Metronidazole Vaginal Gel

VANDAZOLE (metronidazole vaginal gel, 0.75%) is the vaginal dosage form of the nitroimidazole antimicrobial metronidazole at a concentration of 0.75%. Chemically, metronidazole is a 2-methyl-5-nitroimidazole-1-ethanol.

C6H9N3O3     M.W. 171.16

VANDAZOLE is a colorless to yellow gel, containing metronidazole at a concentration of 7.5 mg/g (0.75%). The gel also contains edetate disodium, hypromellose, methylparaben, propylene glycol, propylparaben, purified water, and sodium hydroxide (to adjust pH).

Each applicator full of 5 grams of vaginal gel contains approximately 37.5 mg of metronidazole.

There is no human experience with overdosage of metronidazole vaginal gel. Vaginally applied metronidazole gel, 0.75% could be absorbed in sufficient amounts to produce systemic effects [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Do not use metronidazole vaginal if you have ever had an allergic reaction to it.

Before using metronidazole vaginal, tell your doctor if you are allergic to any drugs, or if you have:

• liver disease;
• a seizure disorder; or
• problems with circulation (such as Raynaud's syndrome).

If you have any of these conditions, you may need a dose adjustment or special tests to safely use metronidazole vaginal.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Metronidazole vaginal may pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Talk with your doctor before you drink alcohol. You may need to avoid drinking alcohol while using metronidazole vaginal gel and for some time after your last dose.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
• Do not douche or use other vaginal products like tampons while you are using metronidazole vaginal gel. You may need to avoid these things for some time after care ends. Talk with your doctor.
• This medicine may affect certain lab tests. Be sure your doctor and lab workers know you use this medicine.

Use metronidazole vaginal gel as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to take this medicine as you have been told by your doctor. Do not use more than you were told to use.
• Wash your hands before and after use.
• To gain the most benefit, do not miss doses.
• Use as you have been told, even if your signs get better.
• Do not take metronidazole vaginal gel by mouth. For vaginal use only. Keep out of your mouth, nose, and eyes (may burn).
• Some products are to be used at bedtime. For some products it does not matter. Check with the pharmacist about how to use this medicine.
• Do not have vaginal sex while using metronidazole vaginal gel.
• Do not use longer than you have been told. A second infection may happen.

What do I do if I miss a dose?

• Use a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not use 2 doses or extra doses.

Metronidazole Vaginal Gel is the intravaginal dosage form of the synthetic antibacterial agent, metronidazole, USP at a concentration of 0.75%. Metronidazole is a member of the imidazole class of antibacterial agents and is classified therapeutically as an antiprotozoal and antibacterial agent. Chemically, metronidazole is a 2-methyl-5-nitroimidazole-1-ethanol. It has a chemical formula of C6H9N3O3, a molecular weight of 171.16, and has the following structure:

Metronidazole Vaginal Gel is a gelled, purified water solution, containing metronidazole at a concentration of 7.5 mg/g (0.75%). The gel is formulated at pH 4.0. The gel also contains carbomer 934P, edetate disodium, methylparaben, propylparaben, propylene glycol, and sodium hydroxide.

Each applicator full of 5 grams of vaginal gel contains approximately 37.5 mg of metronidazole.

Clinical Trials:

There were no deaths or serious adverse events related to drug therapy in clinical trials involving 800 non-pregnant women who received Metronidazole Vaginal Gel.

In a randomized, single-blind clinical trial of 505 non-pregnant women who received Metronidazole Vaginal Gel 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 Metronidazole Vaginal Gel 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 Metronidazole Vaginal Gel 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

Metronidazole Vaginal Gel 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 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.

The recommended dose is one applicator full of Metronidazole Vaginal Gel (approximately 5 grams containing approximately 37.5 mg of metronidazole) intravaginally once or twice a day for 5 days. For once-a-day dosing, Metronidazole Vaginal Gel should be administered at bedtime.