Flagyl (metronidazole) is an oral synthetic antipro-tozoal and antibacterial agent, 1-(β-hydroxy-ethyl)-2-methyl-5-nitroimidazole, which has the following structural formula:

Flagyl tablets contain 250 mg or 500 mg of met-ronidazole. Inactive ingredients include cellulose, FD&C Blue No. 2 Lake, hydroxypropyl cellulose, hypromellose, polyethylene glycol, stearic acid, and titanium dioxide.

Symptomatic Trichomoniasis

Flagyl is indicated for the treatment of symptomatic trichomoniasis in females and males when the presence of thetrichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures).

Asymptomatic Trichomoniasis

Flagyl is indicated in the treatment of asymptomatic females when the organism is associated with endocervi-citis, cervicitis, or cervical erosion. Since there is evidence that presence of the trichomonad can interfere with accurate assessment of abnormal cytological smears, additional smears should be performed after eradication of the parasite.

Treatment of Asymptomatic Consorts.

T. vagi-nalis infection is a venereal disease. Therefore, asymptomatic sexual partners of treated patients should be treated simultaneously if the organism has been found to be present, in order to prevent reinfection of the partner. The decision as to whether to treat an asymptomatic male partner who has a negative culture or one for whom no culture has been attempted is an individual one. In making this decision, it should be noted that there is evidence that a woman may become reinfected if her consort is not treated. Also, since there can be considerable difficulty in isolating the organism from the asymptomatic male carrier, negative smears and cultures cannot be relied upon in this regard. In any event, the consort should be treated with Flagyl in cases of reinfection.

Amebiasis

Flagyl is indicated in the treatment of acute intestinal amebiasis (amebic dysen-tery)and amebic liver abscess.

In amebic liver abscess, Flagyl therapy does not obviate the need for aspiration or drainage of pus.

Anaerobic Bacterial Infections

Flagyl is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with Flagyl therapy. In a mixed aerobic and anaerobic infection, antimicrobials appropriate for the treatment of the aerobic infection should be used in addition to Flagyl.

In the treatment of most serious anaerobic infections, Flagyl I.V. (metronidazole hydrochloride) or Flagyl I.V. RTU® (metronidazole) is usually administered initially. This may be followed by oral ther-apy with Flagyl (metronidazole) at the discretion of the physician.

INTRA-ABDOMINAL INFECTIONS, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species including the B. fragilis group (B. fragilis, B. distasonis,B. ovatus, B. thetaiotaomicron, B. vulgatus), Clostrid-ium species, Eubacterium species, Peptococcus niger, and Peptostreptococcus species.

SKIN AND SKIN STRUCTURE INFECTIONS caused by Bacteroides species including the B. fragilis group, Clostridium species, Peptococcus niger,Peptostreptococcus species, and Fusobacte-rium species.

GYNECOLOGIC INFECTIONS, including endo-metritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection, caused by Bacteroides species including the B. fragilis group, Clostridium species, Peptococcusniger, and Pepto-streptococcus species.

BACTERIAL SEPTICEMIA caused by Bacteroides species including the B. fragilis group, and Clos-tridium species.

BONE AND JOINT INFECTIONS, as adjunctive therapy, caused by Bacteroides species including the B. fragilis group.

CENTRAL NERVOUS SYSTEM (CNS) INFECTIONS, including meningitis and brain abscess, caused by Bacteroides species including the B.fragilis group.

LOWER RESPIRATORY TRACT INFECTIONS, including pneumonia, empyema, and lung abscess, caused by Bacteroides species including the B. fragilis group.

ENDOCARDITIS caused by Bacteroides species including the B.fragilis group.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Flagyl and other antibacterial drugs, Flagyl should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

In elderly patients, the pharmacokinetics of metro-nidazole may be altered, and, therefore, monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

Trichomoniasis

In the Female

One-day treatment-two grams of Flagyl, 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, 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 in 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 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, Flagyl I.V. (met-ronidazole hydrochloride) or Flagyl I.V. RTU® (met-ronidazole) 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.

Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously. Close monitoring of plasma metronidazole levels²and toxicity is recommended.

The dose of Flagyl should not be specifically reduced in anuric patients since accumulated metabolites may be rapidly removed by dialysis.

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; bottles of 50, 100, and 2,500.

