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FLAGYL®
(metronidazole) tablets
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 bacteria.

WARNING
Metronidazole has been shown to be carcinogenic in mice and rats (seePRECAUTIONS). Unnecessary use of the drug should be avoided. Its use should bereserved for the conditions described in the INDICATIONS AND USAGE section
below.
DESCRIPTIONFLAGYL (metronidazole) tablets, 250 mg or 500 mg is an oral formulation of thesynthetic nitroimidazole antimicrobial, 2-methyl-5-nitro-1H-imidazole-1-ethanol, which
has the following structural formula:

FLAGYL (metronidazole) tablets contain 250 mg or 500 mg of metronidazole. Inactive
ingredients include cellulose, FD&C Blue No. 2 Lake, hydroxypropyl cellulose,
hypromellose, polyethylene glycol, stearic acid, and titanium dioxide.
CLINICAL PHARMACOLOGY
Absorption
Disposition of metronidazole in the body is similar for both oral and intravenous dosage
forms. 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. Oraladministration 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.

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Distribution
Metronidazole is the major component appearing in the plasma, with lesser quantities ofmetabolites also being present. Less than 20% of the circulating metronidazole is boundto plasma proteins. Metronidazole appears in cerebrospinal fluid, saliva, and breast milkin concentrations similar to those found in plasma. Bactericidal concentrations ofmetronidazole have also been detected in pus from hepatic abscesses.
Metabolism/Excretion
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-(ßhydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-ylacetic acid] and glucuronide conjugation, with unchanged metronidazole accounting for
approximately 20% of the total. Both the parent compound and the hydroxyl metabolite
possess in vitro antimicrobial activity.
Renal clearance of metronidazole is approximately 10 mL/min/1.73 m2. The average
elimination half-life of metronidazole in healthy subjects is eight hours.
Renal Impairment
Decreased renal function does not alter the single-dose pharmacokinetics ofmetronidazole.
Subjects with end-stage renal disease (ESRD; CL CR = 8.1±9.1 mL/min) and who received
a single intravenous infusion of metronidazole 500 mg had no significant change inmetronidazole pharmacokinetics but had 2-fold higher Cmax of hydroxy-metronidazole
and 5-fold higher Cmax of metronidazole acetate, compared to healthy subjects withnormal renal function (CL CR = 126±16 mL/min). Thus, on account of the potential
accumulation of metronidazole metabolites in ESRD patients, monitoring for
metronidazole associated adverse events is recommended (see PRECAUTIONS).
Effect of Dialysis
Following a single intravenous infusion or oral dose of metronidazole 500 mg, theclearance of metronidazole was investigated in ESRD subjects undergoing hemodialysis
or continuous ambulatory peritoneal dialysis (CAPD). A hemodialysis session lasting for
4 to 8 hours removed 40% to 65% of the administered metronidazole dose, depending on
the type of dialyzer membrane used and the duration of the dialysis session. If theadministration of metronidazole cannot be separated from the dialysis session,
supplementation of metronidazole dose following hemodialysis should be considered (seeDOSAGE AND ADMINISTRATION). A peritoneal dialysis session lasting for
7.5 hours removed approximately 10% of the administered metronidazole dose. No
adjustment in metronidazole dose is needed in ESRD patients undergoing CAPD.
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Hepatic Impairment
Following a single intravenous infusion of 500 mg metronidazole, the mean AUC 24 of
metronidazole was higher by 114% in patients with severe (Child-Pugh C) hepatic
impairment, and by 54% and 53% in patients with mild (Child-Pugh A) and moderate(Child-Pugh B) hepatic impairment, respectively, compared to healthy control subjects.
There were no significant changes in the AUC 24 of hydroxyl-metronidazole in thesehepatically impaired patients. A reduction in metronidazole dosage by 50% is
recommended in patients with severe (Child-Pugh C) hepatic impairment (see DOSAGE
AND ADMINISTRATION). No dosage adjustment is needed for patients with mild tomoderate hepatic impairment. Patients with mild to moderate hepatic impairment should
be monitored for metronidazole associated adverse events (see PRECAUTIONS andDOSAGE AND ADMINISTRATION).
Geriatric Patients
Following a single 500 mg oral or IV dose of metronidazole, subjects >70 years old with
no apparent renal or hepatic dysfunction had a 40% to 80% higher mean AUC ofhydroxy-metronidazole (active metabolite), with no apparent increase in the mean AUC
of metronidazole (parent compound), compared to young healthy controls <40 years old.
In geriatric patients, monitoring for metronidazole associated adverse events is
recommended (see PRECAUTIONS).
Pediatric Patients
In one study, newborn infants appeared to demonstrate diminished capacity to eliminate
metronidazole. The elimination half-life, measured during the first 3 days of life, wasinversely related to gestational age. In infants whose gestational ages were between 28
and 40 weeks, the corresponding elimination half-lives ranged from 109 to 22.5 hours.
Microbiology
Mechanism of Action
Metronidazole, a nitroimidazole, exerts antibacterial effects in an anaerobic environment
against most obligate anaerobes. Once metronidazole enters the organism by passive
diffusion and activated in the cytoplasm of susceptible anaerobic bacteria, it is reduced;
this process includes intracellular electron transport proteins such as ferredoxin, transfer
of an electron to the nitro group of the metronidazole, and formation of a short-lived
nitroso free radical. Because of this alteration of the metronidazole molecule, aconcentration gradient is created and maintained which promotes the drug’s intracellulartransport. The reduced form of metronidazole and free radicals can interact with DNA
leading to inhibition of DNA synthesis and DNA degradation leading to death of thebacteria. The precise mechanism of action of metronidazole is unclear.

