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Description
A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections;
giardiasis; anaerobic bacteria; and treponemal infections. It has also been proposed
as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on
Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be
anticipated to be a carcinogen (Merck, 11th ed).
Structure
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Methronidazole
Metronidazol
Metronidazole Benzoate
Metronidazole Hcl
Metronidazole in Plastic Container
Metronidazolo
Synonyms
Methronidazole
Metronidazol
Metronidazole Benzoate
Metronidazole Hcl
Metronidazole in Plastic Container
Metronidazolo
Name Company
Arilin
Atrivyl
Bayer 5360
Bexon
Clont
Cont
Danizol
Brand mixtures
Helidac
Categories
Anti-Infective Agents
Anti-Infectives
Radiation-Sensitizing Agents
Antiprotozoals
Antiprotozoal Agents
CAS number 443-48-1
Weight
Average: 171.154
Monoisotopic: 171.064391169
Chemical Formula C6H9N3O3
InChI Key
InChIKey=VAOCPAMSLUNLGC-UHFFFAOYSA-N
InChI InChI=1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3
Plain Text
IUPAC Name 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethan-1-ol
SMILES
CC1=NC=C(N1CCO)[N+]([O-])=O
Plain Text
Mass Spec
Taxonomy
Kingdom
Organic
Classes
Nitroimidazoles
Substructures
Nitroimidazoles
Hydroxy Compounds
Oxoazaniums
Nitro compounds
Alcohols and Polyols
Imidazoles
Heterocyclic compounds
Aromatic compounds
Imines
Cyanamides
Pharmacology
Indication
For the treatment of anaerobic infections and mixed infections, surgical
prophylaxis requiring anaerobic coverage, Clostridium difficile-associated diarrhea
and colitis, Helicobacter pylori infection and duodenal ulcer disease, bacterial
vaginosis, Giardia lamblia gastro-enteritis, amebiasis caused by Entamoeba
histolytica, acne rosacea (topical treatment), and Trichomonas infections.
Pharmacodynamics
Metronidazole, a synthetic antibacterial and antiprotozoal
agent of the nitroimidazole class, is used against protozoa such as Trichomonas
vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against
anaerobic bacterial infections and is also used to treat Crohn's disease, antibioticassociated diarrhea, and rosacea.
Mechanism of action
Metronidazole is a prodrug. Unionized metronidazole is
selective for anaerobic bacteria due to their ability to intracellularly reduce
metronidazole to its active form. This reduced metronidazole then covalently binds
to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis and
resulting in bacterial cell death.
Absorption Well absorbed (at least 80%) with peak plasma concentrations
achieved in 1-3 hours following oral administration of therapeutic doses of
immediate release formulation.
Volume of distribution
Protein binding
Not Available
Not Available
Half life
6-8 hours
Clearance
Not Available
Toxicity
LD50=500 mg/kg/day (orally in rat). Adverse effects include reversible
peripheral neuropathy with prolonged therapy, CNS toxicity, disulfiram effect with
alcohol, dark red-brown urine, metallic taste, nausea, epigastric distress, dizziness,
vertigo and paresthesias associated with high doses, and neutropenia (reversible
and mild).
Affected organisms
Pathways
Not Available
Pharmacoeconomics
Manufacturers
Gd searle llc
Actavis Group
Liberty Pharmaceuticals
Major Pharmaceuticals
Mckesson Corp.
Medisca Inc.
Medvantx Inc.
Mississippi State Dept Health
Murfreesboro Pharmaceutical Nursing Supply
Mutual Pharmaceutical Co.
Nord Ost Corp.
Nucare Pharmaceuticals Inc.
Nycomed Inc.
Obagi Medical Products Inc.
Palmetto Pharmaceuticals Inc.
Pangeo Pharma Quebec Inc.
Par Pharmaceuticals
Patheon Inc.
Patient First Corp.
PCA LLC
PD-Rx Pharmaceuticals Inc.
Pfizer Inc.
Pharmacia Inc.
Pharmedix
Pharmpak Inc.
Physicians Total Care Inc.
Pliva Inc.
Prasco Labs
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Oral
Cream
Intravaginal
Cream
Topical
Gel
Intravaginal
Gel
Topical
Liquid Intravenous
Lotion Topical
Solution
Intravenous
Tablet Oral
Tablet, extended release Oral
Prices
Unit description
Cost
Unit
193.2 USD
kit
89.86 USD
bottle
80.87 USD
tube
74.0 USD
tube
68.53 USD
tube
DrugBank does not sell nor buy drugs. Pricing information is supplied for
informational purposes only.
Patents
Country
Patent Number
United States
6881726
2002-02-21 2022-02-21
United States
5536743
1993-07-16 2013-07-16
Canada
2470492
2010-02-23 2022-11-07
Canada
2161737
1998-10-20 2015-10-30
Properties
State solid
Approved
Expires (estimated)
Melting point
160 oC
Experimental Properties
water solubility
Property
<0.1g/100mL
logP
-0.1
logS
Value Source
PhysProp
PhysProp
Predicted Properties
water solubility
PhysProp
Property
5.92e+00 g/l
logP
-0.15 ALOGPS
logP
logS
-1.5
ALOGPS
pKa
ChemAxon Molconvert
Value Source
ALOGPS
ChemAxon Molconvert
ChemAxon Molconvert
ChemAxon Molconvert
References
Synthesis Reference
Not Available
Resource
Link
4173
PubChem Substance
46508911
ChemSpider 4029
ChEBI 6909
ChEMBL
6909
DAP000534
649074
RxList http://www.rxlist.com/cgi/generic/metron.htm
Drugs.com
http://www.drugs.com/metronidazole.html
Wikipedia
http://en.wikipedia.org/wiki/Metronidazole
ATC Codes
A01AB17
D06BX01
G01AF01
J01XD01
P01AB01
AHFS Codes 84:04.92
84:04.04
08:30.92
PDB Entries Not Available
FDA label
Drug Interaction
Metronidazole may increase the anticoagulant effect of
Butethal
Carbamazepine
Dicumarol
Dihydroquinidine barbiturate
The barbiturate, dihydroquinidine barbiturate,
decreases the effect of metronidazole.
Disulfiram
Methohexital
metronidazole.
Methylphenobarbital
The barbiturate, methylphenobarbital, decreases the
effect of metronidazole.
Pentobarbital
metronidazole.
Phenobarbital
metronidazole.
