Ivermectin: pharmacology and therapeutic applications
Keywords:
Antiparasitic, Onchocerciasis, Strongyloidiasis, Scabies, Trichuris trichiura, FilariasisAbstract
Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety. It belongs to the family of avermectins. It binds to glutamate-gated chloride iron channels, which are present in invertebrate nerve and muscle cells, and causes the paralysis and death of the parasite. Ivermectin is approved by the US Food and Drug Administration, and used worldwide to treat patients with onchocerciasis and strongyloidiasis. It is also used against a wide range of endoparasites (nematodes) and ectoparasites (insects, acarine) of animals and humans.
References
Del Guidice P, Marty P. Ivermectin: A new therapeutic weapon in dermatology? Arch Dermatol 1999;135:705-6.
Dourmishev AL, Dourmishev LA, Schwartz RA. Ivermectin: pharmacology and application in dermatology. Int J Dermatol 2005;44:981-8.
Bennett DG. Clinical pharmacology of ivermectin. JAMA 1986;189:100-4.
Turner MJ, Schaeffer JM. Mode of action of ivermectin. In: Campbell WC, editor. Ivermectin and Abamectin, New York: Springer Verlag. 1989;73-88.
Dent JA, Davis MW, Avery L. avr-15 encodes a chloride channel subunit that mediates inhibitory glutametric neuro transmission and ivermectin sensitivity in Caenorhabditis elegans. EMBO J 1997;16:5867-79.
Burkhart CN, Burkhart CG. Ivermectin: a few caveats are warranted before initiating therapy for scabies. Arch Dermatol 1999;135:1549-50.
Campbell WC. Ivermectin, an antiparasitic agent. Med Res Rev 1993;13:61-79.
Edwards G, Dingsdale A, Helsby N, et al. The relative systemic availability of ivermectin after administration as capsule, tablet, and oral solution. Eur J Clin Pharmacol 1988;35:681-4.
Fink DW, Porra AG. Pharmacokinetics of ivermectin in animals and humans. In: Campbell WC, editor. Ivermectin and Abamectin, New York: Springer Verlag.1989;113-30.
Aranzazu GC, Ana M. Sahagun P, Jose DLM et al. The Pharmacokinetics and Interactions of Ivermectin in Humans- A mini Review. AAPS J 2008;10:42-46.
Baraka OZ, Mahmoud BM, Marschke CK, et al. Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus. Eur J Clin Pharmacol 1996;50:407-10.
Haas N, Lindemann U, Frank K, et al. Rapid and preferential sebum secretion of ivermectin: a new factor that may determine drug responsiveness in patients with scabies. Arch Dermatol 2002;138:1618-9.
Whithworth JA, Morgan D, Maude GH, Downham MD, Taylor DW. A community trial of ivermectin for onchocerciasis in Sierra Leone: clinical and parasitological responses to the initial dose. Trans R Soc Trop Med Hyg 1991;85:92-6.
Paasch U, Haistein UF. Management of endemic outbreaks of scabies with allethrin, permetrin and ivermectin. Int J Dermatol 2000;39:463-70.
Barkwell R, Shiels S. Deaths associated with ivermectin treatment of scabies. Lancet 1997;349:1144-5.
Reintjes R, Hoek C. Deaths associated with ivermectin for scabies. Lancet 1997;350:215.
Alexander NDE, Bockaric MJ, Kastens WA. Absence of ivermectin associated excess deaths [letter]. Tran R Soc Trop Med Hyg 1998;92:342.
Hoerauf A, Mand S, Adjei O, Fleischer B, Buttner DW. Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet 2001;357:1415-6.
Awadzi K, Opoku NO, Attah SK, et al. The safety and efficacy of amorcazine in African onchocerciasis and the influence of ivermectin on the clinical and parasitological response to treatment. Ann Trop Med Parasitol 1997;91:281-96.
Awadzi K, Edwards G, Opoku NO, et al. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol 2004;98:595-614.
Ismail MM, Jayakody RL. Efficacy of albendazole and its combinations with ivermectin or diethylcarbamazine (DEC) in the treatment of Trichuris trichiura infections in Sri Lanka. Ann Trop Med Parasitol 1999;93:501-4.
Shu EN, Onwujekwe EO, and Okonkwo PO. Do alcoholic beverages enhance availability of ivermectin? Eur J Clin Pharmacol 2000;56:437-8.
Vanapalli SR, Chen Y, Ellingrod VL, et al. Orange juice decreases the oral bioavailability of ivermectin in healthy volunteers. Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. Washington (USA). 2003 Apr 2-5.
Okulicz JF, Stibich AS, Schwartz RA, et al. African river blindness: onchocercoma. Intern J Dermatol 2004;43:170-2.
