r ti and under the individual headings below. Itis used topically of serious adverse events in patients with high numbers of P.r.�P.�. �_ c:>.n.�...... in the treatment of head pediculosis (see also p. 157.2). microfilaria. Low-dose regimens (about 25 micrograms/kg) ProprietaryPreparations (details are given in Volume B) In the treatment of , a single oral dose of have been investigated9 but did not seem to offer much Single-ingredient Preparations. Arg.: Flumoxal; Fr.: Fluvermal; iverrnectin, based roughly on 150 micrograms/kg may be advantage in redudng neurotoxicity. Port.: Fluvermal; Teniverme; Spain: Flicumt; Venez. : Fluver­ given to patients weighing more than 15 kg; re-treatrnentis 1. Martin-Prevel Y, et al. Reduction of microfilaraemia with single high­ mox. usually required, and is given after an interval of at least 3 dose of iverrnectin in loiasis. Lancet 1993; 342: 442. months. For mass treatment in infected areas (see p. 157.1) 2. Ranque S, et a!. Decreased prevalence and intensity of infection in a community treated with ivermectin every three months for two the dose is given annually or every 6 months. No food years. Trans R Soc Trap Med Hyg 1996; 90: 429-30. Haloxon (BAN, r/NN) should be taken for 2 hours before or after the dose. Similar 3. Duong TH, et a!. Reduced Loa loa microfilaria count ten to twelve or slightly higher doses, plus a dose of albendazole, are months after a single dose of ivermectin. Trans R Soc Trop Med Hyg 1997; Hafoxonum; advocated by WHO in the mass treatment of lymphatic 91: 592-3. Haroxone; fanOKCOH. 4. Gardon J, et a!. Marked decrease in Loa loa microfilaraemia six and ·Bis(2Halox6n;-chloroe th}tl) -yl (see p. 157.1 for details). twelve months after a single dose of ivermectin. Trans R Soc Trop Med Hyg · For the treatment of , iverrnectin 1997; 91: 593--4. phate, . 3:ch!or6-4-methy!coumarin-7 ,.1H ,�CI30tP':'415,6 200 micrograms/kg as a single oral dose, or daily on two 5. Chippaux J-P, et al. Impact of repeated large scale iverrnectin treatments consecutive days, is given to patients weighing more than on the transmission of Loa loa. Trans R Soc Trop Med Hyg 1998; 92: 454--8. CC4S 6. Anonymous. Encephalitis following treatment of loiasis. WHODrng In{ 15kg. 32_:_1_ -ss- r: 1991; 5: ll3-14. A TC QP51A804. Ivermectin is used in the treatment of head pediculosis 7. Gardon J, et al. Serious reactions after mass treatment of onchocerciasis UNil - with iverrnectin in an area endemic for Loa loa infection. Lancet 1 997; TSKXA37iJ68. as a single topical application of a 0.5% lotion in adults and children from 6 months of age. It should be applied to dry 350: 18-22. 8. Bourguinat C, et a!. Analysis of the mdr- 1 gene in patients co-infected hair, left on for 10 minutes and then washed out. Profile with and Loa loa who experienced a post-ivermectin serious adverse event. Am J Trap Med Hyg 2010; 83: 28--32. Haloxon is an organophosphorus compound (see Organo­ Reviews. l. Ottesen EA, Campbell WC. Ivermectin in human medicine. Antimicrob 9. Kamgno J, et at. Randomi7ed, controlled, double-blind trial with 1 phosphorus Insecticides, p. 2158.3) used as an anthelmintic Chemother 1994; 34: 195-203. iverrnectin on Loa loa microfilaraemia: efficacy of a low dose (-25 g/kg) versus current standard dose ( 150 g/kg). Trans R Soc Trap Med in veterinary medicine. 2. Omura S. Jvermectin: 25 years and still going strong. Int Antimicrob � 1.1 1 Agents 2008; 31: 91--8. Hyg 2007; 101: 777-85.