Primidone
Quinidine barbiturate
The barbiturate, quinidine barbiturate, decreases the
effect of metronidazole.
Secobarbital The barbiturate, secobarbital, decreases the effect of metronidazole.
Tacrolimus
Talbutal
Food Interactions
Avoid alcohol.
1. DNA
Pharmacological action: yes
Actions: binder
References:
Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev
Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of
drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Salles JM, Salles MJ, Moraes LA, Silva MC: Invasive amebiasis: an update on
diagnosis and management. Expert Rev Anti Infect Ther. 2007 Oct;5(5):893-901.
Pubmed
Li AQ, Dai N, Yan J, Zhu YL: [Screening for metronidazole-resistance associated gene
fragments of Helicobacter pylori by suppression subtractive hybridization.] Zhejiang
Da Xue Xue Bao Yi Xue Ban. 2007 Sep;36(5):465-9. Pubmed
Edwards DI: Nitroimidazole drugsaction and resistance mechanisms. I.
Mechanisms of action. J Antimicrob Chemother. 1993 Jan;31(1):9-20. Pubmed
References:
Sisson G, Jeong JY, Goodwin A, Bryden L, Rossler N, Lim-Morrison S, Raudonikiene A,
Berg DE, Hoffman PS: Metronidazole activation is mutagenic and causes DNA
fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H.
pylori RdxA(+) (Nitroreductase) gene. J Bacteriol. 2000 Sep;182(18):5091-6.
Pubmed
Chisholm SA, Owen RJ: Mutations in Helicobacter pylori rdxA gene sequences may
not contribute to metronidazole resistance. J Antimicrob Chemother. 2003
Apr;51(4):995-9. Epub 2003 Mar 13. Pubmed
Debets-Ossenkopp YJ, Pot RG, van Westerloo DJ, Goodwin A, Vandenbroucke-Grauls
CM, Berg DE, Hoffman PS, Kusters JG: Insertion of mini-IS605 and deletion of
adjacent sequences in the nitroreductase (rdxA) gene cause metronidazole
resistance in Helicobacter pylori NCTC11637. Antimicrob Agents Chemother. 1999
Nov;43(11):2657-62. Pubmed
Pisharath H, Parsons MJ: Nitroreductase-mediated cell ablation in transgenic
zebrafish embryos. Methods Mol Biol. 2009;546:133-43. Pubmed
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN,
Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Pubmed
References:
Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev
Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of
drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Kutty R, Bennett GN: Studies on inhibition of transformation of 2,4,6-trinitrotoluene
catalyzed by Fe-only hydrogenase from Clostridium acetobutylicum. J Ind Microbiol
Biotechnol. 2006 May;33(5):368-76. Epub 2006 Jan 28. Pubmed
Enzymes
References:
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S,
Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on
Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions.
Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24.
Pubmed
References:
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S,
Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on
Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions.
Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24.
Pubmed
Actions: inhibitor
(. Metronidazolum, : 1-(b-)-2-5-)
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Reactii adverse: Greata, gust metalic, limba incarcata, cefalee (relativ frecvent),
diaree, uscaciunea gurii, neplacere epigastrica, varsaturi, arsuri vaginale, eruptii
cutanate, ameteli, somnolenta, leucopenie trecatoare (rareori); febra, congestie
nazala, disurie, scaderea libidoului, polinevrita, vertij, ataxie, convulsii (foarte rar).
Contraindicatii si precautii: Metronidazolul este contraindicat la bolnavii cu discrazii
sanguine (tratamentul se face sub controlul hemoleucogramei), psihoze si boli
neurologice active, alergie la medicamente; se evita in primele 3 luni de sarcina si
prudenta in continuare; nu se administreaza la lauze si in perioada de alaptare.
[Cina SJ et al; : Am J Forensic Med Pathol 17 (4): 343-6 (1996)] **PEER REVIEWED**
PubMed Abstract
/CASE REPORTS/ Peripheral neuropathy was reported in 33 year old male with
Crohn's disease. Patient had been taking metronidazole in dosage of 400 mg 3
times daily for 6 months.
[Bradley WG et al; Br Med J 2: 610 (1977)] **PEER REVIEWED** PubMed Abstract
Drug Warnings:
Metronidazole crosses the placenta and enters the fetal circulation rapidly.
Adequate and well-controlled studies in humans have not been done. ... However,
the use of metronidazole in the treatment of trichomoniasis is not recommended
during the first trimester. If metronidazole is used during the second and the third
trimesters for trichomoniasis it is recommended that its use be limited to those
patients whose symptoms are not controlled by local palliative treatment. Also, the
1 day course of therapy should not be used since this results in higher maternal and
fetal serum concentrations.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2070] **PEER REVIEWED**
Furry tongue, glossitis, and stomatitis have been reported with oral metronidazole
and may be due to overgrowth of Candida which may occur during metronidazole
therapy. Candidiasis was reported in 3% of nonpregnant women receiving oral
metronidazole (administered as extended-release tablets) for the treatment of
bacterial vaginosis.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Upper respiratory tract infection, rhinitis, sinusitis, and pharyngitis were each
reported in less than 5% of nonpregnant women receiving oral metronidazole
(administered as extended-release tablets) for the treatment of bacterial vaginosis.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Flattening of the T-wave has been reported rarely in ECG tracings of patients
receiving oral metronidazole.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Although a definite causal relationship to the drug has not been established,
bacterial infection and flu-like symptoms have been reported in 7 and 6%,
respectively, of nonpregnant women receiving oral metronidazole (administered as
extended-release tablets) for the treatment of bacterial vaginosis. Myopia in a
woman receiving metronidazole for trichomoniasis also has been associated with,
but not causally related to, the drug.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
... Metronidazole should be used with caution in patients with evidence or a history
of blood dyscrasias, and total and differential leukocyte counts should be performed
before and after treatment with the drug, especially when repeated courses of
therapy are necessary.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Metronidazole should be used with caution and in reduced dosage in patients with
severe hepatic impairment. The manufacturers recommend that plasma
... Safe use of IV metronidazole in children for any indication and safe use of oral
metronidazole in children for any indication except amebiasis have not been
established; however, oral metronidazole has been used in children for indications
other than amebiasis (e.g., trichomoniasis, giardiasis) without unusual adverse
effects. The AAP and other clinicians recommend that children with trichomoniasis
be treated with oral metronidazole.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
... The CDC, and other experts state that use of the drug during the first trimester
of pregnancy is contraindicated. Although evidence from case-controlled studies,
pooled analysis of cohort and case-controlled studies, and other information,
including some experience during first-trimester exposure, suggests that
metronidazole is not associated with a clinically important teratogenic or fetotoxic
risk, conflicting evidence potentially implicating an association between the drug
and certain fetal effects (e.g., cleft palate) also has been reported.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well
controlled studies in pregnant women have not shown increased risk of fetal
abnormalities despite adverse findings in animals, or, in the absence of adequate
human studies, animal studies show no fetal risk. The chance of fetal harm is
remote but remains a possibility./
**PEER REVIEWED**
Medical Surveillance:
PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in
particular when exposure to a carcinogen has occurred, ad hoc decisions should be
taken concerning ... /cytogenetic and/or other/ tests that might become useful or
mandatory. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer,
A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the
Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France:
International Agency for Research on Cancer, 1979., p. 23] **PEER REVIEWED**
Metronidazole crosses the placenta and enters the fetal circulation rapidly.
