish-white, 6-legged, wingless insects typically measuring 2 mm to 3 mm in length, or about the size of a sesame seed.^3,5

Because lice crawl and do not jump, head-to-head contact is the primary route of transmission.^2,5 Once on the scalp, lice attach eggs to the base of hair shafts a few millimeters from the scalp surface.⁵

Once laid, eggs hatch within 9 to 12 days, and the resulting nymph matures into an adult louse over the subsequent 9 to 12 days, for a full reproductive cycle of approximately 3 weeks’ duration.⁵

After hatching, lice feed on human blood.² To enable feeding, louse saliva contains vasodilatory and anticoagulant components.

Pruritus develops after sensitization to these components in louse saliva, usually after the lice have been present for 4 to 6 weeks. However, in patients who have had prior cases of lice, sensitization has already occurred, so pruritus may develop within 1 to 2 days of a second infestation.^3-5

Head Lice Diagnosis

Because lice eggs are located on hair shafts approximately 4 mm from the scalp, it is often easier to identify eggs by searching at the back of the hairline, where they are most visible.⁴ As a further aid, the American Academy of Dermatology (AAD) recommends moistening the hair with water and using a bright light as well as a fine-toothed comb to search for lice and lice eggs (nits).⁶

At least 1 study supports wetting hair before combing to improve diagnostic reliability. In a 224-patient study, combing wet hair detected head lice in 22% of patients (n=49), while the traditional dry hair method detected only 14% (n=32) of cases present in the sample.⁷

Dandruff flakes, scabs, or droplets of hairspray are often mistaken for empty lice egg casings, even by health care professionals. Due to this confusion, current guidelines from the American Academy of Pediatrics (AAP) recommend initiating treatment only when living lice have been identified.^4,5

Head Lice OTC Treatments

Permethrin

Permethrin is a fully synthetic product in a 1% lotion that has been available OTC in the United States since 1990. Pruritus, erythema, and edema are possible adverse events, and the product labeling cautions that patients with a ragweed allergy may experience difficulty breathing or an asthmatic episode resulting from treatment.

Patients using permethrin should be told to wash their hair as usual with a shampoo that does not contain any conditioners, then dry the hair, apply the lotion, and leave the product in the hair for at least 10 minutes before rinsing. Any remaining residue should be left in the hair. Retreatment 7 to 10 days after the initial application is recommended.^4,5,8

Importantly, permethrins are not ovicidal, meaning they do not completely kill lice eggs. A considerable body of evidence suggests that resistance to these agents is increasing. In addition, virtually all shampoos on the market today contain additives that prevent permethrin from adhering to hair properly, further reducing the effectiveness of treatment.^4,5,8

Pyrethrins

Another OTC option for head lice treatment is the combination of pyrethrins and piperonyl butoxide. The piperonyl butoxide component extends the action of pyrethrins by inhibiting microsomal enzymes that break down pyrethrins.⁹

Pyrethrins exert neurotoxic effects in lice, but have negligible toxicity in humans. Because pyrethrins are extracted from a natural product (chrysanthemums), patients with an allergy to chrysanthemums should not use the product.

Although product labeling also recommends avoiding use of pyrethrins in patients with allergies to ragweed, the AAP does not consider this a true contraindication due to the low risk of true allergic reactions in patients with ragweed allergy treated with these products.^4,5,10

Mousse or shampoo formulations of pyrethrins are available. Both are applied to dry hair and left on for 10 minutes before rinsing.

Unlike permethrins, pyrethrins do not leave a residue in the hair that continues to exert pediulocidal effects. In addition, pyrethrins, which are derived from a natural product, are more prone to causing allergic reactions than permethrins, which are fully synthetic.

