Metronidazole

• Flagyl is used to treat parasitic infections including Giardia infections of the small intestine, amebic liver abscess, and amebic dysentery (infection of the colon causing bloody diarrhea), bacterial vaginosis, trichomonas vaginal infections, and carriers of trichomonas (both sexual partners) who do not have symptoms of infection.
• Flagyl is also used alone or in combination with other antibiotics in treating abscesses in the liver, pelvis, abdomen, and brain caused by susceptible anaerobic bacteria.
• Flagyl is also used in treating infection of the colon caused by a bacterium called C. difficile. Many commonly-used antibiotics can alter the type of bacteria that inhabit the colon. C. difficile is an anaerobic bacterium that can infect the colon when the normal types of bacteria in the colon are inhibited by common antibiotics. This leads to inflammation of the colon (pseudomembranous colitis) with severe diarrhea and abdominal pain.)
• Flagyl also is used in combination with other drugs to treat Helicobacter pylori (H. pylori) that causes stomach or intestinal ulcers.
• Flagyl topical gel is used for treating acne rosacea.
• Flagyl vaginal gel is used for treating bacterial vaginosis.

• Alcohol should be avoided because metronidazole and alcohol together can cause severe nausea, vomiting, cramps, flushing, and headache.
• Metronidazole can increase the blood thinning effects of warfarin (Coumadin, Jantoven) and increase the risk of bleeding probably by reducing the breakdown of warfarin.
• Cimetidine (Tagamet) increases blood levels of metronidazole while cholestyramine (Questran, Questran Light) reduces blood levels of metronidazole by reducing its absorption.
• Metronidazole should not be combined with amprenavir (Agenerase) for treating human immunodeficiency disease (infection with HIV) because amprenavir contains propylene glycol.
• Metronidazole blocks the breakdown of propylene glycol in the liver leading to accumulation of propylene glycol in blood. Accumulation of propylene glycol could cause seizures, increased heart rate, and lead to kidney failure.
• Metronidazole increases the blood levels of carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol), lithium (Eskalith, Lithobid) and cyclosporine though unknown mechanisms. Serious reactions may occur if these drugs are taken with metronidazole.

FLAGYL 250-mg tablets are round, blue, film coated, with SEARLE and 1831 debossed on one side and FLAGYL and 250 on the other side; supplied as bottles of 50 and 100.

FLAGYL 500-mg tablets are oblong, blue, film coated, with FLAGYL debossed on one side and 500 on the other side; bottles of 50 and 100.

Storage And Stability

Store below 77°F (25°C) and protect from light.

Distributed by: G.D. Searle, Division of Pfizer Inc., NY, NY, 10017. Revised: July 2016

Interaction With Alcohol

Discontinue consumption of alcoholic beverages or products containing propylene glycol while taking FLAGYL and for at least three days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur (see CONTRAINDICATIONS and PRECAUTIONS, DRUG INTERACTIONS).

Treatment Of Bacterial And Parasitic Infections

Patients should be counseled that FLAGYL should only be used to treat bacterial and parasitic infections. FLAGYL does not treat viral infections (e.g., the common cold). When FLAGYL is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by FLAGYL in the future.

METROGEL contains metronidazole, USP. Chemically, metronidazole is 2-methyl-5-nitro-1 H-imidazole-1-ethanol. The molecular formula for metronidazole is C6H9N3O3. It has the following structural formula:

Metronidazole has a molecular weight of 171.16. It is a white to pale yellow crystalline powder. It is slightly soluble in alcohol and has solubility in water of 10 mg/mL at 20°C. Metronidazole belongs to the nitroimidazole class of compounds.

METROGEL is an aqueous gel; each gram contains 10 mg of metronidazole in a base of betadex, edetate disodium, hydroxyethyl cellulose, methylparaben, niacinamide, phenoxyethanol, propylene glycol, propylparaben and purified water.

METROGEL-VAGINAL 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:

METROGEL-VAGINAL 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.

