ADVERSE EVENTS
Clinical Trials:
There were no deaths or serious adverse events related to drug therapy in clinical trials involving 800 non-pregnant women who received METROGEL-VAGINAL.
In a randomized, single-blind clinical trial of 505 non-pregnant women who received METROGEL-VAGINAL 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%:
Reproductive:
Vaginal discharge (12%),
Symptomatic Candida cervicitis/vaginitis (10%),
Vulva/vaginal irritative symptoms (9%),
Pelvic discomfort (3%).
Gastrointestinal:
Gastrointestinal discomfort (7%),
Nausea and/or vomiting (4%),
Unusual taste (2%),
Diarrhea/loose stools (1%),
Decreased appetite (1%),
Abdominal bloating/gas; thirsty, dry mouth.
Neurologic:
Headache (5%),
Dizziness (2%),
Depression.
Dermatologic:
Generalized itching or rash.
Other:
Unspecified cramping (1%),
Fatigue,
Darkened urine.
In previous clinical trials submitted for approved labeling of METROGEL-VAGINAL the following was also reported:
Laboratory:
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 metro‑nidazole 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 metronidazole:
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, insomnia.
Gastrointestinal: Abdominal discomfort, nausea, vomiting, diarrhea, an unpleasant metallic taste, anorexia, epigastric distress, abdominal cramping, constipation, “furry” tongue, glossitis, stomatitis, pancreatitis, and modification of taste of alcoholic beverages.
Genitourinary: Overgrowth of Candida in the vagina, dyspareunia, decreased libido, proctitis.
Hematopoietic: Reversible neutropenia, reversible thrombocytopenia.
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.
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