Splitting Hairs: Pharmacist-Focused Strategies for Individualizing Treatment Mary M. Bridgeman, PharmD, BCPS, Clinical Assistant Professor Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey Piscataway, New Jersey Faculty Information Presenter: Mary M. Bridgeman, PharmD, BCPS, Clinical Assistant Professor Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey Piscataway, New Jersey Moderator: Steve Lin, PharmD Director of Scientific Affairs Pharmacy Times Office of CPE Plainsboro, New Jersey 1
Faculty Disclosures and COI Resolution Mary Bridgeman, PharmD Is an employee of Rutgers, The State University of New Jersey Does not have a vested interest in or affiliation with any commercial entities (or their competitors) whose products are mentioned in this presentation Is not affiliated with an organization that has a specific interest in the therapeutic areas under discussion Disclosures and COI Resolution (cont.) Ernest Mario School of Pharmacy, Rutgers University Planning Staff Evelyn R. Hermes-DeSantis, PharmD, BCPS, Clinical Professor; Chair, Continuing Education Committee has no financial relationships with commercial interests to disclose. Pharmacy Times Office of Continuing Professional Education Planning Staff Judy V. Lum, MPA, Steve Lin, PharmD, David Heckard, and Donna W. Fausak have no financial relationships with commercial interests to disclose. An anonymous peer reviewer has been used as part of content validation and conflict resolution. The peer reviewer has no relevant financial relationships with commercial interests to disclose. The content of this webinar may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Pharmacists should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products. 2
Pharmacy Accreditation Ernest Mario School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 1.0 contact hour (0.1 CEU) under the ACPE universal activity 0038-9999-13-011-H01-P and 0038-9999-13-011-H01-T. The activity is available for CE credit through August 23, 2013. Type of Activity: Knowledge This program is in co-sponsorship with Ernest Mario School of Pharmacy, Rutgers University and Pharmacy Times Office of Continuing Professional Education and is supported by an educational grant from Sanofi Pasteur U.S. Splitting Hairs: Pharmacist-Focused Strategies for Individualizing Treatment Mary M. Bridgeman, PharmD, BCPS, Clinical Assistant Professor Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey Piscataway, New Jersey 3
Learning Objectives Upon completion of this educational activity, participants should be able to: Examine the incidence and public health impact of head lice infestation Describe the differences between available lice treatment options regarding safety, efficacy, application and pediculicide resistance Discuss the role of the pharmacist in individualizing treatment of head lice, promoting the correct use of products for self-care, and prevention re-infestation through patient education Head Lice: A Historical Perspective Ancient pest attributed to causing human infestation for thousands of years Fossils of louse eggs found on human hair dating to 10,000 BC Referenced in the Bible Found on mummified remains of ancient Egyptians Colloquial terms (eg, lousy, nit-wit) attributed to outbreaks of infestation Parasitol Today 2000;16:279.; Paleomicrobiology: Past Human Infections. Berlin, Germany: Springer_verlag;2008:215-222. 4
Epidemiology of Infestations Most common among: Preschool-aged children attending daycare Elementary school-aged children Household members of infested children Exact annual prevalence difficult to estimate Estimates often derived from over-the-counter (OTC) pediculicide sales data 6 to 12 million infestations likely to occur each year in children aged 3-12 years Int J Dermatol 2006;45(8):891-6.; Centers for Disease Control and Prevention. Available from: http://www.cdc.gov/ncidod/dpd/parasites/lice.; World Health Organization Pesticide Evaluation Scheme; 1997. Public Health Impact No-nit school policies Estimated > 12-24 million missed school days annually due to head lice infestation Historically, children required to stay home for at least 24 hours after head lice discovery Presence of nits not necessarily indicative of active infestation Can remain glued to hair follicles for several days after treatment May be empty egg casings, not live eggs Int J Dermatol 2006;45(8):891-6.; Centers for Disease Control and Prevention. Available from: http://www.cdc.gov/ncidod/dpd/parasites/lice.; Gratz NG. World Health Organization, Division of Control of Tropical Disease, WHO Pesticide Evaluation Scheme; 1997. 5