Lymphatic filariasis. Ivermectin is used in the manage­ Hygromycin B Administration in children. Iverrnectin may be given oral­ . ly to children weighing more than 15 kg and over 5 years i ment of (p. 146.3). In endemic areas Higromicina B; Hygromycine of age, for the management of onchocerciasis and lympha­ mass treatment of the entire population (excluding neo­ O·&Amino-6-d<=oxy·c-glycer o•r>galacto-heprB; fMrpoMliif.lW>-e b.·opytanos yli· tic filariasis and also for the treatment of strongyloidiasis. nates, pregnant women, and debilitated individuals) can 3 dene-( 1 -2-3)·0ci3·D· IB!opytaf'l0syl· 5)•2·deoxy-N - Doses used are the same by weight as those used for adults reduce the intensity of transmission and the incidence of (1.-. (see above). disease. In countries where there is co-endemic loiasis or onchocerciasis, the Global Programme to Eliminate Lym­ , There are some reports1•5 of phatic Filariasis launched by WHO, with other interna­ tional agencies, advocates a single oral dose of ivermectin - ivermectin being effective in the treatment of cutaneous !50 to 200 micrograms/kg with a single oral dose of UN/! JX0223380B. larva migrans (p. 144.3). An oral dose of 200 rnicro­ grams/kg daily for I to 2 days has been recommended 6 albendazole 400 mg given once each year for at least 5 Profile l. Caumes E, et al. Efficacy of ivermectin in the therapy of cutaneous larva years. migrans. Arch Dermatol 1992; 128: 994--5. Higher doses of albendazole and ivermectin ( 800 mg and Hygromycin B is used as a feed additive in veterinary 2. Caumes E, et al. A randomized trial of ivennectin versus albendazole for 400 micrograms/kg respectively) given twice a year for 2 the treatment of cutaneous larva migrans. Am Trop Med Hyg 1993; 49: practice; use over several weeks is moderately effective in .J years, to 25 residents of an area of high controlling gastrointestinal roundworms in pigs and 641--4. 3. Bouchaud 0, et a!. Cutaneous larva migrans in travelers: a prospective endemicity in Mali, were found to be more effective in poultry. study, with assessment of therapy with ivermectin. Clin lnfed Dis 2000; reducing microfilarial levels than the standard annual dose 31: 493-8. Correction. ibid. 2001; 32: 523. regimen reconunended by WHO. Higher-dose and/or more 4. delMar S<1ez-De-Ocariz M, eta!. Treatment of 18 children with scabies or frequent treatment regimens could therefore potentially cutaneous larva migrans using ivermectin. Clin ExpDermatol 2002; 27: 1 lvermectin (BAN, USAN, r/NN) 264--7. reduce the time necessary to interrupt transmission. 5. Senba Y, et a!. Case of creeping disease treated with ivermectin. ' .J l. Dembele B, et al. Use of high-dose, twice-yearly albendazole and tve rmectind; lverrnectine; lvermectinum; tvermektiini; l.ver- Dennatol 2009; 36: 86-9. ivermectin to suppress Wuchereria bancrofti microfilarial levels. Clin Infect mektin;. lv rmektlnas; 6. Abramowicz M, ed. Drugs for parasitic infedions. 3rd ed. New Rochelle Dis 2010; 51: 1229-35. � · · · :- 70288-$6-7 (ivem'!Vlsepl\leii'IH>:l.ectin): {component 8;,J; NY: The Medical Letter, 2013. C45 (component 81;,!. 1182NJ3-7 Malaria. It has been suggested that iverrnectin, given as Intestinal infections. Ivermectin activity has part of mass treatment programs for filarial infections, 7020.....:9-8L3 been seen in man against , Strongyloides 1 may also kill malarial mosquitos when they bite treated A TC PG2CFO /. stercora/is, and Trichuris tn"chiura;1 although some have · patients, resulting in a reduction in malaria transrnis­ ATCi;JNI! Ve -t-OP54AA01; Q502QA03. failed to detect activity against 2 ivermectin given Trichuris, sion.u 8883YP2R6D {i\i'ermect(n): 91Y22020UW Pvermectin with albendazole in doses similar to those recommended mmpo11ent OW28L"'Yt.nu (ivermec.tin component 1. Kobylinski KC, et al. Ivermectin mass drug administration to humans for mass treatment in the management of lymphatic filar­ disrupts malaria parasite transmission in Senegalese villages. Am Trop 1 H iasis (see p. 157.1), has been studied for the treatment of Med Hyg 2011; 85: 3-5. Pharmacopoeias..Bril In Bur. (see p. vii) and US. (p. 149.1) and may prove useful in areas 2. Ianne JH. Antiparasite drug ivermectin cuts mosquito numbers by 80%. Ph. Eur. 8: (Ivermectin). A mixture of ivermectin where soil-transmitted worm infections and lymphatic BMJ2011; 343: d43 55. component H2B 1, (5-0-demethyl-22,23-dihydroavermectin filariasis are public health problems.' A randomised, con­ A1a; C48H740t4 =875.1) and ivermectin component H2B 1b trolled study in 548 school children in