Adequate and well-controlled studies in humans have not been done. ... However,
the use of metronidazole in the treatment of trichomoniasis is not recommended
during the first trimester. If metronidazole is used during the second and the third
trimesters for trichomoniasis it is recommended that its use be limited to those
patients whose symptoms are not controlled by local palliative treatment. Also, the
1 day course of therapy should not be used since this results in higher maternal and
fetal serum concentrations.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2070] **PEER REVIEWED**
/SIGNS AND SYMPTOMS/ Some patients receiving metronidazole experience ... incr
in blood pressure caused by release of sympathomimetic amines.
[American Medical Association, AMA Department of Drugs, AMA Drug Evaluations.
3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 1066] **PEER
REVIEWED**
/CASE REPORTS/ Peripheral neuropathy was reported in 33 year old male with
Crohn's disease. Patient had been taking metronidazole in dosage of 400 mg 3
times daily for 6 months.
[Bradley WG et al; Br Med J 2: 610 (1977)] **PEER REVIEWED** PubMed Abstract
Drug Warnings:
Metronidazole crosses the placenta and enters the fetal circulation rapidly.
Adequate and well-controlled studies in humans have not been done. ... However,
the use of metronidazole in the treatment of trichomoniasis is not recommended
during the first trimester. If metronidazole is used during the second and the third
trimesters for trichomoniasis it is recommended that its use be limited to those
patients whose symptoms are not controlled by local palliative treatment. Also, the
1 day course of therapy should not be used since this results in higher maternal and
fetal serum concentrations.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2070] **PEER REVIEWED**
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 889]
**PEER REVIEWED**
Furry tongue, glossitis, and stomatitis have been reported with oral metronidazole
and may be due to overgrowth of Candida which may occur during metronidazole
therapy. Candidiasis was reported in 3% of nonpregnant women receiving oral
metronidazole (administered as extended-release tablets) for the treatment of
bacterial vaginosis.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Upper respiratory tract infection, rhinitis, sinusitis, and pharyngitis were each
reported in less than 5% of nonpregnant women receiving oral metronidazole
(administered as extended-release tablets) for the treatment of bacterial vaginosis.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Flattening of the T-wave has been reported rarely in ECG tracings of patients
receiving oral metronidazole.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Although a definite causal relationship to the drug has not been established,
bacterial infection and flu-like symptoms have been reported in 7 and 6%,
respectively, of nonpregnant women receiving oral metronidazole (administered as
extended-release tablets) for the treatment of bacterial vaginosis. Myopia in a
woman receiving metronidazole for trichomoniasis also has been associated with,
but not causally related to, the drug.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
... Metronidazole should be used with caution in patients with evidence or a history
of blood dyscrasias, and total and differential leukocyte counts should be performed
before and after treatment with the drug, especially when repeated courses of
therapy are necessary.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Metronidazole should be used with caution and in reduced dosage in patients with
severe hepatic impairment. The manufacturers recommend that plasma
metronidazole concentrations be monitored in patients with severe hepatic
impairment. The manufacturers state that commercially available metronidazole
injection should be used with caution in patients receiving corticosteroids and in
patients predisposed to edema because the injection contains 28 mEq of sodium
per gram of metronidazole.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
... Safe use of IV metronidazole in children for any indication and safe use of oral
metronidazole in children for any indication except amebiasis have not been
established; however, oral metronidazole has been used in children for indications
other than amebiasis (e.g., trichomoniasis, giardiasis) without unusual adverse
effects. The AAP and other clinicians recommend that children with trichomoniasis
be treated with oral metronidazole.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
... The CDC, and other experts state that use of the drug during the first trimester
of pregnancy is contraindicated. Although evidence from case-controlled studies,
pooled analysis of cohort and case-controlled studies, and other information,
including some experience during first-trimester exposure, suggests that
metronidazole is not associated with a clinically important teratogenic or fetotoxic
risk, conflicting evidence potentially implicating an association between the drug
and certain fetal effects (e.g., cleft palate) also has been reported.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well
controlled studies in pregnant women have not shown increased risk of fetal
abnormalities despite adverse findings in animals, or, in the absence of adequate
human studies, animal studies show no fetal risk. The chance of fetal harm is
remote but remains a possibility./
**PEER REVIEWED**
Medical Surveillance:
PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in
particular when exposure to a carcinogen has occurred, ad hoc decisions should be
taken concerning ... /cytogenetic and/or other/ tests that might become useful or
mandatory. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer,
A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the
Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France:
International Agency for Research on Cancer, 1979., p. 23] **PEER REVIEWED**
Metronidazole crosses the placenta and enters the fetal circulation rapidly.
Adequate and well-controlled studies in humans have not been done. ... However,
the use of metronidazole in the treatment of trichomoniasis is not recommended
during the first trimester. If metronidazole is used during the second and the third
trimesters for trichomoniasis it is recommended that its use be limited to those
patients whose symptoms are not controlled by local palliative treatment. Also, the
1 day course of therapy should not be used since this results in higher maternal and
fetal serum concentrations.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2070] **PEER REVIEWED**
The following Overview, *** METRONIDAZOLE AND RELATED AGENTS ***, is relevant
for this HSDB record chemical.
Life Support:
o This overview assumes that basic life support measures
have been instituted.
Clinical Effects:
0.2.1 SUMMARY OF EXPOSURE
A) USES: Metronidazole is a synthetic 5-nitroimidazole
compound. Secnidazole and tinidazole are related
compounds and are long-acting 5-nitroimidazole
derivatives. These drugs have antiprotozoal and
antibacterial activity and are used in the treatment of
protozoal and anaerobic bacterial infections.
