No information provided.
General: Topical metronidazole formulations have been reported to cause tearing
of the eyes. Therefore, contact with the eyes should be avoided. If a reaction
suggesting local irritation occurs, patients should be directed to use the medication
less frequently or discontinue use. Metronidazole is a nitroim-idazole and should
be used with care in patients with evidence or history of blood dyscrasia.
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 but not in studies involving
hamsters. Neither carcinogenicity nor photocarcinogenicity studies have been
performed by the topical route with MetroLotion® Topical Lotion or any marketed
In several long-term studies in mice, oral doses of approximately 198 mg/m2/day
or greater (approximately 29 to 71 times the human topical dose on a mg/m2
basis) were associated with an increase in lung tumors in male mice and lymphomas
in female mice.
Several long-term studies by the oral route in rats have shown statistically
significant increases in mammary and hepatic tumors in female rats and testicular
tumors and pituitary adenomas in male rats at doses (in feed) of 1593 mg/m2/day
or greater (approximately 230 to 573 times the human topical dose on a mg/m2
basis). In another oral study (by gavage), mammary tumors in female rats were
observed with a dose of 177 mg/m2/day (approximately 26 to 64 times
the human topical dose on a mg/m2 basis).
In a published study, the ultraviolet radiation-induced carcinogenesis was
enhanced in albino hairless mice by intraperitoneal administration of 45 mg/m2
metronidazole, as shown by a decreased latency period to the development of
skin neoplasms. The concentration of metronidazole in the skin following the
intraperitoneal administration was not determined. This study did not distinguish
whether metronidazole must be present during the exposure to ultraviolet radiation
in order to enhance tumor formation or whether metronidazole could promote tumor
formation from preexisting ultraviolet radiation-initiated cells. The significance
of these results in the topical use of metronidazole for the treatment of rosacea
Metronidazole has shown evidence of mutagenic activity in several in vitro
bacterial assay systems. In addition, a dose-response increase in the frequency
of micronuclei was observed in mice after intraperitoneal injections. An increase
in chromosome aberrations in peripheral blood lymphocytes was reported in patients
with Crohn's disease who were treated with 200-1200 mg/day of metronidazole
for 1 to 24 months. However, in another study, no excess chromosomal aberrations
in circulating human lymphocytes were observed in patients treated for 8 months.
In rats, oral metronidazole at doses of 1770 mg/m2/day (approximately
255 to 637 times the human topical dose on a mg/m2 basis) induced
inhibition of spermatogenesis and severe testicular degeneration. In two strains
of mice (ICR and CF1), conflicting results have been reported indicating either
no effect or a similar effect to that reported in rats.
Teratogenic Effects: Pregnancy Category B
There are no adequate and well-controlled studies with the use of MetroLotion®
Topical Lotion in pregnant women. Metronidazole crosses the placental barrier
and enters the fetal circulation rapidly. No fetotoxicity was observed after
oral administration of metronidazole in rats or mice. However, because animal
reproduction studies are not always predictive of human response and since oral
metronidazole has been shown to be a carcinogen in some rodents, this drug should
be used during pregnancy only if clearly needed.
After oral administration, metronidazole is secreted in breast milk in concentrations
similar to those found in the plasma. Even though blood levels are significantly
lower with topically applied metronida-zole than those achieved after oral administration
of metronidazole, a decision should be made whether to discontinue nursing or
to discontinue the drug, taking into account the importance of the drug to the
Safety and effectiveness in pediatric patients have not been established.