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METRONIDAZOLE
CASRN: 443-48-1
For other data, click on the Table of Contents
Human Health Effects:
Human Toxicity Excerpts:
SOME PT 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. 1066]**PEER
REVIEWED**
SIGNIFICANT INCR IN CHROMOSOME ABERRATION FREQUENCY NOTED IN
15 PT WITH CROHN'S DISEASE UNDER TREATMENT WITH
METRONIDAZOLE 200-1200 MG/DAY COMPARED TO 7 PT WITH CROHN'S
DISEASE NOT TREATED WITH METRONIDAZOLE & 10 HEALTHY
CONTROLS.
[MITELMAN F ET AL; LANCET 2: 802 (1976)]**PEER REVIEWED**
NEUROPATHY IN 20 YR OLD GIRL IN WHICH COMPLETE SUBJECTIVE
RECOVERY HAS NOT APPARENTLY RESULTED 2 YR AFTER
DISCONTINUING DRUG IS REPORTED. PT WAS TREATED WITH 800 MG
ORALLY TWICE DAILY FOR 7 WK BEFORE DEVELOPING NUMBNESS OF
HANDS & FEET.
[HISHON S, PILLING J; BR MED J 2: 832 (1977)]**PEER REVIEWED**
PERIPHERAL NEUROPATHY WAS REPORTED IN 33 YR OLD MALE WITH
CROHN'S DISEASE. PT HAD BEEN TAKING METRONIDAZOLE IN DOSAGE
OF 400 MG 3 TIMES DAILY FOR 6 MO.
[BRADLEY WG ET AL; METRONIDAZOLE NEUROPATHY; BR MED J 2: 610
(1977)]**PEER REVIEWED**
Adults tolerate oral doses of 100 mg/kg/day for a month without toxicity. Higher doses
may produce tremor, weakness, muscle spasticity, and ataxia.
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed.
Ames, Iowa: Iowa State University Press, 1982. 885]**PEER REVIEWED**
Serious blood dyscrasia has not been recorded in humans during medication with this
blood. In an appreciable proportion of treated patients, a moderate leukopenia has been
observed. The white cell count returns to normal ... following completion of the course of
medication.
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed.
Ames, Iowa: Iowa State University Press, 1982. 885]**PEER REVIEWED**
In human patients receiving 750 mg/day, mutagenic activity was found in the urine, using
Salmonella typhimurium as a genetic indicator. A 2-4-fold increase in the occurrence of
chromosome abnormalities was observed in cultured peripheral leucocytes from patients
with Crohn's disease being treated with 200-1,200 mg/day metronidazole for 1-24
months.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 118 (1977)]**PEER REVIEWED**
Drug Warnings:
Although the drug has not been shown to be teratogenic in animals or humans, benefits
and risks should be weighed carefully before it is given to pregnant women or nursing
mothers.
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1545]**PEER REVIEWED**
.../METRONIDAZOLE/ APPEARS TO BE SPECIFIC FOR TRICHOMONADS; IT IS
INACTIVE AGAINST MONILIA ALBICANS. ...
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed.
Easton, Pennsylvania: Mack Publishing Co., 1975. 1161]**PEER REVIEWED**
TRICHOMONAS VAGINALIS WAS RESISTANT TO 2 STD SCHEDULES OF 500
MG ORALLY TWICE DAILY FOR 5 DAYS ALSO TO FURTHER TREATMENT
WITH 10 DAY COURSE OF 1.0 G TWICE DAILY.
[THURNER J, MEINGASSNER JG; ISOLATION OF TRICHOMONAS VAGINALIS
RESISTANT TO METRONIDAZOLE; LANCET 2: 738 (1978)]**PEER
REVIEWED**
Drugs Whose Effects on Nursing Infants is Unknown but may be of Concern:
Metronidazole: In vitro mutagen; may discontinue breast-feeding 12-24 h to allow
excretion of dose when single-dose therapy given to mother. /from Table 4/
[Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1):
139 (1994)]**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.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
No information is available on the relationship of age to the effects of metronidazole in
geriatric patients. However, elderly patients are more likely to have an age-related
decrease in hepatic function, which may require an adjustment in dosage in patients
receiving metronidazole.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Metronidazole may cause dry mouth, an unpleasant or sharp metallic taste, and
alteration of taste sensation. Dry mouth may contribute to the development of caries,
periodontal disease, oral candidiasis, and discomfort.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Side/Adverse Effects: Those indicating need for medical attention: Incidence less
frequent: Peripheral neuropathy (numbness, tingling, pain, or weakness in hands or feet) usually with high doses or prolonged use; seizures - usually with high doses. Incidence
rare: CNS toxicity (ataxia - clumsiness or unsteadiness; encephalopathy - mood or other
mental changes); hypersensitivity (skin rash, hives, redness, or itching); leukopenia (sore
throat and fever); pancreatitis (severe abdominal and back pain, anorexia, nausea and
vomiting); thrombophlebitis (pain, tenderness, redness, or swelling at site of injection);
vaginal candidiasis (any vaginal irritation, discharge, or dryness not present before
therapy.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1906]**PEER REVIEWED**
Side/Adverse Effects: Those indicating need for medical attention only if they continue
or are bothersome: Incidence more frequent: CNS effects (dizziness or lightheadedness,
headache); gastrointestinal disturbance (diarrhea, loss of appetite, nausea or vomiting,
stomach pain or cramps). Incidence less frequent or are: Change in taste sensation;
dryness of mouth; unpleasant or sharp metallic taste. Those not indicating need for
medical attention: Incidence less frequent or rare: Dark urine.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1906]**PEER REVIEWED**
Metronidazole is contraindicated in patients with active disease of the CNS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The
Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990.
1004]**PEER REVIEWED**
Potential adverse effects on fetus: Mutagenic in bacteria and carcinogenic in rodents. No
known teratogenicity in humans. Potential side effects on breast-fed infant: Use not
recommended in lactating mother, but breast-feeding may be resumed 48 hours after
treatment is completed. Comments: Fetal serum levels 20%-50% of maternal. FDA
Category: B (B = Studies in laboratory animals have not demonstrated a fetal risk, but
there are no controlled studies in pregnant women; or animal studies have shown an
adverse effect (other than a decrease in fertility), but controlled studies in pregnant
women have not demonstrated a risk to the fetus in the first trimester and there is no
evidence of a risk in later trimesters.) /from Table II/
[Stockton, D.L. and A.S. Paller. J Am Acad Dermatol 23 (1):87-103 (1990)]**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, 1979.23]**PEER REVIEWED**
Emergency Medical Treatment:
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The following Overview, *** METRONIDAZOLE ***, 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) OVERDOSE EFFECTS 1) Severe toxicity following acute overdosage appears to
be uncommon; single oral doses up to 15 grams have been
tolerated with minimal effects. Acute ingestion of 12
grams in a 19-year-old female did not result in
significant signs and symptoms of toxicity. Another
patient ingested 12.5 grams and only developed a
transient increase in hepatic enzymes; permanent
sequelae did not occur.