Metronidazole and tinidazole are used for the treatment
of trichomoniasis, amebic liver abscesses, intestinal
amebiasis, pelvic inflammatory disease, bacterial
vaginosis, giardiasis, and Clostridium
difficile-associated diarrhea as well as for
perioperative prophylaxis. Secnidazole is used to treat
giardiasis, intestinal amebiasis, bacterial vaginosis,
and vaginal trichomoniasis, but secnidazole is not
seizures.
E) ANTIDOTE
1) None.
F) NAUSEA
1) Antiemetics may be used to control nausea.
G) TACHYCARDIA
1) If the patient cannot tolerate fluids, IV fluids can be
given. If anxiety from a disulfiram-like reaction is
present, a benzodiazepine can be given.
H) HYPOTENSION
1) If patient is hypotensive, it is either from a
disulfiram-like reaction or a co-ingestant. Secure
intravenous access and put patient in supine position.
Initiate treatment with IV fluids. Initiate pressors if
necessary and titrate to a mean arterial pressure of at
least 60 mmHg. If a pressor is needed to increase blood
pressure, a direct-acting agent such as norepinephrine
or epinephrine is best. Insert foley bladder catheter
and monitor urine output.
I) HEADACHE
1) Oral analgesics can be given if tolerated. If the
patient is nauseated, IV analgesics can be given.
J) SEIZURES
1) Seizures are rare and often self-limited but may be a
result of CNS stimulation. Treatment includes IV
benzodiazepines. If seizures persist, use propofol or
barbiturates.
K) ENHANCED ELIMINATION
1) Hemodialysis and hemoperfusion are UNLIKELY to be of
compared to 7 patients with Crohn's disease not treated with metronidazole and 10
healthy controls.
[Mitelman F et al; Lancet 2: 802 (1976)] **PEER REVIEWED** PubMed Abstract
Ecotoxicity Values:
LD50 Anas platyrhynchos (Mallard duck, 19 weeks old) oral >5000 mg/kg
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
LC50 Anas platyrhynchos (Mallard duck, 17 days old) diet >5000 ppm/8 days
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
LC50 Colinus virginianus (Bobwhite quail, 12 days old) diet >5000 ppm/8 days
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
LC50 Americamysis bahia (Opossum shrimp, age 2 days) 182 ppm/96 hr (95%
confidence limit: 140-230 ppm); static /98% AI formulated product/
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
LC50 Cyprinodon variegatus (Sheepshead minnow, weight 0.46 g) 1060 ppm/96 hr;
static /98% AI formulated product/
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
EC50 Daphnia magna (Water flea, age <24 hr; intoxication, immobilization) >1000
ppm/48 hr; static /99% AI formulated product/
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
LC50 Lepomis macrochirus (Bluegill sunfish, weight 0.1g) >100 ppm/96 hr; static /
99.4% AI formulated product/
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
LC50 Oncorhynchus mykiss (Rainbow trout, weight 0.3 g) >100 ppm/96 hr; static /
99.4% AI formulated product/
[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 2Methyl-5-nitro-1H-imidazole-1-ethanol (443-48-1). Available from, as of May 10,
2006: http://cfpub.epa.gov/ecotox/quick_query.htm **PEER REVIEWED**
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
Approximately 30-60% of an oral or IV dose of metronidazole is metabolized in the
liver by hydroxylation, side-chain oxidation, and glucuronide conjugation. The major
metabolite, 2-hydroxy metronidazole, has some antibacterial and antiprotozoal
activity.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 892]
**PEER REVIEWED**
... Four other nitro-group-containing metabolites have been identified, each derived
from side-chain oxidation of ethyl and/or methyl group. They include 1-acetic acid-2methyl-5-nitroimidazole and 1-(2-hydroxyethyl)-2-carboxylic acid-5-nitroimidazole
salt.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer,
1972-PRESENT. (Multivolume work). Available at:
http://monographs.iarc.fr/index.php p. V13 118 (1977)] **PEER REVIEWED**
The liver is the main site of metabolism, and this accounts for over 50% of the
systemic clearance of metronidazole. The 2 principal metabolites result from
oxidation of side chains, a hydroxy derivative and an acid. The hydroxy metabolite
has a longer half-life (about 12 hr) and nearly 50% of the antitrichomonal activity of
metronidazole. Formation of glucuronides also is observed. Small quantities of
reduced metabolites, including ring-cleavage products, are formed by the gut flora.
The urine of some patients may be reddish-brown owing to the presence of
unidentified pigments derived from the drug.
[Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The
Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001.,
p. 1106] **PEER REVIEWED**
Distributed to saliva, bile, seminal fluid, breast milk, bone, liver and liver abscesses,
lungs, and vaginal secretions; crosses the placenta and blood-brain barrier, also.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2069] **PEER REVIEWED**
Following oral administration of metronidazole 750 mg once daily as the extendedrelease tablet for 7 consecutive days in healthy, adult women, steady-state peak
plasma concentrations average 12.5 mcg/mL and are attained an average of 6.8
hours after the dose when the drug is given under fasting conditions; when the drug
is given at the same dosage under nonfasting conditions, steady-state peak plasma
concentrations average 19.4 mcg/mL and are attained an average of 4.6 hours after
the dose. Administration of metronidazole extended-release tablets with food
increases the rate of absorption and peak plasma concentrations of the drug.
According to the manufacturer, metronidazole extended-release and conventional
tablets are bioequivalent at a dose of 750 mg given under fasting conditions.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 892]
**PEER REVIEWED**
Metronidazole is widely distributed into most body tissues and fluids including
bone, bile, saliva, pleural fluid, peritoneal fluid, vaginal secretions, seminal fluid,
CSF, and cerebral and hepatic abscesses. Distribution is similar whether the drug is
administered orally or by IV infusion. Concentrations of metronidazole in CSF are
reported to be 43% of concurrent plasma concentrations in patients with uninflamed
meninges and equal to or greater than concurrent plasma concentrations of the
drug in patients with inflamed meninges. The drug also distributes into
erythrocytes. Limited data suggest that the volume of distribution of metronidazole
may be reduced in geriatric individuals as compared with younger individuals,
perhaps as a result of decreased erythrocyte uptake of the drug in such patients.
