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Ivermectin is an
antiparasitic Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic ...
drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat
heartworm ''Dirofilaria immitis'', also known as heartworm or dog heartworm, is a parasitic roundworm that is a type of filarial worm, a small thread-like worm, and which causes dirofilariasis. It is spread from host to host through the bites of mosqui ...
and
acariasis Acariasis is a medical condition characterized by infestation of human or animal tissues by mites, a diverse group of microscopic arthropods belonging to the order Acari. This condition can manifest in multiple ways, ranging from skin-related ...
. Approved for human use in 1987, it is used to treat infestations including
head lice The head louse (''Pediculus humanus capitis'') is an obligate ectoparasite of humans. Head lice are wingless insects that spend their entire lives on the human scalp and feed exclusively on human blood. Humans are the only known hosts of this s ...
,
scabies Scabies (; also sometimes known as the seven-year itch) is a contagious human skin infestation by the tiny (0.2–0.45 mm) mite ''Sarcoptes scabiei'', variety ''hominis''. The word is from . The most common symptoms are severe itchiness a ...
,
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
(onchocerciasis),
strongyloidiasis Strongyloidiasis is a human parasitic disease caused by the nematode called '' Strongyloides stercoralis'', or sometimes the closely related ''S. fülleborni''. These helminths belong to a group of nematodes called roundworms. These intestinal ...
,
trichuriasis Trichuriasis, also known as whipworm infection, is an infection by the parasitic worm '' Trichuris trichiura'' (whipworm). If the infection is only with a few worms, there are often no symptoms. In those who are infected with many worms, there ...
,
ascariasis Ascariasis is a disease caused by the parasitic roundworm ''Ascaris lumbricoides''. Infections have no symptoms in more than 85% of cases, especially if the number of worms is small. Symptoms increase with the number of worms present and may in ...
and
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide, impacting over a hundred million people and manifesting itself in ...
. It works through many mechanisms to kill the targeted parasites, and can be taken
by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...
, or applied to the skin for external infestations. It belongs to the
avermectin The avermectins are a group of 16-membered Macrolide, macrocyclic lactone derivatives with potent anthelmintic and Insecticide, insecticidal properties. These naturally occurring compounds are generated as fermentation products by ''Streptomyces a ...
family of medications. William Campbell and
Satoshi Ōmura is a Japanese biochemist. He is known for the discovery and development of hundreds of pharmaceuticals originally occurring in microorganisms. In 2015, he was awarded the Nobel Prize in Physiology or Medicine jointly with William C. Campbell f ...
were awarded the 2015
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
for its discovery and applications. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
, and is approved by the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) as an antiparasitic agent. In 2022, it was the 314th most commonly prescribed medication in the United States, with more than 200,000 prescriptions. It is available as a
generic medicine A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. Ivermectin is available in a
fixed-dose combination A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...
with albendazole.
Misinformation Misinformation is incorrect or misleading information. Misinformation and disinformation are not interchangeable terms: misinformation can exist with or without specific malicious intent, whereas disinformation is distinct in that the information ...
has been widely spread claiming that ivermectin is beneficial for treating and preventing
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
. Such claims are not backed by credible scientific evidence. Multiple major health organizations, including the US Food and Drug Administration, the US
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
, the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
, and the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
have advised that ivermectin is not recommended for the treatment of COVID-19.


Medical uses

Ivermectin is used to treat human diseases caused by
roundworm The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (hel ...
s and a wide variety of external parasites.