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

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

REFERENCES

2. Ralph, E.D., and Kirby, W.M.M.: Bioassay of Met-ronidazole With Either Anaerobic or Aerobic Incubation, J. Infect. Dis. 132:587-591 (Nov.) 1975; or Gulaid, et al.: Determination of Metronidazole and Its Major Metabolites in Biological Fluids by High Pressure Liquid Chromatography, Br. J. Clin. Phar-macol. 6:430-432, 1978.

Revised: August 2003
G.D. Searle LLC
A subsidiary of Pharmacia Corporation Chicago, IL 60680, USA
Flagyl®
metronidazole tablets
FDA rev date: 3/17/2004

Two serious adverse reactions reported in patients treated with Flagyl (metronidazole) have been convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of Flagyl, patients should be specifically warned about these reactions and should be told to stop the drug and report immediately to their physicians if any neu-rologic symptoms occur.

The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea reported by about 12% of patients, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epi-gastric distress; and abdominal cramping. Constipation has also been reported.

The following reactions have also been reported during treatment with Flagyl (metronidazole):

Mouth: A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, and sto-matitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy.

Hematopoietic: Reversible neutropenia (leuko-penia); rarely, reversible thrombocytopenia.

Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings.

Central Nervous System: Convulsive seizures, peripheral neuropathy, dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia.

Hypersensitivity: Urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever.

Renal: Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance.

Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling &ldquoserum sickness.” If patients receiving Flagyl drink alcoholic beverages, they may experience abdominal distress, nausea, vomiting, flushing, or headache. A modification of the taste of alcoholic beverages has also been reported. Rare cases of pan-creatitis, which generally abated on withdrawal of the drug, have been reported.

Crohn's disease patients are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn's disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established. Crohn's disease is not an approved indication for Flagyl.

Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. This possible drug interaction should be considered when Flagyl (metronidazole) is prescribed for patients on this type of anticoagulant therapy.

The simultaneous administration of drugs that induce microsomal liver enzymes, such as phe-nytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.

The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole. In patients stabilized on relatively high doses of lithium, short-term Flagyl therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Serum lithium and serum cre-atinine levels should be obtained several days after beginning metronidazole to detect any increase that may precede clinical symptoms of lithium intoxication.

Alcoholic beverages should not be consumed during Flagyl therapy and for at least one day afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.

Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.

Drug/Laboratory test interactions

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine amino-transferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD⁺← → NADH). Interference is due to the similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.

Convulsive Seizures and Peripheral Neuropathy

Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with metronidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of Flagyl (metronidazole) therapy. Flagyl should be administered with caution to patients with central nervous system diseases.

General

Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously.

Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with Flagyl (metronidazole) and requires treatment with a candidacidal agent.

Prescribing Flagyl in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Laboratory tests

Flagyl (metronidazole) is a nitro-imidazole and should be used with caution in patients with evidence of or history of blood dys-crasia. A mild leukopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to metro-nidazole have been observed in clinical studies. Total and differential leukocyte counts are recommended before and after therapy for trichomonia-sis and amebiasis, especially if a second course of therapy is necessary, and before and after therapy for anaerobic infections.

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.

Prominent among the effects in the mouse was the promotion of pulmonary tumorigenesis. This has been observed in all six reported studies in that species, including one study in which the animals were dosed on an intermittent schedule (administration during every fourth week only). At very high dose levels (approx. 500 mg/kg/day which is approximately 33 times the most frequently recommended human dose for a 50 kg adult based on mg/kg body weight) there was a statistically significant increase in the incidence of malignant liver tumors in males. Also, the published results of one of the mouse studies indicate an increase in the incidence of malignant lym-phomas as well as pulmonary neoplasms associated with lifetime feeding of the drug. All these effects are statistically significant.

Several long-term, oral-dosing studies in the rat have been completed. There were statistically significant increases in the incidence of various neo-plasms, particularly in mammary and hepatic tumors, among female rats administered metroni-dazole over those noted in the concurrent female control groups.

Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative.

Although metronidazole has shown mutagenic activity in a number of in vitro assay systems, studies in mammals (in vivo) have failed to demonstrate a potential for genetic damage.