Metronidazole is less than 20% bound to plasma proteins.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 892]
**PEER REVIEWED**
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 892]
**PEER REVIEWED**
Whole-body arg /Autoradiography/ showed that IV or oral dose of ... (14)Cmetronidazole crossed blood-brain and placental barriers in pregnant mice. Uptake
from blood was rapid. Level of (14)C in maternal brain and fetus were similar to
those in maternal blood.
[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A
Review of the Literature Published Between 1970 and 1971. London: The Chemical
Society, 1972., p. 110] **PEER REVIEWED**
Biological Half-Life:
Half-life: Neonates 25-75 hours; Others: 6-8 hours, increases with hepatic
impairment.
[Lelkin, J.B., Paloucek, F.P., Poisoning & Toxicology Compendium. LEXI-COMP Inc. &
American Pharmaceutical Association, Hudson, OH 1998., p. 390] **PEER
REVIEWED**
Mechanism of Action:
Microbicidal; active against most obligate anaerobic bacteria and protozoa by
undergoing intracellular chemical reduction via mechanisms unique to anaerobic
metabolism. Reduced metronidazole, which is cytotoxic but short-lived, interacts
with DNA to cause loss of helical structure, strand breakage, and resultant inhibition
of nucleic acid synthesis and cell death.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2069] **PEER REVIEWED**
Results of in vitro studies using leukocytes obtained from patients with Crohns
disease indicate that exposing the cells to metronidazole concentrations of 10 or 50
mcg/mL improved both spontaneous and induced leukocyte migration in cells that
previously exhibited reduced migration; the drug had no effect on leukocytes
obtained from healthy adults or patients with Crohns disease when the cells
exhibited normal migration prior to exposure to the drug. This effect on leukocyte
migration also was observed in vivo in adults with Crohn's disease who received a
single 400-mg dose of metronidazole. It has been suggested that metronidazole
may increase leukocyte migration by a direct effect on the leukocytes, possibly by
causing the release of surface-bound immune complexes from the cell surface.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 891]
**PEER REVIEWED**
Interactions:
It is recommended that metronidazole not be used concurrently with, or for at least
1 day following, ingestion of alcohol; accumulation of acetaldehyde by interference
with the oxidation of alcohol may occur, resulting in disulfiram-like effects such as
abdominal cramps, nausea, vomiting, headache, or flushing; in addition,
modifications in the taste of alcoholic beverages have been reported during
concurrent use.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2070] **PEER REVIEWED**
Pharmacology:
Therapeutic Uses:
Mesh Heading: Anti-infective agents, antiprotozoal agents, radiation-sensitizing
agents
[National Library of Medicine, SIS; ChemIDplus Record for <<insert chemical name
here; for example: Osmium>> <<(CAS#) i.e.(7440-04-2).>> Available from the
search page at http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp as of <<date
info was found; i.e. March 18, 2005>>.] **PEER REVIEWED**
Metronidazole is indicated in the treatment of skin and soft tissue infections caused
by Bacteroides species, including the Bacteroides fragilis group. Clostridium species,
Fusobacterium species, Peptococcus species, and Peptostreptococcus species.
/Included in US product labeling/
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2069] **PEER REVIEWED**
Drug Warnings:
Metronidazole crosses the placenta and enters the fetal circulation rapidly.
Adequate and well-controlled studies in humans have not been done. ... However,
the use of metronidazole in the treatment of trichomoniasis is not recommended
during the first trimester. If metronidazole is used during the second and the third
trimesters for trichomoniasis it is recommended that its use be limited to those
patients whose symptoms are not controlled by local palliative treatment. Also, the
1 day course of therapy should not be used since this results in higher maternal and
fetal serum concentrations.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2070] **PEER REVIEWED**
Furry tongue, glossitis, and stomatitis have been reported with oral metronidazole
and may be due to overgrowth of Candida which may occur during metronidazole
therapy. Candidiasis was reported in 3% of nonpregnant women receiving oral
metronidazole (administered as extended-release tablets) for the treatment of
bacterial vaginosis.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Upper respiratory tract infection, rhinitis, sinusitis, and pharyngitis were each
reported in less than 5% of nonpregnant women receiving oral metronidazole
(administered as extended-release tablets) for the treatment of bacterial vaginosis.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Flattening of the T-wave has been reported rarely in ECG tracings of patients
receiving oral metronidazole.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Although a definite causal relationship to the drug has not been established,
bacterial infection and flu-like symptoms have been reported in 7 and 6%,
respectively, of nonpregnant women receiving oral metronidazole (administered as
extended-release tablets) for the treatment of bacterial vaginosis. Myopia in a
woman receiving metronidazole for trichomoniasis also has been associated with,
but not causally related to, the drug.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
... Metronidazole should be used with caution in patients with evidence or a history
of blood dyscrasias, and total and differential leukocyte counts should be performed
before and after treatment with the drug, especially when repeated courses of
therapy are necessary.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
Metronidazole should be used with caution and in reduced dosage in patients with
severe hepatic impairment. The manufacturers recommend that plasma
... Safe use of IV metronidazole in children for any indication and safe use of oral
metronidazole in children for any indication except amebiasis have not been
established; however, oral metronidazole has been used in children for indications
other than amebiasis (e.g., trichomoniasis, giardiasis) without unusual adverse
effects. The AAP and other clinicians recommend that children with trichomoniasis
be treated with oral metronidazole.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
... The CDC, and other experts state that use of the drug during the first trimester
of pregnancy is contraindicated. Although evidence from case-controlled studies,
pooled analysis of cohort and case-controlled studies, and other information,
including some experience during first-trimester exposure, suggests that
metronidazole is not associated with a clinically important teratogenic or fetotoxic
risk, conflicting evidence potentially implicating an association between the drug
and certain fetal effects (e.g., cleft palate) also has been reported.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 890]
**PEER REVIEWED**
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well
controlled studies in pregnant women have not shown increased risk of fetal
abnormalities despite adverse findings in animals, or, in the absence of adequate
human studies, animal studies show no fetal risk. The chance of fetal harm is
remote but remains a possibility./
**PEER REVIEWED**
Interactions:
It is recommended that metronidazole not be used concurrently with, or for at least
1 day following, ingestion of alcohol; accumulation of acetaldehyde by interference
with the oxidation of alcohol may occur, resulting in disulfiram-like effects such as
abdominal cramps, nausea, vomiting, headache, or flushing; in addition,
modifications in the taste of alcoholic beverages have been reported during
concurrent use.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1,
Greenwood Village, CO. 2006., p. 2070] **PEER REVIEWED**
Drug Tolerance:
Natural and acquired resistances to metronidazole have been reported occasionally
in some strains of Trichomonas vaginalis. Although the clinical importance is
unclear, in vitro studies indicate that while some T. vaginalis isolates with reduced
susceptibility to metronidazole also have reduced susceptibility to tinidazole, the
minimum lethal concentration (MLC) of tinidazole for these strains may be lower
than the MLC of metronidazole. Rarely, resistance to the drug also has been
reported in Bacteroides fragilis and other anaerobic bacteria following long-term
therapy. There has been at least one report of a strain of metronidazole-resistant B.
