Safety Considerations

Ivermectin has been shown to be very safe in humans, as in other species. The specific issues that necessitated a very conservative start to the development programme in humans included concerns about use in pregnancy and possible central nervous system toxicity. Such concerns have not been validated in extensive clinical experience. One study of pregnant women in Ecuador showed that there was a lower rate of miscarriages in ivermectin-treated women than in untreated women, possibly related to the lowering of microfilarial loads (Guderian et al., 1997). The most serious clinical adverse experiences attributed to ivermectin have been the cases of encephalopathy in patients with concomitant onchocerciasis and loiasis, with high levels of Loa loa microfilariae in the blood and sometimes in the cerebrospinal fluid (Boussinesq et al., 1998). The presumed explanation for the high degree of safety in humans is that P-glycoprotein in the placenta (MacFarland et al., 1994) and in the blood-brain barrier serves to exclude ivermectin from critical receptor access, as is the case for animals (Lankas et al., 1997). The extensive programmes in humans have demonstrated the high degree of safety to the point where the manufacturer, while not recommending ivermectin use in pregnancy, does not withhold the drug from mass distribution programmes that choose to treat pregnant women. Furthermore, its paediatric use has been extended to include children who are as small as 15 kg, regardless of age (Brown, 1998).

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