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Resistance
A potential for development of resistance exists against metronidazole.
Resistance may be due to multiple mechanisms that include decreased uptake of the drug,
altered reduction efficiency, overexpression of the efflux pumps, inactivation of the drug,
and/or increased DNA damage repair.
Metronidazole does not possess any clinically relevant activity against facultative
anaerobes or obligate aerobes.
Antimicrobial Activity
Metronidazole has been shown to be active against most isolates of the following bacteria
both in vitro and in clinical infections as described in the INDICATIONS AND USAGE
section.
Gram-positive anaerobes
Clostridium species
Eubacterium species
Peptococcus species
Peptostreptococcus species
Gram-negative anaerobes
Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron,B.vulgatus)
Fusobacterium species
Protozoal parasites
Entamoeba histolytica
Trichomonas vaginalis
The following in vitro data are available, but their clinical significance is unknown:
Metronidazole exhibits in vitro minimal inhibitory concentrations (MIC’s) of 8 mcg/mLor less against most (≥ 90%) isolates of the following bacteria; however, the safety andeffectiveness of metronidazole in treating clinical infections due to these bacteria havenot been established in adequate and well-controlled clinical trials.
Gram-negative anaerobes
Bacteroides fragilis group (B. caccae, B. uniformis)
Prevotella species (P. bivia, P. buccae, P. disiens)

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Susceptibility Testing
For specific information regarding susceptibility test interpretive criteria and associatedtest methods and quality control standards recognized by FDA for this drug, please see:https://www.fda.gov/STIC.
INDICATIONS AND USAGE
Symptomatic Trichomoniasis. FLAGYL is indicated for the treatment of T. vaginalis
infection in females and males when the presence of the trichomonad has been confirmed
by appropriate laboratory procedures (wet smears and/or cultures).
Asymptomatic Trichomoniasis. FLAGYL is indicated in the treatment of asymptomatic
T. vaginalis infection in females when the organism is associated with endocervicitis,
cervicitis, or cervical erosion. Since there is evidence that presence of the trichomonadcan interfere with accurate assessment of abnormal cytological smears, additional smears
should be performed after eradication of the parasite.
Treatment of Asymptomatic Sexual Partners. T. vaginalis infection is a venereal
disease. Therefore, asymptomatic sexual partners of treated patients should be treatedsimultaneously 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 malepartner who has a negative culture or one for whom no culture has been attempted is anindividual one. In making this decision, it should be noted that there is evidence that awoman may become reinfected if her sexual partner is not treated. Also, since there canbe 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 sexual
partner should be treated with FLAGYL in cases of reinfection.
Amebiasis. FLAGYL is indicated in the treatment of acute intestinal amebiasis (amebic
dysentery) 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 shouldbe 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.
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), Clostridium species,
Eubacterium species, Peptococcus species, and Peptostreptococcus species.

