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Advancements in the Treatment of Head Lice in Pediatrics

      Abstract

      Head lice infestations occur commonly each year in children of all socioeconomic statuses. However, head lice have become more of a nuisance as resistance to first-line agents, such as permethrin 1% and pyrethrins, has increased. Newer topical products provide unique mechanisms of action without current signs of resistance. As with older agents, proper application of products must be emphasized to ensure that treatment is effective. In addition, nonpharmacologic measures should be taken to avoid reinfestation in the patient and to prevent the spread of lice to close personal contacts.

      Key Words

      Teri Woo, PhD, RN, CPNP, FAANP
      Corresponding Editor
      Pacific Lutheran University
      Tacoma, Washington
      Elizabeth Farrington, PharmD, FCCP, FCCM, BCPS
      University of North Carolina, Eshelman School of Pharmacy
      Chapel Hill, North Carolina
      New Hanover Regional Medical Center
      Wilmington, North Carolina
      Brady S. Moffett, PharmD, MPH
      Clinical Pharmacy Specialist-Pediatric Cardiology
      Texas Children's Hospital, Department of Pharmacy
      Houston, Texas

      Objectives

      • 1.
        Review the mechanisms of action by which pediculicides eradicate head lice.
      • 2.
        Compare efficacy and safety of older pediculicides to newer agents and recommend appropriate treatment based on age, cost, and past usage of pediculicides.
      • 3.
        Counsel patients and caregivers on proper application and reapplication of lice treatments.
      • 4.
        Recommend appropriate nonpharmacologic strategies to avoid reinfestation and the spread of head lice.
      • 5.
        Describe the advantages and disadvantages of no-nit policies at schools, camps, and child care.
      An 8-year-old girl presents to your clinic with her third episode of head lice in the past 2 months. Her mother has been applying permethrin 1% créme rinse (Nix OTC) and states that for the past two episodes of lice, they needed to reapply the rinse after 7 days. She is unsure if the last rinse was effective. She believes she spotted a few more live lice after the reapplication. She is very concerned about her daughter's education; the school has a “no-nit” policy, so her daughter has already missed more than 3 weeks of class. She wants to know the best way to kill the lice and prevent another infestation. She is tired of spraying chemicals on their furniture and in the car, applying the lice treatments, and washing all of her daughter's belongings. Her daughter is embarrassed and upset that she has been excluded from her friends' sleepovers.
      This case illustrates the challenge of successful eradication of head lice. This article will discuss the background of head lice infestation, diagnosis, the use of older pediculicides and increasing resistance, new pediculicides, unproven therapies (including home remedies), novel agents, “no nit” policies, and patient and caregiver education.

      Background and Diagnosis

      Infestations of head lice, or Pediculosis humanus capitis, are commonplace in patients aged 3 to 11 years (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). An estimated 6 to 12 million cases of head lice occur in the United States each year, more of which affect girls (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). The annual cost of head lice in the United States may be as high as $1 billion (
      • McCormack P.L.
      Spinosad: In Pediculosis capitis.
      ) because of costs for treatment, appointments with a provider, prescription medications, time spent by school nurses to inspect students, and time out of work for caregivers who must stay home with their children during the infestation.
      The life cycle of the louse involves three stages. Nits, or eggs, may take between 7 and 10 days to hatch and must stay warm to do so (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ;
      • Ferri F.F.
      Ferri's clinical advisor.
      ). Once hatched, nymphs feed on blood drawn from the scalp of their host and grow into adult lice (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ). They then are able to reproduce for 2 to 3 weeks, and the female louse may lay up to eight nits each day (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ;

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). In general, adult lice that successfully feed on a human host may survive up to 30 days but cannot live more than 48 hours away from a feeding source (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ;

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). Both saliva and fecal matter from the lice may lead to inflammation of the host's scalp, and itching may continue for weeks after treatment (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ;
      • Ferri F.F.
      Ferri's clinical advisor.
      ). Infestation of head lice rarely leads to secondary infection, but it is possible in patients who scratch the affected area. Live lice can be transmitted through close personal contact or sharing of personal items such as pillows, hats, or hairbrushes (
      • Ferri F.F.
      Ferri's clinical advisor.
      ). Lice are only known to crawl, not hop or fly (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ). Head lice are not spread or eradicated when a patient is swimming; when immersed in sea water or chlorinated water, head lice have been observed to become immobile and grip firmly to the patient's hair (
      • Canyon D.
      • Speare R.
      Do head lice spread in swimming pools?.
      ;

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). As soon as head lice are removed from the water, they begin to feed (
      • Canyon D.
      • Speare R.
      Do head lice spread in swimming pools?.
      ). Death was not observed within 4 hours after a 30-minute submersion and recovery in both types of water (
      • Canyon D.
      • Speare R.
      Do head lice spread in swimming pools?.
      ).
      Diagnosis of lice is made by physical examination, which can be performed by a parent or caregiver. Visual inspection may identify only up to 50% of infestations, and thus a fine-tooth comb or magnifying glass may be used to increase the accuracy of diagnosis (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ;
      • Ferri F.F.
      Ferri's clinical advisor.
      ). In clinical settings, Wood's lamp (an ultraviolet light) examination can help diagnose head lice (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). Nits will be gray to white and located on the hair shaft approximately 3 to 4 mm from the scalp, particularly at the back of the head and neck and behind the ears (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ;
      • Ferri F.F.
      Ferri's clinical advisor.
      ). They can be discerned from dandruff because nits are not easily removed from the hair. Nits are described as the size of a knot in thread (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). Active or live lice are clear but become reddish-brown to black while feeding (
      Therapeutic Research Center
      Commentary: Natroba (Spinosad) for the treatment of head lice. (Detail-Document #270904.).
      ). The size of an adult louse is comparable to a sesame seed, and they are known to move quickly (
      Therapeutic Research Center
      Commentary: Natroba (Spinosad) for the treatment of head lice. (Detail-Document #270904.).
      ). If nits are identified, parents or caregivers may choose to monitor their child, but they should not provide treatment unless live lice are present.
      Resistance to permethrin and pyrethrins has increased, and several warnings have been issued regarding the use of lindane.
      Several pediculicides are available for the treatment of head lice in children; however, the use of many of these agents are limited for safety reasons in younger age groups. Resistance to permethrin and pyrethrins has increased, and several warnings have been issued regarding the use of lindane. In addition, application and reapplication of these products can be challenging for patients and caregivers. Lastly, improper eradication of head lice often results in high treatment failures.