Worm infections

For
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
(onchocerciasis) and
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide, impacting over a hundred million people and manifesting itself in ...
, ivermectin is typically given as part of
mass drug administration The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration (MDA) or mass dispensing. This article describes the administration of antimalarial drugs to whole populations, an interven ...
campaigns that distribute the drug to all members of a community affected by the disease. Adult worms survive in the skin and eventually recover to produce larval worms again; to keep the worms at bay, ivermectin is given at least once per year for the 1015-year lifespan of the adult worms. The
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
(WHO) considers ivermectin the drug of choice for
strongyloidiasis Strongyloidiasis is a human parasitic disease caused by the nematode called '' Strongyloides stercoralis'', or sometimes the closely related ''S. fülleborni''. These helminths belong to a group of nematodes called roundworms. These intestinal ...
. Ivermectin is also the primary treatment for ''
Mansonella ozzardi ''Mansonella ozzardi'' is a filarial (arthropod-borne) nematode (roundworm). This filarial nematode is one of two that causes serous cavity filariasis Filariasis is a filarial infection caused by parasitic nematodes (roundworms) spread by d ...
'' and
cutaneous larva migrans Cutaneous larva migrans (abbreviated CLM) is a skin disease in humans, caused by the larvae of various nematode parasites of the hookworm family ( Ancylostomatidae). The parasites live in the intestines of dogs, cats, and wild animals; they should ...
. The US
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
(CDC) recommends ivermectin,
albendazole Albendazole is a broad-spectrum antihelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworm infection, trichuri ...
, or
mebendazole Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections and hydatid di ...
as treatments for
ascariasis Ascariasis is a disease caused by the parasitic roundworm ''Ascaris lumbricoides''. Infections have no symptoms in more than 85% of cases, especially if the number of worms is small. Symptoms increase with the number of worms present and may in ...
. Ivermectin is sometimes added to albendazole or mebendazole for
whipworm ''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large intest ...
treatment, and is considered a second-line treatment for gnathostomiasis. When co-administered, ivermectin and albendazole act in synergy. Ivermectin targets the parasite's nervous and muscular systems, causing paralysis, while albendazole disrupts the parasite's metabolism and energy production. This dual approach immobilizes and kills the parasite and improves the treatment's effectiveness. In January 2025, the
Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...
(CHMP) of the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
(EMA) adopted a positive scientific opinion for ivermectin/albendazole for the treatment of infections caused by several types of worm parasites including lymphatic filariasis, a neglected tropical disease. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Ivermectin/albendazole is
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for use in people aged five years of age or older, for the treatment of soil-transmitted helminth infections, caused by different types of intestinal parasitic worms, which are spread through soil contaminated by human feces in areas with poor sanitation. Among the worms responsible for these diseases are hookworms (Ancylostoma duodenale, Necator americanus), roundworms (''
Ascaris lumbricoides ''Ascaris lumbricoides'' is a large parasitic worm, parasitic Nematoda, roundworm of the genus ''Ascaris.'' It is the most common parasitic worm in humans. An estimated 807 million–1.2 billion people are infected with ''Ascaris lumbricoides'' ...
''), whipworms (''
Trichuris trichiura ''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large inte ...
'') and a roundworm called ''
Strongyloides stercoralis ''Strongyloides stercoralis'' is a human pathogenic parasitic roundworm causing the disease strongyloidiasis. Its common name in the US is threadworm. In the UK and Australia, however, the term ''threadworm'' can also refer to nematodes of t ...
''. Ivermectin/albendazole is also indicated for the treatment of microfilaraemia (the presence of worm larvae in the blood) in people with lymphatic filariasis. Lymphatic filariasis is a neglected tropical disease commonly known as elephantiasis, which impairs the lymphatic system and can lead to the abnormal enlargement of body parts, causing pain, severe disability and social stigma. Ivermectin/albendazole is indicated for the treatment of cases of lymphatic filariasis caused by ''
Wuchereria bancrofti ''Wuchereria bancrofti'' is a filarial (arthropod-borne) nematode (roundworm) that is the major cause of lymphatic filariasis. It is one of the three parasitic worms, together with ''Brugia malayi'' and '' B. timori'', that infect the lymphati ...
'', a parasite which is responsible for 90% of cases worldwide.