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SKIN AND SKIN STRUCTURE INFECTIONS caused by Bacteroides species including
the B. fragilis group, Clostridium species, Peptococcus species, Peptostreptococcus
species, and Fusobacterium species.
GYNECOLOGIC INFECTIONS, including endometritis, endomyometritis, tubo-ovarian
abscess, and postsurgical vaginal cuff infection, caused by Bacteroides species including
the B. fragilis group, Clostridium species, Peptococcus species, Peptostreptococcus
species, and Fusobacterium species.
BACTERIAL SEPTICEMIA caused by Bacteroides species including the B. fragilisgroup and Clostridium 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, andlung 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 inselecting or modifying antibacterial therapy. In the absence of such data, local
epidemiology and susceptibility patterns may contribute to the empiric selection oftherapy.
CONTRAINDICATIONSHypersensitivity
FLAGYL Tablets is contraindicated in patients with a prior history of hypersensitivity tometronidazole or other nitroimidazole derivatives.
In patients with trichomoniasis, FLAGYL Tablets is contraindicated during the firsttrimester of pregnancy (see PRECAUTIONS).
Psychotic Reaction with Disulfiram
Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who
were using disulfiram concurrently. Do not administer metronidazole to patients who

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have taken disulfiram within the last two weeks (see PRECAUTIONS, Drug
Interactions).
Interaction with Alcohol
Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol,
including abdominal cramps, nausea, vomiting, headaches, and flushing. Discontinue
consumption of alcohol or products containing propylene glycol during and for at least
three days after therapy with metronidazole (see PRECAUTIONS, Drug Interactions).
Cockayne Syndrome
FLAGYL Tablets are contraindicated in patients with Cockayne syndrome. Severe
irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after
initiation of metronidazole in patients with Cockayne syndrome (see ADVERSE
REACTIONS).
WARNINGS
Central and Peripheral Nervous System Effects
Encephalopathy and peripheral neuropathy: Cases of encephalopathy and peripheral
neuropathy (including optic neuropathy) have been reported with metronidazole.
Encephalopathy has been reported in association with cerebellar toxicity characterized byataxia, dizziness, and dysarthria. CNS lesions seen on MRI have been described inreports of encephalopathy. CNS symptoms are generally reversible within days to weeks
upon discontinuation of metronidazole. CNS lesions seen on MRI have also been
described as reversible.
Peripheral neuropathy, mainly of sensory type has been reported and is characterized bynumbness or paresthesia of an extremity.
Convulsive seizures have been reported in patients treated with metronidazole.
Aseptic meningitis: Cases of aseptic meningitis have been reported with metronidazole.
Symptoms can occur within hours of dose administration and generally resolve after
metronidazole therapy is discontinued.
The appearance of abnormal neurologic signs and symptoms demands the prompt
evaluation of the benefit/risk ratio of the continuation of therapy (see ADVERSE
REACTIONS).

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PRECAUTIONSGeneralHepatic Impairment
Patients with hepatic impairment metabolize metronidazole slowly, with resultant
accumulation of metronidazole in the plasma. For patients with severe hepatic
impairment (Child-Pugh C), a reduced dose of FLAGYL is recommended. For patientswith mild to moderate hepatic impairment, no dosage adjustment is needed but thesepatients should be monitored for metronidazole associated adverse events (seeCLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).
Renal Impairment
Patients with end-stage renal disease may excrete metronidazole and metabolites slowly
in the urine, resulting in significant accumulation of metronidazole metabolites.
Monitoring for metronidazole associated adverse events is recommended (seeCLINICAL PHARMACOLOGY).
Fungal Superinfections
Known or previously unrecognized candidiasis may present more prominent symptoms
during therapy with FLAGYL and requires treatment with a candidacidal agent.
Use in Patients with Blood Dyscrasias
Metronidazole is a nitroimidazole and should be used with caution in patients withevidence of or history of blood dyscrasia. A mild leukopenia has been observed during its
administration; however, no persistent hematologic abnormalities attributable tometronidazole have been observed in clinical studies. Total and differential leukocyte
counts are recommended before and after therapy.
Drug-Resistant Bacteria and Parasites
Prescribing FLAGYL in the absence of a proven or strongly suspected bacterial orparasitic infection or a prophylactic indication is unlikely to provide benefit to the patientand increases the risk of the development of drug-resistant bacteria and parasites.

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Information for PatientsInteraction 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 andparasitic 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 thelikelihood that bacteria will develop resistance and will not be treatable by FLAGYL in
the future.
Drug Interactions
Disulfiram
Psychotic reactions have been reported in alcoholic patients who are using metronidazoleand disulfiram concurrently. Metronidazole should not be given to patients who havetaken disulfiram within the last two weeks (see CONTRAINDICATIONS).
Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, and flushing may occur if alcoholic
beverages or products containing propylene glycol are consumed during or following
metronidazole therapy (see CONTRAINDICATIONS).
Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin andother oral coumarin anticoagulants, resulting in a prolongation of prothrombin time.
When FLAGYL is prescribed for patients on this type of anticoagulant therapy,
prothrombin time and INR should be carefully monitored.
Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole
therapy has been associated with elevation of serum lithium and, in a few cases, signs oflithium toxicity. Serum lithium and serum creatinine levels should be obtained several