Safety data from 302 patients who used NORITATE (metronidazole) (n=200) or vehicle control (n=102) once daily in clinical trials and experienced an adverse event considered to be treatment-related include: application site reaction (NORITATE (metronidazole) 1, vehicle 1), condition aggravated (NORITATE (metronidazole) 1, vehicle 0), paresthesia (NORITATE (metronidazole) 0, vehicle 1), acne (NORITATE (metronidazole) 1, vehicle 0), dry skin (NORITATE (metronidazole) 0, vehicle 2). The majority of adverse reactions were mild to moderate in severity.

Two patients treated with NORITATE (metronidazole) once daily discontinued treatment because of adverse events: one for a severe flare of comedonal acne and one for rosacea aggravated.

• Yeast Infection (in Women and Men)

Metronidazole is an antibiotic that fights bacteria in the body.

Metronidazole topical (for the skin) is used to treat skin lesions caused by rosacea.

Metronidazole topical may also be used for other purposes not listed in this medication guide.

Before taking metronidazole, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to metronidazole or to any of its ingredients
• have or have had Crohn’s disease
• have or have had liver problems
• have or have had kidney problems
• have or have had blood disorders
• have or are being treated for alcohol dependence
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

• Advise patients that antibacterials (including metronidazole) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).152 197 430

• Importance of completing full course of therapy, even if feeling better after a few days.152 197 430

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with metronidazole or other antibacterials in the future.152 197 430

• Metronidazole extended-release tablets should be taken at least 1 hour before or 2 hours after meals; optimum absorption occurs under fasting conditions.430

• Advise patients to avoid alcohol during and for at least 1 day after conventional tablets152 or at least 3 days after receiving metronidazole capsules or extended-release tablets.197 430

• Advise patients to promptly discontinue metronidazole and contact clinician if abnormal neurologic signs occur.152 197 430

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.152 197 430

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.152 197 430

• Importance of advising patients of other important precautionary information.152 197 430 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Trichomoniasis:

In the Female:

One-day treatment – two grams of Metronidazole, given either as a single dose or in two divided doses of one gram each, given in the same day.

Seven-day course of treatment – 250 mg three times daily for seven consecutive days. There is some indication from controlled comparative studies that cure rates as determined by vaginal smears and signs and symptoms, may be higher after a seven-day course of treatment than after a one-day treatment regimen.

The dosage regimen should be individualized. Single-dose treatment can assure compliance, especially if administered under supervision, in those patients who cannot be relied on to continue the seven-day regimen.

A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain appropriate treatment. Further, some patients may tolerate one treatment regimen better than the other.

Pregnant patients should not be treated during the first trimester (see CONTRAINDICATIONS). In pregnant patients for whom alternative treatment has been inadequate, the one-day course of therapy should not be used, as it results in higher serum levels which can reach the fetal circulation (see PRECAUTIONS, Pregnancy). When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and that the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leukocyte counts should be made before and after re-treatment.

In the Male: Treatment should be individualized as it is for the female.

Amebiasis

Adults:

For acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days.

For amebic liver abscess: 500 mg or 750 mg orally three times daily for 5 to 10 days.

Pediatric patients: 35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days.

Anaerobic Bacterial Infections

In the treatment of most serious anaerobic infections, intravenous Metronidazole is usually administered initially. The usual adult oral dosage is 7.5 mg/kg every six hours (approx. 500 mg for a 70-kg adult). A maximum of 4 g should not be exceeded during a 24-hour period.

The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.

Dosage Adjustments

Patients with Severe Hepatic Impairment

For patients with severe hepatic impairment (Child-Pugh C), the dose of Metronidazole should be reduced by 50% (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Patients Undergoing Hemodialysis:

Hemodialysis removes significant amounts of Metronidazole and its metabolites from systemic circulation. The clearance of Metronidazole will depend on the type of dialysis membrane used, the duration of the dialysis session, and other factors. If the administration of Metronidazole cannot be separated from the hemodialysis session, supplementation of Metronidazole dosage following the hemodialysis session should be considered, depending on the patient’s clinical situation (see CLINICAL PHARMACOLOGY).