      Older Pediculicides

      As of 2010, the CDC and the American Academy of Pediatrics (AAP) recommend over-the-counter permethrin and synergized pyrethrins (pyrethrins/piperonyl butoxide) as first-line treatment for head lice. Other older pediculicides are available, such as malathion and lindane, but the risks of treatment with these agents often outweigh the potential benefits.

      Permethrin (Nix OTC)

      Permethrin 1% créme rinse (Nix OTC) works on head lice by inhibiting sodium ion influx, resulting in delayed repolarization through cell membrane channels and thus paralysis and death. Although permethrin eliminates adult lice, it is not capable of killing eggs (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ;
      • Frankowski B.L.
      • Bocchini Jr., J.A.
      Head lice.
      ). It can be used in patients as young as 2 months of age and is Pregnancy Category B (
      Lexi-Comp Online
      Lexi-Drugs.
      ; Box 1). Caution should be used in patients with a ragweed allergy, because respiratory difficulty or asthmatic episodes may occur with permethrin use in such patients (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). The manufacturer recommends washing hair without conditioner because conditioner may decrease the effectiveness of permethrin (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). After rinsing, the hair should be damp, not wet, before saturating the hair with the pediculicide (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). Permethrin should be left on hair for 10 minutes and dried with a towel after rinsing (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). If live lice are seen after at least 7 days, permethrin should be reapplied (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). Each application should be followed by thorough nit combing.
      Food and Drug Administration–approved age and pregnancy category for use of head lice agents
      • Permethrin (Nix OTC): 2 months and older; Pregnancy Category B
      • Pyrethrins/piperonyl butoxide (Rid OTC): 2 years and older; Pregnancy Category C
      • Malathion (Ovide): 6 years and older; Pregnancy Category B
      • Lindane: not recommended for use in children by AAP and FDA
      • Benzyl alcohol (Ulesfia): 6 months and older; Pregnancy Category B
      • Spinosad (Natroba): 4 years and older; Pregnancy Category B
      • Ivermectin (Sklice): 6 months and older; Pregnancy Category C
      AAP, American Academy of Pediatrics; FDA, Food and Drug Administration; OTC, over the counter.
      In two recent studies comparing spinosad 0.9% with permethrin 1%, treatment success occurred in 44.9% and 42.9% of patients applying permethrin with nit combing under at-home conditions (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). A 2001 study described the success rate as 79.5% after treatment by parents or caregivers (
      • Hipolito R.B.
      • Mallorca F.G.
      • Zuniga-Macaraig Z.O.
      • Apolinario P.C.
      • Wheeler-Sherman J.
      Head lice infestation: Single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole.
      ). Another U.S. study in 2004 comparing the efficacy of permethrin with malathion demonstrated a failure rate of 45% with permethrin (
      • Meinking T.L.
      • Vicaria M.
      • Eyerdam D.H.
      • Villar M.E.
      • Reyna S.
      • Suarez G.
      Efficacy of a reduced application time of Ovide Lotion (0.5% malathion) compared to Nix Créme Rinse (1% permethrin) for the treatment of head lice.
      ). These lower rates are likely due to resistance and lack of ovicidal activity, as well as improper application of the product. In terms of safety, ocular hyperemia was observed in 3.3% of patients, application-site erythema was observed in 6.8%, and application-site irritation was noted in 1.5% (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ).

      Pyrethrins/Piperonyl Butoxide (Rid OTC)

      Pyrethrins/piperonyl butoxide 0.33/4% shampoo (Rid OTC) includes a pyrethrum extract derived from chrysanthemum flowers. Its mechanism is similar to that of dichlorodiphenyltrichloroethane (DDT), and the inclusion of piperonyl butoxide decreases metabolism of pyrethrins by arthropods. It is not ovicidal and should be reapplied after 9 days (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). In terms of efficacy, a study from 2000 observed that the shampoo appears to eliminate up to 75% of lice 30 minutes after treatment; however, this is an example of the “resurrection effect” of head lice (
      • Meinking T.L.
      • Entzel P.
      • Villar M.E.
      • Vicaria M.
      • Lemard G.A.
      • Porcelain S.L.
      Comparative efficacy of treatments for Pediculosis capitis infestations.
      ). Three hours after the treatment, only 53% of the lice were actually dead, because lice can survive for more than an hour without oxygen while avoiding respiratory or muscle movement so as to appear dead (
      • Meinking T.L.
      • Entzel P.
      • Villar M.E.
      • Vicaria M.
      • Lemard G.A.
      • Porcelain S.L.
      Comparative efficacy of treatments for Pediculosis capitis infestations.
      ).
      Pyrethrins/piperonyl butoxide should be applied to dry hair and allowed to set for 10 minutes before shampooing and rinsing (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). Nit combing also is recommended after use of the treatment shampoo. In terms of safety, pyrethrins should not be used in patients with hypersensitivity to chrysanthemum flowers or ragweed; however, case reports of true allergic reactions have been uncommon (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ;
      • Frankowski B.L.
      • Bocchini Jr., J.A.
      Head lice.
      ). It is approved by the Food and Drug Administration (FDA) for children 2 years and older and is Pregnancy Category C (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ).