2) Dark urine (green/black) was reported following
overdose in a 15-year-old female.
B) ADVERSE EFFECTS AT THERAPEUTIC DOSE 1) Characteristic adverse effects include: nausea,
vomiting, anorexia, metallic taste, headache, vertigo
and less frequently insomnia, drowsiness, CNS
depression, and darkening of the urine. Seizures and
ototoxicity have been reported rarely.
0.2.5 CARDIOVASCULAR
A) A healthy individual developed an acute reaction with
low blood pressure following therapeutic use of
tinidazole.
0.2.7 NEUROLOGIC
A) Insomnia, vertigo, CNS depression, and rarely seizures
may be noted. Peripheral neuropathy has been noted in
children receiving chronic therapy.
0.2.8 GASTROINTESTINAL
A) Nausea, vomiting, metallic taste, anorexia, and dry
mouth may be noted. A disulfiram-like reaction may be
noted following concurrent metronidazole therapy and
ethanol ingestion.
0.2.9 HEPATIC
A) A transient increase in hepatic enzymes was reported in
one patient following overdose of metronidazole.
0.2.10 GENITOURINARY
A) Darkening of the urine may be noted rarely during
therapeutic use; it has also been reported in one case
of overdose.
0.2.13 HEMATOLOGIC
A) Leukopenia has been reported in about 1% of patients
receiving therapeutic doses.
0.2.14 DERMATOLOGIC
A) Skin rash may be noted.
0.2.20 REPRODUCTIVE
A) Metronidazole has been reported to be
mutagenic/carcinogenic and is not recommended for use in
children or pregnant females.
Laboratory:
A) Plasma metronidazole levels are not clinically useful.
B) Obtain CBC in symptomatic patients. No other laboratory
work is needed unless otherwise indicated.
Treatment Overview:
0.4.2 ORAL/PARENTERAL EXPOSURE
A) SYMPTOMATIC AND SUPPORTIVE THERAPY is generally all that
is required. Toxicity is unlikely unless after acute
ingestion of less than 2 grams in an adult.
Range of Toxicity:
A) Single oral doses of metronidazole of 15 grams have been
tolerated with only minimal clinical effects.
B) Neurotoxic effects which have included seizures and
peripheral neuropathy have occurred after 5 to 7 days of
doses of 6 grams to 10.4 grams every other day.
C) Acute ingestion of 12 grams in a 19-year-old female
occurred without serious adverse effects.
AND FUNGICIDES
[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO,
2004; CCIS Volume 122, edition expires Nov, 2004. Hall AH & Rumack BH (Eds):
TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume
122, edition expires Nov, 2004.]**PEER REVIEWED**
Animal Toxicity Studies:
Non-Human Toxicity Excerpts:
METRONIDAZOLE WAS ADMIN AT CONCN OF 0.135% IN DIET TO
WEANLING FEMALE SPRAGUE-DAWLEY RATS FOR 66 WK... 36 RATS
SURVIVED...MORE THAN 10 WK. 12 RATS DEVELOPED BENIGN MAMMARY
FIBROADENOMAS & 3 MAMMARY ADENOCARCINOMAS.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 117 (1977)]**PEER REVIEWED**
METRONIDAZOLE WAS ADMIN FOR LIFE...IN DIET OF...6-8 WK OLD
/FEMALE/ SWISS MICE AT LEVELS OF /0.06% (10 MICE), 0.15% (20), 0.3% (20) &
0.5% (36)/. ... INCIDENCE OF LUNG TUMORS ROSE...FROM 20% IN
UNTREATED...TO 40, 50, 70 & 44% IN TREATED FEMALES. .../ALSO
SIGNIFICANT INCR/ IN LYMPHOMAS AT 2 HIGHEST DOSE LEVELS...
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 116 (1977)]**PEER REVIEWED**
METRONIDAZOLE WAS ADMIN FOR LIFETIME IN DIET OF...6-8 WK OLD
/MALE/ SWISS MICE AT LEVELS OF /0.06% (9 MICE), 0.15% (19 MICE), 0.3%(18
MICE) & 0.5% (35 MICE)/. ... INCIDENCE OF LUNG TUMORS ROSE FROM 19%
IN UNTREATED MALES TO 33, 58, 67, & 77% IN TREATED MALES...
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 116 (1977)]**PEER REVIEWED**
NO MUTAGENIC ACTIVITY WAS FOUND IN URINE OF MICE TREATED FOR 4
DAYS WITH DAILY DOSES...TO 400 MG/KG METRONIDAZOLE, &
MARGINAL ACTIVITY WAS REPORTED IN HOST-MEDIATED ASSAY WHEN
MICE WERE TREATED WITH 400 MG/KG FOR 5 DAYS. S TYPHIMURIUM WAS
USED AS GENETIC INDICATOR IN BOTH TESTS.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 118 (1977)]**PEER REVIEWED**
METRONIDAZOLE CAUSED POINT MUTATIONS IN SALMONELLA
TYPHIMURIUM TA100 WITHOUT ADDITION OF LIVER HOMOGENATE. IT IS
MUTAGENIC ONLY UNDER ANAEROBIC CONDITIONS IN MUTANT OF TA100
THAT IS DEFICIENT IN AEROBIC NITROREDUCTASE ACTIVITY. ... IN
FLUCTUATION TEST, METRONIDAZOLE INDUCED STREPTOMYCINRESISTANT MUTANTS IN K PNEUMONIAE.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 117 (1977)]**PEER REVIEWED**
IN VITRO STUDIES SHOWED THAT METRONIDAZOLE PRODUCES
INHIBITION OF ALDEHYDE DEHYDROGENASE & OTHER ALCOHOLOXIDIZING ENZYMES.
[Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American
Pharmaceutical Assn., 1976, 1978. 158]**PEER REVIEWED**
MUTAGENIC ACTIVITY FOUND IN URINE OF 10 PT GIVEN THERAPEUTIC
DOSES OF METRONIDAZOLE ORALLY OR VAGINALLY. ACTIVITY ASSOC
WITH UNMODIFIED METRONIDAZOLE & AT LEAST 4 KNOWN URINARY
METAB. ACTIVITY ALSO IN REGION OF CHROMATOGRAM HERETOFORE
NOT ASSIGNED TO ITS METABOLITES.
[SPECK WT ET AL; J NATL CANCER INST 56: 283 (1976)]**PEER REVIEWED**
Metronidazole, along with several other nitroheterocyclic compounds, was tested for
embryotoxicity in cultured rat embryos, and the effects were compared with those of
other 5-membered heterocycles. Sprague-Dawley rat embryos were explanted on day 10
of gestation and grown in culture medium to which the test compounds were added. After
26 hr in culture, the embryos were removed and examined for malformations.
Metronidazole, a nitroheterocycle with a low single-electron redox potential, failed to
elicit axial asymmetry and did not cause embryotoxicity, even at 2.0 mM concentration.