Mites and insects

Ivermectin is also used to treat infection with parasitic arthropods.
Scabies Scabies (; also sometimes known as the seven-year itch) is a contagious human skin infestation by the tiny (0.2–0.45 mm) mite ''Sarcoptes scabiei'', variety ''hominis''. The word is from . The most common symptoms are severe itchiness a ...
– infestation with the mite ''
Sarcoptes scabiei ''Sarcoptes scabiei'' (/sɑː''r''ˈkɒptiːz skeɪˈbiːaɪ/ Traditional English pronunciation of Latin) or the itch mite is a parasite, parasitic mite found in all parts of the world that burrows into skin and causes scabies. Humans become Inf ...
'' – is most commonly treated with topical
permethrin Permethrin is a medication and an insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed onto outer clothing or mosquito nets to kill the insects ...
or oral ivermectin. A single application of permethrin is more efficacious than a single treatment of ivermectin. For most scabies cases, ivermectin is used in a two-dose regimen: the first dose kills the active mites, but not their eggs. Over the next week, the eggs hatch, and a second dose kills the newly hatched mites. The two-dose regimen of ivermectin has similar efficacy to the single dose permethrin treatment. Ivermectin is, however, more effective than permethrin when used in the mass treatment of endemic scabies. For severe "crusted scabies", where the parasite burden is orders of magnitude higher than usual, the CDC recommends up to seven doses of ivermectin over the course of a month, along with a topical antiparasitic. Both
head lice The head louse (''Pediculus humanus capitis'') is an obligate ectoparasite of humans. Head lice are wingless insects that spend their entire lives on the human scalp and feed exclusively on human blood. Humans are the only known hosts of this s ...
and
pubic lice In vertebrates, the pubis or pubic bone () forms the lower and anterior part of each side of the hip bone. The pubis is the most forward-facing (ventral and anterior) of the three bones that make up the hip bone. The left and right pubic bones ar ...
can be treated with oral ivermectin, an ivermectin lotion applied directly to the affected area, or various other insecticides. Ivermectin is also used to treat
rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, en ...
and
blepharitis Blepharitis, sometimes known as granulated eyelids, is one of the most common ocular conditions characterized by inflammation, scaling, reddening, and crusting of the eyelid. This condition may also cause swelling, burning, itching, or a grainy ...
, both of which can be caused or exacerbated by ''
Demodex folliculorum ''Demodex folliculorum'' is a microscopic mite that can survive only on the skin of humans. Most people host ''D.folliculorum'' on their skin particularly on the face, where sebaceous glands are most concentrated. Usually, the mites do not caus ...
'' mites.


Contraindications

The only absolute contraindication to the use of ivermectin is hypersensitivity to the active ingredient or any component of the formulation. In children under the age of five or those who weigh less than , there is limited data regarding the efficacy or safety of ivermectin, though the available data demonstrate few adverse effects. However, the
American Academy of Pediatrics The American Academy of Pediatrics (AAP) is the largest professional association of pediatricians in the United States. It is headquartered in Itasca, Illinois, and maintains an office in Washington, D.C. The AAP has published hundreds of poli ...
cautions against use of ivermectin in such patients, as the blood–brain barrier is less developed, and thus there may be an increased risk of particular CNS side effects such as encephalopathy, ataxia, coma, or death. The
American Academy of Family Physicians The American Academy of Family Physicians (AAFP) was founded in 1947 to promote and maintain high-quality standards for family medicine, an offshoot of the classical general practitioner. It is headquartered in Leawood, Kansas. AAFP is one of ...
also recommends against use in these patients, given a lack of sufficient data to prove drug safety. Ivermectin is secreted in very low concentration in breast milk. It remains unclear if ivermectin is safe during pregnancy.