Zanzibar' found infections, The response of Mansonella infec­ (5-0-demethyl-25-de( 1 -methylpropyl)-25-( 1 -methy­ that single oral doses of ivermectin (200 micrograms/kg) tions (p. 147.2) to iverrnectin depends on the species. It lethyl)-22,23-dihydroaverrnectin AI,; c.,Hn014 = 861.1). plus either albendazole ( 400 mg) or mebendazole ( 500 mg) may be effective against Mansonella ozzardi, but studies in A white or yellowish-white, slightly hygroscopic, crystalline improved cure and egg reduction rates against T. trichiura. M. perstans infection have not shown ivermectin to pro­ 1 powder. Practically insoluble in water; soluble in alcohol; The highest cure and egg reduction rates were achieved duce a substantial reduction in microfilaraemia, ,2 even 4 freely soluble in dichloromethane. Store in airtight with ivermectin plus mebendazole (55 and 97% respec­ used with albendazole. 3. A good response to a single oral containers. tively), while lower rates were seen with ivermectin plus dose of 150 micrograms/kg of ivermectin has been reported in infections with M. streptocerca. 5,6 USP 36: (Ivermectin). A mixture of component H B ,(5-0- albendazole (38% cure rate and 91% egg reduction rate). 2 1 1. Van den Enden E, et al. Treatmem failure of a single high dose of demethyl-22, 2 3 -dihydro- a ver1nectin A ; Roundworm expulsion has also been reported as a 'side­ 1 a iverrnectin for filariasis. Trans R Soc Trap Med Hyg effect' of ivermectin when used in community-based treat­ C48H740 14 = 875.1) and component H2B 1b(5-0-demethyl- 1993; 87: 90. 25-de( 1 -methylpropyl) -22,23-dihydro-25-( 1 -methy­ ment of onchocerciasis.5 In a controlled study,6 single oral 2. Schul:r.-Key H, et al. Efficacy of ivermectin in the treatment of doses of ivermectin 150 or 200 micrograms/kg produced concomitant Mansonella perstans infections in onchocerciasis patients. lethyl)-avermectin A ,; C47H7 0 4 =861.1). It may contain 1 2 1 Trans R Soc Trap Med Hyg 1993; 87: 227�9. small amounts of suitable antoxidant and chelating agents. cure rates of 94% in strongyloidiasis (see p. 157.3) and above 67% in , trichuriasis, and enterobiasis. 3. Asia SM, et al. Mansonella perstans: safety and efficacy of iverrnectin A white to yellowish-white, slightly hygroscopic, crystalline alone, albendazole alone and the two drugs in combination. Ann Trap Although some activity has been seen against Necator powder. Practically insoluble in water and in petroleum Med Parasito/ 2009; 103: 31-7. americanus, 1 cure rates for were considered 4. Asio SM, etal. A randomised, double-blind field trial of ivennectin alone spirit; soluble in acetone and in acetonitrile; freely soluble in unsatisfactory. 6 and in combination with albendazole for the treatment of Mansonella dichloromethane and in methyl alcohol. Store in airtight perstans infections in Uganda. Trans R Soc Trop Med Hyg 2009; 103: 274-- l. Freedman DO, et a!. The efficacy of ivermectin in the chemotherapy ol containers at a temperature of 2 degrees to 8 degrees. Where 9. gastrointestinal in humans. Infed Dis 1989; 159: 1 51-3. 1 J 5. Fischer P, et a!. Treatment of human Mansonella streptocerca infection the use of an antoxidant is allowed, store at 25 degrees, 2. Whitworth JAG, et al. A field study of the effect of iverrnectin on with ivermectin. Trop Med Int Health 1997; 2: 191-9. intestinal helminths in man. Trans R Soc Trap Med Hyg 1991; 85: 232--4. excursions permitted between 15 degrees and 30 degrees. 6. Fischer P, et a!. Long-term suppression of Mansonella streptocerca 3. Belizario et al. A comparison of the efficacy of single doses of VY, microfilariae after treatment with iverrnectin. J Infect Dis 1999; 180: albendazole, ivennectin, and diethylcarbamazine alone or in combina­ 1403-5. Uses and Administration tions against Ascaris and Trichuris spp. Bull WHO 2003; 81: 35--42. 4. Knopp S, et al. Albendazole and mebendazole administered alone or in Ivermectin is a semisynthetic derivative of one of the combination with ivennectin against : a randomized Onchocerciasis. Ivermectin has a microfilaricidal action avermectins, a group of macrocyclic lactones produced by controlled trial. Clin Infect Dis 2010; 51: 1420-8. against Onchocerca volvulus and is the main drug used in Streptomyces avermitilis. 