Only one abnormality in 11 fetuses was observed at that concentration and this was
characterized as an abnormal rotation of flexure. All the tested nitroheterocycles with
high redox potential elicited axial asymmetry in the embryos.
[Greenaway JC et al; Toxicol Appl Pharmacol 82:307-315 (1986)]**PEER
REVIEWED**
Metronidazole has been shown to be carcinogenic in a number of studies in mice.
Pulmonary tumorigenesis has been reported in six studies in mice, including one study in
which the animals were dosed on an intermittent schedule (every four weeks). malignant
hepatic tumors have also been reported in male mice given very high doses
(approximately 500 mg/kg/day). Malignant lymphomas have been reported in one
lifetime feeding study in mice.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Metronidazole has also been shown to be carcinogenic in rats. Several long-term, oraldosing studies in rats have shown that metronidazole causes a statistically significant
increase in the incidence of various neoplasms, especially mammary and hepatic tumors,
in female rats.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Studies in rats, given doses of up to 5 times the human dose, have not shown that
metronidazole causes impaired fertility or birth defects in the fetus. Metronidazole,
administered intraperitoneally to pregnant mice at approximately the human dose, has
been shown to cause fetotoxicity.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Studies in rats given doses of up to 5 times the usual human dose have not shown that
metronidazole causes impaired fertility or birth defects in the fetus. Metronidazole,
administered intraperitoneally to pregnant mice at approximately the human dose, has
been shown to cause fetotoxicity. When metronidazole was administered orally, no
fetotoxicity was seen in pregnant mice.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
IN EARLY STUDIES, URINE OF PT TREATED WITH METRONIDAZOLE WAS
FOUND TO CONTAIN SEVERAL EXCRETORY PRODUCTS, OF WHICH 70%
CONSISTED OF UNCHANGED.../DRUG/ PLUS MAJOR
METABOLITE...IDENTIFIED AS 1-(2-HYDROXYETHYL)-2-HYDROXYMETHYL5-NITROIMIDAZOLE. 2-METHYL-5-NITROIMIDAZOLE-1-ACETIC ACID
ACCOUNTS FOR ABOUT 10% OF DOSE IN MAN.
[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A
Review of the Literature Published Between 1960 and 1969. London: The Chemical
Society, 1970. 212]**PEER REVIEWED**
...FOUR OTHER NITRO-GROUP-CONTAINING METABOLITES HAVE BEEN
IDENTIFIED, EACH DERIVED FROM SIDE-CHAIN OXIDATION OF ETHYL
&/OR METHYL GROUP. THEY INCL 1-ACETIC ACID-2-METHYL-5NITROIMIDAZOLE & 1-(2-HYDROXYETHYL)-2-CARBOXYLIC ACID-5NITROMIDAZOLE SALT.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 118 (1977)]**PEER REVIEWED**
The compound is at least partly metabolized in the body. Following high doses,
metabolites of the drug may darken urine.
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed.
Ames, Iowa: Iowa State University Press, 1982. 885]**PEER REVIEWED**
Metabolites include 2-hydroxymethylmetronidazole (bacterial and antiprotozoal activity);
acetyl metronidazole; metronidazole glucuronide; a glucuronide conjugate of
hydroxymetronidazole; and a sulfate conjugate. The urine may be dark or reddish brown
in color after oral or intravenous metronidazole because of metabolites.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of
Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988.
375]**PEER REVIEWED**
Absorption, Distribution & Excretion:
Well absorbed orally; bioavailability at least 80%.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
IN 4 HEALTHY MALE SUBJECTS GIVEN 750 MG (14)C-LABELLED
METRONIDAZOLE, 14% OF ACTIVITY WAS EXCRETED IN FECES & 77% IN
URINE WITHIN 5 DAYS. ... IN WOMEN GIVEN 250 MG...ORALLY DURING
PREGNANCY OR LACTATION, DRUG WAS FOUND IN LOW CONCN (0.25
MG/KG) IN EMBRYONIC TISSUE & IN MILK.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 118 (1977)]**PEER REVIEWED**
WHOLE-BODY ARG /AUTORADIOGRAPHY/ SHOWED THAT IV OR ORAL
DOSE OF... (14)C-METRONIDAZOLE CROSSED BLOOD-BRAIN & PLACENTAL
BARRIERS IN PREGNANT MICE. UPTAKE FROM BLOOD WAS RAPID. LEVEL
OF (14)C IN MATERNAL BRAIN & FETUS WERE SIMILAR TO THOSE IN
MATERNAL BLOOD. LEVELS...HIGH IN LIVER, KIDNEYS & GI TRACT FOR AT
LEAST 4 HR...
[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. 110]**PEER REVIEWED**
FOLLOWING IV ADMIN OF 1,2-(14)C-METRONIDAZOLE TO MICE, ACTIVITY
WAS FOUND IN LIVER & KIDNEY & IN HEART, BRAIN, SALIVARY GLAND, GI
TRACT, SPLEEN & SKELETAL MUSCLE & WAS SHOWN TO CROSS PLACENTA
TO FETUS. IN RATS.../IT/ WAS CONJUGATED IN LIVER & EXCRETED IN BILE
& URINE.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 117 (1977)]**PEER REVIEWED**
OF INTEREST WAS CONSIDERABLE SECRETION OF (14)C/METRONIDAZOLE/ INTO STOMACH /OF PREGNANT MICE/ AFTER IV DOSE.
[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. 111]**PEER REVIEWED**
BINDING OF METRONIDAZOLE AND ITS DERIVATIVES TO PLASMA
PROTEINS.
[SANVORDEKER DR ET AL; BINDING OF METRONIDAZOLE & ITS DERIV TO
PLASMA PROTEINS: AN ASSESSMENT OF DRUG BINDING PHENOMENON; J
PHARM SCI 64: 1797 (1975)]**PEER REVIEWED**
Distributed to saliva, bile, seminal fluid, breast milk, bone, placenta and blood-brain
barrier, also.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is widely distributed into most body tissue and fluids, including bone,
saliva, pleural fluid, peritoneal fluid, vaginal secretions, seminal fluid, cerebrospinal
fluid, and cerebral and hepatic abscesses... One gram of metronidazole four times daily
produces cerebrospinal fluid levels of 58 to 80.4 ug/ml. Distribution is similar by either
oral or intravenous administartion. The apparent volume of distribution is 0.6-0.8 l/kg;
after 400 mg IV, it is 1.05 l/kg.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of
Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988.
375]**PEER REVIEWED**
The elimination half-life is 6-12 hours. Metronidazole is metabolized by the liver and
excreted through the kidneys. It is in the bile where it attains concentrations similar to
that in serum. Metronidazole and its metabolites are eliminated primarily by the urine
(60-80% of the dose). Urinary excretion of unchanged metronidazole is less than 10% of
a dose.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of
Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988.
375]**PEER REVIEWED**
Biological Half-Life:
The normal half-life of metronidazole is approximately eight hours.