Adverse effects

Side effects, although uncommon, include fever, itching, and skin rash when taken by mouth; and red eyes, dry skin, and burning skin when used topically for head lice. It is unclear if the drug is safe for use during
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
, but it is probably acceptable for use during
breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...
. Ivermectin is considered relatively free of toxicity in standard doses (around 300 μg/kg). Based on the data drug safety sheet for ivermectin, side effects are uncommon. However, serious adverse events following ivermectin treatment are more common in people with very high burdens of larval ''
Loa loa ''Loa loa'' is a filarial (arthropod-borne) nematode (roundworm) that causes Loa loa filariasis, ''Loa loa'' filariasis. ''Loa loa'' actually means "worm worm", but is commonly known as the "eye worm", as it localizes to the conjunctiva of the e ...
'' worms in their blood. Those who have over 30,000 microfilaria per
milliliter The litre (Commonwealth English, Commonwealth spelling) or liter (American English, American spelling) (SI symbols L and l, other symbol used: ℓ) is a metric units, metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic c ...
of blood risk inflammation and capillary blockage due to the rapid death of the microfilaria following ivermectin treatment. One concern is
neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...
after large overdoses, which in most mammalian species may manifest as
central nervous system depression Central nervous system depression (or CNS depression) is a nervous system disorder characterized by a severely impaired physiological state in which patients may exhibit decreased rate of breathing, decreased heart rate, and loss of consciousnes ...
,
ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
, coma, and death, as might be expected from potentiation of inhibitory chloride channels. Since drugs that inhibit the enzyme
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
often also inhibit
P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
transport, the risk of increased absorption past the blood-brain barrier exists when ivermectin is administered along with other CYP3A4 inhibitors. These drugs include
statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...
s,
HIV protease inhibitors The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
, many
calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s,
lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia and ventricular fibrillation. When used for local anae ...
,
benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...
s, and
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...
s such as
dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...
. During a typical treatment course, ivermectin can cause minor aminotransferase elevations. In rare cases it can cause mild clinically apparent
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...
. To provide context for the dosing and toxicity ranges, the of ivermectin in mice is 25 mg/kg (oral), and 80 mg/kg in dogs, corresponding to an approximated human-equivalent dose LD50 range of 2.02–43.24 mg/kg, which is far more than its FDA-approved usage (a single dose of 0.150–0.200 mg/kg to be used for specific parasitic infections). While ivermectin has also been studied for use in COVID-19, and while it has some ability to inhibit SARS-CoV-2 in vitro, achieving 50% inhibition in vitro was found to require an estimated oral dose of 7.0 mg/kg (or 35x the maximum FDA-approved dosage), high enough to be considered ivermectin poisoning. Despite insufficient data to show any safe and effective dosing regimen for ivermectin in COVID-19, doses have been taken far more than FDA-approved dosing, leading the CDC to issue a warning of overdose symptoms including nausea, vomiting, diarrhea,
hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
,
decreased level of consciousness An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousn ...
, confusion, blurred vision, visual hallucinations, loss of coordination and balance, seizures, coma, and death. The CDC advises against consuming doses intended for livestock or doses intended for external use and warns that increasing misuse of ivermectin-containing products is increasing harmful overdoses.


Pharmacology


Mechanism of action

Ivermectin and its related drugs act by interfering with the nerve and muscle functions of
helminths Parasitic worms, also known as helminths, are a polyphyletic group of large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other par ...
and insects. The drug binds to
glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...
-gated
chloride channel Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Several ...
s common to invertebrate nerve and muscle cells. The binding pushes the channels open, which increases the flow of chloride ions and hyper-polarizes the cell membranes, paralyzing and killing the invertebrate. Ivermectin is safe for mammals (at the normal therapeutic doses used to cure parasite infections) because mammalian glutamate-gated chloride channels only occur in the brain and spinal cord: the causative avermectins usually do not cross the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
, and are unlikely to bind to other mammalian ligand-gated channels.


Pharmacokinetics

Ivermectin can be given by mouth, topically, or via injection. Oral doses are absorbed into systemic circulation; the alcoholic solution form is more orally available than tablet and capsule forms. Ivermectin is widely distributed in the body. Ivermectin does not readily cross the blood-brain barrier of mammals due to the presence of
P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
(the ''MDR1'' gene mutation affects the function of this protein). Crossing may still become significant if ivermectin is given at high doses, in which case brain levels peak 2–5 hours after administration. In contrast to mammals, ivermectin can cross the blood-brain barrier in tortoises, often with fatal consequences. Ivermectin is metabolized into eight different products by human
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
, two of which (M1, M2) remain toxic to mosquitos. M1 and M2 also have longer elimination half-lives of about 55 hours.
CYP3A5 Cytochrome P450 3A5 is a protein that in humans is encoded by the ''CYP3A5'' gene. Tissue distribution ''CYP3A5'' encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the ...
produces a ninth metabolite.


Chemistry

Fermentation of ''
Streptomyces avermitilis ''Streptomyces avermitilis'' is a species of bacteria in the genus ''Streptomyces''. This bacterium was discovered by Satoshi Ōmura in Shizuoka Prefecture, Japan. The first complete genome sequence of ''S. avermitilis'' was completed in 2003. ...
'' yields eight closely related
avermectin The avermectins are a group of 16-membered Macrolide, macrocyclic lactone derivatives with potent anthelmintic and Insecticide, insecticidal properties. These naturally occurring compounds are generated as fermentation products by ''Streptomyces a ...
homologues, of which B1a and B1b form the bulk of the products isolated. In a separate chemical step, the mixture is
hydrogenated Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organi ...
to give ivermectin, which is an approximately 80:20 mixture of the two 22,23-dihydroavermectin compounds. Ivermectin is a macrocyclical lactone.


