Pregnancy: Teratogenic Effects—Pregnancy Cate-
gory B. Metronidazole crosses the placental bar-
rier and enters the fetal circulation rapidly. Repro-
duction 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 adminis-
tered orally to pregnant mice at 20 mg/kg/day,
approximately one and a half times the most fre-
quently 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 Flagyl for trichomoniasis during preg-
nancy should be restricted to those in whom alter-
native treatment has been inadequate. Use of
Flagyl (metronidazole) for trichomoniasis in preg-
nancy 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 metroni-
dazole. However, plasma clearance of metronida-
zole is decreased in patients with decreased liver
function. Therefore, in elderly patients, monitoring
of serum levels may be necessary to adjust the
metronidazole dosage accordingly.
Pediatric use: Safety and effectiveness in pediatric
patients have not been established, except for the
treatment of amebiasis.
ADVERSE REACTIONS
Two serious adverse reactions reported in patients
treated with Flagyl (metronidazole) have been con-
vulsive seizures and peripheral neuropathy, the
latter characterized mainly by numbness or pares-
thesia of an extremity. Since persistent peripheral
neuropathy has been reported in some patients
receiving prolonged administration of Flagyl,
patients should be specifically warned about these
reactions and should be told to stop the drug and
report immediately to their physicians if any neu-
rologic symptoms occur.
The most common adverse reactions reported
have been referable to the gastrointestinal tract,
particularly nausea reported by about 12% of
patients, sometimes accompanied by headache,
anorexia, and occasionally vomiting; diarrhea; epi-
gastric distress; and abdominal cramping. Consti-
pation has also been reported.
The following reactions have also been reported
during treatment with Flagyl (metronidazole):
Mouth: A sharp, unpleasant metallic taste is not
unusual. Furry tongue, glossitis, and sto-
matitis have occurred; these may be asso-
ciated with a sudden overgrowth of Candida
which may occur during therapy.
Hematopoietic: Reversible neutropenia (leuko-
penia); rarely, reversible thrombocytopenia.
Cardiovascular: Flattening of the T-wave may be
seen in electrocardiographic tracings.
Central Nervous System: Convulsive seizures,
peripheral neuropathy, dizziness, vertigo,
incoordination, ataxia, confusion, irritability,
depression, weakness, and insomnia.
Hypersensitivity: Urticaria, erythematous rash,
flushing, nasal congestion, dryness of the
mouth (or vagina or vulva), and fever.
Renal: Dysuria, cystitis, polyuria, incontinence,
and a sense of pelvic pressure. Instances of
darkened urine have been reported by
approximately one patient in 100,000.
Although the pigment which is probably
responsible for this phenomenon has not
been positively identified, it is almost cer-
tainly a metabolite of metronidazole and
seems to have no clinical significance.
Other: Proliferation of Candida in the vagina,
dyspareunia, decrease of libido, proctitis,
and fleeting joint pains sometimes resem-
bling “serum sickness.” If patients receiving
Flagyl
metronidazole tablets