5. Whitworth JAG, et a!. Community-based treatment with iverrnectin. the control of onchocerciasis (p. 147.2). A single oral dose Lancet 1988; ii: 97-8. It has a microfilaricidal action in onchocerciasis and 6. Naquira C, et a!. Ivermectin for human strongyloidiasis and other rapidly eliminates microfilariae from the skin, with maxi­ reduces the microfilarial load without the toxicity seen with intestinal helminths. Am J Trop Med Hyg 1989; 40: 304--9. mum effect after I to 2 months, 1 and gradually eliminates diethylcarbamazine. Ivermectin also has a microfilaricidal them from the cornea and anterior chamber of the eye.2 action in lymphatic filariasis and is used in endemic areas as Loiasis. There is evidence of reduced microfilaraemia after Ivermectin has little effect on the adult worms but does part of a mass treatment regimen. Ivermectin is active in ivermectin treatment1"5 in patients with loiasis (p. 146.2), suppress the release of microfilariae from the adult worm some other worm infections. It is used in the treatment of but concern exists over its potential for neurotoxicity in for several cycles which accounts for its prolonged activity. strongyloidiasis and has been tried in some Mansonella patients with a high microfilarial burden.6·7 There is some Ivennectin therefore only controls the disease; it does not infections. For details of these infections and their evidence8 that a genetic predisposition to altered distribu­ cure or eradicate it. Its action against 0. volvulus has been treatment, see under Choice of Anthelmintic, p. 143.1, tion of ivermectin may be a co-factor for the development attributed to a GABA-agonist effect. Studies have also

The symbol denotes a preparation no longer actively marketed t 156 Anthelmintics

indicated that ivermectin inhibits the transmission of tion by the fourth week. Ivermectin does not sterilise the 13. Leung V, et al. Case report: failure of subcutaneous ivermectin in treating microfilariae by reducing their uptake from man by the scabies eggs and in order to kill newly hatched mites a sec­ Strongyloides hyperinfection. Am J Trop Med Hyg 2008; 79: 853-5. 14. Lichtenberger P, et al. Hyperinfection strongyloidiasis in a liver insect vector. 3·6 ond dose of ivermectin is recommended, given at least 7 transplant recipient treated with parenteral ivermectin. Transpl Infect Dis Ivermectin is donated by Merck through the Mectizan days after the first dose.4 A single oral dose of ivermectin 2009; ll: 137-42. Expert Committee (MEC) for human use in community­ 150 micrograms/kg was partially effective in an outbreak wide mass treatment programmes in all countries in which of scabies in 1153 Tanzanian patients.' A systematic Trichostrangyliasis. For mention of the use of ivermectin onchocerciasis is endemic, where it is given at a standard review' on the treatment of scabies found that oral iver­ in infections, see p. 148.3. oral dose of 150 micrograms/kg once or twice a year to all mectin was less effective than topical permethrin, but but pregnant women, breast-feeding mothers of recently appeared to be as effective as topical benzyl benzoate and born babies, children weighing less than 15 kg, and those more effective than topical lindane. However, a rando­ unable to walk or otherwise seriously i!F The adult worms mised, open -label study6 found that one or two applica­ live for about 15 years, therefore treatment will need to be tions of 12.5% benzyl benzoate, each left on for 24 hours, The adverse effects reported with ivermectin in patients continued for many years. Several studies have confirmed were more effective than a single oral dose of ivermectin with filariasis are generally consistent with a mild Mazzotti the long-term safety and efficacy of such programmes '·" of 150 to 200 micrograms/kg; bacterial superinfection also reaction arising from its effect on microfilariae. They include Studies have reported that increasing the frequency of the occurred more often in those given ivermectin. than in fever, pruritus, rashes, arthralgia, myalgia, asthenia, standard doses of ivermectin to every 3 or 6 months appears those treated with benzyl benzoate. orthostatic hypotension, tachycardia, oedema, lymphade­ to increase efficacy compared with annual treatments13•14 Crusted (Norwegian) scabies has also been reported to be nopathy, gastrointestinal symptoms, sore throat, cough, and and that 3-monthly regimens may also reduce risk of effectively treated by a single oral dose of 12 mg of headache. The effects tend to be transient and if treatment is adverse effects.'4.1 5 No additional benefit was noted by ivermectin in addition to topical application of 3% salicylic required they respond to analgesics and antihistamines. increasing the dose of ivermectin to 400 or 800 micro­ add ointment in 2 patients; the treatment was effective in Ivermectin may cause mild ocular