Fertility studies have been performed in mice at doses up to six times the maximum recommended human dose based on mg/m² and have revealed no evidence of impaired fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category B. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Reproduction studies have been performed in rats at doses up to five times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to metronidazole. No fetotoxicity was observed when metronidazole was administered orally to pregnant mice at 20 mg/kg/day, approximately one and a half times the most frequently recommended human dose (750 mg/day) based on mg/kg body weight; however in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed. The relationship of these findings to the drug is unknown. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed.

Use of Flagyl for trichomoniasis during pregnancy should be restricted to those in whom alternative treatment has been inadequate. Use of Flagyl (metronidazole) for trichomoniasis in pregnancy should be carefully evaluated because metronidazole crosses the placental barrier and its effects on the human fetal organogenesis are not known (see above).

Nursing mothers

Because of the potential for tumorigenicity, shown for metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance ofthe drug to the mother. Metronidazole is secreted in human milk in concentrations similar to those found in plasma.

Geriatric use

Decreased renal function does not alter the single-dose pharmacokinetics of metroni-dazole. However, plasma clearance of metronida-zole is decreased in patients with decreased liver function. Therefore, in elderly patients, monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

Pediatric use

Safety and effectiveness in pediatric patients have not been established, except for the treatment of amebiasis.

Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported include nausea, vomiting, and ataxia.

Oral metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to 10.4 g every other day.

Treatment

There is no specific antidote for Flagyl overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.

Flagyl is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.

In patients with trichomoniasis, Flagyl is contraindicated during the first trimester of pregnancy. (See WARNINGS.)

Disposition of metronidazole in the body is similar for both oral and intravenous dosage forms, with an average elimination half-life in healthy humans of eight hours.

The major route of elimination of metronidazole and its metabolites is via the urine (60 to 80% of the dose), with fecal excretion accounting for 6 to 15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation [1-(β-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid] and glucuronide conjugation, with unchanged metronidazole accounting for approximately 20% of the total. Renal clearance of metronidazole is approximately 10 mL/min/ 1.73m².

Metronidazole is the major component appearing in the plasma, with lesser quantities of the 2-hydroxymethyl metabolite also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria and in vitro trichomonacidal activity.

Metronidazole appears in cerebrospinal fluid, saliva, and human milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.

Following oral administration, metronidazole is well absorbed, with peak plasma concentrations occurring between one and two hours after administration. Plasma concentrations of metronidazole are proportional to the administered dose. Oral administration of 250 mg, 500 mg, or 2,000 mg produced peak plasma concentrations of 6 mcg/mL, 12 mcg/mL, and 40 mcg/mL, respectively. Studies reveal no significant bioavailability differences between males and females; however, because of weight differences, the resulting plasma levels in males are generally lower.

Decreased renal function does not alter the single-dose pharmacokinetics of metronidazole. However, plasma clearance of metronidazole is decreased in patients with decreased liver function.

Microbiology

Trichomonas vaginalis, Entamoeba histolytica

Flagyl (metronidazole) possesses direct tri-chomonacidal and amebacidal activity against T. vaginalis and E. histolytica. The in vitro minimal inhibitory concentration (MIC) for most strains of these organisms is 1 mcg/mL or less.

Anaerobic Bacteria

Metronidazole is active in vitro against most obligate anaerobes but does not appear to possess any clinically relevant activity against facultative anaerobes or obligate aerobes.

Against susceptible organisms, metronidazole is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations. Metronidazole has been shown to have in vitro and clinical activity against the following organisms:

Anaerobic gram-negative bacilli, including

Bacteroides species including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus) Fusobacterium species

Anaerobic gram-positive bacilli, including

Clostridium species and susceptible strains of Eubacterium

Anaerobic gram-positive cocci, including

Peptococcus niger
Peptostreptococcus species

Susceptibility Tests

Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to metronidazole; however, the rapid, routine susceptibility testing of individual isolates of anaerobic bacteria is not always practical, and therapy may be started while awaiting these results.

Quantitative methods give the most precise estimates of susceptibility to antibacterial drugs. A standardized agar dilution method and a broth microdilution method are recommended.¹

Control strains are recommended for standardized susceptibility testing. Each time the test is performed, one or more of the following strains should be included: Clostridium perfringens ATCC 13124, Bacteroides fragilis ATCC 25285, and Bac-teroidesthetaiotaomicron ATCC 29741. The mode metronidazole MICs for those three strains are reported to be 0.25, 0.25, and 0.5 mcg/mL, respectively.