Physiology and Biology of the Louse Ectoparasites Live on the skin and hair of body Feed exclusively on human blood Species of louse known to affect humans Pediculus humanus capitis Pediculus humanus corporis Pthirus pubis Transmission Infestation Wingless, sesame seed-sized parasites Move by crawling Spread by direct contact with hair of affected individual Head-to-head contact poses greatest risk of transmission Fomites (eg, hats, scarves, combs, brushes) represent uncommon means of transmission Head lice survive for one day or less when removed from host Curr Probl Dermatol 1999;11:73-120.; Pediatrics 2010;126:392-403. 6
Lifecycle of the Head Louse Three distinct stages: Egg Nymph Adult Adult female head louse has lifespan of 3-4 weeks May lay up to 10 eggs per day Pediatrics 2010;126:392-403. http://www.cdc.gov/parasites/lice/head/biology.html Head Lice Images Unhatched head louse nit Female head louse Images from Centers for Disease Control and Prevention [CDC], Atlanta, GA. CDC Public Health Image Library, Image number 377 (louse) and 378 (nit). Available from: http://phil.cdc.gov/phil/home.asp. 7
Signs and Symptoms of Infestation Scalp symptoms Tickling feeling Sensation of movement Pruritus (sometimes severe) Allergic, macular rash where bitten Pruritus and concerns May result in scalp excoriation Secondary bacterial skin infections Diagnosis Gold-standard technique Locate live louse on affected individual s scalp Strategies to slow louse movement: Dampen scalp Coat head with conditioner Visualizing nits May be easier to locate, especially behind ears or at nape of neck Pediatrics 2010;126:392-403.; Nurs Times 2002;98(46):57. 8
Prevention of Infestation Teach children: Not to share personal care items (eg, combs, brushes, hair clips) Do not allow refusal to wear protective headgear due to fear of lice Symptom awareness Teachers and child care providers should be aware of signs and symptoms of infestation Early detection and treatment to minimize transmission Pediatrics 2010;126:392-403.; Nurs Times 2002;98(46):57. Management Initiate management strategies and treatment only when diagnosis is clear Two-fold treatment strategy: Prevention of infestation of others Environmental sanitization practices Elimination of human reservoirs Pharmacologic treatment of individuals with active infestation Pediatrics 2010;126:392-403.; Nurs Times 2002;98(46):57. 9
Environmental Control Strategies Recommend sanitization of all personal hair care items Suggest washing in hot water or dry cleaning all household items utilized by infected individual Clothing Pillow cases Bedding Towels Advocate vacuuming furniture, car seats, carpeting Pediatrics 2010;126:392-403.; Diaz JH. Lice (pediculosis). In: Mandell GL, Bennett JR, Dolin R, eds. Principles and Practice of Infectious Diseases, 6 th ed. New York, NY: Elsevier Churchill Livingstone; 2010:3629-3632. Nit Combs Can be difficult and tedious! Recommend using fine-toothed, specialized nit comb Useful for removing: Nits Dead lice after pharmacologic treatment Image from: http://www.headlice.org/catalog/ Pediatrics 2010;126:392-403.; Nurs Times 2002;98(46):57. 10
Hot Air Therapy Image from: http://www.lousebuster.com LouseBuster FDA-approved device Reported to eradicate head lice with one 30- minute hot air treatment Mechanism of action Hot air treatment results in louse desiccation Should not be tried at home! Pediatrics 2010;126:392-403.; Pediatrics 2006;118(5):1962-1970. Pharmacologic Treatment of Head Lice Permethrin (Elimite ; Nix ) Pyrethrin combined with piperonyl butoxide (Licide ; Pronto ; RID ) Lindane (Kwell ) Malathion (Ovide ) Spinosad (Natroba ) Benzyl alcohol (Ulesfia ) Ivermectin (Sklice ) 11
Pediculicidal or Ovicial? Pediculicidal agents: Benzyl alcohol (Ulesfia ) Ivermectin (Sklice ) Permethrin (Elimite ; Nix ) Pyrethrin combined with piperonyl butoxide (Licide ; Pronto ; RID ) Pediculicidal and ovicidal agents: Lindane (Kwell ) Malathion (Ovide ) Spinosad (Natroba ) Criteria for Self-Treatment Infestation confined to scalp No symptoms of secondary bacterial skin infection Not pregnant or breast-feeding All products require topical application Recommend washing affected hair in sink rather than bath or shower Minimize systemic exposure and toxicities Pediatrics 2010;126:392-403.; Contemp Pediatr 1998;15(11):181-192. 12