irritation. Somno­ grams/kg given either 3-monthly or annually. under one week. 2 A single oral dose of ivermectin lence, transient eosinophilia, and raised liver enzyme values In non-endemic areas, repeated doses may be necessary 200 micrograms/kg was effective for crusted scabies in a 2- have also been reported. to reduce recurrence; a study in the UK found that patients year-old infant who had contracted the disease following Ivermectin is not recommended during pregnancy. Mass given three doses at monthly intervals had fewer relapses at long-term corticosteroid use.7 Ivermectin has also been treatment is generally withheld from pregnant women (see 6 months than patients who received a single dose, but successfully used in a small number of patients with Pregnancy, p. 158.2), children under 15kg, and the relapses were nevertheless seen in 50% of patients at 12 treatment-resistant scabies.8 seriously ill. months. 16 Ivermectin has also been investigated' as a possible The ocular microfilarial load can be safely reduced by treatment for pediculosis (p. 2147.3) although, again, Incidence of adverse Some studies have shown ivermectin2•17 and early lesions of the anterior segment of topically applied insecticides are the usual method i:>f quite a high incidence effects.of adverse effects with ivermectin the eye have improvedP A reduction in the incidence18 and control. A study in vitro and in showed that and have associated the effects with the severity of infec­ progression 19 of optic nerve damage has also been reported, ivermectin killed nymphs and females of the human body tion. 1"3 However, in none of these studies were the reac­ but the effect on posterior segment disease is less certain.20 A louse Ivermectin was known (Pediculus humanus humanus). tions considered to be life-threatening and only sympto­ systematic review of 5 placebo-controlled studies, with data to be effective against other louse species that infect a range matic treatment was required. The severity, incidence, and from 3810 individuals, found no statistically significant of animals.10 Ivermectin has also been shown to be effective duration of adverse reactions was reported to be reduced difference between ivermectin and placebo groups for against head lice: two oral doses of 400 micrograms/kg at an after repeated annual doses.4 preventing visual acuity loss.21 Improvements in skin interval of 7 days were more effective than applications of When larger groups of patients were considered in the lesions have been reported. 22 malathion 0.5% in a controlled double-blind study in Onchocerciasis Control Programme (OCP) in West Africa, a patients with refractory infestations. A 0. 5% topical lotion 1. Basclfiez MG. et al. Effect of single-dose ivermectin on Onchocerca u much lower incidence of adverse reactions was seen in volvulus: a systematic review and meta-analysis. Lancet Infect Dis 2008; 8: has been licensed in the USA for the treatment of head patients given ivermectin for the first time5 and when 310-22. pediculosis (see Uses and Administration, p. 155.1). 2. Newland HS, et al. Effect of single-dose ivermectin therapy on human treatment was repeated a year later that incidence was Onchocerca volvulus infection with onchocercal ocular involvement. Br 1. Meinking TL, et al. The treatment of scabies with ivermectin. N Enol J reduced even further. The results from several studies in this Med 1995; 333: 26-30. 1 Ophthalmol l988; 72: 561-9. programme• showed 93 severe reactions in 50 929 patients 3. Taylor HR. et al. Impact of mass treatment of onchocerciasis with 2. Aubin F, Humbert P. Ivermectin for crusted (Norwegian) scabies. N Eng! ivermectin on the transmission of infection. Science 1990; 2.50: 116-1 8. J Med 1995; 332.: 612. (1.83%), most of the reactions being orthostatic hypo­ 4. Trpis M, et al. Effect of mass treatment of a human population with 3. Strong M. Johnstone PW. Interventions for treating scabies. Available in tension or dizziness (53). In a 3-year randomised, double­ ivermectin on transmission of Onchocerca volvulus by Simulium The Cochrane Database of Systematic Reviews; Issue 3. Chichester: John blind, controlled study of ivermectin for onchocerciasis Wiley; 2007 (accessed 21108/09). yahense in Liberia, West Africa. Am J Trop Med Hyg 1990; 42: 148-56. control in 572 patients/ 3-monthiy treatment with the 5. Chavasse DC, et al. Low level ivermectin coverage and the transmission 4. Currie BJ, McCarthy JS. Permethrin and ivermectin for scabies. N Engl J of onchocerciasis. Trans R Soc TropM ed Hyg 1995; 89: 534-7. Med 2010; 362.: 