      Malathion (Ovide)

      Malathion 0.5% lotion (Ovide) is an ovicidal agent. Although it is effective, it should be used with caution. It is a weak organophosphate that inhibits cholinesterase activity of head lice, resulting in acute toxicity followed by cell death (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). Malathion is flammable, and hair dryers or other heat-producing appliances must not be used (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ); therefore, it is recommended that after application of malathion, the hair should be allowed to dry naturally. After 8 to 12 hours, the hair can be shampooed and rinsed, and a nit comb should be used to remove dead lice and nits (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). If active lice are identified after 7 to 10 days, malathion should be reapplied (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ).
      Malathion was approved based on efficacy in two controlled clinical trials that evaluated patients who applied up to 2 oz of product to their hair and scalp (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). Presence of live scalp lice was evaluated immediately after application, 24 hours after application, and 7 days after application (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). Compared with placebo, most patients treated with malathion lotion remained free of live lice 7 days after application (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). Presence of nits at day 7 and presence of live lice or nits at day 14 were not evaluated (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ).
      Use of malathion in patients younger than 6 years is not recommended, and its use is contraindicated for neonates and infants because of increased permeability of the scalp (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). Malathion has not been studied in pregnant or breastfeeding women, because up to 8% of the topically applied dose has been reported to be absorbed systemically (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). It is Pregnancy Category B based on studies in rats and rabbits at doses 40 to 180 times greater than the dose applied to a 60-kg adult (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). In terms of adverse effects, malathion can be irritating to the scalp and skin, and ophthalmic exposure can lead to mild conjunctivitis (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ). Patients may experience a stinging sensation after application of malathion (

      Taro Pharmaceuticals. (2005). Ovide lotion: Highlights of prescribing information. Retrieved from http://www.rx4headlice.com/media/oMedia/head%20lice%20treatment%20prescribing%20information.pdf

      ).

      Lindane (Kwell)

      Lindane 1% (Kwell) is an organochloride and slow killer of lice that is no longer recommended as a pediculicide by the AAP. Overuse, misuse, or accidental ingestion may be toxic to the central nervous system (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). The Agency for Toxic Substances and Disease Registry has listed lindane as a hazardous substance. At high levels of exposure, the chemical itself (hexachlorocyclohexane or γ-HCH) can result in blood disorders, dizziness, headaches, and seizures. The Department of Health & Human Services states that any isomer of HCH has the potential to cause cancer. Although HCH has been shown to cross the placenta, it is uncertain whether HCH causes birth defects. HCH has been detected in human breast milk, but the effects on the newborn are unknown. The FDA issued a public health advisory in 2003 regarding the use of topical lindane in neonates and infants, children, the elderly, persons weighing less than 50 kg, persons with human immunodeficiency virus, persons with a seizure disorder, and women who are pregnant or breastfeeding. It cautions users that any of the aforementioned persons may be at increased risk of lindane toxicity and should avoid use. Reported adverse events primarily have been due to misuse—that is, treatment of persons with contraindications to lindane, use in excessive amounts, and use not in accordance with product labeling (

      U.S. Food and Drug Administration. (2009, April 30). FDA public health advisory: Safety of topical lindane products for the treatment of scabies and lice. Retrieved from http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110845.htm

      ). The advisory also reminds consumers that reapplication is not necessary based on the lone symptom of persistent itching after initial treatment. California and parts of Europe have banned the use of lindane because of toxicity and environmental effects. In addition, resistance has become common worldwide (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). The CDC states that lindane should be reserved for patients for whom other lice treatments have failed and/or for persons who cannot tolerate other pediculicides.

      Newer Agents

      Several pediculicides have been developed in the past few years in hopes of remedying the issues of resistance and safety with older agents. The new agents have different mechanisms of action and are designed to reduce the need for reapplication; however, the cost is much greater than that of permethrin or pyrethrins/piperonyl butoxide. These agents include benzyl alcohol, spinosad, and ivermectin.

      Benzyl Alcohol (Ulesfia)

      Benzyl alcohol 5% lotion (Ulesfia) was approved in 2009 by the FDA for the treatment of head lice in patients aged 6 months and older. It is the first non-neurotoxic agent and has a unique mechanism of action. Benzyl alcohol works by “suffocating” lice because it prevents the closing of the respiratory spiracles via obstruction, leading to asphyxiation (
      Lexi-Comp Online
      Lexi-Drugs.
      ). It does not have ovicidal activity (
      Lexi-Comp Online
      Lexi-Drugs.
      ). Benzyl alcohol has not been studied in pregnant or breastfeeding women and is classified as Pregnancy Category B (
      Lexi-Comp Online
      Lexi-Drugs.
      ). The efficacy and safety of benzyl alcohol was evaluated in phase II trials to Rid (pyrethrins/piperonyl butoxide) and then in phase III trials to vehicle placebo.
      The phase II trials demonstrated that benzyl alcohol was safe in subjects 2 to 70 years of age. Enough benzyl alcohol must be applied to completely saturate the hair in order to achieve efficacy comparable with that of Rid; a 10-minute application of benzyl alcohol was equally as effective as a 30-minute application (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). Use of Rid or benzyl alcohol demonstrated a kill rate (ratio of total lice minus live lice/total lice) greater than 80% compared with vehicle placebo (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). Complete saturation of the hair for one to two applications lasting 10 minutes resulted in 100% treatment success (N = 44;
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ).
      The phase III trials included two randomized, multicenter, double-blind, vehicle-controlled trials and one open-label study. Each randomized trial assigned the youngest member of participating households to the primary treatment cohort for evaluation of efficacy and safety (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). All other infested household members were assigned to the secondary treatment cohort to evaluate safety only (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). Subjects or caregivers were instructed to apply benzyl alcohol to hair for 10 minutes before washing it out. Application occurred at home to mimic real-life usage. Treatment failures were defined as subjects with evidence of live lice 24 hours after application (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). These subjects had the option of continuing as part of the open-label study to evaluate effectiveness of reapplication of benzyl alcohol 7 days later. The overall primary outcome at that point was treatment success or no live lice 14 days after the final application. Subjects who started in a randomized trial and were transferred to the open-label trial were collectively evaluated at baseline, 24 hours after each application of benzyl alcohol, and at 1 and 2 weeks after the second treatment (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ).
      The phase III trials demonstrated the following outcomes: the effectiveness of benzyl alcohol (study 1: 48 [76.2%], N = 63; study 2: 48 [75.0%], N = 64) was statistically significant compared with vehicle placebo (study 1: 3 [4.8%], N = 62; study 2: 16 [26.2%], N = 61); benzyl alcohol could be used safely in subjects ages 6 months and older; and under conditions mimicking real-life usage, treatment success of 75% could be achieved (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). The investigators concluded that reinfestation was likely the contributing factor to the decrease in treatment success, rather than resistance (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ).
      Because of the lack of ovicidal activity, it is recommended that benzyl alcohol be applied twice, with 7 days between applications (
      Lexi-Comp Online
      Lexi-Drugs.
      ). Parents and caregivers should ensure that they are using enough benzyl alcohol lotion to cover the entire scalp and all scalp hair (Table 1). The lotion should be massaged into the dry hair and allowed to sit for 10 minutes before it is rinsed off. Shampoo may be used after application is complete, and a nit comb may be used to remove the dead lice. Parents and caregivers should keep in mind that although each bottle of benzyl alcohol is approximately $50.54, up to six bottles may be required per application.
      Table 1Guidelines for application of Ulesfia 5% lotion
      From Shionogi Pharma. (2010).
      Hair length (in)Amount per application
      Oz227-gm (8-oz) bottle
      Short
       0-24-6½-¾ bottle
       2-46-8¾-1 bottle
      Medium
       4-88-121-1½ bottles
       8-1612-241½-3 bottles
      Long
       16-2224-323-4 bottles
       > 2232-484-6 bottles
      In terms of safety, adverse effects of benzyl alcohol observed in clinical trials include pruritus (12%), erythema (10%), pyoderma (7%), and ocular irritation (6%;
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). Concern exists with regard to the increased risk of gasping syndrome in patients younger than 6 months who are exposed to benzyl alcohol. Patients of this age are at an increased risk of systemic absorption as a result of both a potentially immature skin barrier and a high ratio of skin surface area to body mass (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). Signs and symptoms of neonatal gasping syndrome include central nervous system depression, metabolic acidosis, gasping respirations, intracranial hemorrhage, hepatic and renal failure, hypotension, bradycardia, seizures, and high levels of benzyl alcohol and its metabolites in the blood and urine (

