Ivermectin dosing

Avermectins and Ivermectin. The avermectias are pentacycHc lactones isolated from fermentation products of Streptomjces avermitilis and ivermectin is a semisynthetic chemical, 22,23-dihydroavermectia (46). Ivermectin is effective in very low doses for the control of red spider mites on deciduous fmits, in baits for the control of imported fire ants, and as a parasiticide for Onchocerca volvulus in humans and for catde gmbs. These insecticides appear to function as agonists for the neuroinhibitory transmitter y-aminobutyric acid (GABA) (see Antiparasitic agents, avermectins). 

Systemic reactions are less severe than with diethylcarbama2ine. The most commonly seen reactions are fever, rash, and lymph-node pain or swelling. Suppressive ivermectin therapy consists of a single oral dose every 6—18 months. The required duration of suppressive therapy is unknown, probably at least three years (36). Ivermectin is available from the CDC Dmg Service on request. It is manufactured by Merck Sharp and Dohme in the United States and England. 

The activity of ivermectin against the filarial parasite Dirofilaria immitis in dogs suggested a possible role for the control of filarial parasites of humans (20). It has been extensively tested in human onchocerciasis and is now considered to be the dmg of choice. In a single yearly oral dose, it suppresses microfilariae in the skin and eyes and, in most cases, prevents the progression of the disease to blindness. Table 4 shows the results of a 30-patient double-blind study recorded over one year. 

Ten patients received a single oral dose of ivermectin, 12 mg. 

Two forms of lymphatic filariasis are found in India. The Bancroftian form is the most common and accounts for more than 90% of the disease whereas Bmgian filariasis accounts for the rest. In a study carried out in India (6) in 40 patients with Wuchereria Bancwfti filariasis treated with single oral doses, all of the dose levels chosen (25, 50, 100, and 200 mg/kg) were efficacious in clearing microfilariae from the blood of all patients treated. However, after three months some microfilaria recurred in the blood of most patients (Table 5). Further studies are planned and some are underway using different doses and regimens. Ivermectin still appears to hold promise as a new treatment for lymphatic filariasis. 

Since the avermectins exhibit unprecedented potency, they are used at unusually low doses of 6 —300 )-lg/kg, which makes the detection and isolation of residues and metaboUtes from animal tissue a new challenge. For this reason a sensitive analytical assay requires a derivative suitable for detection at concentrations down to 1/10 or 1/100 of one ppm. Ivermectin and avermectin B are therefore converted into an aromatic derivative which allows detection by fluorescence absorbance. To achieve this derivatization, avermectin B, ivermectin, or their derivatives are heated with acetic anhydride in pyridine at 100°C for 24 h (30). The reaction time can be reduced to 1 h by using /V-methylimidazole as a catalyst (31). The resultant... 

The agent of choice for scabies is permerthrin 5% (Elimite) cream. Alternative agents in subjects who cannot use permethrin are crotamiton 10% (Eurax) and oral ivermectin (Stromectal) 200 mcg/kg as a single dose. To initiate the treatment with permerthrin, the skin should be scrubbed in a warm soapy bath to remove the scabs. The permerthrin lotion should then be applied to the whole body, avoiding the face, mucous membranes, and eyes, and left on for 8 to 14 hours. A single application eradicates 97% of scabies. All close contacts should be treated appropriately. The pruritus associated with scabies may persist for 2 to 4 weeks because of the remnants of mite parts in the skin. 

Antihistamines may be given for the first few days of therapy to limit allergic reactions, and corticosteroids should be started and doses of diethylcarbamazine lowered or interrupted if severe reactions occur. Cures may require several courses of treatment. For patients with high L loa worm burdens (more than 2500 circulating parasites/mL), strategies to decrease risks of severe toxicity include apheresis, if available, to remove microfilariae before treatment with diethylcarbamazine or therapy with albendazole, which is slower acting and better tolerated, before therapy with diethylcarbamazine or ivermectin. 