717-2 5. standard dose of 150 micrograms/kg was associated with a 5. Leppard B, Naburi The use of ivermectin in controlling an outbreak 6. Boussinesq M, et al. Onchocerca volvulus: striking decrease in AE. reduced risk of adverse reactions, especially oedema, transmission in the Vina valley (Cameroon) after eight annual large of scabies in a prison. Br J Dermato/ 2000; 143: 520-3. pruritus, and back pain, when compared with the same dose 6. Ly F, et al. Ivermectin versus benzyl benzoate applied once or twice to scale ivermectin treatments. Trans R Soc Trop Med Hyg 1997; 91: 8.2-6. given annually. Higher doses of 400 then 800 micro­ 7. Pond B. Distribution of ivermectin by health workers. Lancet 1990; 335: treat human scabies in Dakar, Senegal: a randomized controlled trial. 1539. Bull WHO 2009; 87: 424-30. grams/kg, given either 3-monthly or annually, were 8. De Sole G, et al. Adverse reactions after large-scale treatment of 7. Marlif:re V, et al. Crusted (Norwegian) scabies induced by use of topical associated with subjective ocular problems. onchocerciasis with ivermectin: combined results from eight community corticosteroids and treated successfully with ivermectin. J Pediatr 1999; Another study8 found 22 severe reactions in 17 877 trials. Bull WHO 1989; 67: 707-19. 135: 122-4. 8. Cook AM Romanelli F. Ivermectin for the treatment of resistant scabies. patients treated for onchocerciasis in an area also endemic 9. Pacque M, et al. Safety of and compliance with community-based , ivermectin therapy. Lancet 1990; 335: 1377-80. Ann Pharmawther 2003; 37: 279-81. for Loa loa infection, and showed a relationship to heavy L. 10. Pacquc! M, et al. Community-based tfeatment of onchocerciasis with 9. Foucault C, et al. Oral ivermectin in the treatment of body lice. J Infect Dis loa microfilaraemia. The Mectizan Expert Committee and ivermectin: safety, efficacy, and acceptability of yearly treatment. J Infect 2006; 193: 474-6. the Technical Consultative Committee have reported the 10. Mumcuoglu KY, et a!. Systemic activity of ivermectin on the human Dis 1991; 163: 381-5. incidence of encephalopathy after ivermectin treatment of 11. Steel C, et al. Immunologic responses to repeated ivennectin treatment body louse (Anoplura: Pediculidae). J Med Entomo/ 1990; 2.7: 72-5. in patients with onchocerciasis. J Infect Dis 1991; 164: 581-7. ll. Chosidow 0, et al. Oral ivermectin versus malathion lotion for difficult­ onchocerciasis in Loa loa endemic areas to be less than 1 case 12. Whitworth JAG, et a!. A community trial of ivermectin for to-treat head lice. N Eng/ J Med 2010; 362.: 896-905. Correction. ibid.; in 10 000 treatments' and have implemented recommenda­ onchocerciasis in Sierra Leone: clinical and parasitological responses to 1647. tions for ivermectin mass treatment programmes of four doses given at six-monthly interval. Trans R Soc Trop Med Hyg 1992; onchocerciasis in areas co-endemic for loiasis to reduce 86: 277-80. Strangylaidiasis. Ivermectin is effective in the treatment 13. Greene BM, et al. A comparison of 6-, 12-, and 24-monthly dosing with the risk of serious adverse events, especially in areas where ivermectin for treatment of onchocerciasis. J Infect Dis 1991; 163: 376- of strongyloidiasis (p. 148.2) and is considered by some the population is ivermectin naive. 80. authorities to be the drug of choice. Subcutaneous use has Some supervision is considered necessary after doses of 14. Gardon J,et al. Effects of standard and high doses of ivermectin on adult been investigated in patients with severe, disseminated ivermectin;2•6 the OCP recomrnendation6 is for resident worms of Onchocerca volvulus: a randomised controlled trial. Lancet disease. 2002; 360: 203-10. nurses to monitor patients for a period of 36 hours after 15. Kamgno J, et al. Adverse systemic reactions to treatment of References. treatment, whatever the level of endemicity. However, the a onchocerciasis with ivermectin t normal and high doses given annually I. Naquira C, et al. Ivermectin for human strongyloidiasis and other incidence of adverse reactions reported after repeated doses or three-monthly. 98: Trans R Soc Trop Med Hy9 2004; 496-504. intestinal helminths. Am J Trop MedHy9 1989; 40: 304-9. appears to be lower than after the first dose and the need for 16. Churchill DR. et al. A trial of a three-dose regimen of ivermectin for the 2. Wijesundera M de S, Sanmuganathan PS. Ivermectin therapy in chronic supervision on re-treatment has been questioned.10 treatment of patients with onchocerciasis in the UK. Trans R Soc Trop Med strongyloidiasis. Trans R Soc Trop Med Hy9 1992; 86: 291. Hyg 1994; 88: 242. 