Mebendazole

Mebendazole
Clinical data
Trade names Vermox[1]
AHFS/Drugs.com Monograph
MedlinePlus a682315
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
    Routes of
    administration    		 By mouth
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 2–10%
    Protein binding 95%
    Metabolism Extensive liver
    Elimination half-life 3–6 hours
    Excretion Faeces, urine (5–10%)
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard 100.046.017 Edit this at Wikidata
    Chemical and physical data
    Formula C16H13N3O3
    Molar mass 295.30 g·mol−1
    3D model (JSmol)
    Melting point 288.5 °C (551.3 °F)
      (verify)

    Mebendazole (MBZ) is a medication used to treat a number of parasitic worm infestations.[3] This includes ascariasis, pinworm disease, hookworm infections, guinea worm infections, hydatid disease, and giardia, among others.[3] It is taken by mouth.[3]

    Mebendazole is usually well tolerated.[3] Common side effects include headache, vomiting, and ringing in the ears.[3] If used at large doses it may cause bone marrow suppression.[3] It is unclear if it is safe in pregnancy.[3] Mebendazole is a broad-spectrum antihelminthic agent of the benzimidazole type.[3]

    Mebendazole came into use in 1971, after it was developed by Janssen Pharmaceutica in Belgium.[4] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] Mebendazole is available as a generic medication.[6] The wholesale cost in the developing world is between 0.004 and 0.04 USD per dose.[7] In the United States a single dose is about 440.00 USD as of 2016, while in Australia and the UK it costs about 5 USD.[8]

    Medical use

    Mebendazole is a highly effective, broad-spectrum antihelmintic indicated for the treatment of nematode infestations, including roundworm, hookworm, whipworm, threadworm, pinworm, and the intestinal form of trichinosis 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.[9] 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, either before or instead of mebendazole. Piperazine paralyses the parasites, causing them to pass in the feces.[10] It is also used rarely in the treatment of hydatid disease. Evidence for effectiveness for this disease, however, is poor.[11]

    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.[9]

    Special populations

    Mebendazole is pregnancy category C, which means it 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.[12]

    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,[12][13] with a risk of agranulocytosis in rare cases

    Drug interactions

    Carbamazepine and phenytoin lower serum levels of mebendazole. Cimetidine does not appreciably raise serum mebendazole (in contrast to the similar drug albendazole), consistent with its poor systemic absorption.[14][15]

    Stevens–Johnson syndrome and the more severe toxic epidermal necrolysis can occur when mebendazole is combined with high doses of metronidazole.[16]

    Mechanism

    Mebendazole is thought to work by selectively inhibiting the synthesis of microtubules in parasitic worms, and by destroying extant cytoplasmic microtubules in their intestinal cells, thereby blocking the uptake of glucose and other nutrients, resulting in the gradual immobilization and eventual death of the helminths.[9]

    Society and culture

    Availability

    Mebendazole is available as a generic medication.[6] Mebendazole is distributed in international markets by Johnson and Johnson and a number of generic manufacturers.[17]

    Cost

    In the developing world the wholesale cost is between 0.004 and 0.04 USD per dose as of 2014.[7] In the United States a single dose was about 18 USD in 2015.[3] In 2016 the price increased to 440.00 USD per dose in the U.S. as Amedra Pharmaceuticals acquired the rights from Teva in 2013.[8]

    In 2010, Amedra also bought the U.S. Marketing rights to the only other interchangeable anti-parasitic medication, albendazole, from GSK. The result of these acquisitions created a monopoly these medications and the price increased dramatically.[18]

    Research

    Several studies show mebendazole exhibits potent antitumor properties. MBZ significantly inhibited cancer cell growth, migration, and metastatic formation of adrenocortical carcinoma, both in vitro and in vivo.[19] Treatment of lung cancer cell lines with MBZ caused mitotic arrest, followed by apoptotic cell death with the feature of caspase activation and cytochrome c release.[20] MBZ induced a dose- and time-dependent apoptotic response in human lung cancer cell lines,[21] and apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells.[22]