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ;

      Shionogi Pharma. (2010). Ulesfia lotion: Highlights of prescribing information. Retrieved from https://www.ulesfialotion.com/ulesfia/hcp/prescribing_information/Ulesfia_Prescribing_Information.pdf

      ). In general, gasping syndrome has been associated with intravenous administration of benzyl alcohol at doses >99 mg/kg/day in preterm neonates (

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ;

      Shionogi Pharma. (2010). Ulesfia lotion: Highlights of prescribing information. Retrieved from https://www.ulesfialotion.com/ulesfia/hcp/prescribing_information/Ulesfia_Prescribing_Information.pdf

      ). The absorption of topical benzyl alcohol was observed in 19 patients with head lice in two age groups: 6 months to 3 years and 4 to 11 years (

      Shionogi Pharma. (2010). Ulesfia lotion: Highlights of prescribing information. Retrieved from https://www.ulesfialotion.com/ulesfia/hcp/prescribing_information/Ulesfia_Prescribing_Information.pdf

      ). Patients younger than 6 months were not studied. Topical benzyl alcohol was applied for 30 minutes, which is three times the normal duration of exposure (

      Shionogi Pharma. (2010). Ulesfia lotion: Highlights of prescribing information. Retrieved from https://www.ulesfialotion.com/ulesfia/hcp/prescribing_information/Ulesfia_Prescribing_Information.pdf

      ). Plasma samples were evaluated 1 hour after administration, and benzyl alcohol was detectable in three subjects aged 6 months to 3 years and one subject aged 4 to 11 years (

      Shionogi Pharma. (2010). Ulesfia lotion: Highlights of prescribing information. Retrieved from https://www.ulesfialotion.com/ulesfia/hcp/prescribing_information/Ulesfia_Prescribing_Information.pdf

      ). The minimum amount of topical benzyl alcohol at which toxic effects may occur is unknown.

      Spinosad (Natroba)

      Spinosad 0.9% topical suspension (Natroba) is a new pediculicide that was approved in January 2011 for treatment in patients aged 4 years and older. Although the suspension has been shown to be effective in patients as young as 6 months of age, systemic safety has not been evaluated for subjects younger than 4 years. Spinosad originated from the fermentation of bacteria known as Saccharopolyspora spinosa, which is found in the soil (
      Therapeutic Research Center
      Commentary: Natroba (Spinosad) for the treatment of head lice. (Detail-Document #270904.).
      ). Spinosad causes neuronal excitation and involuntary muscle contractions in head lice, leading to paralysis and death (
      • McCormack P.L.
      Spinosad: In Pediculosis capitis.
      ;

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ;
      Therapeutic Research Center
      Commentary: Natroba (Spinosad) for the treatment of head lice. (Detail-Document #270904.).
      ). This neuronal excitation is caused by interfering with the parasite's nicotinic acetylcholine receptors (
      • McCormack P.L.
      Spinosad: In Pediculosis capitis.
      ;
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). Cross resistance is not expected because this mechanism of action differs from that of older pediculicides (
      • McCormack P.L.
      Spinosad: In Pediculosis capitis.
      ).
      The efficacy of spinosad was confirmed in two phase III, multicenter clinical trials. A total of 1083 patients aged 6 months and older were randomized to at-home applications of spinosad 0.9% without nit combing or permethrin 1% with nit combing (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). Other infested household members were instructed to apply the same product. A smaller third group was assigned to apply spinosad with nit combing for descriptive analysis only. Patients were instructed to apply their treatment one to two times depending on whether live lice were identified after the first treatment (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). All subjects were evaluated at baseline, day 7, and day 14 (if spinosad was applied twice;
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). The primary outcome was number of treatment failures, defined as the presence of live lice 14 days after treatment for the groups applying spinosad without combing or permethrin with combing (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). This evaluation period of 14 days was selected on the basis of the maximum amount of time lice can remain in the ovum stage (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). This outcome was analyzed as intention to treat. The secondary outcome was the proportion of all patients applying spinosad without combing or permethrin with combing (including other household members) who required one or two applications (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ).
      Compliance was high in both studies considering the spinosad was applied at home by parents without study supervision (87.8% and 96.9%, respectively); however, the groups treated with spinosad were the most compliant (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). The superiority of spinosad over permethrin was demonstrated, with success rates reported as 84.6% and 86.7% of patients treated with spinosad versus 44.9% and 42.9% of those treated with permethrin (p < .001;
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). The number of patients requiring a second application was similar between groups treated with spinosad and those with permethrin (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). In conclusion, use of spinosad was superior to use of permethrin and compliance easier to achieve without the need for nit combing.
      Adverse reactions observed in 552 patients included application site erythema (3%), ocular erythema (2%), and application site irritation (1%;
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). Fewer than 1% of patients experienced application site dryness and exfoliation, alopecia, and dry skin (