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days after beginning metronidazole to detect any increase that may precede clinicalsymptoms of lithium intoxication.
BusulfanMetronidazole has been reported to increase plasma concentrations of busulfan, which
can result in an increased risk for serious busulfan toxicity. Metronidazole should not be
administered concomitantly with busulfan unless the benefit outweighs the risk. If notherapeutic alternatives to metronidazole are available, and concomitant administration
with busulfan is medically needed, frequent monitoring of busulfan plasma concentration
should be performed and the busulfan dose should be adjusted accordingly.
Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme
activity, such as cimetidine, may prolong the half-life and decrease plasma clearance ofmetronidazole.
Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzymes, such as
phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in
reduced plasma levels; impaired clearance of phenytoin has also been reported.
Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administeredwith drugs with the potential for prolonging the QT interval.
Drug/Laboratory Test Interactions
Metronidazole may interfere with certain types of determinations of serum chemistryvalues, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase(ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and glucose hexokinase.
Values of zero may be observed. All of the assays in which interference has beenreported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide
adenine dinucleotide (NAD+NADH). Interference is due to the similarity inabsorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Tumors affecting the liver, lungs, mammary, and lymphatic tissues have been detected inseveral studies of metronidazole in rats and mice, but not hamsters.
Pulmonary tumors have been observed in all six reported studies in the mouse, including
one study in which the animals were dosed on an intermittent schedule (administration
during every fourth week only). Malignant liver tumors were increased in male mice
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treated at approximately 1500 mg/m2 (similar to the maximum recommended daily dose,
based on body surface area comparisons). Malignant lymphomas and pulmonary
neoplasms were also increased with lifetime feeding of the drug to mice. Mammary andhepatic tumors were increased among female rats administered oral metronidazole
compared to concurrent controls. Two lifetime tumorigenicity studies in hamsters havebeen performed and reported to be negative.
Metronidazole has shown mutagenic activity in in vitro assay systems including theAmes test. Studies in mammals in vivo have failed to demonstrate a potential for genetic
damage.
Metronidazole failed to produce any adverse effects on fertility or testicular function inmale rats at doses up at 400 mg/kg/day (similar to the maximum recommended clinicaldose, based on body surface area comparisons) for 28 days. However, rats treated at thesame dose for 6 weeks or longer were infertile and showed severe degeneration of theseminiferous epithelium in the testes as well as marked decreases in testicular spermatid
counts and epididymal sperm counts. Fertility was restored in most rats after an eight
week, drug-free recovery period.
Pregnancy:
Teratogenic Effects:
There are no adequate and well controlled studies of FLAGYL in pregnant women. There
are published data from case-control studies, cohort studies, and 2 meta-analyses that
include more than 5000 pregnant women who used metronidazole during pregnancy.
Many studies included first trimester exposures. One study showed an increased risk ofcleft lip, with or without cleft palate, in infants exposed to metronidazole in-utero;
however, these findings were not confirmed. In addition, more than ten randomized
placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess theuse of antibiotic treatment (including metronidazole) for bacterial vaginosis on theincidence of preterm delivery. Most studies did not show an increased risk for congenital
anomalies or other adverse fetal outcomes following metronidazole exposure during
pregnancy. Three studies conducted to assess the risk of infant cancer following
metronidazole exposure during pregnancy did not show an increased risk; however, theability of these studies to detect such a signal was limited.
Metronidazole crosses the placental barrier and its effects on the human fetalorganogenesis are not known. Reproduction studies have been performed in rats, rabbits,
and mice at doses similar to the maximum recommended human dose based on bodysurface area comparisons. There was no evidence of harm to the fetus due tometronidazole.
Nursing Mothers
Metronidazole is present in human milk at concentrations similar to maternal serum
levels, and infant serum levels can be close to or comparable to infant therapeutic levels.
Because of the potential for tumorigenicity shown for metronidazole in mouse and rat
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drug, taking into account the importance of the drug to the mother. Alternatively, anursing mother may choose to pump and discard human milk for the duration of
metronidazole therapy, and for 24 hours after therapy ends and feed her infant stored
human milk or formula.
Geriatric Use
In elderly geriatric patients, monitoring for metronidazole associated adverse events is
recommended (see CLINICAL PHARMACOLOGY, PRECAUTIONS). Decreased
liver function in geriatric patients can result in increased concentrations of metronidazolethat may necessitate adjustment of metronidazole dosage (see DOSAGE AND
ADMINISTRATION).
Pediatric Use
Safety and effectiveness in pediatric patients have not been established, except for thetreatment of amebiasis.
ADVERSE REACTIONS
The following reactions have been reported during treatment with metronidazole:
Central Nervous System: The most serious adverse reactions reported in patients treatedwith metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis,
optic and peripheral neuropathy, the latter characterized mainly by numbness orparesthesia of an extremity. Since persistent peripheral neuropathy has been reported insome patients receiving prolonged administration of metronidazole, patients should bespecifically warned about these reactions and should be told to stop the drug and report
immediately to their physicians if any neurologic symptoms occur. In addition, patients
have reported headache, syncope, dizziness, vertigo, incoordination, ataxia, confusion,
dysarthria, irritability, depression, weakness, and insomnia (see WARNINGS).
Gastrointestinal: The most common adverse reactions reported have been referable to
the gastrointestinal tract, particularly nausea, sometimes accompanied by headache,anorexia, and occasionally vomiting; diarrhea; epigastric distress; and abdominal
cramping and constipation.
Mouth: A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, andstomatitis have occurred; these may be associated with a sudden overgrowth of Candida
which may occur during therapy.
Dermatologic: Erythematous rash and pruritus.
Hematopoietic: Reversible neutropenia (leukopenia); rarely, reversible
thrombocytopenia.