OTC vs. Prescription-Only Products OTC products: Permethrin (Elimite ; Nix ) Pyrethrin combined with piperonyl butoxide (Licide ; Pronto ; RID ) Prescription-only treatments: Lindane (Kwell ) Malathion (Ovide ) Benzyl alcohol (Ulesfia ) Spinosad (Natroba ) Ivermectin (Sklice ) OTC Products for Head Lice Infestation Active ingredients and brand names Permethrin (Elimite ; Nix ) Pyrethrin combined with piperonyl butoxide (Licide ; Pronto ; RID ) Considered safe and effective in most cases Often first treatment sought by parents and caregivers due to availability Dosage based on patient s age Resistance documented due to overuse, improper use, or insufficient contact time Pediatrics 2010;126:392-403.; Arch Dermatol 2002;138:220 4.; Arch Dermatol 2001;137:287 91. 13
Permethrin 1% (Elimite ; Nix ) Agent of choice in treatment of head lice infestation Most-studied pediculicide in U.S. Least toxic to humans Mechanism of action Neurotoxin Disrupts sodium channels in central nervous system (CNS) of louse Delays repolarization and causes paralysis Clin Infect Dis 2003;36 (11): 1355-1361.; Pediatrics 2010;126:392-403.; Diaz JH. Lice (pediculosis). In: Mandell GL, Bennett JR, Dolin R, eds. Principles and Practice of Infectious Diseases, 6 th ed. New York, NY: Elsevier Churchill Livingstone; 2010:3629-3632. Product-Specific Information Permethrin 1% Contraindications Infants younger than 2 months of age Allergy to ragweed or chrysanthemums Directions for Use Shampoo and towel-dry hair Wet hair and scalp with product Leave on for 10 minutes, rinse, and use nit comb Need to Reapply? Not necessary Can retreat in 7-10 days if live lice observed Adverse Effects Scalp irritation, pruritis, erythema, burning Stinging, tingling, numbness of scalp Clin Infect Dis 2003;36 (11): 1355-1361.; Pediatrics 2010;126:392-403.; Nix (permethrin) shampoo, 1%. Langhorne, PA: Insight Pharmaceuticals; 2009. 14
Pyrethrins and Piperonyl Butoxide (Licide ; Pronto ; RID ) Pyrethrins Resins from chrysanthemum flower Work by blocking nerve impulse transmission, causing paralysis and death to louse Piperonyl butoxide Petroleum derivative Helps augment effect of pyrethrins by inhibiting activity of louse s cytochrome P450 enzymes Clin Infect Dis 2003;36 (11): 1355-1361.; Pediatrics 2010;126:392-403.; Diaz JH. Lice (pediculosis). In: Mandell GL, Bennett JR, Dolin R, eds. Principles and Practice of Infectious Diseases, 6 th ed. New York, NY: Elsevier Churchill Livingstone; 2010:3629-3632. Product-Specific Information Pyrethrins and Piperonyl Butoxide Contraindications Infants younger than 2 years of age Allergy to ragweed or chrysanthemums Directions for Use Apply product to dry hair or massage into wet hair Leave on for 10 minutes Rinse hair with regular shampoo, and use nit comb Need to Reapply? No residual pediculicidal activity Second treatment recommended in 7-10 days to kill any remaining lice Adverse Effects Irritation Erythema Itching Localized swelling Clin Infect Dis 2003;36 (11): 1355-1361.; Pediatrics 2010;126:392-403.; Piperonyl butoxide and pyrethrum extract shampoo. Allegan, MI: Major Pharmaceuticals; 2012. 15
Prescription-Only Products Active ingredients and brand names Lindane (Kwell ) Malathion (Ovide ) Benzyl alcohol (Ulesfia ) Spinosad (Natroba ) Ivermectin (Sklice ) Can be utilized: In lieu of OTC products when resistance is suspected In patients who have failed treatment with OTC products Pediatrics 2010;126:392-403. Lindane Shampoo 1% (Kwell ) Mechanism of action Organochloride pesticide Inhibits gamma-amino butyric acid (GABA) receptors in CNS of louse Results in hyperexcitability and inability to feed Place in therapy Second-line treatment due to potential for causing neurotoxicity (black box warning) Clin Infect Dis 2003;36 (11): 1355-1361.; Pediatrics 2010;126:392-403.; Diaz JH. Lice (pediculosis). In: Mandell GL, Bennett JR, Dolin R, eds. Principles and Practice of Infectious Diseases, 6 th ed. New York, NY: Elsevier Churchill Livingstone; 2010:3629-3632. 16
