There were no deaths or serious adverse events related to
drug therapy in clinical trials involving 800 non-pregnant women who received
In a randomized, single-blind clinical trial of 505
non-pregnant women who received METROGELVAGINAL once or twice a day, 2 patients
(one from each regimen) discontinued therapy early due to drug-related adverse
events. One patient discontinued drug because of moderate abdominal cramping and
loose stools, while the other patient discontinued drug because of mild vaginal
burning. These symptoms resolved after discontinuation of drug.
Medical events judged to be related, probably related, or
possibly related to administration of METROGEL-VAGINAL once or twice a day were
reported for 195/505 (39%) patients. The incidence of individual adverse
reactions were not significantly different between the two regimens. Unless percentages
are otherwise stipulated, the incidence of individual adverse reactions listed
below was less than 1%:
Vaginal discharge (12%),
Symptomatic Candida cervicitis/vaginitis (10%),
Vulva/vaginal irritative symptoms (9%),
Pelvic discomfort (3%).
Gastrointestinal discomfort (7%),
Nausea and/or vomiting (4%),
Unusual taste (2%),
Diarrhea/loose stools (1%),
Decreased appetite (1%),
Abdominal bloating/gas; thirsty, dry mouth.
Generalized itching or rash.
Unspecified cramping (1%),
In previous clinical trials submitted for approved
labeling of METROGEL-VAGINAL the following was also reported:
Increased/decreased white blood cell counts (1.7%).
Other Metronidazole Formulations
Other effects that have been reported in association with
the use of topical (dermal) formulations of metronidazole include skin
irritation, transient skin erythema, and mild skin dryness and burning. None of
these adverse events exceeded an incidence of 2% of patients.
METROGEL-VAGINAL affords minimal peak serum levels and
systemic exposure (AUC) of metronidazole compared to 500 mg oral metronidazole
dosing. Although these lower levels of exposure are less likely to produce the
common reactions seen with oral metronidazole, the possibility of these and
other reactions cannot be excluded presently.
The following adverse reactions and altered laboratory
tests have been reported with the oral or parenteral use of
Cardiovascular: Flattening of the T-wave may be
seen in electrocardiographic tracings.
Central Nervous System: (See WARNINGS.)
Headache, dizziness, syncope, ataxia, confusion, convulsive seizures,
peripheral neuropathy, vertigo, incoordination, irritability, depression, weakness,
Gastrointestinal: Abdominal discomfort, nausea,
vomiting, diarrhea, an unpleasant metallic taste, anorexia, epigastric
distress, abdominal cramping, constipation, &ldqou;furry&rdqou; tongue,
glossitis, stomatitis, pancreatitis, and modification of taste of alcoholic
Genitourinary: Overgrowth of Candida in the
vagina, dyspareunia, decreased libido, proctitis.
Hematopoietic: Reversible neutropenia, reversible
Hypersensitivity Reactions: Urticaria;
erythematous rash; flushing; nasal congestion; dryness of the mouth, vagina, or
vulva; fever; pruritus; fleeting joint pains.
Renal: Dysuria, cystitis, polyuria, incontinence,
a sense of pelvic pressure, darkened urine.