Aziz MA, Diallo S, Diop IM et al. Efficacy and tolerance of ivermectin in onchocerciasis. Lancet 1982;2:171-3.
De Sol G, Dadzie KY, Giese J, et al. Lack of adverse reactions in ivermectin treatment for onchocerciasis. Lancet 1990;335:1106-7.
Newland HS, White AT, Greene BM, et al. Effect of single dose ivermectin therapy on human Onchocerca volvulus infection with onchocercal ocular involvement. Br J Ophthalmol 1988;72:561-9.
Unnasch TR. River blindness. Lancet 2002;360:182-3.
Gardon J, Boussinesq M, Kamgno J, Gardon-Wendel N, Demanga-Ngangue J, Duke BO. Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial. Lancet 2002;360:203-10.
Ottesen EA, Vijayesekaran V, Kumaraswami V, et al. A controlled trial of ivermectin and diethylcarbazamine in lymphatic filariasis. N Engl J Med 1990;322:1113-7.
Bockarie MJ, Alexander ND, Hyun P, et al. Randomized community based of annual single dose diethylcarbazamine with or without ivermectin against Wucheria bancrofti infection in human beings and mosquitoes. Lancet 1998;351:162-8.
Dunyo SK, Nkrumah FK, Simonsen PE. Single-dose treatment of Wuchereria bancrofti infections with ivermectin and albendazole alone or in combination: evaluation of the potential for control at 12 months after treatment. Trans R Soc Trop Med Hyg 2000;94:437-43.
Caumes E, Darty A, Paris L, et al. Efficacy of ivermectin in the therapy of cutaneous larva migrans. Arch Dermatol 1992;128:994-5.
Caumes E, Carrieri J, Darty A, et al. A randomized trial of ivermectin versus albendazole for the treatment of cutaneous larva migrans. Am J Trop Med Hyg 1993;49:641-4.
Bouchard O, Houze S, Scheimann R, et al. Cutaneous larva migrans in travelers: a prospective study, with assessment of therapy with ivermectin. Clin Infect Dis 2000;31:493-8.
Tarlow MM, Schwartz RA. Strongyloidiasis. eMedicine Dermatology 2002. [Journal serial online]. Available at: http://author.emedicine.com /derm /topic838.htm.
Caumes E, Datry A, Mayorga R et al. Efficacy of ivermectin in the therapy of cutaneous larva currens. Arch Dermatol 1994;130:932.
Victoria Y, Trujillo R, Barreto M. Myiasis: a successful treatment with topical ivermectin. Int J Dermatol 1999;38:142-4.
Jelinek T, Nothdurf HD, Reider N, et al. Cutaneous myasis, review of 13 cases in travelers returning from tropical countries. Int J Dermatol 1995;34:624-6.
Kombila M, Duong TH, Ferrer A, Perret JC, Marion MC, Nguiri C, et al. Short and long-term action of multiple doses of ivermectin on loiasis microfilaremia. Am J trop Med Hyg 1998;58:458-60.
Boussinesq M, Gardon J, Gardon-Wendel N, Ka mgno J, Ngoumou P, Chippaux JP. Three probable cases of Loa loa encephalopathy following ivermectin treatment for onchocerciasis. Am J Trop Med Hyg 1998;58:461-9.
Chappuis F, Farinelli T, Loutan L. Ivermectin treatment of a traveler who returned from Peru with cutaneous gnathostomiasis. Clin Infect Dis 2001;33:e17-9.
Nontasut P, Bussaratid V, Chullawichit S, Charoensook N, Visetsuk K. Comparison of ivermectin and albendazole treatment for gnathostomiasis. Southeast Asian J Trop Med Public Health 2000;31:374-7.
del Giudice P, Chosidow O, Caumes E. Ivermectin in dermatology. J Drugs Dermatol 2003;2:13-21.
Momcuoglu KY, Miller J, Rosen LJ, et al. Systemic activity of ivermectin on the human body louse (Anoplura: Pediculidae). Med Entomol 1990;27:72-5.
Glaziou P, Nguyen LN, Moulia-Pelat JP, et al. Efficacy of ivermectin for the treatment of head lice (pediculosis capitis). Trop Med Parasitol 1994;45:253-4.
Victoria J, Ahumada N, Gonzaile F. Pediculosis capitis. treatmento de 100 ninos con ivermectin. Acta Terap Dermatol 1997;20:99-103.
Burkhart CG, Burkhart CN, Burkhart KM. An assessment of topical and oral prescription and over-the-counter treatment for head lice. J Am Acad Dermatol 1998;38:979-82.
Burkhart CG, Burkhart CN. Oral ivermectin therapy of phthiriasis palpebrarum. Arch Ophthalmmol 2000;118:134-35.