Product-Specific Information Lindane Shampoo 1% Contraindications Premature infants or neonates Children and individuals weighing less than 50 kg (110 lbs.) Immunocompromised patients Pregnant women Directions for Use Apply product to clean, dry hair Leave on scalp for 4 minutes Dampen hair, lather, and wash off Use no more than 2 ounces per single application Need to Reapply? Not recommended due to risk of serious side effects when applied too soon for retreatment No data available to indicate what is optimal time for reapplication Adverse Effects CNS effects seizures, convulsions, death Localized itching or burning Dry skin Skin rash Clin Infect Dis 2003;36 (11): 1355-1361.; Pediatrics 2010;126:392-403.; US Food and Drug Administration. Available from: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm110848.htm#5. Malathion Lotion 0.5% (Ovide ) Mechanism of action Organophosphate pesticide Inhibits cholinesterase activity of louse Place in therapy Indicated for treatment of head lice infestation in children 6 years of age and older Resistance common in European countries Formulation available in U.S. contains terpineol, dipentene, and pine needle oil May improve efficacy and reduce resistance Pediatrics 2010;126:392-403.; Diaz JH. Lice (pediculosis). In: Mandell GL, Bennett JR, Dolin R, eds. Principles and Practice of Infectious Diseases, 6 th ed. New York, NY: Elsevier Churchill Livingstone; 2010:3629-3632.; Malathione Lotion 5% [prescribing information]. Woodcliff Lake, NJ: Karalex Pharma, LLC; 2008. 17
Product-Specific Information Malathion Lotion 0.5% Contraindications Children younger than 24 months of age Directions for Use Apply to dry hair Allow to air dry NO heat Wash off 8-12 hours later Comb with nit comb Need to Reapply? Can retreat in 7-9 days if live lice observed Adverse Effects Chemical burns of scalp Skin and scalp irritation, stinging Conjunctivitis Pediatrics 2010;126:392-403.; Malathione Lotion 5% [prescribing information]. Woodcliff Lake, NJ: Karalex Pharma, LLC; 2008. Benzyl Alcohol Lotion (Ulesfia ) Mechanism of action Obstructs respiratory spiracles of louse Results in asphyxiation Efficacy data Established in two studies of more than 600 people with active head lice infestation Intervention Two 10-minute treatments with either benzyl alcohol 5% lotion or placebo one week apart Outcomes Approximately 75% of patients who received benzyl alcohol 5% lotion were lice-free 14 days after treatment, compared to 26% who received placebo Pediatrics 2010;126:392-403.; Diaz JH. Lice (pediculosis). In: Mandell GL, Bennett JR, Dolin R, eds. Principles and Practice of Infectious Diseases, 6 th ed. New York, NY: Elsevier Churchill Livingstone; 2010:3629-3632. ; Ulesfia (benzyl alcohol) Lotion, 5% [product information]. Florham Park, NJ: Shionogi Inc.; 2012. 18
Product-Specific Information Benzyl Alcohol Lotion Contraindications None Not indicated for use in children younger than 6 months of age Directions for Use Apply product to dry hair Leave on for 10 minutes Rinse hair with water Need to Reapply? Repeat application recommended in 7 days Adverse Effects Occular irritation Application site irritation Application site anesthesia and hypoesthesia Pediatrics 2010;126:392-403.; Ulesfia (benzyl alcohol) Lotion, 5% [product information]. Florham Park, NJ: Shionogi Inc.; 2012. Spinosad (Natroba ) Mechanism of action Causes neuronal excitation in louse Results in paralysis and death Efficacy data Significantly more effective vs. permethrin 1% in two phase III clinical trials Intervention 1038 patients given either spinosad (without comb) or permethrin (with comb) Outcomes 84.6% (study 1) and 86.7% (study 2) of spinosadtreated patients found to be lice-free at day 14 Natroba (spinosad) topical suspension, 0.9% [product information]. Carmel, IN: ParaPRO LLC; 2011. 19
Product-Specific Information Spinosad Contraindications None Not recommended for children younger than 4 years of age Directions for Use Apply product to dry hair and scalp Leave on for 10 minutes and rinse with warm water No combing required Need to Reapply? May need retreatment in 7 days if live lice seen Adverse Effects Application-site redness Redness of eyes Application-site irritation Natroba (spinosad) topical suspension, 0.9% [product information]. Carmel, IN: ParaPRO LLC; 2011. Ivermectin (Sklice ) Mechanism of action Antiparasitic agent Paralytic Binds to glutamate-gated chloride ion channels of nerve and muscle cells. Results in paralysis, rendering lice unable to feed Also penetrates nits, affecting ability of emerging nymphs to feed, ultimately preventing them from thriving and maturing into adult lice Efficacy data In phase III trials, shown to resolve most infestations with one 10-minute application without combing Two weeks after initial treatment, 71-76% of treated patients were lice-free Sklice (ivermectin) Lotion [prescribing information]. Swiftwater, PA: Sanofi Pasteur Inc.; 2012. 20