A clinical laboratory is considered under acceptable control if the results of the control strains are within one doubling dilution of the mode MICs reported for metronidazole.

A bacterial isolate may be considered susceptible if the MIC value for metronidazole is not more than 16 mcg/mL. An organism is considered resistant if the MIC is greater than 16 mcg/mL. A report of “resistant” from the laboratory indicates that the infecting organism is not likely to respond to therapy.

REFERENCES

1. Proposed standard: PSM-11-Proposed Reference Dilution Procedure for Antimicrobic Susceptibility Testing of Anaerobic Bacteria, National Committee for Clinical Laboratory Standards; and Sutter, et al.: Collaborative Evaluation of a Proposed Reference Dilution Method of Susceptibility Testing of Anaerobic Bacteria, Antimicrob. Agents Chemother. 16:495-502 (Oct.) 1979; and Tally, et al.: In Vitro Activity of Thienamycin, Antimicrob. Agents Chemother. 14:436-438 (Sept.) 1978.

Alcoholic beverages should be avoided while taking Flagyl and for at least one day afterward. See DRUG INTERACTIONS.

Patients should be counseled that antibacterial drugs including Flagyl should only be used to treat bacterial infections. They do 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 or other antibacterial drugs in the future.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

METRONIDAZOLE - ORAL

(meh-troh-NID-uh-zole)

COMMON BRAND NAME(S): Flagyl

USES: Metronidazole is used to treat a variety of infections. It belongs to a class of antibiotics known as nitroimidazoles. It works by stopping the growth of bacteria and protozoa.

This antibiotic only treats bacterial and protozoal infections. It will not work for viral infections (e.g., common cold, flu). Unnecessary use or overuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: This medication may be taken with food or a full glass of water or milk to prevent stomach upset. Dosage is based on your medical condition, the type of infection being treated, and your response to therapy.

Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals.

Continue to take this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria/protozoa to continue to grow, which may result in a relapse of the infection.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Dizziness, headache, diarrhea, nausea, stomach pain, loss of appetite, constipation, changes in taste, and dry mouth may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

This drug may cause urine to darken in color. This is harmless.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: unsteadiness, seizures, mental/mood changes, numbness/tingling of hands/feet, painful urination.

Tell your doctor immediately if any of these rare but very serious side effects occur: sore throat, persistent fever, unusual bleeding/bruising, severe stomach pain, persistent nausea/vomiting.

This medication may rarely cause a severe intestinal condition (pseudomembranous colitis) due to a type of resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have any of the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection). Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking metronidazole, tell your doctor or pharmacist if you are allergic to it; or to other nitroimidazoles such as tinidazole; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, nervous system disorders (e.g., seizures), blood disorders, Crohn's disease.

Avoid alcoholic beverages while taking this medication and for at least 1 day (3 days if you are taking the oral capsules) after finishing this medicine because drinking alcohol may result in severe stomach upset/cramps, nausea, vomiting, headache and flushing.

This drug may make you dizzy; use caution engaging in activities requiring alertness such as driving or using machinery.

The elderly may be at greater risk for side effects while using this drug.

Tell your doctor if you are pregnant before using this drug. It should not be used during the first 3 months of pregnancy and used only with caution during the last 6 months, unless your infection has not improved on other antibiotics.

This medication passes into breast milk. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: alcohol-containing products (e.g., cough and cold syrups, aftershave), amprenavir oral solution, disulfiram, lopinavir/ritonavir oral solution.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting metronidazole.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (e.g., warfarin), busulfan, cimetidine, fluorouracil, lithium, live bacterial vaccines, drugs for seizures (e.g., phenobarbital, phenytoin).

This medication may interfere with certain laboratory tests (including liver function tests, blood triglyceride levels), possibly causing false test results. Make sure laboratory personnel and your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include nausea, vomiting, severe dizziness, and seizures.

NOTES: Do not share this medication with others.

Treatment of certain infections (trichomoniasis) may require that sexual partners be treated as well to avoid re-infection. During therapy, refrain from sexual intercourse or always use a condom.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in those cases.

Laboratory and/or medical tests (e.g., blood counts) should be performed from time to time to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Tablets should be stored at room temperature below 77 degrees F (25 degrees C) away from light. Capsules should be stored at or below room temperature between 59-77 degrees F (15-25 degrees C). Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.