fragilis that was cross-resistant in vitro to amoxicillin and clavulanate potassium,
imipenem, and tetracycline; the strain was susceptible to chloramphenicol and
clindamycin in vitro. Resistance to metronidazole may be due to poor cell
penetration and/or decreased nitroreductase activity.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 892]
**PEER REVIEWED**
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of
23(SRC), determined from a log Kow of -0.02(2) and a regression-derived
equation(3), indicates that metronidazole is expected to have very high mobility in
soil(SRC). Volatilization of metronidazole from moist soil surfaces is not expected to
be an important fate process(SRC) given an estimated Henry's Law constant of
Environmental Biodegradation:
AEROBIC: The biodegradation half-lives in sandy soil-manure slurry were 9.7 to 14.7
days and in clay soil-manure slurry were 13.1 to 26.9 days(1). Metronidazole was
found to be non-degradable in sewage treatment conditions(2). Metronidazole did
not degrade in closed bottle tests at concentrations of 5.95 ug/L and 5.95 mg/L(3).
[(1) Ingerslev F, Halling-Sorensen B; Ecotox Environ Safety 48: 311-20 (2001) (2)
Richardson ML, Bowron JM; J Pharm Pharmacol 37: 1-12 (1985) (3) Alexy R et al;
Chemosphere 57: 505-12 (2004)] **PEER REVIEWED**
Environmental Bioconcentration:
[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants.
ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 22
(1995) (2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999) (3) Franke C et
al; Chemosphere 29: 1501-14 (1994)] **PEER REVIEWED**
Soil Adsorption/Mobility:
The Koc of metronidazole is estimated as 23(SRC), using a log Kow of -0.02(1) and a
regression-derived equation(2). According to a classification scheme(3), this
estimated Koc value suggests that metronidazole is expected to have very high
mobility in soil.
[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants.
ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 22
(1995) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods.
Washington, DC: Amer Chem Soc pp. 4-9 (1990) (3) Swann RL et al; Res Rev 85: 1728 (1983)] **PEER REVIEWED**
Effluent Concentrations:
FIFRA Requirements:
As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive
review of older pesticides to consider their health and environmental effects and
make decisions about their future use. Under this pesticide reregistration program,
EPA examines health and safety data for pesticide active ingredients initially
registered before November 1, 1984, and determines whether they are eligible for
reregistration. In addition, all pesticides must meet the new safety standard of the
Food Quality Protection Act of 1996. Pesticides for which EPA had not issued
Registration Standards prior to the effective date of FIFRA, as amended in 1988,
were divided into three lists based upon their potential for human exposure and
other factors, with List B containing pesticides of greater concern and List D
pesticides of less concern. Metronidazole is found on List C. Case No: 3096;
Pesticide type: antimicrobial; Case Status: No products containing the pesticide are
actively registered ... The case /is characterized/ as "cancelled." Under FIFRA,
pesticide producers may voluntarily cancel their registered products. EPA also may
cancel pesticide registrations if registrants fail to pay required fees or make/meet
certain reregistration commitments, or if EPA reaches findings of unreasonable
adverse effects.; Active ingredient (AI): metronidazole; Data Call-in (DCI) Date(s):
09/23/93; AI Status: The active ingredient is no longer contained in any registered
pesticide products ... "cancelled."
[United States Environmental Protection Agency/ Prevention, Pesticides and Toxic
Substances; Status of Pesticides in Registration, Reregistration, and Special Review.
(1998) EPA 738-R-98-002, p. 265] **PEER REVIEWED**
FDA Requirements:
Chemical/Physical Properties:
Molecular Formula:
C6-H9-N3-O3
**PEER REVIEWED**
Molecular Weight:
171.15
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p.
1095] **PEER REVIEWED**
Color/Form:
Cream-colored crystals
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p.
1095] **PEER REVIEWED**
Odor:
ODORLESS
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th
ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1161] **PEER REVIEWED**
Melting Point:
158-160 deg C
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p.
1095] **PEER REVIEWED**
Dissociation Constants:
pKa = 2.38
[Tolls J; Environ Sci Technol 35: 3397-406 (2001)] **PEER REVIEWED** PubMed
Abstract
pH:
pH of saturated aq soln is 5.8
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p.
1095] **PEER REVIEWED**
Solubilities:
g/100 ml at 20 deg C: 1.0 in water, 0.5 in ethanol, less than 0.05 in ether,
chloroform; sol in dilute acids; sparingly sol in dimethylformamide
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p.
1096] **PEER REVIEWED**
Spectral Properties:
IR: 14987 (Sadtler Research Laboratories IR Grating Collection)
[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I.
3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 3207] **PEER REVIEWED**
UV: 2561 (Absorption Spectra in the UV and visible Regions, Academic Press, New
York)
[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I.
3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 3207] **PEER REVIEWED**
Intense mass spectral peaks: 54 m/z, 81 m/z, 124 m/z, 171 m/z
[Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons
and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal
Republic of Germany. 1985., p. 244] **PEER REVIEWED**
Vapor Pressure:
3.1X10-7 mm Hg at 25 deg C (est)
[US EPA; Estimation Program Interface (EPI) Suite. Ver.3.12. Nov 30, 2004. Available
from, as of Dec 21, 2005: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
**PEER REVIEWED**
solutions may occur when they are in contact with aluminum for periods of 6 hours
or longer.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 893]
**PEER REVIEWED**
Preventive Measures:
PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or
of food & beverage containers or utensils, & the application of cosmetics should be
prohibited in any laboratory. All personnel should remove gloves, if worn, after
completion of procedures in which carcinogens have been used. They should ...
wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly.