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Cardiovascular: QT prolongation has been reported, particularly when metronidazole
was administered with drugs with the potential for prolonging the QT interval. Flatteningof the T-wave may be seen in electrocardiographic tracings.
Hypersensitivity: Urticaria, erythematous rash, Stevens-Johnson Syndrome, toxic
epidermal necrolysis, flushing, nasal congestion, dryness of the mouth (or vagina or
vulva), and fever.
Renal: Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instancesof 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 noclinical significance.
Hepatic: Cases of severe irreversible hepatotoxicity/acute liver failure, including caseswith fatal outcomes with very rapid onset after initiation of systemic use of
metronidazole, have been reported in patients with Cockayne syndrome (latency fromdrug start to signs of liver failure as short as 2 days) (see CONTRAINDICATIONS).
Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis,
and fleeting joint pains sometimes resembling “serum sickness.” Rare cases ofpancreatitis, which generally abated on withdrawal of the drug, have been reported.
Patients with Crohn’s disease are known to have an increased incidence ofgastrointestinal 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 beentreated with metronidazole at high doses for extended periods of time. A cause and effectrelationship has not been established. Crohn’s disease is not an approved indication for
FLAGYL tablets.
OVERDOSAGE
Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts andaccidental overdoses. Symptoms reported include nausea, vomiting, and ataxia.
Oral metronidazole has been studied as a radiation sensitizer in the treatment ofmalignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, havebeen reported after 5 to 7 days of doses of 6 to 10.4 g every other day.
Treatment of Overdosage: There is no specific antidote for metronidazole overdose;
therefore, management of the patient should consist of symptomatic and supportive
therapy.

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DOSAGE AND ADMINISTRATION
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 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 assurecompliance, 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 toobtain appropriate treatment. Further, some patients may tolerate one treatment regimen
better than the other.
Pregnant patients should not be treated during the first trimester (seeCONTRAINDICATIONS). 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 fourto six weeks elapse between courses and that the presence of the trichomonad bereconfirmed 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 isusually administered initially.
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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 FLAGYL
should be reduced by 50% (see CLINICAL PHARMACOLOGY and
PRECAUTIONS).
Patients Undergoing Hemodialysis:
Hemodialysis removes significant amounts of metronidazole and its metabolites fromsystemic circulation. The clearance of metronidazole will depend on the type of dialysis
membrane used, the duration of the dialysis session, and other factors. If theadministration of metronidazole cannot be separated from the hemodialysis session,
supplementation of metronidazole dosage following the hemodialysis session should beconsidered, depending on the patient’s clinical situation (see CLINICALPHARMACOLOGY).
HOW SUPPLIEDFLAGYL 250-mg tablets are round, blue, film coated, with SEARLE and 1831 debossedon one side and FLAGYL and 250 on the other side; supplied as bottles of 50 and 100.
NDC Number
0025-1831-50
0025-1831-31

Sizebottle of 50
bottle of 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.
NDC Number
0025-1821-50
0025-1821-31

Sizebottle of 50
bottle of 100

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

15

Reference ID: 4904507

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda

LAB-0162-17.0
Revised: 12/2021

16

Reference ID: 4904507