Mebendazole

"MBZ" redirects here. For the automobile brand abbreviated as "MBZ", see Mercedes-Benz.
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 P02CA01 (WHO) QP52AC09 (WHO)
Legal status
Legal status
Pharmacokinetic data
Bioavailability 2–10%
Protein binding 95%
Metabolism Extensive liver
Biological half-life 3–6 hours
Excretion Faeces, urine (5–10%)
Identifiers
CAS Number 31431-39-7 YesY
PubChem (CID) 4030
DrugBank DB00643 YesY
ChemSpider 3890 YesY
UNII 81G6I5V05I YesY
KEGG D00368 YesY
ChEBI CHEBI:6704 YesY
ChEMBL CHEMBL685 YesY
ECHA InfoCard 100.046.017
Chemical and physical data
Formula C16H13N3O3
Molar mass 295.293 g/mol
3D model (Jmol) Interactive image
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.[4] It is included in the WHO Model List of Essential Medicines, the most important medications needed in a basic 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 18 USD.[3]

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.[8] 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.[9] It is also used rarely in the treatment of hydatid disease. Evidence for effectiveness for this disease, however, is poor.[10]

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.[8]

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.[11]

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,[11][12] 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.[13][14]

Stevens–Johnson syndrome and the more severe toxic epidermal necrolysis can occur when mebendazole is combined with high doses of metronidazole.[15]

Mechanism

Mebendazole is thought to work by selectively inhibiting the synthesis of microtubules in parasitic worms, and by destroying extant cytoplasmic microtubes in their intestinal cells, thereby blocking the uptake of glucose and other nutrients, resulting in the gradual immobilization and eventual death of the helminths.[8]

Society and culture

Cost

Mebendazole is available as a generic medication.[6] The wholesale cost is between 0.004 and 0.04 USD per dose.[7] In the United States a single dose is about 18 USD.[3]

As of 2016, pricing has dramatically increased in the U.S. as Amedra Pharmaceuticals acquired the rights to this drug from Teva in 2013. It should also be noted that 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 for this 40+ year old medication and its alternative medication.[16] The retail price was approximately 380 USD per 100 mg tablet in Florida in September, 2016, and marketed under the brand name, Emverm, by Amedra Pharmaceuticals.

Availability

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

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.[18] 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.[19] MBZ induced a dose- and time-dependent apoptotic response in human lung cancer cell lines,[20] and apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells.[21]

References

  1. ↑ Ebadi, Manuchair (2008). Desk reference of clinical pharmacology (2 ed.). Boca Raton: CRC Press. p. 403. ISBN 9781420047448.
  2. ↑ http://www.evidence.nhs.uk/formulary/bnf/current/5-infections/55-anthelmintics/551-drugs-for-threadworms/mebendazole
  3. 1 2 3 4 5 6 7 8 9 10 "Mebendazole". The American Society of Health-System Pharmacists. Retrieved Aug 18, 2015.
  4. ↑ Mehlhorn, Heinz (2001). Encyclopedic reference of parasitology. 107 tables (2 ed.). Berlin [u.a.]: Springer. p. 259. ISBN 9783540668299.
  5. ↑ "WHO Model List of EssentialMedicines" (PDF). World Health.
  6. 1 2 Hamilton, Richard J. (2012). Tarascon pocket pharmacopoeia (13 ed.). Burlington, Mass.: Jones & Bartlett Learning. p. 33. ISBN 9781449624286.
  7. 1 2 "Mebendazole". International Drug Price Indicator Guide. Retrieved 18 August 2015.
  8. 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.
  9. ↑ 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
  10. ↑ "Mebendazole". drugs.com. Retrieved 25 January 2015.
  11. 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.
  12. ↑ 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.
  13. ↑ "Drug Interactions". Medicine chest. Retrieved 2008-05-06.
  14. ↑ 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.
  15. ↑ 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 1447769Freely accessible. PMID 12604501.
  16. ↑ High-Cost Generic Drugs — Implications for Patients and Policymakers Jonathan D. Alpern, M.D., William M. Stauffer, M.D., M.S.P.H., and Aaron S. Kesselheim, M.D., J.D., M.P.H. N Engl J Med 2014; 371:1859-1862
  17. ↑ Global Pharmaceutical Pricing and Reimbursement Database, zenRx Research, archived from the original on 30 June 2015, retrieved 2014-06-12
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
This article is issued from Wikipedia - version of the 10/2/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.