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1546]**PEER REVIEWED**
Mechanism of Action:
POSSIBLE BIOLOGICAL ACTIVITY OF /MAJOR METABOLITE/, 1-(2HYDROXYETHYL)-2-HYDROXYMETHYL-5-NITROIMIDAZOLE HAS NOT
BEEN CONFIRMED.
[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A
Review of the Literature Published Between 1960 and 1969. London: The Chemical
Society, 1970. 212]**PEER REVIEWED**
The selective bactericidal action of metronidazole is due to preferential reduction of the
5'-nitro group of the parent drug by anaerobic organisms, presumably by a ferredoxin-like
system. An anaerobic environment is required for reduction to proceed. The short-lived
active intermediate products formed subsequently interact with bacterial DNA and
perhaps other macromolecules. Although the exact mechanism of action is unknown,
double-strand scissions in DNA probably are produced. Metronidazole is not activated
by, and therefore fails to inhibit, most aerobic and facultative organisms.
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1544]**PEER REVIEWED**
Interactions:
Metronidazole inhibits the metabolism of warfarin and other coumarins, which
potentiates their anticoagulant effect. ... Metronidazole appears to reduce the clearance
and thus possibly increase the toxicity of of fluorouracil. ... Metronidazole has caused an
intolerance to alcohol similar to that produced by disulfiram. ... This drug should never be
administered concomitantly with disulfiram ... .
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1546]**PEER REVIEWED**
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.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Effects may be potentiated when /coumarin- or indandione-derivative anticoagulants/ are
used concurrently with metronidazole, because of inhibition of enzymatic metabolism of
anticoagulants; periodic prothrombin time determinations may be required during therapy
to determine if dosage adjustments of anticoagulants are necessary.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Hepatic metabolism of metronidazole may be decreased when metronidazole and
cimetidine are used concurrently, possibly resulting in delayed elimination and increased
serum metronidazole concentrations; monitoring of serum concentrations as a guide to
dosage is recommended since dosage adjustments of metronidazole may be necessary
during and after cimetidine therapy.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
It is recommended that metronidazole not be used concurrently with, or for 2 weeks
following, disulfiram in alcoholic patients; such use may result in confusion and
psychotic reactions because of combined toxicity.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Concurrent use of metronidazole with other neurotoxic medications may increase the
potential for neurotoxicity.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Phenobarbital may induce microsomal liver enzymes, increasing metronidazole's
metabolism and resulting in a decrease in half-life and plasma concentrations.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Metronidazole may impair the clearance of phenytoin, increasing phenytoin's plasma
concentration.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Pharmacology:
Therapeutic Uses:
Anti-Infective Agents; Antitrichomonal Agents; Carcinogens; Radiation-Sensitizing
Agents
[National Library of Medicine's Medical Subject Headings online file (MeSH,
1999)]**QC REVIEWED**
MEDICATION (VET): EXPTL USE: PARENTERALLY (IV, IM) & TOPICALLY, IN
SUCCESSFUL LIMITED EXPTL TREATMENT OF BOVINE TRICHOMONIASIS.
IN VITRO STUDIES INDICATE 0.01-1.0% CONCN ARE NOT ONLY EFFECTIVE
BUT WITHOUT DETRIMENT TO BULL SPERMATOZOA. ...ITS USE IN
RATS...PRODUCE SIGNIFICANT DECR IN VOLUNTARY ALCOHOL
CONSUMPTION.
[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company,
1974. 364]**PEER REVIEWED**
.../SRP: METRONIDAZOLE HAS BEEN USED/ IN TREATMENT ACUTE
ULCERATIVE GINGIVITIS. .../IT/ IS DIRECTLY TRICHOMONACIDAL. IT
DESTROYS 99% OF MICROORGANISMS IN CULTURES OF TRICHOMONAS
VAGINALIS WITHIN 24 HR AT CONCN OF 2.5 UG/ML.
[Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th
ed. New York: Macmillan Publishing Co., Inc., 1975. 1086]**PEER REVIEWED**
METRONIDAZOLE.../PRC: FORMERLY HAS BEEN USED/ IN TREATMENT OF
ALCOHOLISM BY DECR INDIVIDUAL'S DESIRE FOR ALCOHOL & MAKING
ALCOHOL INGESTION UNPLEASANT.
[Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American
Pharmaceutical Assn., 1976, 1978. 158]**PEER REVIEWED**
USE OF METRONIDAZOLE IN TREATMENT OF ACNE ROSACEA HAS BEEN
SUGGESTED RECENTLY...& GOOD CLINICAL RESPONSES WAS ALSO
REPORTED TO OCCUR IN SMALL NUMBER OF PT WITH ACNE VULGARIS...
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 115]**PEER REVIEWED**
VET: IT IS VERY EFFECTIVE IN CONTROL OF TRICHOMONIASIS IN
PIGEONS...
[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company,
1974. 364]**PEER REVIEWED**
MEDICATION (VET): The success of metronidazole in treating human infections of
giardiasis, vaginal and oral trichomoniasis, and hepatic and intestinal amoebiasis has lead
to investigation of its potential use against certain protozoan diseases of domestic
animals. These are principally bovine urogenital trichomoniasis and canine, feline, or
primate intestinal giardiasis, trichomoniasis, amoebiasis, or Balantidium infection. ...
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed.
Ames, Iowa: Iowa State University Press, 1982. 885]**PEER REVIEWED**
Oral metronidazole is used in the treatment of bacterial vaginosis caused by Gardnerella
vaginalis. /NOT included in US or Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is used in the treatment of periodontal infections caused by Bacteroides
species. /NOT included in US or Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Oral metronidazole is used in the treatment of giardiasis caused by Giardia lamblia.
/NOT included in US and Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Some studies indicate that metronidazole may be effective, in combination with bismuth
subsalicylate or colloidal bismuth subcitrate, and other oral antibiotic therapy, such as
ampicillin or amoxicillin, in the treatment of Helicobacter pylori-associated gastritis and
duodenal ulcer. However, metronidazole resistance may occur, especially in patients
who have been previously exposed to metronidazole. /NOT included in US and
Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is used in the treatment of dracunculiasis (guinea worm infection) caused
by Dracunculus medinensis. It decreases the inflammation around the ulcer, increasing
the ease of removing the worm. /NOT included in US and Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is used in the treatment of antibiotic-associated diarrhea and colitis
caused by Clostridium difficile. /NOT included in US and Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is used in the treatment of inflammatory bowel disease. /NOT included in
US and Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is used in the treatment of Balantidium coli infection. /NOT included in
US or Canadian product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Oral metronidazole is indicated in the treatment of symptomatic and asymptomatic
trichomoniasis, in males and females, caused by Trichomonas vaginalis. /Included in US
product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**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/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of bacterial septicemia caused by
Bacteroides species, including the Bacteroides fragilis group, and Clostridium species.
/Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of lower respiratory tract infections,
including pneumonia, emphysema, and lung abscess, caused by Bacteroides species,
including the Bacteroides fragilis group. /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Intravenous metronidazole is indicated for the prophylaxis of perioperative infections
during colorectal surgery. /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of female pelvic infections, including
endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff
infections, caused by Bacteroides species, including the Bacteroides fragilis group,
Clostridium species, Peptoccus species, and Peptostreptococcus species. /Included in US
product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of intra-abdominal infections, including
peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species,
including the Bacteroides fragilis group, Clostridium species, Eubacterium species,
Peptococcus species, and Peptostreptococcus species. /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of endocarditis caused by Bacteroides
species, including the Bacteroides fragilis group. /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of CNS infections, including meningitis,
caused by Bacteroides species, including the Bacteroides fragilis group. /Included in US
product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of brain abscess caused by Bacteroides
species, including the Bacteroides fragilis group. /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of bone and joint infections caused by
Bacteroides species, including the Bacteroides fragilis group (Bacteroides fragilis,
Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides
vulgatus). /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Oral metronidazole is indicated in the treatment of acute intestinal amebiasis caused by
Entamoeba histolytica. Metronidazole may not eradicate intestinal amebic infections,
requiring treatment with a luminal amebicide. /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is indicated in the treatment of extraintestinal amebiases, including
amebic liver abscess, caused by Entamoeba histolytica. When used in the treatment of
invasive amebiasis, metronidazole should be administered concurrently or sequentially
with a luminal amebicide (eg, iodoquinol, paromomycin, tetracycline, diloxanide
furoate). /Included in US product labeling/
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
Metronidazole is the drug of first choice in the rare case of endocarditis caused by
penicillin-resistant Bacteriodes species, most commonly B. fragilis. ... Oral
metronidazole is the preferred drug to treat bacterial vaginosis (formerly called
nonspecific vaginitis), a syndrome now believed to be caused by the interaction of several
species of vaginal bacteria, including anaerobes ... .
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1545]**PEER REVIEWED**
Metronidazole is not effective against facultative anaerobes, obligate aerobes,
Propionibacterium acnes, Actinomyces species, or Candida albicans.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1904]**PEER REVIEWED**
MEDICATION (VET): ANTIPROTOZOAL; TREPONEMICIDE
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 968]**PEER REVIEWED**
Drug Warnings:
Although the drug has not been shown to be teratogenic in animals or humans, benefits
and risks should be weighed carefully before it is given to pregnant women or nursing
mothers.
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1545]**PEER REVIEWED**
.../METRONIDAZOLE/ APPEARS TO BE SPECIFIC FOR TRICHOMONADS; IT IS
INACTIVE AGAINST MONILIA ALBICANS. ...
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed.
Easton, Pennsylvania: Mack Publishing Co., 1975. 1161]**PEER REVIEWED**
TRICHOMONAS VAGINALIS WAS RESISTANT TO 2 STD SCHEDULES OF 500
MG ORALLY TWICE DAILY FOR 5 DAYS ALSO TO FURTHER TREATMENT
WITH 10 DAY COURSE OF 1.0 G TWICE DAILY.
[THURNER J, MEINGASSNER JG; ISOLATION OF TRICHOMONAS VAGINALIS
RESISTANT TO METRONIDAZOLE; LANCET 2: 738 (1978)]**PEER
REVIEWED**
Drugs Whose Effects on Nursing Infants is Unknown but may be of Concern:
Metronidazole: In vitro mutagen; may discontinue breast-feeding 12-24 h to allow
excretion of dose when single-dose therapy given to mother. /from Table 4/
[Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1):
139 (1994)]**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.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
No information is available on the relationship of age to the effects of metronidazole in
geriatric patients. However, elderly patients are more likely to have an age-related
decrease in hepatic function, which may require an adjustment in dosage in patients
receiving metronidazole.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Metronidazole may cause dry mouth, an unpleasant or sharp metallic taste, and
alteration of taste sensation. Dry mouth may contribute to the development of caries,
periodontal disease, oral candidiasis, and discomfort.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Side/Adverse Effects: Those indicating need for medical attention: Incidence less
frequent: Peripheral neuropathy (numbness, tingling, pain, or weakness in hands or feet) usually with high doses or prolonged use; seizures - usually with high doses. Incidence
rare: CNS toxicity (ataxia - clumsiness or unsteadiness; encephalopathy - mood or other
mental changes); hypersensitivity (skin rash, hives, redness, or itching); leukopenia (sore
throat and fever); pancreatitis (severe abdominal and back pain, anorexia, nausea and
vomiting); thrombophlebitis (pain, tenderness, redness, or swelling at site of injection);
vaginal candidiasis (any vaginal irritation, discharge, or dryness not present before
therapy.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1906]**PEER REVIEWED**
Side/Adverse Effects: Those indicating need for medical attention only if they continue
or are bothersome: Incidence more frequent: CNS effects (dizziness or lightheadedness,
headache); gastrointestinal disturbance (diarrhea, loss of appetite, nausea or vomiting,
stomach pain or cramps). Incidence less frequent or are: Change in taste sensation;
dryness of mouth; unpleasant or sharp metallic taste. Those not indicating need for
medical attention: Incidence less frequent or rare: Dark urine.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1906]**PEER REVIEWED**
Metronidazole is contraindicated in patients with active disease of the CNS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The
Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990.
1004]**PEER REVIEWED**
Potential adverse effects on fetus: Mutagenic in bacteria and carcinogenic in rodents. No
known teratogenicity in humans. Potential side effects on breast-fed infant: Use not
recommended in lactating mother, but breast-feeding may be resumed 48 hours after
treatment is completed. Comments: Fetal serum levels 20%-50% of maternal. FDA
Category: B (B = Studies in laboratory animals have not demonstrated a fetal risk, but
there are no controlled studies in pregnant women; or animal studies have shown an
adverse effect (other than a decrease in fertility), but controlled studies in pregnant
women have not demonstrated a risk to the fetus in the first trimester and there is no
evidence of a risk in later trimesters.) /from Table II/
[Stockton, D.L. and A.S. Paller. J Am Acad Dermatol 23 (1):87-103 (1990)]**PEER
REVIEWED**
Interactions:
Metronidazole inhibits the metabolism of warfarin and other coumarins, which
potentiates their anticoagulant effect. ... Metronidazole appears to reduce the clearance
and thus possibly increase the toxicity of of fluorouracil. ... Metronidazole has caused an
intolerance to alcohol similar to that produced by disulfiram. ... This drug should never be
administered concomitantly with disulfiram ... .