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ). Laboratory parameters were evaluated in 27 pediatric patients, and no significant changes were noted in hematology or serum chemistry measures (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). An additional open-label study evaluated the potential of spinosad for systemic absorption in 14 subjects aged 4 to 15 years of age (

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ). After a single, 10-minute application using double-strength spinosad (1.8%), plasma levels were below the limit of quantitation (less than 3 ng/mL;

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ).
      Concern for gasping syndrome also exists with spinosad, because benzyl alcohol is one of the product's inactive ingredients. The manufacturer cautions against the use of spinosad in patients younger than 6 months because of this risk (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). Spinosad has not been adequately studied in women who are pregnant and is classified as Pregnancy Category B (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). Spinosad itself is not systemically absorbed, but the benzyl alcohol used to create the suspension may present a risk in women who are breastfeeding (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ). It is advised that lactating women who must use spinosad pump and discard breast milk for 8 hours after application of spinosad to avoid infant ingestion via breastfeeding (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ).
      Spinosad suspension should be applied to dry hair by saturating the scalp and then working outward to the ends of the hair, which may require an entire bottle (

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ). For patients with shorter, thinner hair (i.e., pediatric patients), less suspension may be required to completely coat the hair (

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ). Spinosad should be left on for 10 minutes before rinsing it off. If live lice are still present after 7 days, spinosad should be reapplied at that time (

      ParaPRO. (2011). Natroba topical suspension: Highlights of prescribing information. Retrieved from http://www.natroba.com/Full%20Prescribing%20Information.pdf

      ). After treatments, nit combing may be used to remove dead lice and nits but is not required because spinosad is ovicidal (
      • Stough D.
      • Shellabarger S.
      • Quiring J.
      • Gabrielsen A.A.
      Efficacy and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice).
      ). Spinosad is available by prescription only and costs approximately $210.35 per bottle.

      Ivermectin (Sklice)

      Ivermectin 0.5% lotion (Sklice) was approved by the FDA in February 2012. It is indicated for the treatment of head lice in patients aged 6 months and older. It is an antihelmintic derived from the fermentation of soil-dwelling bacteria known as Streptomyces avermitilis (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). Ivermectin has been used orally to treat other parasites such as onchocerciasis and strongyloidiasis. It works by binding selectively to glutamate-gated chloride channels in nerve and muscle cells of parasites (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). This binding results in increased permeability of the nerve or muscle cell, resulting in paralysis and death of lice (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ).
      Two identical, multicenter, phase III trials (NCT 01066585 and NCT 01068158) were completed in 2011 to evaluate the efficacy of ivermectin 0.5% cream versus vehicle placebo in subjects 6 months and older. The primary outcome was the proportion within each treatment group of subjects who were lice-free after 15 days. Secondary outcomes included assessment of reported adverse events and observed skin/scalp reactions and ocular irritation. Subjects were treated with up to 4 oz of ivermectin cream 0.5% on day 1. Treatment was considered to have failed if live lice were present at any time after administration of ivermectin up to the final evaluation. Results of the first study demonstrated that 76.1% of subjects in the treatment group remained lice free versus 16.2% in the vehicle group (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). The second study showed similar results, with 71.4% of subjects in the treatment group remaining lice free versus 18.9% in the vehicle group (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). At this time, no publications describing these trials are available.
      In terms of toxicity, ivermectin has a low affinity for mammalian ligand-gated chloride channels and thus is not believed to readily cross the blood-brain barrier in humans (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). The most common adverse effects observed in phase III trials include conjunctivitis, ocular hyperemia, eye irritation, dandruff, dry skin, and skin burning sensation (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). Each of these effects was reported in fewer than 1% of subjects (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). Topical ivermectin has not been studied in patients younger than 6 months and is not recommended because of the potential for increased systemic absorption through an immature skin barrier (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). Topical ivermectin also has not been adequately studied in pregnant women and is thus Pregnancy Category C (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). Ivermectin has been detected in human milk after oral administration; however, levels have not been evaluated following topical administration (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). If topical ivermectin is accidentally ingested, patients may require parenteral fluids and electrolytes, respiratory support, pressor agents, and/or gastric lavage (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ).
      Ivermectin lotion should be applied to dry hair, thoroughly coating the hair and scalp (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). Up to one tube (4 oz) may be used per application. The lotion should be rinsed off after 10 minutes (

      Sanofi Pasteur. (2012). Highlights of prescribing information [Sklice lotion prescribing guide]. Retrieved from http://products.sanofi.us/Sklice/Sklice.pdf

      ). Prescribing information does not instruct as to when shampoo and/or conditioner may be used again after administration of ivermectin. The manufacturer advises that the treatment not be repeated without contacting a health care provider first. At this time, a price for the 4-oz lotion is not yet available from the manufacturer.

      Unproven Therapies

      Several other pharmacologic agents have been touted as effective treatments for head lice; however, they do not carry FDA approval at this time. These agents should not be used as first-line therapy, because the level of evidence for efficacy and safety is not strong. In addition, certain home remedies may present risks that vary between patients. Home remedies for head lice should not be applied without first discussing them with a health care professional.

      Pharmacologic Agents

      Oral ivermectin (Stromectol) has been effective in some studies but is not approved by the FDA for pediculosis (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ;
      • Frankowski B.L.
      • Bocchini Jr., J.A.
      Head lice.
      ). It is suggested that oral ivermectin be given as a single dose of 200 μg/kg, with a second dose given after 9 to 10 days (

      American Academy of Pediatrics (2009). Pediculosis capitis (head lice). Red Book Online, 1,495. Retrieved from http://aapredbook.aappublications.org/cgi/content/full/2009/1/3.94