Dunne CL, Malone CJ, Whitworth JA. A field study of the effects of ivermectin on ectoparasites of man. Trans R Soc Trop Med Hyg 1991;85:550-1.
Youssef MY, Sadaka HA, Eissa MM, et al. Topical application of ivermectin for human ectoparasites. Am J Trop Med Hyg 1995;53:652-3.
Macotela-Ruiz, Pena-Gonzalez G. Treatment of scabies with oral ivermectin. Gac Med Mex 1993;129:201-5.
Glaziou P, Cartel JL, Alzieu P, et al. Comparison of ivermectin and benzoyl benzoate for treatment of scabies. Trop Med Parasitol 1993;4:331-2.
Chouela EN, Abeldano AM, Pellerano G, Forgia ML, Papale RM, and Garsd A, et al. Equivalent Therapeutic Efficacy and Safety of Ivermectin and Lindane in the Treatment of Human Scabies. Arch Dermatol 1999;135:651-5.
Madan V, Jaskiran K, Gupta U, Gupta DK. Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion. J Dermatol 2001;28:481-4.
Usha V, Gopalakrishnan Nair TV. A comparative study of oral ivermectin and topical permethrin cream in the treatment of scabies. J Am Acad Dermatol 2000;42:236-40.
Brooks P, Grace R. Ivermectin is better than benzyl benzoate for childhood scabies in developing countries. J Paediatr Child Health 2002;38:401-4.
Sule HM, Thacher TD. Comparison of ivermectin and benzyl benzoate lotion for scabies in nigerian patients. Am J Trop Med Hyg 2007;76:393-5.
Bachewar NP, Thawani VR, Mali SN, Gharpure KJ, Shingada VP, Dakhale GN. Comparison of safety, efficacy, and cost effectiveness of benzyl benzoate, permethrin, and ivermectin in patients of scabies. Indian J Pharmacol 2009;41:9-14.
Fatimata LY, Eric C, Cheick AT, Bassirou N, Antoine M. Ivermectin versus benzyl benzoate applied once or twice to treat human scabies in Dakar, Senegal: a randomized controlled trial. Bull World Health Organ 2009;87:424-30.
Offidiani A, Cellini A, Simonetti O, Fumelli C. Treatment of scabies with ivermectin. Eur J Dermatol 1999;9:100-1.
Bauer J, Blum A, Sonnichsen K, Metzler G, Rassner G, Garbe C. Nodular scabies detected by computed dermatoscopy. Dermatology 2001;203:190-1.
Marty P, Gari-Toussaint M, Le Fichoux Y, Gaxotte P. Efficacy of ivermectin in the treatment of an epidemic of sarcoptic scabies. Ann Trop Med Parasitol 1994;88:453.
Del Giudice P, Carles M, Couppie P, Bernard E, Lacour JP, Marty P, Pradinaud R, Ortonne JP, Dellamonica P, Le Fichoux Y. Successful treatment of crusted (Norwegian) scabies with ivermectin in two patients with human immunodeficiency virus infection. Br J Dermatol 1996;135:494-5.
Patel A, Hogan P, Walder B. Crusted scabies in two immuno-compromised children: successful treatment with oral ivermectin. Aust J Dermatol 1999;40:37-40.
Yeruham I, Hadani A. Control of human scabies by topical application of ivermectin. Ann Trop Med Parasitol 1998;92:627-9.
Victoria J, Trujillo R. Topical ivermectin: a new successful treatment for scabies. Pediatr Dermatol 2001;18:63-65.
Aubin F, Humbert P. Ivermectin for crusted (Norwegian) scabies. N Engl J Med 1995;332:612.
Meinking TL, Taplin D, Jorge L, et al. The treatment of scabies with ivermectin. N Engl Med J 1995;333:26-30.
Jaramillo-Ayerbe F, Berrio-Munoz J. Ivermectin for crusted Norwegian scabies induced by use of topical steroids. Arch Dermatol 1998;134:143-5.
Huffam SE, Currie BJ. Ivermectin for Sarcoptes scabiei hyperinfestation. Int J Infect Dis 1998;2:152-4.
Walton SF, Myerscough MR, Currie BJ. Studies in vitro on the relative efficacy of current acaricides for Sarcoptes scabiei var hominis. Trans R Soc Trop Med Hyg 2000;94:92-6.
Fawcett RS. Ivermectin use in Scabies. Am Fam Physician 2003;68:1089-92.
Alberici F, Pagani L, Ratti G, Viale P. Ivermectin alone or in combination with benzyl benzoate in the treatment of human immunodeficiency virus-associated scabies. Br J Dermatol 2000;142:969-72.
Coralith G, David I, Angelica T, Marco C, Eduardo G. Use of ivermectin to treat an institutional outbreak of scabies in low resource setting. Infect Control Hosp Epidemiol 2007;28:1337-8.
