Ivermectin, Avermectin, Rosacea, Antiparasitic, Anti-inflammatory



  1. Rasmussen, Annelise
  2. Jacob, Sharon E.


ABSTRACT: A drug is defined as a substance that exerts a physiologic effect upon introduction to a biological system. These drugs may come in various forms including ingested pills, topical creams or ointments, and inhaled or injected substances. The purpose of this column is to bring attention to common drugs used in dermatology, their usage and purpose, their mechanisms, and available alternatives. This edition focuses on ivermectin and its usage in treatment of rosacea.


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A vermectin, a macrocyclic lactone, was discovered in 1978 by Satoshi Omura who isolated the compound from soil samples and William C. Campbell who showed its anthelmintic activity in domestic farm animals (Campbell, Fisher, Stapley, Albers-Schonberg, & Jacob, 1983; Omura et al., 1979). The compound was refined and underwent its first clinical trial in 1981, successfully treating patients with onchocerciasis (river blindness). Omura and Campbell were awarded the Nobel Prize in Physiology or Medicine in 2015 for this work (Nobel Committee, 2014). Ivermectin, a derivative of avermectin, has been used since the early 1980s in treatment of strongyloidiasis (threadworm), onchocerciasis (river blindness), and more recently, scabies and head lice (Nobel Committee, 2014).


The ubiquitous Demodex mite is a parasite that resides on the human skin, primarily around the face. Although long believed to be innocuous, current research suggests that overpopulation of Demodex mites may trigger an immune reaction that can lead to inflammatory conditions of the skin, including papulopustular rosacea (Forton, 2012). In papulopustular rosacea, abnormally high levels of Toll-like receptor 2 are produced and induce production of abnormal forms of cathelicidins, peptides important in innate immunity. An exaggerated immune response occurs as Demodex mites penetrate the skin and results in the inflammatory papules and pustules of rosacea (Forton, 2012). In 2014, the Food and Drug Administration approved ivermectin 1% cream for treatment of rosacea. Ivermectin is believed to improve rosacea through antiparasitic and anti-inflammatory properties (Galderma Laboratories, 2014).



Current therapeutic regimens include avoidance of triggers including elevated temperatures, sunlight, alcohol, and strenuous exercise by patients with rosacea (Taieb et al., 2015). The erythema typical of rosacea is due to chronic inflammation and vascular dysfunction (Steinhoff, Schmelz, & Schauber, 2016). Various laser treatments have been tried to address symptoms of rosacea including treatment of telangiectasia with the aim of eliminating enlarged capillaries near the skin's surface and treatment of rhinophyma with the aim of removing excess tissue and reducing pore size (Weinkle, Doktor, & Emer, 2015). Medications aimed primarily at inflammation control include topical metronidazole, azelaic acid, and doxycycline (see Table 1).

Table 1 - Click to enlarge in new windowTABLE 1 Common Rosacea Drugs and Their Actions


Ivermectin is believed to reduce inflammation by decreasing levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-[alpha]) and interleukin-1[beta] through inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-[kappa]B) and mitogen-activated protein (MAP) kinase pathways in lipopolysaccharide-induced inflammation. Ivermectin also increases production of the anti-inflammatory cytokine interleukin-10, further reducing inflammation (see Figure 1) (Xinxin et al., 2009).

Figure 1 - Click to enlarge in new windowFIGURE 1. A simplified diagram showing the proposed effect ivermectin has on lipopolysaccharide-induced inflammation. Ivermectin increased interleukin-10 expression and decreased TNF-[alpha], interleukin-1[beta], and NF-[kappa]B expression (

Although the mechanism is still to be fully elucidated, ivermectin's antiparasitic activity is well established. It functions by inhibiting chloride channels in parasites, resulting in cellular hyperpolarization and death (Campbell et al., 1983). Orally, ivermectin has shown to decrease the number of Demodex mites in other conditions characterized by mite overpopulation, such as blepharitis and demodicidosis (Filho et al., 2011). It is postulated that ivermectin has a similar effect in rosacea, reducing Demodex mite population and alleviating the associated inflammatory reaction (Taieb et al., 2015).



Ivermectin has been found to be efficacious and well tolerated. In Phase III randomized, controlled double-blinded studies, ivermectin proved significantly more effective than the vehicle cream in reducing number of inflammatory lesions in patients. In addition, more patients on ivermectin rated their complexion improvement as "excellent" or "good" compared with those on the vehicle cream and were more likely to report increased quality of life (Stein et al., 2014). Furthermore, in a Phase III randomized, investigator-blinded trial, ivermectin 1% cream applied once daily was shown to reduce papulopustular rosacea inflammatory lesion number compared with topical metronidazole 0.75% applied twice daily (a reduction of 83.0% vs. 71.7%, p < .001) and received better patient- and physician-reported outcomes. Improvement was seen as early as 3 weeks and continued through the 4-month treatment (Taieb et al., 2015). Currently, there are no trials comparing ivermectin with other antiparasitics used in treatment of rosacea, such as permethrin, although a combination of the two has been used in treatment of rosacea-like demodicidosis (Forstinger et al., 1999).



Although ivermectin has been shown to be efficacious, a risk-benefit profile should be evaluated before use. Topical ivermectin has been reported to cause skin irritation, dryness, hypersensitivity, allergic dermatitis, aggravation of rosacea, and erythema in some patients. These symptoms resolved upon cessation of treatment (Taieb et al., 2015). Compared with vehicle cream, fewer subjects on the topical ivermectin were observed to have dryness or itching (Stein et al., 2014). When compared with patients on metronidazole cream, patients on ivermectin experienced fewer and less severe side effects (Taieb et al., 2015). The effectiveness and safety of topical ivermectin have not been fully evaluated in pediatric, pregnant, or breastfeeding patients.


Notably, orally administrated ivermectin is designated as a Pregnancy category C drug and only indicated if the potential benefit to the mother justifies the risk to the fetus (U.S. Food and Drug Administration, 2014). Low concentrations of ivermectin have been reportedly excreted in the breast milk of mothers after oral ivermectin administration (U.S. Food and Drug Administration, 2014).



Evidence suggests that ivermectin is an efficacious, well-tolerated treatment for papulopustular rosacea. The approval of this medication indicates the necessity of continued research into the etiology of rosacea and the ongoing need for development of novel therapeutics.




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