      ). This oral dose would need to be compounded, and few stability data are available for doing this. The risk of neurotoxicity exists if ivermectin crosses the blood brain-barrier, and thus the AAP does not recommend the use of oral ivermectin in children weighing less than 15 kg.
      Oral trimethoprim-sulfamethoxazole (TMP/SMX) has not been evaluated by the FDA for the treatment of head lice, but limited data suggest efficacy (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ;
      • Frankowski B.L.
      • Bocchini Jr., J.A.
      Head lice.
      ). A study in 2001 compared treatment in children aged 2 to 13 years with permethrin 1%, a 10-day course of TMP/SMX (at a dosage of 10 mg/kg/day based on trimethoprim, in two divided doses), and a combination of permethrin 1% and a 10-day course of TMP/SMX (
      • Hipolito R.B.
      • Mallorca F.G.
      • Zuniga-Macaraig Z.O.
      • Apolinario P.C.
      • Wheeler-Sherman J.
      Head lice infestation: Single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole.
      ). Each treatment arm also used nit combing. Evaluation at 2 weeks showed success rates of 79.5%, 83%, and 95% for each treatment arm, respectively (
      • Hipolito R.B.
      • Mallorca F.G.
      • Zuniga-Macaraig Z.O.
      • Apolinario P.C.
      • Wheeler-Sherman J.
      Head lice infestation: Single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole.
      ). After reapplication for appropriate subjects, evaluation at 4 weeks showed success rates of 72%, 78%, and 92.5%, respectively (
      • Hipolito R.B.
      • Mallorca F.G.
      • Zuniga-Macaraig Z.O.
      • Apolinario P.C.
      • Wheeler-Sherman J.
      Head lice infestation: Single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole.
      ). Adverse effects observed with use of TMP/SMX included nausea, vomiting, minor rash, and an allergic-appearing rash. TMP/SMX appears to kill lice by eradicating their intestinal flora, resulting in the inability to synthesize B vitamins (
      • Hipolito R.B.
      • Mallorca F.G.
      • Zuniga-Macaraig Z.O.
      • Apolinario P.C.
      • Wheeler-Sherman J.
      Head lice infestation: Single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole.
      ). It is approved for use in children aged 2 years and older for other infections.
      Crotamition 10% topical lotion is a scabicidal agent that has not been evaluated by the FDA for use in children or in the treatment of head lice (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ;
      • Frankowski B.L.
      • Bocchini Jr., J.A.
      Head lice.
      ). Studies suggest that it may need to be left on hair for 24 hours to be effective (
      American Society of Health-System Pharmacists
      AHFS drug information.
      ).

      Home Remedies

      Although it is assumed that petrolatum jelly, mayonnaise, or olive oil may be able to suffocate lice, the lice are still able to close their respiratory spiracles to resist effective penetration of the substance (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). Once the treatment is washed away, the lice reopen their spiracles. Asphyxiation is thus prevented, unlike with benzyl alcohol, which prevents the spiracles from closing (
      • Meinking T.L.
      • Villar M.E.
      • Vicaria M.
      • Eyerdam D.H.
      • Paquet D.
      • Mertz-Rivera K.
      • Reyna S.
      • et al.
      The clinical trials supporting benzyl alcohol lotion 5% (Ulefsia™): A safe and effective topical treatment for head lice (Pediculosis humanus capitis).
      ). In addition, petrolatum jelly or mayonnaise can be difficult to remove, with the latter subsequently serving as a growth medium for bacteria (
      Therapeutic Research Center
      Commentary: Natroba (Spinosad) for the treatment of head lice. (Detail-Document #270904.).
      ). Another home remedy, tea tree oil, also is not recommended because topical application often leads to local irritation and inflammation, allergic contact eczema, and allergic contact dermatitis as a result of eucalyptol and limonene content (
      Therapeutic Research Center
      Commentary: Natroba (Spinosad) for the treatment of head lice. (Detail-Document #270904.).
      ). The

      National Pediculosis Association. (1997-2009). FAQs: Alternative treatments. Retrieved from http://www.headlice.org/faq/treatments/alternatives.htm

      also strongly recommends avoiding tea tree oil because pure tea tree oil is contraindicated in neonates, infants, and pregnant women because of a lack of information regarding safety and efficacy.

      Novel Agents

      Phase II and III studies have confirmed the safety of a new malathion formulation (0.5% gel) in patients aged 2 years and older. Investigators conducting another phase II open-label trial (NCT 00752973) currently are recruiting patients ages 6 to 24 months to evaluate safety. The gel formulation also has been compared with Nix Créme Rinse (permethrin 1%) and Ovide Lotion (malathion 0.5%) and was found to have similar efficacy after a 30-minute application. The primary advantage of this gel would be decreased application time compared with malathion because Ovide lotion must remain on the hair for 8 to 12 hours before rinsing it off.
      A one-time application of hot air has been studied by the University of Utah, based on the consensus that washing or dry-cleaning clothing and other items at 130° to 150°F (54.4°-65.6°C) for 20 minutes is effective in killing lice. The application was tested in patients aged 6 years and older for approximately 30 minutes in an open-label trial. No adverse effects were observed, and nearly all subjects were lice free when examined 1 week after the hot air treatment. On the basis of these results, the device known as the LouseBuster was developed. The device was tested in 56 subjects, and results showed 94.8% mortality of lice with treatment performed by experienced operators. The mortality rate also was satisfactory with novice operators after a short training session. Consumers seeking a safe, nonchemical alternative can either purchase the device or go to a lice treatment center for application by an experienced operator. The device is sold primarily to professionals for use in schools and clinics. The machine currently costs $2000, and each one-time-use applicator tip is $11. Training is provided at no additional cost. Resistance is unlikely because the mechanism of action of the LouseBuster is desiccation.