History

The
avermectin The avermectins are a group of 16-membered Macrolide, macrocyclic lactone derivatives with potent anthelmintic and Insecticide, insecticidal properties. These naturally occurring compounds are generated as fermentation products by ''Streptomyces a ...
family of compounds was discovered by
Satoshi Ōmura is a Japanese biochemist. He is known for the discovery and development of hundreds of pharmaceuticals originally occurring in microorganisms. In 2015, he was awarded the Nobel Prize in Physiology or Medicine jointly with William C. Campbell f ...
of
Kitasato University is a private medical university headquartered in Shirokane, Minato, Tokyo, Japan. The head of the university is on the Shirokane campus, neighboring the original Kitasato Institute, the first private medical research facility in Japan which w ...
and William Campbell of Merck. In 1970, Ōmura isolated a strain of ''
Streptomyces avermitilis ''Streptomyces avermitilis'' is a species of bacteria in the genus ''Streptomyces''. This bacterium was discovered by Satoshi Ōmura in Shizuoka Prefecture, Japan. The first complete genome sequence of ''S. avermitilis'' was completed in 2003. ...
'' from woodland soil near a golf course along the southeast coast of
Honshu , historically known as , is the largest of the four main islands of Japan. It lies between the Pacific Ocean (east) and the Sea of Japan (west). It is the list of islands by area, seventh-largest island in the world, and the list of islands by ...
, Japan. Ōmura sent the bacteria to William Campbell, who showed that the bacterial culture could cure mice infected with the roundworm '' Heligmosomoides polygyrus''. Campbell isolated the active compounds from the bacterial culture, naming them "avermectins" and the bacterium ''Streptomyces avermitilis'' for the compounds' ability to clear mice of worms (in Latin: ''a'' 'without', ''vermis'' 'worms'). Of the various avermectins, Campbell's group found the compound "avermectin B1" to be the most potent when taken orally. They synthesized modified forms of avermectin B1 to improve its pharmaceutical properties, eventually choosing a mixture of at least 80% 22,23-dihydroavermectin B1a and up to 20% 22,23-dihydroavermectin B1b, a combination they called "ivermectin". The discovery of ivermectin has been described as a combination of "chance and choice." Merck was looking for a broad-spectrum anthelmintic, which ivermectin is; however, Campbell noted that they "...also found a broad-spectrum agent for the control of ectoparasitic insects and mites." Merck began marketing ivermectin as a veterinary antiparasitic in 1981. By 1986, ivermectin was registered for use in 46 countries and was administered massively to cattle, sheep, and other animals. By the late 1980s, ivermectin was the bestselling veterinary medicine in the world. Following its blockbuster success as a veterinary antiparasitic, another Merck scientist, Mohamed Aziz, collaborated with the World Health Organization to test the safety and efficacy of ivermectin against
onchocerciasis Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
in humans. They found it to be highly safe and effective, triggering Merck to register ivermectin for human use as "Mectizan" in France in 1987. A year later, Merck CEO Roy Vagelos agreed that Merck would donate all ivermectin needed to eradicate river blindness. In 1998, that donation would be expanded to include ivermectin used to treat lymphatic filariasis. Ivermectin earned the title of "wonder drug" for the treatment of nematodes and arthropod parasites. Ivermectin has been used safely by hundreds of millions of people to treat river blindness and lymphatic filariasis. Half of the 2015
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
was awarded jointly to Campbell and Ōmura for discovering ivermectin, "the derivatives of which have radically lowered the incidence of
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
and
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide, impacting over a hundred million people and manifesting itself in ...
, as well as showing efficacy against an expanding number of other parasitic diseases".


Society and culture


COVID-19 misinformation


Economics

The initial price proposed by Merck in 1987 was per treatment, which was unaffordable for patients who most needed ivermectin. The company donated hundreds of millions of courses of treatments since 1988 in more than 30 countries. Between 1995 and 2010, using donated ivermectin to prevent
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
, the program is estimated to have prevented seven million years of disability at a cost of . Ivermectin is considered an inexpensive drug. As of 2019, ivermectin tablets (Stromectol) in the United States were the least expensive treatment option for lice in children at approximately , while Sklice, an ivermectin lotion, cost around for . , the
cost effectiveness Cost-effectiveness analysis (CEA) is a form of economic analysis that compares the relative costs and outcomes (effects) of different courses of action. Cost-effectiveness analysis is distinct from cost–benefit analysis, which assigns a monetar ...
of treating scabies and lice with ivermectin has not been studied.