Product-Specific Information Ivermectin Contraindications None Not indicated for children younger than 6 months of age Directions for Use Apply product to dry hair and scalp Leave on for 10 minutes Rinse hair and scalp with water only Need to Reapply? No reapplication required Adverse Effects Conjunctivitis Ocular hyperemia Eye irritation Dandruff Dry skin and burning Sklice (ivermectin) Lotion [prescribing information]. Swiftwater, PA: Sanofi Pasteur Inc.; 2012. Comparison of Pharmacologic Treatment Options Active Ingredients Benzyl alcohol Brand Name Dosage Form Need for Reapplication? Ulesfia Topical lotion 5% Yes in 7 days Ivermectin Sklice Topical lotion 0.5% No Lindane Kwell Topical shampoo 1% Malathion Ovide Topical lotion 0.5% Spinosad Natroba Permethrin Pyrethrin combined with piperonyl butoxide Elimite Nix Licide Pronto RID Topical suspension 0.9% Topical cream, lotion, solution 1% Shampoo, topical oil, solution of pyrethrins 0.33% and piperonyl butoxide 4% No Yes in 7 days if live lice observed Yes in 7 days if live lice observed Yes in 7 days if live lice observed Yes in 7 days Prescription or Over-the- Counter? Prescription Only Over-the- Counter Pediculicidal/Ovicidal Pediculicidal against live lice only Pediculicidal and ovicidal against live lice and nits Pediculicidal against live lice only 21
Alternative Medicines Insufficient data to recommend in lieu of conventional therapies None considered curative or FDA-approved Topical spray coconut, anise, ylang ylang oils 92% effective for treatment of head lice in children Comparable to spray containing permethrin, malathion, piperonyl butoxide, and isododecane Further data needed Recommend against agents that may be flammable or toxic Pediatrics 2010;126:392-403.; Isr Med Assoc J 2002;4:790-3. What About Young Children? Pharmacologic products vary based on age indications If patient is too young: Consider recommending wet-combing Using occlusive therapy Petroleum jelly Cetaphil Pediatrics 2010;126:392-403. 22
The Pharmacist s Role Pharmacy counter is primary point of contact for many patients Pharmacists need to be versed in proper questions before recommending self-care Older lice-killing products Contain neurotoxic pediculicides Safety risks for children Resistance a growing problem and concern Head Lice. Mayo Clinic website. Available from: www.mayoclinic.com/health/head- lice/ds00953/dsection=treatments-anddrugs. Accessed April 19, 2013.; Lancet 2003;363:889-891.; J Am Acad Dermatol 2004;50:1-14.; Hosp Pharm 2003;38:241-246. Pediculicide Resistance Estimated to occur 1-2 times per week in 58.1% of pharmacists practices May result in: More frequent treatment Use of higher doses of pesticides Head Lice. Mayo Clinic website. Available from: www.mayoclinic.com/health/head- lice/ds00953/dsection=treatments-anddrugs. Accessed April 19, 2013.; Lancet 2003;363:889-891.; J Am Acad Dermatol 2004;50:1-14.; Hosp Pharm 2003;38:241-246. 23
Strategies to Minimize Resistance Counsel parents and caregivers on proper use of prescription and OTC products Particularly with regard to reapplication Many patients will fail to reapply in 7 to 10 days after initial treatment Only recommend treatment for individuals with active infestation Avoid product overuse Recommend nonpharmacologic therapies (including combs) to improve efficacy Pediatrics 2010;126:392-403.; Head Lice. Mayo Clinic website. Available from: www.mayoclinic.com/health/headlice/ds00953/dsection=treatments-and-drugs. Accessed April 19, 2013.; Lancet 2003;363:889-891.; J Am Acad Dermatol 2004;50:1-14.; Hosp Pharm 2003;38:241-246. Prevention of Re-Infestation Check all household members for presence of live head lice Treat those: Found to have live lice and nits Who share bed with infested individual Clean all hair care products and implement environmental controls Managing infestations in schools Routine screening not recommended Notification to parents or caregivers No need for child to be sent home Pediatrics 2010;126:392-403. 24
Dispelling Common Myths About Head Lice No need for prophylactic treatment Gold-standard of diagnosis is live louse No need to treat members of household without signs of active infestation Natural doesn t equate with safe or more efficacious product Educate parents and caregivers to avoid products and home remedies with little data to support safety of efficacy Gasoline Kerosene Other dangerous treatments Pediatrics 2010;126:392-403. Conclusions Head lice is extremely common type of parasitic infestation affecting school-aged children Affected individuals may feel ostracized, humiliated and embarrassed Pharmacists can provide empathy and encouragement when counseling to help affected individuals overcome these feelings 25
Thank You! 26