      “No-nit” Policies

      Many schools have adopted “no-nit” policies that require children to stay home until they no longer have nits. However, this policy has many disadvantages, and no evidence exists that these policies significantly reduce the spread of lice at schools. Head to head transmission is uncommon; spread is more often due to sharing hats, combs, and other clothing. Oftentimes the reference to “nits” includes both eggs that have yet to hatch and dead eggs or nit casings. This misinterpretation often leads to many valuable days lost at school and extra costs to the parent or caregiver for treatment and missing work to keep the child at home. A small study of 1729 elementary school children identified 28 children as having live lice and 63 as having nits without lice (
      • Williams L.K.
      • Reichert A.
      • MacKenzie W.R.
      • Hightower A.W.
      • Blake P.A.
      ). Fifty of the children with nits only were evaluated after 14 days from initial screening and revealed that only 9 (18.0%) actually converted to an active infestation (
      • Williams L.K.
      • Reichert A.
      • MacKenzie W.R.
      • Hightower A.W.
      • Blake P.A.
      ). Although the presence of nits near the scalp was considered a risk factor for conversion, the majority of children remained lice free (
      • Williams L.K.
      • Reichert A.
      • MacKenzie W.R.
      • Hightower A.W.
      • Blake P.A.
      ).
      It is estimated that 4 to 8 million children in the United States are inappropriately treated for lice each year, with 12 to 24 million school days missed (
      • Mumcuoglu K.Y.
      • Meinking T.A.
      • Burkhart C.N.
      • Burkhart C.G.
      Head louse infestations: The “no nit” policy and its consequences.
      ). The cost in work days to parents and caregivers who need to stay home with their children (in particular for those subjected to no-nit policies) is estimated to be $4 to $8 million (
      • Mumcuoglu K.Y.
      • Meinking T.A.
      • Burkhart C.N.
      • Burkhart C.G.
      Head louse infestations: The “no nit” policy and its consequences.
      ). In addition, children often are dismissed from school as soon as nits or live lice are spotted. This practice is likely unnecessary because it may take a full 1 to 2 months before a child is truly infested, and thus a few more hours at school is not going to lead to any significant transmission (
      • Mumcuoglu K.Y.
      • Meinking T.A.
      • Burkhart C.N.
      • Burkhart C.G.
      Head louse infestations: The “no nit” policy and its consequences.
      ). Mumcuoglu and colleagues propose that children with lice infestations should be dismissed at the end of the school day, and parents should be advised by the school to treat their child. After treatment, parents should fill out a form for the school describing which agent they selected for treatment and when the application occurred (
      • Mumcuoglu K.Y.
      • Meinking T.A.
      • Burkhart C.N.
      • Burkhart C.G.
      Head louse infestations: The “no nit” policy and its consequences.
      ). If treated, children would be allowed to return to school after the first application, at which point the school nurse should check them periodically with a nit comb and inform the parents whether reapplication is needed (
      • Mumcuoglu K.Y.
      • Meinking T.A.
      • Burkhart C.N.
      • Burkhart C.G.
      Head louse infestations: The “no nit” policy and its consequences.
      ).
      The CDC is not a regulatory agency and has no bearing over a school's no-nit policy. The use of this policy often is determined by a local school board.

      Patient and Caregiver Education

      The most important point of counseling is proper identification of lice and nits.
      Patients and caregivers should be counseled on the points outlined in Box 2, as well as the fact that persons of all socioeconomic background or age can be affected by head lice. The most important point of counseling is proper identification of lice and nits. Hair shafts at the back of the head and neck and behind the ears should be examined at 3 to 4 mm from the scalp, with the aid of a fine-tooth comb. If nits are seen further than that from the scalp, they are in fact empty egg casings or dead eggs (
      • Aronson S.S.
      • Shope T.R.
      Managing infectious diseases in child care and schools: A quick reference guide.
      ). Nits should be removed with the fine-tooth comb, particularly if the pediculicide is not ovicidal, but this task can be tedious. Combing longer hair may take up to 1 to 2 hours (

      Insight Pharmaceuticals. (2011). Nix créme rinse: Highlights of prescribing information. Retrieved from http://www.nixlice.com/sites/default/Nix_Creme_Rinse_Nit_Removal_Combs_Product_Fact_Label.pdf

      ). Applying vinegar (diluted 1:1 with water) before combing may or may not aid in loosening the nits (
      • Mumcuoglu K.Y.
      • Meinking T.A.
      • Burkhart C.N.
      • Burkhart C.G.
      Head louse infestations: The “no nit” policy and its consequences.
      ;
      Therapeutic Research Center
      Commentary: Natroba (Spinosad) for the treatment of head lice. (Detail-Document #270904.).
      ). It is recommended that hair remain slightly damp while combing and that hair be divided into sections that can easily be clipped up when completed (

      Insight Pharmaceuticals. (2011). Nix créme rinse: Highlights of prescribing information. Retrieved from http://www.nixlice.com/sites/default/Nix_Creme_Rinse_Nit_Removal_Combs_Product_Fact_Label.pdf

      ). It is important to get the teeth of the comb close to the scalp and comb down from scalp to the end of the hair (

      Insight Pharmaceuticals. (2011). Nix créme rinse: Highlights of prescribing information. Retrieved from http://www.nixlice.com/sites/default/Nix_Creme_Rinse_Nit_Removal_Combs_Product_Fact_Label.pdf

      ). The comb should be cleaned throughout the session to avoid reinfestation. The scalp should be checked daily to remove any more visible nits.
      Patient and caregiver education
      • Proper identification of live lice and nits
      • Instructions of nit combing
      • Indication for treatment is the presence of live lice
      • Selection of treatment based on ovicidal activity, formulations, and cost (Table 2)
      • Selection of treatment based on safety in children and pregnant women (Box 1)
      • Proper application of lice treatments
      • Reasons for reapplication:
        • Decreased effectiveness because of use with conditioner
        • Failure to completely saturate scalp and scalp hair
        • Inadequate length of exposure to lice treatment
        • Resistance
        • Reinfestation
      • Nonpharmacologic measures to reduce reinfestation and prevent spread of lice
      Table 2Available head lice formulations
      AgentGenericPrescription/OTCOvicidal activityFormulationsRetail cost
      Based on pricing from Cardinal Health.
      Permethrin 1% (Nix OTC)N/AOTCNo60-mL créme rinse$8.69
      120-mL créme rinse$13.98
      Complete Lice Kit
      Includes Nix créme rinse, Nix premium metal two-sided comb, disposable gloves, hair salon cape, and drop cloth.
      $13.82
      Pyrethrins/piperonyl butoxide 0.33%/4% (Rid OTC)N/AOTCNo60-mL shampoo$6.09
      120-mL shampoo$9.04
      Rid Complete Lice Kit
      Includes Rid shampoo, lice and egg comb, comb-out gel, and home lice control spray.
      $15.15
      Malathion 0.5% (Ovide)
      Contains isopropyl alcohol 78%.
      YesPrescription onlyYes59-mL lotion$145.86 (generic)
      $154.12 (brand)
      Lindane 1%YesPrescription onlyYes (weak)60-mL lotion$105.17
      60-mL shampoo$105.17
      Benzyl alcohol 5% (Ulesfia)NoPrescription onlyNo227-gm lotion$50.54
      Spinospad 0.9% (Natroba)NoPrescription onlyYes120-mL topical suspension$210.35
      Ivermectin 0.5% (Sklice)NoPrescription only?
      Information regarding ovicidal activity is unavailable from the manufacturer.
      4-oz lotionN/A
      Retail price not yet available from the manufacturer.
      OTC, Over the counter.
      a Based on pricing from Cardinal Health.
      b Includes Nix créme rinse, Nix premium metal two-sided comb, disposable gloves, hair salon cape, and drop cloth.
      c Includes Rid shampoo, lice and egg comb, comb-out gel, and home lice control spray.
      d Contains isopropyl alcohol 78%.
      e Information regarding ovicidal activity is unavailable from the manufacturer.
      f Retail price not yet available from the manufacturer.
      Instructions for use of pediculicides should be reviewed with patients, because application is often tricky. Parents and caregivers should be reminded that products should only be used on the scalp and scalp hair, eye contact should be avoided, anyone who touches the product should wash their hands after application, and clothing and/or a hair salon cape worn by the infested person should be washed after application (