Brand names

It is sold under the brand names Heartgard, Sklice, and Stromectol in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT in Nepal by Alive Pharmaceutical and Ivexterm in Mexico by
Valeant Pharmaceuticals International Bausch Health Companies Inc. is a global, diversified American-Canadian pharmaceutical company. Its global corporate headquarters are located in Laval, Quebec, Canada, and its U.S. headquarters are in Bridgewater, New Jersey. It develops, manufa ...
. In Southeast Asian countries, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6. The formulation for rosacea treatment is sold under the brand name Soolantra. While in development, it was assigned the code MK-933 by Merck.


Research


Parasitic disease

Ivermectin has been researched in laboratory animals, as a potential treatment for
trichinosis Trichinosis, also known as trichinellosis, is a parasitic disease caused by roundworms of the '' Trichinella'' genus. During the initial infection, invasion of the intestines can result in diarrhea, abdominal pain, and vomiting. Migration of ...
and
trypanosomiasis Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus ''Trypanosoma''. In humans this includes African trypanosomiasis and Chagas disease. A number of other disea ...
. Ivermectin has also been tested on
zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...
infected with '' Pseudocapillaria tomentosa''.


Tropical diseases

Ivermectin is also of interest in the prevention of
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
, as it is toxic to both the malaria
plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a Hematophagy, blood-feeding insect host (biology), host which then inj ...
itself and the
mosquito Mosquitoes, the Culicidae, are a Family (biology), family of small Diptera, flies consisting of 3,600 species. The word ''mosquito'' (formed by ''Musca (fly), mosca'' and diminutive ''-ito'') is Spanish and Portuguese for ''little fly''. Mos ...
s that carry it. A direct effect on malaria parasites could not be shown in an experimental infection of volunteers with ''
Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans and is the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mos ...
''. Use of ivermectin at higher doses necessary to control malaria is probably safe, though large clinical trials have not yet been done to definitively establish the efficacy or safety of ivermectin for prophylaxis or treatment of malaria. Mass drug administration of a population with ivermectin to treat and prevent nematode infestation is effective for eliminating malaria-bearing mosquitos and thereby potentially reducing infection with residual
malaria parasites ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a verteb ...
. Whilst effective in killing malaria-bearing mosquitos, a 2021 Cochrane review found that, to date, the evidence shows no significant impact on reducing incidence of malaria transmission from the community administration of ivermectin. One alternative to ivermectin is
moxidectin Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle, sheep and wombats. Moxidectin kills some of the most common internal ...
, which has been approved by the Food and Drug Administration for use in people with river blindness. Moxidectin has a longer half-life than ivermectin and may eventually supplant ivermectin as it is a more potent microfilaricide, but there is a need for additional clinical trials, with long-term follow-up, to assess whether moxidectin is safe and effective for treatment of nematode infection in children and women of childbearing potential. There is tentative evidence that ivermectin kills
bedbug Bed bugs are parasitic insects from the genus ''Cimex'', which are micropredators that feed on blood, usually at night. Their bites can result in a number of health impacts, including skin rashes, psychological effects, and allergic symptom ...
s, as part of
integrated pest management Integrated pest management (IPM), also known as integrated pest control (IPC) integrates both chemical and non-chemical practices for economic control of pests. The UN's Food and Agriculture Organization defines IPM as "the careful consideratio ...
for
bedbug infestation Bed bugs are parasitic insects from the genus ''Cimex'', which are micropredators that feed on blood, usually at night. Their bites can result in a number of health impacts, including skin rashes, psychological effects, and allergic symptoms. ...
s. However, such use may require a prolonged course of treatment which is of unclear safety.


NAFLD

In 2013, ivermectin was demonstrated as a novel ligand of the
farnesoid X receptor The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the ''NR1H4'' gene in humans. Function FXR is expressed at high level ...
, a therapeutic target for nonalcoholic fatty liver disease (NAFLD).


COVID-19

During the COVID-19 pandemic, ivermectin was researched for possible utility in preventing and treating COVID-19, but no good evidence of benefit was found.