Despite these minor differences, neither product is ovicidal, and the effectiveness of both has waned over time with increasing levels of resistance.^4,5,10

The AAD recommends waiting 2 days to wash the hair and using a lice comb daily for 2 weeks after applying the second treatment to help improve the effectiveness of OTC permethrins and pyrethrins.⁶

Head Lice Prescription Treatments

Prescription options for head lice treatment recommended by the AAP include malathion 0.5%, benzyl alcohol 5%, spinosad 0.9% suspension, and ivermectin 0.5% lotion.⁵

Malathion

Malathion is a neurotoxic organophosphate lotion available by prescription only. It should be applied to dry hair and washed off 8 to 12 hours later.

Malathion should be reapplied 7 to 9 days later if lice are still present. Use is contraindicated in children younger than 24 months, and no safety or efficacy data are available with malathion in children younger than 6 years of age.

Malathion is also highly flammable due to its high alcohol content; hair containing malathion can ignite in the presence of heat (eg, from a hair dryer, curling iron, or cigarette).^5,11

The comparative efficacy of malathion is generally greater than that of OTC pyrethrins or permethrins, but it was temporarily removed from the US market on 2 occasions due to formulation concerns related to administration, flammability, and odor. If accidentally ingested, malathion may theoretically cause systemic toxicity, including respiratory depression; however, cases of accidental ingestion have not been reported.^5,11

Benzyl alcohol

Benzyl alcohol 5% topical lotion is a lice asphyxiation agent approved by the FDA in 2009 and indicated for use in children ages 6 months and older. The treatment should be applied to dry hair in a quantity large enough to saturate the entire scalp and all hair.

After application, the medication should be left on the hair for 10 minutes, and treatment should be repeated 7 to 9 days after the initial application.

Common adverse events include pruritus, erythema, pyoderma, and ocular irritation.^5,12

Spinosad

Spinosad 0.9% suspension is indicated for use in children ages 6 months or older and contains 2 natural compounds derived from the fermentation of a type of soil bacteria (Saccharopolyspora spinosa). The 2 neurotoxic compounds in spinosad are ovicidal and pediulocidal, which have demonstrated superior efficacy over permethrin.

Spinosad 0.9% suspension should be applied to dry hair using a quantity sufficient enough to saturate the entire scalp and all hair, and it should be rinsed out 10 minutes later. If live lice are still present on the scalp, the treatment should be repeated 7 days after the initial application.

Common adverse events include erythema, ocular erythema, and application site irritation.^5,13

Ivermectin

Ivermectin 0.5% lotion was approved by the FDA in 2012 and indicated for use in children ages 6 months and older. It works by increasing chloride ion permeability in lice muscle cells, thereby leading to paralysis and death.

Ivermectin is unique among FDA-approved lice treatments in that it consists of a single application, with no need for a second one. Repeat applications are unnecessary because ivermectin disables active lice and their eggs by paralyzing muscles that enable developing lice to feed after hatching.^5,14

The lotion should be applied to dry hair and the scalp, and it should be left on for 10 minutes before rinsing.

Adverse events including irritation of the skin or eyes and erythema, burning, or dryness have been reported with topical ivermectin.^5,14

Head Lice Treatment Resistance

According to the AAP, the ideal head lice treatment should be safe and easy to use, and also rapidly kill lice, nits, and eggs. Unfortunately, OTC products have become less reliable over time with the emergence and worldwide proliferation of treatment-resistant lice.⁵

Widespread resistance to pyrethrins has been documented throughout the United States in such locations as Idaho, Florida, and Texas, and resistance has become progressively worse over the past several decades.

For instance, in the late 1980s, head lice cure rates with permethrins and pyrethrins were very high, with 93.7% to 100% efficacy often from a single treatment. By the late 1990s, OTC treatments had effectiveness rates lower than 80%, and by the early 2000s, OTC permethrin efficacy rates hovered in the 45% to 55% range.^5,9

Head lice treatment resistance is not limited to OTC therapies. Increasing rates of resistance to prescription-only malathion have been identified around the world.

