Mebendazole

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Mebendazole
Mebendazol.svg
Mebendazole ball-and-stick animation.gif
Systematic (IUPAC) name
methyl (5-benzoyl-1H-benzimidazol-2-yl)carbamate
Clinical data
Trade namesGeneric (formerly Vermox)
AHFS/Drugs.commonograph
MedlinePlusa682315
Pregnancy cat.B3 (AU) C (US)
Legal statusPharmacy Only (S2) (AU) OTC (CA) GSL (UK) OTC (US)
RoutesOral
Pharmacokinetic data
Bioavailability2-10%
Protein binding95%
MetabolismHepatic (extensive)
Half-life3-6 hours
ExcretionFaeces, urine (5-10%)
Identifiers
CAS number31431-39-7 YesY
ATC codeP02CA01 QP52AC09
PubChemCID 4030
DrugBankDB00643
ChemSpider3890 YesY
UNII81G6I5V05I YesY
KEGGD00368 YesY
ChEBICHEBI:6704 YesY
ChEMBLCHEMBL685 YesY
Chemical data
FormulaC16H13N3O3 
Mol. mass295.293 g/mol
Physical data
Melt. point288.5 °C (551 °F)
 YesY (what is this?)  (verify)
 
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Mebendazole
Mebendazol.svg
Mebendazole ball-and-stick animation.gif
Systematic (IUPAC) name
methyl (5-benzoyl-1H-benzimidazol-2-yl)carbamate
Clinical data
Trade namesGeneric (formerly Vermox)
AHFS/Drugs.commonograph
MedlinePlusa682315
Pregnancy cat.B3 (AU) C (US)
Legal statusPharmacy Only (S2) (AU) OTC (CA) GSL (UK) OTC (US)
RoutesOral
Pharmacokinetic data
Bioavailability2-10%
Protein binding95%
MetabolismHepatic (extensive)
Half-life3-6 hours
ExcretionFaeces, urine (5-10%)
Identifiers
CAS number31431-39-7 YesY
ATC codeP02CA01 QP52AC09
PubChemCID 4030
DrugBankDB00643
ChemSpider3890 YesY
UNII81G6I5V05I YesY
KEGGD00368 YesY
ChEBICHEBI:6704 YesY
ChEMBLCHEMBL685 YesY
Chemical data
FormulaC16H13N3O3 
Mol. mass295.293 g/mol
Physical data
Melt. point288.5 °C (551 °F)
 YesY (what is this?)  (verify)

Mebendazole or MBZ is a benzimidazole drug developed by Janssen Pharmaceutica and marketed in the USA as a generic drug only, according to the FDA Orange Book. It is used to treat infestations by worms including pinworms, roundworms, tapeworms, hookworms, and whipworms.

Mebendazole is a WHO Essential Medicine.

Medical use[edit]

The drug is a highly effective, broad-spectrum antihelmintic indicated for the treatment of nematode infestations, including roundworm, whipworm, threadworm, and hookworm. It is poorly absorbed and has no systemic effects.[citation needed]

Mechanism[edit]

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.

Dosage[edit]

Oral dosage for treatment of pinworms is 100 mg taken once. (500 mg can also be taken instead) This regimen is repeated two weeks later if the infestation has not cleared up. Oral dosage for treatment of whipworm, common roundworm and hookworm is one 100-mg tablet in the morning for three consecutive days in children below 5yrs of age and below 18 kg weight. In adults it is 100 mg twice a day. [1]

Adverse effects[edit]

Mebendazole is relatively free of toxic side effects or adverse reactions, although patients may complain of transient abdominal pain, heart pain, diarrhea, slight headache, fever, dizziness, exanthema, urticaria, and angioedema.

Contraindications[edit]

Pregnancy[edit]

Mebendazole is contraindicated in pregnant women because it has been shown to be embryotoxic and teratogenic in experimental animals.[medical citation needed]

Drug interactions[edit]

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.[2][3]

Stevens–Johnson syndrome and the more severe toxic epidermal necrolysis can occur when mebendazole is combined with high doses of metronidazole.[4]

Oncologic treatment potential[edit]

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.[5] 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.[6] MBZ induced a dose- and time-dependent apoptotic response in human lung cancer cell lines,[7] and apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells.[8]

Discontinuation in United States[edit]

The last manufacturer of mebendazole in the United States, Teva Pharmaceuticals, announced on October 7, 2011, they have ceased manufacture of this product. As of December, 2011, it is no longer available from any manufacturer in the USA. No reason was given publicly for this discontinuation.[9] Mebendazole formulations can be made by a compounding pharmacy at the request of a doctor.

References[edit]

  1. ^ "Mebendazole". Drugs.com. Retrieved 2011-10-29. 
  2. ^ "Drug Interactions". Medicine chest. Retrieved 2008-05-06. 
  3. ^ Luder PJ, Siffert B, Witassek F, Meister F, Bircher J (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. PMID 3816925.  edit
  4. ^ 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. PMC 1447769. PMID 12604501.  edit
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ "Drug Shortages Bulletin 750". American Society of Health-System Pharmacists. Retrieved 2011-12-18.