Ivermectin

As COVID-19 (coronavirus disease 2019) continues to rapidly spread throughout the world, the incidence varies greatly among different countries. These differences raise the question whether nations with a lower incidence share any medical commonalities that could be used not only to explain that lower incidence but also to provide guidance for potential treatments elsewhere. Such a treatment would be particularly valuable if it could be used as a prophylactic against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission, thereby effectively slowing the spread of the disease while we await the wide availability of safe and effective vaccines. Here, we show that countries with routine mass drug administration of prophylactic chemotherapy including ivermectin have a significantly lower incidence of COVID-19. Prophylactic use of ivermectin against parasitic infections is most common in Africa and we hence show that the reported correlation is highly significant both when compared among African nations as well as in a worldwide context. We surmise that this may be connected to ivermectin's ability to inhibit SARS-CoV-2 replication, which likely leads to lower infection rates. However, other pathways must exist to explain the persistence of such an inhibitory effect after serum levels of ivermectin have declined. It is suggested that ivermectin be evaluated for potential off-label prophylactic use in certain cases to help bridge the time until a safe and effective vaccine becomes available.

Rosacea is a chronic and recurrent disease with a variety of cutaneous manifestations. The disorder is a centrofacial inflammatory dermatosis with significant financial, physical and psychological impacts. There are a number of topical, oral and systemic treatments available. Yet, treatment for rosacea remains difficult. The multifactorial nature of the disease combined with an incomplete understanding of the pathophysiology is challenging for providers and patients. Areas covered: This article provides an in-depth review of rosacea treatment and emerging use of ivermectin 1% cream for papulopustular rosacea based on multiple clinical trials. The PubMed database was searched using the combination of keywords "ivermectin, rosacea, and papulopustular." Expert opinion: Topical ivermectin 1% cream has emerged as a novel agent for treatment of papulopustular rosacea. The drug targets the Demodex mite which is increased in patients with rosacea. Though ivermectin 1% is a clinically efficacious medication, poor adherence continues to remain an issue due to topical application. Ultimately, the agent has the potential to be an effective drug when used as a single or combination agent. With the move to limit chronic antibiotic use, topical agents such as ivermectin 1% will continue to thrive as a specialized niche in the rosacea market.

Safety and pharmacokinetics (PK) of the antiparasitic drug ivermectin, administered in higher and/or more frequent doses than currently approved for human use, were evaluated in a double-blind, placebo-controlled, dose escalation study. Subjects (n = 68) were assigned to one of four panels (3:1, ivermectin/placebo): 30 or 60 mg (three times a week) or 90 or 120 mg (single dose). The 30 mg panel (range: 34 7-594 microg/kg) also received a single dose with food after a 1-week washout. Safety assessments addressed both known ivermectin CNS effects and general toxicity. The primary safety endpoint was mydriasis, accurately quantitated by pupillometry. Ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose of 200 microg/kg. All dose regimens had a mydriatic effect similar to placebo. Adverse experiences were similar between ivermectin and placebo and did not increase with dose. Following single doses of 30 to 120 mg, AUC and Cmax were generally dose proportional, with t(max) approximately 4 hours and t1/2 approximately 18 hours. The geometric mean AUC of 30 mg ivermectin was 2.6 times higher when administered with food. Geometric mean AUC ratios (day 7/day 1) were 1.24 and 1.40 for the 30 and 60 mg doses, respectively, indicating that the accumulation of ivermectin given every fourth day is minimal. This study demonstrated that ivermectin is generally well tolerated at these higher doses and more frequent regimens.

Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin--originating solely from a single microorganism isolated at the Kitasato Institute, Tokyo, Japan from Japanese soil--has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Originally introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock and companion animals. It was quickly discovered to be ideal in combating two of the world's most devastating and disfiguring diseases which have plagued the world's poor throughout the tropics for centuries. It is now being used free-of-charge as the sole tool in campaigns to eliminate both diseases globally. It has also been used to successfully overcome several other human diseases and new uses for it are continually being found. This paper looks in depth at the events surrounding ivermectin's passage from being a huge success in Animal Health into its widespread use in humans, a development which has led many to describe it as a "wonder" drug.