A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Flagyl Warnings, Precautions, Pregnancy, Nursing, Abuse - Metronidazole (oral)
Flagyl Warnings, Precautions, Pregnancy, Nursing, Abuse - Metronidazole (oral)
WARNINGS
Convulsive Seizures and Peripheral Neuropathy: Convulsive seizures
and peripheral neuropathy, the latter characterized mainly by numbness
or paresthesia of an extremity, have been reported in patients treated
with metronidazole. The appearance of abnormal neurological signs demands
the prompt discontinuation of metronidazole therapy. Metronidazole should
be administered with caution to patients with central nervous system diseases.
PRECAUTIONS
General
Patients with severe hepatic disease metabolize metronidazole slowly,
with resultant accumulation of metronidazole and its metabolites in the
plasma. Accordingly, for such patients, doses below those usually recommended
should be administered cautiously.
Known or previously unrecognized candidiasis may present more prominent
symptoms during therapy with metronidazole and requires treatment with
a candicidal agent.
Information for Patients
Alcoholic beverages should be avoided while taking metronidazole and
for at least one day afterward. See DRUG
INTERACTIONS.
Laboratory Tests
Metronidazole is a nitroimidazole and should be used with caution in
patients with evidence of or history of blood dyscrasia. A mild leukopenia
has been observed during its administration; however, no persistent hematologic
abnormalities attributable to metronidazole have been observed in clinical
studies. Total and differential leukocyte counts are recommended before
and after therapy for trichomoniasis and amebiasis, especially if a second
course of therapy is necessary, and before and after therapy for anaerobic
infections
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis Impairment of Fertility
Metronidazole has shown evidence of carcinogenic activity in a number
of studies involving chronic, oral administration in mice and rats.
Prominent among the effects in the mouse was the promotion of pulmonary
tumorigenesis. This has been observed in all six reported studies in that
species, including one study in which the animals were dosed on an intermittent
schedule (administration during every fourth week only). At very high
dose levels (approximately 500 mg/kg/day which is approximately 33 times
the most frequently recommended human dose for a 50 kg adult based on
mg/kg body weight) there was a statistically significant increase in the
incidence of malignant liver tumors in males. Also, the published results
of one of the mouse studies indicate an increase in the incidence of malignant
lymphomas as well as pulmonary neoplasms associated with lifetime feeding
of the drug. All these effects are statistically significant.
Several long-term, oral-dosing studies in the rat have been completed.
There were statistically significant increases in the incidence of various
neoplasms, particularly in mammary and hepatic tumors, among female rats
administered metronidazole over those noted in the concurrent female control
groups.
Two lifetime tumorigenicity studies in hamsters have been performed and
reported to be negative.
Although metronidazole has shown mutogenic activity in a number of in
vivo assay systems, studies in mammals (in vivo) have failed
to demonstrate a potential for genetic damage.
Fertility studies have been performed in mice at doses up to six times
the maximum recommended human dose based on mg per sq.m. and have revealed
no evidence of impaired fertility.
Pregnancy
Teratogenic Effects - Pregnancy Category B.
Metronidazole crosses the placental barrier and enters the fetal circulation
rapidly. Reproduction studies have been performed in rats at doses up
to five times the human dose and have revealed no evidence of impaired
fertility or harm to the fetus due to metronidazole. No fetotoxicity was
observed when metronidazole was administered orally to pregnant mice at
20 mg/kg/day approximately one and a half times the most frequently recommended
human dose (750 mg/day) based on mg/kg body weight; however, in a single
small study where the drug was administered intraperitoneally, some intrauterine
deaths were observed. The relationship of these findings to the drug is
unknown. There are however, no adequate and well-controlled studies in
pregnant women. Because animal reproduction studies are not always predictive
of human response, and because metronidazole is a carcinogen in rodents,
this drug should be used during pregnancy only if clearly needed.
Use of metronidazole for trichomoniasis during pregnancy should be restricted
to those in whom alternative treatment has been inadequate. Use of metronidazole
for trichomoniasis in the first trimester of pregnancy should be carefully
evaluated because metronidazole crosses the placental barrier and its
effects on the human fetal organogenesis are not known (see above).
Nursing Mothers
Because of the potential for tumorigenicity shown for metronidazole in
mouse and rat studies a decision should be made whether to discontinue
nursing or to discontinue the drug taking into account the importance
of the drug to the mother. Metronidazole is secreted in human milk in
concentrations similar to those found in plasma.
Geriatric Use
Decreased renal function does not alter the single-dose pharmacokinetics
of metronidazole. However, plasma clearance of metronidazole is decreased
in patients with decreased liver function. Therefore, in elderly patients,
monitoring of serum may be necessasry to adjust the metronidazole dosage
accordingly
Pediatric Use
Safety and effectiveness in pediatric patients have not been established,
except for the treatment of amebiasis.
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