Veterinary use

Ivermectin is routinely used to control parasitic worms in the gastrointestinal tract of
ruminant Ruminants are herbivorous grazing or browsing artiodactyls belonging to the suborder Ruminantia that are able to acquire nutrients from plant-based food by fermenting it in a specialized stomach prior to digestion, principally through microb ...
animals. These parasites normally enter the animal when it is grazing, pass the bowel, and set and mature in the intestines, after which they produce eggs that leave the animal via its droppings and can infest new pastures. Ivermectin is only effective in killing some of these parasites, because of an increase in anthelmintic resistance. This resistance has arisen from the persistent use of the same anthelmintic drugs for the past 40 years. Additionally, the use of Ivermectin for livestock has a profound impact on dung beetles, such as ''T. lusitanicus'', as it can lead to acute toxicity within these insects. In dogs, ivermectin is routinely used as prophylaxis against heartworm. Dogs with defects in the
P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
gene (''MDR1''), often collie-like herding dogs, can be severely poisoned by ivermectin. The mnemonic "white feet, don't treat" refers to Scotch collies that are vulnerable to ivermectin. Some other dog breeds (especially the
Rough Collie The Rough Collie (also known as the Long-Haired Collie) is a long-coated dog breed of medium to large size that, in its original form, was a type of collie used and bred for herding sheep in Scotland. More recent breeding has focused on the Co ...
, the
Smooth Collie The Smooth Collie is a dog breed, breed of dog developed originally for herding. It is a short-coated version of the Rough Collie of Lassie fame. Some breed organisations consider the smooth-coat and rough-coat dogs to be variations of the sa ...
, the
Shetland Sheepdog The Shetland Sheepdog, also known as the Sheltie, is a breed of herding dog that originated in the Shetland Islands of Scotland. It was formally recognized by the Kennel Club in 1909. It was originally called the ''Shetland Collie'', but this c ...
, and the
Australian Shepherd The Australian Shepherd is a breed of herding dog from the United States. The name of the breed is technically a misnomer, as it was developed in California in the 19th century. It is believed to have its origins in sheepdog breeds from northwe ...
), also have a high incidence of mutation within the ''
MDR1 P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
'' gene (coding for P-glycoprotein) and are sensitive to the toxic effects of ivermectin. For dogs, the insecticide
spinosad Spinosad is an insecticide based on chemical compounds found in the bacterial species '' Saccharopolyspora spinosa''. The genus '' Saccharopolyspora'' was discovered in 1985 in isolates from crushed sugarcane. The bacteria produce yellowish-p ...
may have the effect of increasing the toxicity of ivermectin. A 0.01% ivermectin topical preparation for treating
ear mite Ear mites are mites that live in the ears of animals. The most commonly seen species in veterinary medicine is '' Otodectes cynotis'' (Gk. ''oto''=ear, ''dectes''=biter, ''cynotis''=of the dog). This species, despite its name, is also responsibl ...
s in cats is available. Clinical evidence suggests 7-week-old kittens are susceptible to ivermectin toxicity. Ivermectin is sometimes used as an
acaricide Acaricides are pesticides that kill members of the arachnid subclass '' Acari'', which includes ticks and mites. Acaricides are used both in medicine and agriculture, although the desired selective toxicity differs between the two fields. Termi ...
in reptiles, both by injection and as a diluted spray. While this works well in some cases, care must be taken, as several species of reptiles are very sensitive to ivermectin. Use in turtles is particularly contraindicated. A characteristic of the antinematodal action of ivermectin is its potency: for instance, to combat ''
Dirofilaria immitis ''Dirofilaria immitis'', also known as heartworm or dog heartworm, is a Parasitism, parasitic Nematode, roundworm that is a type of Filarioidea, filarial worm, a small thread-like worm, and which causes dirofilariasis. It is spread from host (bi ...
'' in dogs, ivermectin is effective at 0.001 milligram per kilogram of body weight when administered orally.


Notes


References


External links

* * {{Authority control Acaricides Antiparasitic agents GABAA receptor positive allosteric modulators Glycine receptor agonists Insecticides Japanese inventions Macrolides Drugs developed by Merck & Co. Nicotinic agonists Peripherally selective drugs Veterinary drugs World Health Organization essential medicines Chloride channel openers Wikipedia medicine articles ready to translate