3. Lyagoubi M, et al. Chronic persistent strongyloidiasis cured by Neurotoxicity seen in some breeds of dogs has not been 17. Dadzie KY, et al. Changes in ocular onchocerciasis after two rounds of ivermectin. Tram R Soc Trop Med Hyg 1992; 86: 541. seen in cattle or horses11 and nor was it reported in man in the community-based ivermectin treatment in a bolo-endemic onchocer­ 4. Datry A, et a/. Treatment of Strongyloides stercoralis infection with above studies. Another potential concern was the ciasis focus. Trans R Soc Trop Med Hyg 1991; 85: 267-71. ivermectin compared with albendazole: results of an open study of 60 prolongation of prothrombin times seen in 28 patients 18. Abiose A, et al. Reduction in incidence of optic nerve disease with annual cases. Trans R Soc Trop MedHyg 1994; 88: 344-5. 12 ivermectin to control onchocerciasis. Lancet 1993; 341: 130-4. 5. Gann et al. A randomized trial of single- and two-dose ivennectin given ivermectin, but others have not confirmed this PlL 19. Cousens SN, et al. hnpact of annual dosing with ivermectin on versus thiabendazole for treatment of strongyloidiasis. J Infect Dis 1994; effect13 or seen any bleeding disorders.14 progression of onchocercal visual field loss. Bull WHO 1997; 75: 229-36. 169: 1076-9. There has been some concern over the use of ivermectin 20. Whitworth JAG, et al. Effects of repeated doses of ivermectin on ocular 6. H, et al. A comparative trial of a single-dose ivermectin versus Marti to treat scabies in elderly patients after a report suggesting a onchocerciasis: community-based trial in Sierra Liane. Lancet 1991; 338: three days of albendazole for treatment of Strongyloides stercoralis and 1100-1 103. other soil-transmitted helminth infections in children. Am J Trop Med possible link to an increased incidence of death among a . 21. Ejere H, et al. Ivermectin for onchocercal eye disease (river blindness). Hyg 1996; 55: 477-81. cohort of 47 patients.15 It has, however, been argued that no Available in The Cochrane Database of Systematic Reviews; Issue 2. 7. Igual�Adell R. et al. Efficacy and safety of ivermectin and thiabendazole such association has been seen in other populations of Chichester: John Wiley; 2001 (accessed 29107/07). in the treatment of strongyloidiasis. Expert Opin Pharmacother 2004; 5: elderly patients and that the statistical methods used by the 22. �acque M, etal. Improvements in severe onchocercal skin disease after a 2615-9. 1 18 single dose of ivermectin. Am J Med 1991; 90: 590-4. 8. Marty FM, et a!. Treatment of human disseminated strongyloidiasis with original authors were deficient. 6- There was no evidence a parenteral veterinary formulation of ivennectin. Clin Infect Dis 2005; of an increase in death rate associated with ivermectin in a 41: e5-e8. community-based study in Papua New Guinea of diethyl­ Scabies and pediculasis. Scabies (p. 2148.1) is usually 9. Pacanowski J, eta!. Subcutaneous ivermectin as a safe salvage therapy in carbamazine with or without ivermectin for lymphatic Strongyloides stercoralis hyperinfection syndrome: a case report. Am J treated with a topically applied acaricide. However, a sin­ filariasis. 19 gle oral dose of ivermectin has been reported to be effec­ Trop Med Hyg 2005; 73: 122-4. 10. Salluh JL et al. Successful use of parenteral ivennectin in an 1. Kumaraswami V, et a/. Ivermectin for the treatment of Wuchereria tive. J.3 In a study of 11 patients with uncomplicated immunosuppressed patient with disseminated strongyloidiasis and bancrofti filariasis: effiCacy and adverse reactions. lAMA 1988; 259: scabies, a single oral dose of ivermectin 200 micrograms/kg septic shock. Intensive Care Med 2005; 31: 1292. 3150-3. was effective in curing infection after 4 weeks. In a group 11. Hauber HP, et al. Fatal outcome of a hyperinfection syndrome despite 2. Rothova A, et a/. Side-effects of ivermectin in treatment of onchocer­ successful eradication of Strongyloides with subcutaneous ivermectin. ciasis. Lancet 1989; 1439-41. of 11 patients, also infected with IDV, scabies was cured in i: Infection 2005; 33: 383-6. 3. Zea-Flores R, et a!. Adverse reactions after community treatment of 1 8 after 2 weeks. Two of the remaining 3 patients received 12. Turner SA, et al. Parenteral administration of ivermectin in a patient onchocerciasis with ivermectin in Guatemala. Trans R Soc Trop Med Hy9 a second dose of ivermectin which cured the scabies infec- with disseminated strongyloidiasis. Am J Trap Med Hyg 2005; 73: 911-4. 1992; 86: 663-6.