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1546]**PEER REVIEWED**
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.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Effects may be potentiated when /coumarin- or indandione-derivative anticoagulants/ are
used concurrently with metronidazole, because of inhibition of enzymatic metabolism of
anticoagulants; periodic prothrombin time determinations may be required during therapy
to determine if dosage adjustments of anticoagulants are necessary.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Hepatic metabolism of metronidazole may be decreased when metronidazole and
cimetidine are used concurrently, possibly resulting in delayed elimination and increased
serum metronidazole concentrations; monitoring of serum concentrations as a guide to
dosage is recommended since dosage adjustments of metronidazole may be necessary
during and after cimetidine therapy.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
It is recommended that metronidazole not be used concurrently with, or for 2 weeks
following, disulfiram in alcoholic patients; such use may result in confusion and
psychotic reactions because of combined toxicity.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Concurrent use of metronidazole with other neurotoxic medications may increase the
potential for neurotoxicity.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Phenobarbital may induce microsomal liver enzymes, increasing metronidazole's
metabolism and resulting in a decrease in half-life and plasma concentrations.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Metronidazole may impair the clearance of phenytoin, increasing phenytoin's plasma
concentration.
[USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed.
Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus
Updates). 1905]**PEER REVIEWED**
Drug Tolerance:
Acquired resistance to metronidazole is rare. Since it is not related chemically to other
available drugs used in anaerobic bacterial infections, cross resistance does not occur.
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual
1994. Chicago, IL: American Medical Association, 1994. 1544]**PEER REVIEWED**
Environmental Fate & Exposure:
Environmental Standards & Regulations:
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."
[USEPA/OPP; Status of Pesticides in Registration, Reregistration and Special Review
p.265 (Spring, 1998) EPA 738-R-98-002]**QC REVIEWED**
Chemical/Physical Properties:
Molecular Formula:
C6-H9-N3-O3
**PEER REVIEWED**
Molecular Weight:
171.16
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 968]**PEER REVIEWED**
Color/Form:
CREAM-COLORED CRYSTALS
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 968]**PEER REVIEWED**
WHITE TO PALE YELLOW CRYSTALS OR CRYSTALLINE POWDER
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed.
Easton, Pennsylvania: Mack Publishing Co., 1975. 1161]**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. 1161]**PEER REVIEWED**
Melting Point:
158-160 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 968]**PEER REVIEWED**
Dissociation Constants:
2.38
[Hansch, C. and A. Leo. The Log P Database. Claremont, CA: Pomona College,
1987.]**PEER REVIEWED**
Octanol/Water Partition Coefficient:
Log Kow = -0.02 @ 25 deg C
[Hansch, C. and A. Leo. The Log P Database. Claremont, CA: Pomona College,
1987.]**PEER REVIEWED**
pH:
PH OF SATURATED AQ SOLN IS 5.8
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 968]**PEER REVIEWED**
Solubilities:
G/100 ML @ 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
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 968]**PEER REVIEWED**
11000 mg/l in water
[Yalkowsky SH, Dannenfelser RM; Aquasol Database of Aqueous Solubility. 5th ed.
Tucson, AZ University of Arizona College of Pharmacy (1992)]**PEER REVIEWED**
Spectral Properties:
MAX ABSORPTION (ACID): 277 NM (A= 380, 1%, 1 CM)
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical
Rubber Co., 1969. 272]**PEER REVIEWED**
IR: 14987 (Sadtler Research Laboratories IR Grating Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I
and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 764]**PEER REVIEWED**
UV: 2561 (Absorption Spectra in the UV and visible Regions, Academic Press, New
York)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I
and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 764]**PEER REVIEWED**
NMR: 5648 (Sadtler Research Laboratories Spectral Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I
and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 764]**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. 1985.244]**PEER REVIEWED**
Chemical Safety & Handling:
Protective Equipment & Clothing:
PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be
available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory,
personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting
at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves
& gowns should always be worn ... however, gloves should not be assumed to provide
full protection. Carefully fitted masks or respirators may be necessary when working with
particulates or gases, & disposable plastic aprons might provide addnl protection. ...
Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn
outside the laboratory. /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, 1979.8]**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, 1979.8]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should
remove their outdoor clothes & wear protective suits (preferably disposable, one-piece &
close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be
changed daily but ... discarded immediately if obvious contamination occurs ... /also,/
workers should shower immediately. In chemical laboratory, gloves & gowns should
always be worn ... however, gloves should not be assumed to provide full protection.
Carefully fitted masks or respirators may be necessary when working with particulates or
gases, & disposable plastic aprons might provide addnl protection. If gowns are of
distinctive color, this is a reminder that they should not be worn outside of lab. /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, 1979.8]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth &
purification ... should be carried out under well-ventilated hood. Analytical procedures ...
should be carried out with care & vapors evolved during ... procedures should be
removed. ... Expert advice should be obtained before existing fume cupboards are used ...
& when new fume cupboards are installed. It is desirable that there be means for
decreasing the rate of air extraction, so that carcinogenic powders can be handled without
... powder being blown around the hood. Glove boxes should be kept under negative air
pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens
will not occur. /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, 1979.8]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety
cabinets may be used for containment of in vitro procedures ... provided that the exhaust
air flow is sufficient to provide an inward air flow at the face opening of the cabinet, &
contaminated air plenums that are under positive pressure are leak-tight. Horizontal
laminar-flow hoods or safety cabinets, where filtered air is blown across the working area
towards the operator, should never be used ... Each cabinet or fume cupboard to be used
... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving
date of test & avg air-flow measured. This test should be repeated periodically & after
any structural changes. /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, 1979.9]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab
also apply to microbiological & cell-culture labs ... Special consideration should be given
to route of admin. ... Safest method of administering volatile carcinogen is by injection of
a soln. Admin by topical application, gavage, or intratracheal instillation should be
performed under hood. If chem will be exhaled, animals should be kept under hood
during this period. Inhalation exposure requires special equipment. ... Unless specifically
required, routes of admin other than in the diet should be used. Mixing of carcinogen in
diet should be carried out in sealed mixers under fume hood, from which the exhaust is
fitted with an efficient particulate filter. Techniques for cleaning mixer & hood should be
devised before expt begun. When mixing diets, special protective clothing &, possibly,
respirators may be required. /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, 1979.9]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin,
animals should be kept in cages with solid bottoms & sides & fitted with a filter top.
When volatile carcinogens are given, filter tops should not be used. Cages which have
been used to house animals that received carcinogens should be decontaminated. Cagecleaning facilities should be installed in area in which carcinogens are being used, to
avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are
decontaminated, & monitoring methods are necessary. Situations may exist in which the
use of disposable cages should be recommended, depending on type & amt of carcinogen
& efficiency with which it can be removed. /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, 1979.10]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab
could build up during conduct of expt, periodic checks should be carried out on lab
atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods &
airducts. As well as regular monitoring, check must be carried out after cleaning-up of
spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ...
should ... where possible, be simple & sensitive. /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, 1979.10]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has
occurred, such as spillage, should be decontaminated by lab personnel engaged in expt.
Design of expt should ... avoid contamination of permanent equipment. ... Procedures
should ensure that maintenance workers are not exposed to carcinogens. ... Particular care
should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs,
procedures should be used which do not produce aerosols or dispersal of dust, ie, wet
mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which
are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops
should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If
gowns or towels are contaminated, they should not be sent to laundry, but ...
decontaminated or burnt, to avoid any hazard to laundry personnel. /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, 1979.10]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens
are used ... should be marked distinctively with appropriate labels. Access ... limited to
persons involved in expt. ... A prominently displayed notice should give the name of the
Scientific Investigator or other person who can advise in an emergency & who can
inform others (such as firemen) on the handling of carcinogenic substances. /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, 1979.11]**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. 1161]**PEER REVIEWED**
Stable in air
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed.