Ivermectin is used only orally in humans. The drug is rapidly absorbed, reaching maximum plasma concentrations 4 hours after a 12-mg dose. The drug has a wide tissue distribution and a volume of distribution of about 50 L. Its half-life is about 16 hours. Excretion of the drug and its metabolites is almost exclusively in the feces. 

Treatment is with a single oral dose of ivermectin, 150 mcg/kg, with water on an empty stomach. Doses are repeated regimens vary from monthly to less frequent (every 6-12 months) dosing schedules. After acute therapy, treatment is repeated at 12-month intervals until the adult worms die, which may take 10 years or longer. With the first treatment only, patients with microfilariae in the cornea or anterior chamber may be treated with corticosteroids to avoid... 

Basanez MG et al Effect of single-dose ivermectin on Onchocerca volvulus A systematic review and meta-analysis. 

The pharmacokinetics of ivermectin differ with the animal species, formulation, and the route of administration (50). When goats were given a subcutaneous administration of 0.2 mg ivermectin /kg bw, the mean concentrations of ivermectin in plasma and milk increased initially to reach at 2.8 day the maximum levels of 6.12 and 7.26 ppb, respectively (51). The drug could be detected in milk for 25 days postdosing, the total drug amount recovered over this period being estimated at 0.6% of the administered dose. This percentage is low compared with the 4% level determined in sheep (52) and 5.6% in cows (53). 

The crucial role of this export system in protecting the brain can be illustrated by the use of specially bred mice in which the gene for p-glycoprotein is knocked out. When normal and knockout mice are exposed to the antihelminthic drug ivermectin, the null mice experience neurotoxic effects at doses 100 times less than the normal animals and also have levels of the drug in the brain almost 100 times those in the normal (wild type) mice. 

Ivermectin possesses a broad spectrum of antiparasitic activities [51] and is a 22,23-dihydro analogue of the macrocyclic lactone, avermectin B,. Ivermectin is highly effective against microfilariae of O. volvulus at very low doses (50-200/ig/kg) [52] and in comparison with DEC, induces only mild mazzotti reactions and other side-effects. Its effectiveness against D. viteae in M. natalenis [38] and D. immitis [53] is also documented. 

Shenoy RK, Dalia S, John A et al. (1999) Treatment of the mi-crofilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations. Ann Trop Med Parasitol 93 643-651... 

Maximum likelihood problt analysis (65) of dose response data for larval mortality obtained following addition of Ivermectin to defibrinated pig blood fed once in vitro to pregnant G. m. morsltans (x2 (7df) 8.82 ns)... 

Unfortunately, protozoan flagellates like trypanosomes are unaffected by ivermectin (21) but, at least, the animals that take up the ivermectin (with coccidiostat) will be rid of most gastrointestinal nematodes and ectoparasites. Gxtraintestinal filariasis can also be treated for example, microfilarial dermatitis in horses (22) and even onchocerciasis in humans (23). which is transmitted by the bite of infected black flies (Slmulium spp.). However, the doses required (30 - 50 pg/kg) in the latter case were not without short term side effects. 

Ivermectin may cause immediate reactions due to the death of the microfilaria (see diethylcarbamazine). It can be effective in a single dose, but is best repeated at 6-12-month intervals. 

Onchocerciasis (river bNndnossJ ivermectin Cures with single dose. Suppressive treatment a I... 

Scabies fSareopies cobieij Permethrin dermal cream. In retlsiani cases consider monosulfiram or benzyl benzoate. Alternative ivermectin (single dose) especially for outbreaks in dosed communities. Crocamiton or calamine for residual itch. Apply to all members of the household, immediate family or partner Change underclothes and bedclothes after application. 

Table 5 Pharmacokinetic parameters describing the rate of absorption and elimination of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD) after subcutaneous injection (shoulder region) of single doses (200 pg/kg) of the commercially available preparations to 10-month-old hereford calves...

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