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Mebendazole (MBZ), sold under the brand name Vermox among others, is a
medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
used to treat a number of
parasitic worm 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 ...
infestations. This includes
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 ...
,
pinworm infection Pinworm infection (threadworm infection in the UK), also known as enterobiasis, is a human parasitic disease caused by the pinworm, ''Enterobius vermicularis''. The most common symptom is pruritus ani, or itching in the anal area. The perio ...
,
hookworm infection Hookworm infection is an infection by a type of intestinal parasite An intestinal parasite infection is a condition in which a parasite infects the gastro-intestinal tract of humans and other animals. Such parasites can live anywhere in the ...
s, guinea worm infections and
hydatid disease Hydatid may refer to: * Echinococcosis * ''Echinococcus granulosus'', known as the hydatid tapeworm * Hydatid of Morgagni The hydatid of Morgagni can refer to one of two closely related bodily structures: * Appendix of testis (in the male) * Para ...
, among others. It has been used for treatment of
giardiasis Giardiasis is a parasitic disease caused by the protist enteropathogen ''Giardia duodenalis'' (also known as ''G. lamblia'' and ''G. intestinalis''), especially common in children and travellers. Infected individuals experience steatorrhea, a typ ...
but is not a preferred agent. It is 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 ...
. Mebendazole is usually well tolerated. Common side effects include
headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
, vomiting, and
ringing in the ears Tinnitus is a condition when a person hears a ringing sound or a different variety of sound when no corresponding external sound is present and other people cannot hear it. Nearly everyone experiences faint "normal tinnitus" in a completely ...
. If used at large doses it may cause
bone marrow suppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting ( ...
. It is unclear if it is safe in pregnancy. Mebendazole is a broad-spectrum antihelminthic agent of the
benzimidazole Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals. Preparation Benzimi ...
type. Mebendazole came into use in 1971, after it was developed by
Janssen Pharmaceutica Johnson & Johnson Innovative Medicine (formerly Janssen Pharmaceuticals) is a Belgian pharmaceutical company headquartered in Beerse, Belgium, and wholly owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Ph ...
in
Belgium Belgium, officially the Kingdom of Belgium, is a country in Northwestern Europe. Situated in a coastal lowland region known as the Low Countries, it is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeas ...
. 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 ...
. Mebendazole is available as a
generic medication 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 ...
.


Medical use

Mebendazole is a highly effective, broad-spectrum
antihelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them without causing significant damage to the host. They may also ...
indicated for the treatment of
nematode 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 (h ...
infestations, including roundworm, hookworm, whipworm, threadworm (pinworm), and the intestinal form of
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 ...
prior to its spread into the tissues beyond the digestive tract. Other drugs are used to treat worm infections outside the digestive tract, as mebendazole is poorly absorbed into the bloodstream.Petri WA in Brunton LL, Chabner BA, Knollmann BC, Ed. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 12th ed., Chapter 42. McGraw-Hill, 2011 New York. Mebendazole is used alone in those with mild to moderate infestations. It kills parasites relatively slowly, and in those with very heavy infestations, it can cause some parasites to migrate out of the digestive system, leading to appendicitis, bile duct problems, or intestinal perforation. To avoid this, heavily infested patients may be treated with
piperazine Piperazine () is an organic compound with the formula . In term of its structure, it can be described as cyclohexane with the 1- and 4-CH2 groups replaced by NH. Piperazine exists as deliquescent solid with a saline taste. Piperazine is freely sol ...
, either before or instead of mebendazole. Piperazine paralyses the parasites, causing them to pass in the feces. It is also used rarely in the treatment of cystic echinococcosis, also known as hydatid disease. Evidence for effectiveness for this disease, however, is poor. Mebendazole and other benzimidazole antithelmetics are active against both larval and adult stages of nematodes, and in the cases of roundworm and whipworm, kill the eggs, as well. Paralysis and death of the parasites occurs slowly, and elimination in the feces may require several days.


Special populations

Mebendazole has been shown to cause ill effects in pregnancy in animal models, and no adequate studies of its effects in human pregnancy have been conducted. Whether it can be passed by breastfeeding is unknown.Finberg R, Fingeroth J in Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo, Ed. Harrison's Principles of Internal Medicine, 18th ed., McGraw-Hill, 2012, Chapter 217.


Adverse effects

Mebendazole sometimes causes diarrhea, abdominal pain, and elevated liver enzymes. In rare cases, it has been associated with a dangerously low white blood cell count, low platelet count, and hair loss, with a risk of
agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...
in rare cases.


Drug interactions

Carbamazepine Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as ...
and
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...
lower serum levels of mebendazole.
Cimetidine Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. With the development of proton pump ...
does not appreciably raise serum mebendazole (in contrast to the similar drug
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 ...
), consistent with its poor systemic absorption.
Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and #Classification, Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous d ...
and the more severe
toxic epidermal necrolysis Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and f ...
can occur when mebendazole is combined with high doses of
metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...
.


Mechanism

Mebendazole works by selectively inhibiting the synthesis of
microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nanometer, nm and have an inner diameter bet ...
s via binding to the
colchicine Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...
binding site of
β-tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytos ...
, thereby blocking polymerisation of
tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...
dimers in intestinal cells of parasites. Disruption of cytoplasmic microtubules leads to blocking the uptake of
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
and other nutrients, resulting in the gradual immobilization and eventual death of the
helminth 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 ...
s. Poor absorption in the digestive tract makes mebendazole an efficient drug for treating intestinal parasitic infections with limited adverse effects. However mebendazole has an impact on mammalian cells, mostly by inhibiting polymeration of
tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...
dimers, thereby disrupting essential microtubule structures such as
mitotic spindle In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process ...
. Disassembly of the mitotic spindle then leads to
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
mediated via dephosphorylation of
Bcl-2 Bcl-2, encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first a ...
which allows pro-apoptotic protein Bax to dimerize and initiate programmed cell death.


Society and culture


Availability

Mebendazole is available as a
generic medication 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 ...
. Mebendazole is distributed in international markets by
Johnson and Johnson Johnson & Johnson (J&J) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical, biotechnology, and Medical device, medical technologies corporation headquartered in New Brunswick, New Jersey, and publi ...
and a number of generic manufacturers.


Economics

In the United States, mebendazole is sometimes sold at about 200 times the price of the same medication in other countries.


References

{{Portal bar, Medicine Anthelmintics Aromatic ketones Belgian inventions Benzimidazoles Carbamates Embryotoxicants Drugs developed by Johnson & Johnson Janssen Pharmaceutica Wikipedia medicine articles ready to translate Teratogens World Health Organization essential medicines Methyl esters