Resistance to these treatments is associated with certain mutations, including those of voltage-gated sodium channels, glutathione sulfotransferase enzymes, esterases, and monooxygenases. Scientists have even identified strains of lice that have developed resistance to both malathion and permethrin. Resistance to malathion is widespread in the United Kingdom, and it has been documented in the United States in both California and Florida.¹

Lindane is still available in the United States, but not in California or the United Kingdom due to concerns about associated systemic toxicity. Because of this, the AAP strongly recommends against use of lindane for head lice.

Given the toxicity of lindane, and the fact that certain lice populations have been identified with resistance to the drug, better treatment options are available. For instance, scientists have yet to identify ivermectin-resistant head lice.^4,5,15

Ideally, treatment decisions should be made based on knowledge of local resistance patterns, ease of treatment use, and cost. For head lice, OTC permethrin is still recommended as a first-line option by the AAP, although the product’s efficacy may be limited by local resistance patterns and a lack of ovicidal activity.^4,5

Considering OTC permethrin’s high resistance rates and low efficacy rates in the 45% to 55% range, some researchers have questioned the treatment’s cost-effectiveness. Consistent with this, the AAP recommends consideration of local resistance rates in selecting an appropriate initial therapy for head lice.^4,5,9

References

1. Gao J-R, Yoon KS, Frisbie RK, Coles GC, Clark JM. Esterase-mediated malathion resistance in the human head louse, Pediculus capitis (Anoplura: Pediculidae). Pestic Biochem Physiol. 2005:1-10.

2. CDC. Head Lice: Frequently Asked Questions. http://www.cdc.gov/parasites/lice/head/gen_info/faqs.html. Accessed July 15, 2015.

3. Gunning K, Pippitt K, Kiraly B, Sayler M. Pediculosis and scabies: treatment update. Am Fam Physician. 2012;86(6):535-541.

4. Frankowski BL, Bocchini JA Jr; Council on School Health and Committee on Infectious Diseases. Head lice. Pediatrics. 2010;126(2):392-403.

5. Devore CD, Schutze GE; Council on School Health and Committee on Infectious Diseases, American Academy of Pediatrics. Head lice. Pediatrics. 2015;135(5):e1355-e1365.

6. AAD. Head lice: Diagnosis, treatment, and outcome. https://www.aad.org/dermatology-a-to-z/diseases-and-treatments/e---h/head-lice/diagnosis-treatment. Accessed July 15, 2015.

7. De Maeseneer J, Blokland I, Willems S, Vander Stichele R, Meersschaut F. Wet combing versus traditional scalp inspection to detect head lice in schoolchildren: observational study. BMJ.2000;321(7270):1187-1188.

8. Nix (permethrin). http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3d757b15-0bae-45c1-8fae-6ebdf0f7d560. Accessed July 15, 2015.

9. Lebwohl M, Clark L, Levitt J. Therapy for head lice based on life cycle, resistance, and safety considerations. Pediatrics. 2007;119(5):965-974.

10. Lice MD Complete (pyrethrum extract and piperonyl butoxide). http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7509990f-0bc8-44dc-9678-05b27f2c1368. Accessed July 15, 2015.

11. Ovide (malathion lotion 0.5%) [package insert]. Hawthorne, NY: Taro Pharmaceuticals; 2011. Available at: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2024030e-b00d-4fcc-b51d-45dc86933749.

12. Ulesfia (benzyl alcohol 5% lotion) [package insert]. Research Triangle Park, NC: Zylera Pharmaceuticals; 2014. Available at: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5754f979-32b7-4406-a3a9-ed36aac6a37a.

13. Natroba (spinosad) [package insert]. Carmel, IN: ParaPRO LLC; 2015. Available at: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=fa90ccc8-2df0-49f7-8878-2b33e34cd272.

14. Sklice (ivermectin 0.5% lotion) [package insert]. Swiftwater, PA: Sanofi-Pasteur Inc; 2012. Available at: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4c5557cd-c4cf-11df-851a-0800200c9a66.

15. Yoon KS, Gao J-R, Lee SH, et al. Resistance and cross-resistance to insecticides in human head lice from Florida and California. Pestic Biochem Physiol. 2004;80:192-201.