Ames, Iowa: Iowa State University Press, 1982. 885]**PEER REVIEWED**
Shipment Methods and Regulations:
PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should
be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass
bottles or ampoules, which should themselves be placed inside strong screw-cap or snaptop container that will not open when dropped & will resist attack from the carcinogen.
Both bottle & the outside container should be appropriately labelled. ... National post
offices, railway companies, road haulage companies & airlines have regulations
governing transport of hazardous materials. These authorities should be consulted before
... material is shipped. /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, 1979.13]**QC REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following
procedure must be adopted. The carcinogen should be enclosed in a securely sealed,
watertight container (primary container), which should be enclosed in a second,
unbreakable, leakproof container that will withstand chem attack from the carcinogen
(secondary container). The space between primary & secondary container should be filled
with absorbent material, which would withstand chem attack from the carcinogen & is
sufficient to absorb the entire contents of the primary container in the event of breakage
or leakage. Each secondary container should then be enclosed in a strong outer box. The
space between the secondary container & the outer box should be filled with an
appropriate quantity of shock-absorbent material. Sender should use fastest & most
secure form of transport & notify recipient of its departure. If parcel is not received when
expected, carrier should be informed so that immediate effort can be made to find it.
Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ...
/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, 1979.13]**QC 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, 1979.13]**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, 1979.15]**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": There is no universal method of disposal that
has been proved satisfactory for all carcinogenic compounds & specific methods of chem
destruction ... published have not been tested on all kinds of carcinogen-containing waste.
... summary of avail methods & recommendations ... /given/ must be treated as guide
only. /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, 1979.14]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method
for disposal of contaminated laboratory waste from biological expt. However, not all
incinerators are suitable for this purpose. The most efficient type ... is probably the gasfired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio
is followed by a second stage with excess air. Some ... are designed to accept ... aqueous
& organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable
combustible material, such as sawdust. Alternatively, chem destruction may be used, esp
when small quantities ... are to be destroyed in laboratory. /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, 1979.15]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor)
filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed
material can be stripped off at high temp & carcinogenic wastes generated by this
treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal
should be carried out by incineration at temp that ... ensure complete combustion. SOLID
WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed
of by incineration at temp high enough to ensure destruction of chem carcinogens or their
metabolites. /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, 1979.15]**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, 1979.16]**PEER REVIEWED**
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or
acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such
as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various
alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction
medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in
ethanol or similar solvents. ... No method should be applied ... until it has been
thoroughly tested for its effectiveness & safety on material to be inactivated. For
example, in case of destruction of alkylating agents, it is possible to detect residual
compounds by reaction with 4(4-nitrobenzyl)-pyridine. /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, 1979.17]**PEER REVIEWED**
Occupational Exposure Standards:
Manufacturing/Use Information:
Major Uses:
The active ingredient is no longer contained in any registered pesticide products ...
"cancelled."
[USEPA/OPP; Status of Pesticides in Registration, Reregistration and Special Review
p.265 (Spring, 1998) EPA 738-R-98-002]**QC REVIEWED**
Methods of Manufacturing:
JACOB ET AL, US PATENT 2,944,061 (1960 TO RHONE-POULENC; COSSAR ET
AL, ARZNEIMITTEL-FORSCH (16) 23, 1966. ACTIVITY STUDIES: BOCK, IBID
(11) 587, 1961.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and
Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 968]**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**
General Manufacturing Information:
ALTHOUGH METRONIDAZOLE IS CLOSELY RELATED TO NATURAL
ANTITRICHOMONAL AGENT, AZOMYCIN, IT IS NOT KNOWN TO OCCUR IN
NATURE.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 116]**PEER REVIEWED**
NMR SPECTROSCOPY & POLAROGRAPHY WERE USED TO DETECT IN VITRO
INTERACTIONS BETWEEN METRONIDAZOLE & BIOLOGICALLY
IMPORTANT METALS. ONLY CUPRIC ION SHOWED DETECTABLE
INTERACTION.
[CHIEN YW ET AL; INTERACTION OF METRONIDAZOLE WITH METALLIC
IONS OF BIOLOGICAL IMPORTANCE; J PHARM SCI 64: 957 (1975)]**PEER
REVIEWED**
Formulations/Preparations:
METRONIDAZOLE, USP (FLAGYL), IS AVAIL AS 250-MG TABLETS.
UNCOATED VAGINAL INSERTS, EACH CONTAINING 500 MG, ARE ALSO
AVAIL.
[Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th
ed. New York: Macmillan Publishing Co., Inc., 1975. 1087]**PEER REVIEWED**
Laboratory Methods:
Clinical Laboratory Methods:
BIOASSAY PROCEDURES USING AGAR DIFFUSION TECHNIQUES HAVE
BEEN REPORTED: LEVISON ME, ANTIMICROB AGENTS CHEMOTHER (5) 446468, 1974 & RALPH ED ET AL, J INFECT DIS (132) 587-591, 1975. PLASMA; GAS
CHROMATOGRAPHY: MIDHA KK ET AL, J CHROMAT (87) 491-497, 1973 &
WOOD NF, J PHARM SCI (64) 1048-1049, 1975.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 116]**PEER REVIEWED**
SENSITIVE ASSAY WAS DEVELOPED FOR DETERMINATION OF
METRONIDAZOLE IN PLASMA. LIMIT OF DETECTION FOR 2 ML SAMPLE IS
0.1 MCG/ML. ASSAY MAY BE EMPLOYED FOR ANALYSIS OF URINE.
[BROOKS MA ET AL; DETERMINATION OF NITROIMIDAZOLES IN
BIOLOGICAL FLUIDS BY DIFFERENTIAL PULSE POLAROGRAPHY; J PHARM
SCI 65: 112 (1976)]**PEER REVIEWED**
GLC ANALYSIS OF METRONIDAZOLE IN HUMAN PLASMA.
[WOOD NF; GLC ANALYSIS OF METRONIDAZOLE IN HUMAN PLASMA; J
PHARM SCI 64: 1048 (1975)]**PEER REVIEWED**
Analytic Laboratory Methods:
TWO SIMPLE COLORIMETRIC METHODS FOR EST OF METRONIDAZOLE IN
MARKETED TABLETS & SYRUPS ARE DESCRIBED.
[SANGHAVI NM, CHANDRAMOHAN HS; METHODS OF ESTIMATION OF
METRONIDAZOLE; INDIAN J PHARM 36: 151 (1974)]**PEER REVIEWED**
METHODS OF ASSAY OF METRONIDAZOLE TO MEET REGULATORY
REQUIREMENTS FOR PHARMACEUTICAL PRODUCTS COMMONLY EMPLOY
NON-AQ TITRATION. THIS HAS BEEN COMPARED TO POTENTIOMETRIC
METHODS FOR DETERMINATION /OF/...PHARMACEUTICAL PRODUCTS.