Consideration should be given to appropriate methods for cleaning the skin,
depending on nature of the contaminant. No standard procedure can be
recommended, but the use of organic solvents should be avoided. Safety pipettes
should be used for all pipetting. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer,
A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the
Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France:
International Agency for Research on Cancer, 1979., p. 8] **PEER REVIEWED**
Stability/Shelf Life:
Stable in air but darkens on exposure to light.
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th
ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1161] **PEER REVIEWED**
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 893]
**PEER REVIEWED**
Storage Conditions:
PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to
lab in which carcinogens are to be used, so that only small quantities required for ...
expt need to be carried. Carcinogens should be kept in only one section of
cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical
properties ...) that bears appropriate label. An inventory ... should be kept, showing
quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should
be contiguous to storage area. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer,
A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the
Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France:
International Agency for Research on Cancer, 1979., p. 13] **PEER REVIEWED**
Cleanup Methods:
PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or
charcoal filters can be used to minimize amt of carcinogen in exhausted air
ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing
that is designed so that used filters can be transferred into plastic bag without
contaminating maintenance staff is avail commercially. Filters should be placed in
plastic bags immediately after removal ... The plastic bag should be sealed
immediately ... The sealed bag should be labelled properly ... Waste liquids ...
should be placed or collected in proper containers for disposal. The lid should be
secured & the bottles properly labelled. Once filled, bottles should be placed in
plastic bag, so that outer surface ... is not contaminated ... The plastic bag should
also be sealed & labelled. ... Broken glassware ... should be decontaminated by
solvent extraction, by chemical destruction, or in specially designed incinerators.
/Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer,
A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the
Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France:
International Agency for Research on Cancer, 1979., p. 15] **PEER REVIEWED**
Disposal Methods:
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill)
disposal practices are subject to significant revision. Prior to implementing land
disposal of waste residue (including waste sludge), consult with environmental
regulatory agencies for guidance on acceptable disposal practices.
**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can
be destroyed using chem reactions ... but no general rules can be given. ... As a
general technique ... treatment with sodium dichromate in strong sulfuric acid can
be used. The time necessary for destruction ... is seldom known ... but 1-2 days is
generally considered sufficient when freshly prepd reagent is used. ... Carcinogens
that are easily oxidizable can be destroyed with milder oxidative agents, such as
saturated soln of potassium permanganate in acetone, which appears to be a
suitable agent for destruction of hydrazines or of compounds containing isolated
carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also
be used as an oxidizing agent. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer,
A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the
Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France:
International Agency for Research on Cancer, 1979., p. 16] **PEER REVIEWED**
Manufacturing/Use Information:
Major Uses:
For Metronidazole (USEPA/OPP Pesticide Code: 120401) there are 0 labels match.
/SRP: Not registered for current use in the U.S., but approved pesticide uses may
change periodically and so federal, state and local authorities must be consulted for
currently approved uses./
[National Pesticide Informaton Retrieval System's USEPA/OPP Chemical Ingredients
Database on Metronidazole (443-48-1). Available from, as of April 20, 2006:
http://ppis.ceris.purdue.edu/htbin/epachem.com **PEER REVIEWED**
The active ingredient is no longer contained in any registered pesticide products ...
"cancelled."
[United States Environmental Protection Agency/ Prevention, Pesticides and Toxic
Substances; Status of Pesticides in Registration, Reregistration, and Special Review.
(1998) EPA 738-R-98-002, p. 265] **PEER REVIEWED**
Manufacturers:
3M Pharmaceuticals, 3M Center, Bldg. 275-6W-13, P.O. Box 33275, St. Paul, MN
55144, (880)447-4537
[SRI Consulting. 2005 Directory of Chemical Producers - United States, Menlo Park,
CA. 2005, p. 1822] **PEER REVIEWED**
Galderma Laboratories, L.P., 14501 North Freeway, Ft. Worth, TX 76177 (800) 5828225
[SRI Consulting. 2005 Directory of Chemical Producers - United States, Menlo Park,
CA. 2005, p. 1212] **PEER REVIEWED**
Watson Laboratories, Inc., 311 Bonnie Circle, Corona, CA 92880, (800) 760-9224
[SRI Consulting. 2005 Directory of Chemical Producers - United States, Menlo Park,
CA. 2005, p. 3376] **PEER REVIEWED**
Methods of Manufacturing:
Jacob et al., US patent 2,944,061 (1960 to Rhone-Poulenc)
[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p.
1097] **PEER REVIEWED**
Metronidizole is prepared by heating 2-methyl-5-nitroimidizole with excess 2chloroethanol to obtain the crude product which is purified by extraction with
chloroform and recrystallization from ethyl acetate.
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New
York, NY: John Wiley and Sons, 1978-1984., p. V5 525] **PEER REVIEWED**
Formulations/Preparations:
Metronidazole, USP (flagyl), is avail as 250-mg tablets. Uncoated vaginal inserts,
each containing 500 mg, are also available.
[Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics.
5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1087] **PEER
REVIEWED**
Capsule 375 mg; Gel, topical 0.75% [7.5 mg/mL] (30 g); Gel, vaginal 0.75% (5 g
applicator delivering 37.5 mg in 70 g tube); Injection, ready to use 5 mg/mL (100
mL); Powder for injection, as hydrochloride 500 mg; Tablet 250mg, 500 mg
[Lelkin, J.B., Paloucek, F.P., Poisoning & Toxicology Compendium. LEXI-COMP Inc. &
American Pharmaceutical Association, Hudson, OH 1998., p. 391] **PEER
REVIEWED**
Capsules 375 mg, Tablets 250 mg, 500 mg Flagyl 375, Pfizer; Tablets, extendedrelease, film-coated 750 mg Flagyl ER, Pfizer; Tablets, film-coated 250 mg, 500 mg
Flagyl, Pfizer; Parenteral Injection, for IV infusion only 5 mg/mL Flagyl I.V. RTU
(Viaflex [Baxter]), SCS Pharmaceuticals.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information.