      Shionogi Pharma. (2010). Ulesfia lotion: Highlights of prescribing information. Retrieved from https://www.ulesfialotion.com/ulesfia/hcp/prescribing_information/Ulesfia_Prescribing_Information.pdf

      ). Patients should be instructed to keep their eyes closed tightly and to cover their eyes with a towel throughout the application to protect their eyes. It should be emphasized that the topical product must coat the entire scalp, including the back of the head and neck and behind the ears, to ensure that lice do not escape treatment. Parents or caregivers should be informed that since nits may take 7 to 10 days on average to hatch, reapplication often is necessary. Most products also recommend nit combing. If reapplication occurs too late after the initial application, new nits may be deposited by new active live lice (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ). Patients should not be treated more than two to three times with the same agent if it does not seem to be working (

      Centers for Disease Control and Prevention. (2010, November 2). Parasites: Head lice. Retrieved from http://www.cdc.gov/parasites/lice/head/index.html

      ).
      If a pediculicide should get into a patient's eye, the eye should be flushed with water immediately. For accidental ingestion, the poison center should be called. If irritation at the site of application or any other signs of adverse drug reactions persist, a physician should be contacted. For persistent itching and mild burning as a result of the application of topical pediculicides, oral antihistamines and topical over-the-counter corticosteroids may be beneficial (
      • Frankowski B.L.
      • Bocchini Jr., J.A.
      Head lice.
      ). Parents should be advised to contact a physician before applying corticosteroids to the scalp.
      In addition to topical treatment, it is recommended that parents or caregivers use a lice management program to prevent reinfestation and spread of head lice. It is suggested that nonpharmacologic measures be incorporated; however, their effectiveness is debatable. Pets are not carriers of head lice and do not need treatment.

      Nonpharmacologic Measures

      The following nonpharmacologic measures should be taken:
      • Check household members and other personal contacts for head lice.
      • Communicate with the child's school, day care, and/or camp regarding infestation.
      • Avoid unproven remedies such as use of mayonnaise, petrolatum jelly, and tea tree oil.
      • Avoid shaving the child's head; although this measure can effectively interrupt the life cycle of the louse, it can impose an unnecessary psychological effect on the child.
      • Avoid sleepovers during lice outbreaks, because live lice may be found in bedding, pillows, or carpets.
      • Remind children that they should not share personal items such as hats or brushes.
      • Personal items should be washed in hot water (130°-150°F or 54.4°-65.5°C) for 5 to 10 minutes.
      • Clothing should be washed in hot water (130°-150°F or 54.4°-65.5°C) for at least 20 minutes and then dried using the dryer on a hot setting; dry cleaning also will eradicate lice.
      • Freezing belongings is not recommended for killing lice and nits, and it may take several days to be effective.
      • Although chemical treatments such as permethrin 0.5% spray are available, they usually are unnecessary because lice are unable to live away from their human host for more than 48 hours. Vacuuming carpets, car seats, and mattresses offers a safe alternative to sprays.

      Patient Resources

      Patients may learn more about head lice from the National Pediculosis Association at www.headlice.org or the CDC at http://www.cdc.gov/parasites/lice/head/index.html. Directions for the use of the newest pediculicides and FDA-approved patient education leaflets are included with packaging of Ulesfia and Natroba; they also are available online.

      Discussion

      Close attention must be given to safety in children, and parents and caregivers often require education regarding proper application of products to avoid toxicity and ensure treatment success.
      With regard to the 8-year-old patient mentioned at the beginning of this article, both resistance and proper appliance of lice treatment must be considered when determining the cause of treatment failure. This is the third episode of lice for which permethrin has been used. It is important to discuss whether the permethrin was left on for a full 10 minutes, whether a nit comb was used, and if the mother checked for live lice after 7 days before reapplication. Based on the patient's age, benzyl alcohol or spinosad would be safe and effective options. Spinosad has the advantage of ovicidal activity, which may result in a quicker return to school for the patient. In addition, the patient and her mother should be counseled about nonpharmacologic methods to avoid reinfestation; it usually is unnecessary to use chemical sprays because lice are unable to live very long without a host. However, the child's mother should check other family members for lice, wash affected clothing and personal items in hot water, and ensure that her daughter is not sharing hats or brushes.

      Conclusion

      Ovicidal activity, toxicity, and costs are the biggest considerations when selecting a pediculicide. Close attention must be given to safety in children, and parents and caregivers often require education regarding proper application of products to avoid toxicity and ensure treatment success. All pediculicides should be used in conjunction with a lice management program that uses nonpharmacologic strategies to prevent spread of lice and reinfestation. In addition, accurate identification of nits (dead and alive), nit casings, and live lice is imperative to ensure that children are not subject to unnecessary “no-nit” policies that result in loss of school days, loss of work days for parents and caregivers, and high costs for treatment and physician visits.

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      Biography

      Christine Eisenhower, PGY2 Pharmacy Resident, Ambulatory Care, New Hanover Regional Medical Center, Wilmington, NC.
      Elizabeth Anne Farrington, Pharmacist III, Pediatrics, New Hanover Regional Medical Center, Wilmington, NC.