All cross-references refer to entries in Volume A 157

4. Burnham GM. Adverse reactions to ivermectin treatment for oncho­ undergoes metabolism in the liver, mainly via the may be given 2.5 mg/kg as a single dose, repeated after 7 cerciasis: results of a placebo-controlled, double-blind trial in Malawi. cytochrome P450 isoenzyme CYP3A4. It is excreted largely days in cases of severe . Trans R Soc Trop Med Hyg 1993; 87: 313-17. 5. De Sole G, et a!. Lack of adverse reactions in ivermectin treatment of as metabolites over a period of about 2 weeks, chiefly in the Levamisole influences host defences by modulating cell­ onchocerciasis. Lancet 1990; 335: 1106--7. faeces, with less than l% appearing in the urine and less mediated immune responses; it restores depressed T -cell 6. De Sole G, et al. Adverse reactions after large-scale treatment of than 2% in breast milk (see also Breast Feeding, above). functions and has been described as an immunostimulant, onchocerciasis with ivermectin: combined results from eight community although stimulation above normal levels does not seem to trials. Bull WHO 1989; 67: 707-19. References. Gonzalez Canga et a!. The pharmacokinetics and interactions of occur. It has been tried in many disorders, including 7. Kamgno J,et al. Adverse systemic reactions to treatment of onchocer­ L A ciasis with ivermectin at normal and high doses given annually or three­ ivermectin in humans-a mini-review. AAPS J 2008; 10: 42-6. bacterial and viral infections and rheumatic disorders, monthly. Trans R Soc Trop Med Hyg 2004; 98: 496-504. although in these conditions results have not been 8. Gardon J, et al. Serious reactions after mass treatment of onchocerciasis encouraging. with ivermectin in an area endemic for Loa loa infection. Lancet 1997; Levamisole has also been used as an adjunct in patients 350: 18-22. (details are given in Volume B) 9. The Mectizan Expert Committee and The Technical Consultative Proprietary Preparations with malignant disease, although it is not clear that any Committee. Recommendations for the treatment of onchocerciasis with Single-ingredient Preparations. Arg.: Dermoper IV; Dermopero; response is due to its action on the immune system. Mectizan in areas co-endemic for onchocerciasis and loiasis. 2004. Austral.: Braz. : Adjuvant treatment with levamisole and fluorouracil has Available at: http://www.mectizan.org/sites/default/files/ Detebencil; Ivertal; Securo; Stromectol; Iver­ l· EnglishMECTCCLoaRecs-June04_1.pdf (accessed 29107110) mec; Leverctin; Plurimec; Revectina; Vermectil; Chile: Kaonol; been given to reduce recurrence after resection of 10. Whitworth JAG, et a!. A community trial of ivermectin for Medidermt; Fr. : Mectizant; Stromectol; Gr.: Stromectol; India: adenocarcinoma of the colon with regional lymph node onchocerciasis in Sierra Leone: adverse reactions after the first five Ectin; Ectover; Elect; Ifact; Imectin; Ivecop; IverwSol; Ivercid; involvement (but see Malignant Neoplasms, p. 159.1). treatment rounds. Trans R Soc Trop Med HyH 1991; 85: 501-5 Iversan; Iverstar; Ivor; Ivori; Macbi; Mectin; Jpn: Stromectol; 11. WHO. WHO expert committee on onchocerciasis: third report. l-VHO Tech Mex. : Ivexterm; Neth.: Stromectol; NZ: Stromectol; Singapore: Reviews. Rep Ser 1987. Available at: http://libdoc.who.int/trs/WHO_TRS_ 752 l. Amery WKP, Bruynsecls JPJM. Levamisole, the story and the lessons. 752_\part1).pdf and http://libdoc.who.int/trs/WHO_TRS_752_(part2 ). Stromectol; Thai.: Vermectin; USA: Mectizan; Sklice; Stromec­ tol. Int J Immunopharmacol 1992; 14: 481-6. pdf (accessed 16/07/08) 2. Scheinfeld N, et a!. Levamisole in dermatology: a review. Am J Clin 12. Homeida MMA, et a!. Prolongation of prothrombin time with Dermatol 2004; 5: 97-104. ivermectin. Lancet 1988; i: 1346-7. Multi-ingredient Prepara6ons. India: Ablaze-IM; ABZ Plus; Alba­ 13. Richards FO, et al. Ivermectin and prothrombin time. Lancet 1989; i; cos-IR; Albosym-IR; Alvect; Anthel-UP; Ariban Plus; Ascapil A; 1139-40. Bandy Plus; Benrod-I; Benzole; Ectin-A; Elect-A; Eris Plus; Administration in children. Levamisole may be given oral­ 14. Pacque MC, et a!. Ivermectin and prothrombin time. Lancet 1989; i: 1140. Getrid-I; Hymin Plus; Imectin Forte; Ivecop-AB; Ivercid-A; ly to children for the treatment of ascariasis, hookworm 15. Barkwell R, Shields S. Deaths associated with ivermectin treatment of Iverzole; Ivoral; Kidi; Machi Plus; Networm. infections, and mixed asca