TUCKERMAN MM & BICAN-FISTER T, ANALYSIS OF METRONIDAZOLE, J
PHARM SCI (58) 1401-1403, 1969.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 116]**PEER REVIEWED**
PHARMACEUTICAL PRODUCTS; UV SPECTROPHOTOMETRY:
KOMPANTSEVA EV ET AL, FARMATSIYA (MOSCOW) 22, 45-48, 1973; &
COLORIMETRIC METHODS: POPULAIRE P ET AL, ANN PHARM FRANC (26)
549-556, 1968 & SANGHAVI NM ET AL, IND J PHARM (36) 151-152, 1974; &
COMPLEXOMETRIC DETERMINATIONS: GAJEWSKA M, ACTA POL PHARM
(29) 399-404, 1972.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
Geneva: World Health Organization, International Agency for Research on Cancer, 1972PRESENT. (Multivolume work).p. V13 116]**PEER REVIEWED**
Special References:
Special Reports:
U.S. Department of Health & Human Services/National Toxicology Program; Tenth
Report on Carcinogens. National Institutes of Environmental Health Sciences. The
Report on Carcinogens is an informational scientific and public health document that
identifies and discusses substances (including agents, mixtures, or exposure
circumstances) that may pose a carcinogenic hazard to human health. Metronidazole
(443-48-1) was first listed in the Fourth Annual Report on Carcinogens (1985) as
reasonably anticipated to be a human carcinogen.
[]
Synonyms and Identifiers:
Synonyms:
ACROMONA
**PEER REVIEWED**
ATRIVYL
**PEER REVIEWED**
BEXON
**PEER REVIEWED**
CONT
**PEER REVIEWED**
DANIZOL
**PEER REVIEWED**
DEFLAMON-WIRKSTOFF
**PEER REVIEWED**
EFLORAN
**PEER REVIEWED**
ELYZOL
**PEER REVIEWED**
ENTIZOL
**PEER REVIEWED**
1-(BETA-ETHYLOL)-2-METHYL-5-NITRO-3-AZAPYRROLE
**PEER REVIEWED**
EUMIN
**PEER REVIEWED**
FLAGEMONA
**PEER REVIEWED**
FLAGYL
**PEER REVIEWED**
FOSSYOL
**PEER REVIEWED**
GIATRICOL
**PEER REVIEWED**
1-(BETA-HYDROXYETHYL)-2-METHYL-5-NITROIMIDAZOLE
**PEER REVIEWED**
1-(2-HYDROXY-1-ETHYL)-2-METHYL-5-NITROIMIDAZOLE
**PEER REVIEWED**
1-(2-HYDROXYETHYL)-2-METHYL-5-NITROIMIDAZOLE
**PEER REVIEWED**
1-HYDROXYETHYL-2-METHYL-5-NITROIMIDAZOLE
**PEER REVIEWED**
KLION
**PEER REVIEWED**
MERONIDAL
**PEER REVIEWED**
2-METHYL-1-(2-HYDROXYETHYL)-5-NITROIMIDAZOLE
**PEER REVIEWED**
2-METHYL-3-(2-HYDROXYETHYL)-4-NITROIMIDAZOLE
**PEER REVIEWED**
2-METHYL-5-NITROIMIDAZOLE-1-ETHANOL
**PEER REVIEWED**
METRONIDAZ
**PEER REVIEWED**
METRONIDAZOL
**PEER REVIEWED**
MEXIBOL 'SILANES'
**PEER REVIEWED**
MONAGYL
**PEER REVIEWED**
NALOX
**PEER REVIEWED**
NEO-TRIC
**PEER REVIEWED**
NIDA
**PEER REVIEWED**
NOVONIDAZOL
**PEER REVIEWED**
SANATRICHOM
**PEER REVIEWED**
SC 10295
**PEER REVIEWED**
TRICHAZOL
**PEER REVIEWED**
TRICHEX
**PEER REVIEWED**
TRICHOCIDE
**PEER REVIEWED**
TRICHOMONACID 'PHARMACHIM'
**PEER REVIEWED**
TRICHOPOL
**PEER REVIEWED**
TRICOCET
**PEER REVIEWED**
TRICOM
**PEER REVIEWED**
TRICOWAS B
**PEER REVIEWED**
TRIKACIDE
**PEER REVIEWED**
TRIKAMON
**PEER REVIEWED**
TRIKOJOL
**PEER REVIEWED**
TRIKOZOL
**PEER REVIEWED**
TRIMEKS
**PEER REVIEWED**
VAGILEN
**PEER REVIEWED**
VERTISAL
**PEER REVIEWED**
Formulations/Preparations:
METRONIDAZOLE, USP (FLAGYL), IS AVAIL AS 250-MG TABLETS.
UNCOATED VAGINAL INSERTS, EACH CONTAINING 500 MG, ARE ALSO
AVAIL.
[Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th
ed. New York: Macmillan Publishing Co., Inc., 1975. 1087]**PEER REVIEWED**
Administrative Information:
Hazardous Substances Databank Number: 3129
Last Revision Date: 20030829
Last Review Date: Reviewed by SRP on 5/11/1995
Update History:
Complete Update on 2003-08-29, 0 fields added/edited/deleted
Complete Update on 03/05/2003, 2 fields added/edited/deleted.
Field Update on 08/08/2001, 1 field added/edited/deleted.
Complete Update on 03/13/2000, 2 fields added/edited/deleted.
Complete Update on 02/11/2000, 1 field added/edited/deleted.
Complete Update on 02/08/2000, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 05/12/1999, 8 fields added/edited/deleted.
Field Update on 03/19/1999, 1 field added/edited/deleted.
Field Update on 06/02/1998, 1 field added/edited/deleted.
Field Update on 10/26/1997, 1 field added/edited/deleted.
Field Update on 05/01/1997, 2 fields added/edited/deleted.
Complete Update on 01/26/1996, 1 field added/edited/deleted.
Complete Update on 09/13/1995, 32 fields added/edited/deleted.
Field Update on 12/28/1994, 1 field added/edited/deleted.
Complete Update on 09/26/1994, 1 field added/edited/deleted.
Complete Update on 06/16/1994, 1 field added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Complete Update on 01/20/1993, 1 field added/edited/deleted.
Field update on 12/28/1992, 1 field added/edited/deleted.
Complete Update on 04/01/1992, 1 field added/edited/deleted.
Complete Update on 10/23/1990, 3 fields added/edited/deleted.
Field Update on 08/23/1990, 1 field added/edited/deleted.
Field Update on 03/01/1989, 1 field added/edited/deleted.
Complete Update on 04/22/1988, 3 fields added/edited/deleted.
Complete Update on 01/01/1985
Created 19830401 by GCF