American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 893]
**PEER REVIEWED**
Laboratory Methods:
Analyte: metronidazole; matrix: blood, biological fluid; procedure: highperformance liquid chromatography with ultraviolet detection at 250 nm
[Koves EM; J Chromatogr A 692: 103-119 (1995). As cited in: Lunn G; HPLC Methods
for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000.,
p.1360] **PEER REVIEWED**
Analyte: metronidazole; matrix: blood (plasma), urine; procedure: highperformance liquid chromatography with ultraviolet detection at 338 nm; limit of
quantitation: <10 ng/mL
[Okonkwo PO, Eta EI; Life Sci 42: 539-545 (1988). As cited in: Lunn G; HPLC Methods
for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000.,
p.1356] **PEER REVIEWED**
[Lunn G et al; J Pharm Sci 83: 1289-1293 (1994). As cited in: Lunn G; HPLC Methods
for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000.,
p.1360] **PEER REVIEWED**
Multiple oral or intravenous doses given every 6 to 8 hours result in some drug
accumulation with higher serum concentrations as compared with single doses. On
an intravenous dose regimen of 500mg every 8 hours, maximum metronidazole
serum concentrations average 25 [mu]g/ml and minimum concentrations 15
[mu]g/ml. Rectal administration of metronidazole by suppository resulted in peak
serum concentrations approximately one-half those following equivalent oral doses
and occurred at 4 hours after administration; the bioavailability of the rectal
suppository was approximately 80%. From the limited data available, the systemic
absorption of intravaginal metronidazole is very slow with peak serum
concentrations of approximately 2 [mu]g/ml being attained 8 to 24 hours after
administration of a 500mg dose.
Detailed pharmacokinetic analysis of metronidazole has been performed using 1compartment and 2-compartment open models. The serum half-life of unchanged
metronidazole averaged 8.2 hours, as determined by specific chemical methods,
whereas using bioassay methods the half-life was somewhat longer. A 2compartment open model analysis described the serum concentration-time curve
with a rapid [alpha] (distribution) phase (half-life 1.24 hours) and a slower [beta]
(elimination) phase (half-life 9.76 hours). Metronidazole has a large apparent
volume of distribution and serum protein binding of 20% or less. In multiple-dose
regimens the hydroxy metabolite of metronidazole may be present in
concentrations up to 30% of those of the parent drug with a half-life of 9.7 hours.
The acid metabolite is rarely detected in serum. Metronidazole is widely distributed
throughout the body with tissue levels, in most cases, approximating serum levels.
This is especially important in the central nervous system where the drug readily
crosses both the blood-brain and blood-cerebrospinal fluid barriers.
with large doses over a prolonged period). Potentially serious toxicities including
tumourigenicity, dysmorphogenicity, and mutagenicity inferred from certain animal
models and bacterial test systems have not been confirmed in humans.
NAME
1.1 Substance
Metronidazole
(INN)
(WHO, 1992)
1.2 Group
(WHO, 1992)
1.3 Synonyms
Metronidazolo
Bayer-5630
NSC-50364
RP-8823
SC-10295
443-48-1
RTECS
NI5600000
Monocomponent products
Worldwide
Flagyl
Other names
Argentina
Australia
Canada
Denmark
Germany
Hungary
Klion
Italy
Norway
Elyzol
Poland
Entizol
Spain
Tricowas B
Sweden
Elyzol
Switzerland
Metrolag
Combination products
Entamizole D.S.
Dependal
(Reynolds, 1982)
2. SUMMARY
2.3 Diagnosis
3. PHYSICO-CHEMICAL PROPERTIES
Structural formula
Molecular formula
C6H9O3N3
Molecular weight
171.16
Chemical names
2-(2-Methyl-5-nitroimidazol-1-yl)ethanol
2-methyl-5-nitroimidazole-1-ethanol
1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole
1-( beta-ethylol)-2-methyl-5-nitro-3-azapyrrole
3.3.1.1 Colour
3.3.1.2 State/Form
Crystalline powder
3.3.1.3 Description
Injection
3 years.
Tablets
5 years
Suspension
2 years
3.4.4 Bioavailability
(Reynolds, 1993)
4. USES
4.1 Indications
4.1.1 Indications
Protozoal infections
Infections
Amoebiasis
Other
4.1.2 Description
Not relevant.
4.2.1 Adults
Oral
Trichomoniasis
2 g in single dose; or
Anaerobic infections
Giardiasis
Parenteral
Anaerobic infections
Rectal
Anaerobic infections
(Reynolds, 1993)
4.2.2 Children
Oral
Trichomoniasis
Anaerobic infections
Giardiasis
Parenteral
Anaerobic infections
Rectal
Anaerobic infections
(Reynolds, 1993)
4.3 Contraindications
5. ROUTES OF ENTRY
5.1 Oral
5.2 Inhalation
Not relevant.
5.3 Dermal
Not relevant.
5.4 Eye
Not relevant.
5.5 Parenteral
5.6 Other
6. KINETICS
Oral
Rectal
180%
135%
CSF
120%
Abdominal muscles
110%
Fallopian tube
Uterus
100%
95%
Human milk
90%
Ileum
85%
Bone
80%
Colon
70%
(Houghton et al.,1979)
6.4 Metabolism
Major metabolites are 1-(2 hydroxy-ethyl)-2-hydroxy methyl-5nitroimidazole which is active and which gives advantage in
terms of length of action, and the inactive 1-acetic acid-2methyl-5-nitroimadozole.
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
7.2 Toxicity
7.2.1.1 Adults
7.2.1.2 Children
1 to 5 g/kg.
1 to 5 g/kg.
No data available.
7.3 Carcinogenicity
7.4 Teratogenicity
In nursing mothers and neonates there have not been any well
controlled studies, but because it appears in breast milk in
concentration similar to serum, it should not be used except
for amoebiasis.
7.5 Mutagenicity
7.6 Interactions
9. CLINICAL EFFECTS
9.1.1 Ingestion
9.1.2 Inhalation
Not relevant.
Not relevant.
No data available.
9.1.6 Other
No data available.
9.2.1 Ingestion
9.2.2 Inhalation
Not relevant.
Not relevant.
Not relevant.
No data available.
9.2.6 Other
No data available.
9.4.1 Cardiovascular
No data available.
9.4.2 Respiratory
No data available.
9.4.3 Neurological
No data available.
No data available.
9.4.4 Gastrointestinal
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Other
No data available.
9.4.8 Dermatological
No data available.
No data available.
9.4.10 Haematological
9.4.11 Immunological
No data available.
9.4.12 Metabolic
No data available.
No data available.
9.4.12.3 Others
No data available.
No data available.
No data available.
No data available.
9.5 Other
No data available.
9.6 Summary
No data available.
10. MANAGEMENT
No data available.
10.4 Decontamination
10.5 Elimination
10.6.1 Adults
10.6.2 Children
Not required.
No data available.
No data available.
No data available.
No data available.
No data available.
12.3 Other
No data available.