    References

    1. ↑ Ebadi, Manuchair (2008). Desk reference of clinical pharmacology (2 ed.). Boca Raton: CRC Press. p. 403. ISBN 9781420047448. Archived from the original on 2017-09-08.
    2. ↑ "Archived copy". Archived from the original on 2016-10-23. Retrieved 2016-04-29.
    3. 1 2 3 4 5 6 7 8 9 "Mebendazole". The American Society of Health-System Pharmacists. Archived from the original on 2015-09-07. Retrieved Aug 18, 2015.
    4. ↑ Mehlhorn, Heinz (2001). Encyclopedic reference of parasitology. 107 tables (2 ed.). Berlin [u.a.]: Springer. p. 259. ISBN 9783540668299. Archived from the original on 2017-09-08.
    5. ↑ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
    6. 1 2 Hamilton, Richard J. (2012). Tarascon pocket pharmacopoeia (13 ed.). Burlington, Mass.: Jones & Bartlett Learning. p. 33. ISBN 9781449624286. Archived from the original on 2017-09-08.
    7. 1 2 "Mebendazole". International Drug Price Indicator Guide. Archived from the original on 5 March 2017. Retrieved 18 August 2015.
    8. 1 2 Crow, David (18 December 2016). "US drugmaker charges 200 times UK price for common worm pill". www.ft.com. Archived from the original on 8 January 2017. Retrieved 8 January 2017. (Subscription required (help)).
    9. 1 2 3 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.
    10. ↑ Martin AR in Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry, 8th edition, Doerge RF, ed. J.B. Lippincott, 1982, Chapter 4
    11. ↑ "Mebendazole". drugs.com. Archived from the original on 22 February 2015. Retrieved 25 January 2015.
    12. 1 2 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.
    13. ↑ Andersohn F, Konzen C, Garbe E (May 2007). "Systematic review: agranulocytosis induced by nonchemotherapy drugs". Ann. Intern. Med. 146 (9): 657–65. doi:10.7326/0003-4819-146-9-200705010-00009. PMID 17470834. Archived from the original on 2014-01-08.
    14. ↑ "Drug Interactions". Medicine chest. Archived from the original on 2007-02-06. Retrieved 2008-05-06.
    15. ↑ Luder PJ, Siffert B, Witassek F, Meister F, Bircher J; Siffert; Witassek; Meister; Bircher (1986). "Treatment of hydatid disease with high oral doses of mebendazole. Long-term follow-up of plasma mebendazole levels and drug interactions". European journal of clinical pharmacology. 31 (4): 443–448. doi:10.1007/bf00613522. PMID 3816925.
    16. ↑ Chen, K. T.; Twu, S. J.; Chang, H. J.; Lin, R. S. (2003). "Outbreak of Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Associated with Mebendazole and Metronidazole Use Among Filipino Laborers in Taiwan". American Journal of Public Health. 93 (3): 489–492. doi:10.2105/ajph.93.3.489. PMC 1447769. PMID 12604501.
    17. ↑ Global Pharmaceutical Pricing and Reimbursement Database, zenRx Research, archived from the original on 30 June 2015, retrieved 2014-06-12
    18. ↑ "High-Cost Generic Drugs — Implications for Patients and Policymakers". New England Journal of Medicine. 372 (7): 685. 2015. doi:10.1056/NEJMc1415471.
    19. ↑ Martarelli D, Pompei P, Baldi C, Mazzoni G (April 2008). "Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice". Cancer Chemother. Pharmacol. 61 (5): 809–17. doi:10.1007/s00280-007-0538-0. PMID 17581752.
    20. ↑ Sasaki J, Ramesh R, Chada S, Gomyo Y, Roth JA, Mukhopadhyay T (November 2002). "The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells". Mol. Cancer Ther. 1 (13): 1201–9. PMID 12479701.
    21. ↑ Mukhopadhyay T, Sasaki J, Ramesh R, Roth JA (September 2002). "Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo". Clin. Cancer Res. 8 (9): 2963–9. PMID 12231542.
    22. ↑ Doudican N, Rodriguez A, Osman I, Orlow SJ (August 2008). "Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells". Mol. Cancer Res. 6 (8): 1308–15. doi:10.1158/1541-7786.MCR-07-2159. PMID 18667591.
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