Flagyl Injection

Metronidazole Injection, USP RTU, is a parenteral dosage form of the synthetic antibacterial agent 1-(ß-hydroxyethyl)-2-methyl-5-nitroimidazole.

Metronidazole Injection, USP RTU, in 100 mL VIAFLEX Plus single dose plastic container, is a sterile, nonpyrogenic, iso-osmotic, buffered solution of 500 mg Metronidazole, USP, 790 mg Sodium Chloride, USP, 47.6 mg Dibasic Sodium Phosphate Dried, USP and 22.9 mg Citric Acid Anhydrous, USP. Metronidazole Injection, USP RTU has an osmolarity of 310 mOsmol/L (calc) and a pH of 5.5 (4.5 to 7.0). Each container contains 14 mEq of sodium.

The plastic container is fabricated from a specially formulated polyvinyl chloride plastic. Water can permeate from inside the container into the overwrap in amounts insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.

Metronidazole is a synthetic antibacterial compound. 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 (60-80% of the dose), with fecal excretion accounting for 6-15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation [1-(ß-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/1.73 m2.

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.

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

Plasma concentrations of metronidazole are proportional to the administered dose. An eight-hour intravenous infusion of 100-4,000 mg of metronidazole in normal subjects showed a linear relationship between dose and peak plasma concentration.

In patients treated with intravenous metronidazole, using a dosage regimen of 15 mg/kg loading dose followed six hours later by 7.5 mg/kg every six hours, peak steady-state plasma concentrations of metronidazole averaged 25 mcg/mL with trough (minimum) concentrations averaging 18 mcg/mL.

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.

In one study newborn infants appeared to demonstrate diminished capacity to eliminate metronidazole. The elimination half-life, measured during the first three days of life, was inversely 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:

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 species

Peptostreptococcus species

Many nonspore-forming, gram-positive anaerobic rods are resistant to metronidazole1

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 accurate estimates of susceptibility to antibacterial drugs. A standardized agar dilution method and a broth microdilution method are recommended1. Interpretive criteria for determining the susceptibility of an organism to metronidazole are:

A bacterial isolate may be considered susceptible if the MIC value for metronidazole is not more than 8 mcg/mL. An organism with a metronidazole MIC of 16 mcg/mL is considered intermediate in susceptibility. An organism is considered resistant if the MIC is greater than 16 mcg/mL. The intermediate range was established because of the difficulty in reading endpoints and the clustering of MICs at or near breakpoint concentrations. Where data are available, the interpretive guidelines are based on pharmacokinetic data, population distributions of MICs, and studies of clinical efficacy. To achieve the best possible levels of a drug in abscesses and/or poorly perfused tissues, which are encountered commonly in these infections, maximum approved dosages of antimicrobial agents are recommended for therapy of anaerobic infections. When maximum dosages are used along with appropriate ancillary therapy, it is believed that organisms with susceptible endpoints are generally amenable to therapy, and those with intermediate endpoints may respond, but patient response should be carefully monitored. Ancillary therapy, such as drainage procedures and debridement, are of great importance for the proper management of anaerobic infections. A report of "resistant" from the laboratory indicates that the infecting organism is not likely to respond to therapy. Routine testing of metronidazole for management of C difficile-associated diarrhea is not recommended because correlation with clinical failures has not been established.1

Control strains are recommended for standardized susceptibility testing. Each time the test is performed, one or more control strains should be included. A clinical laboratory test is considered under acceptable control if the results of the control strains are within the MIC ranges reported below.2

For reference agar dilution testing, metronidazole MIC ranges associated with control strains are:

 For broth microdilution testing, metronidazole MIC ranges associated with control strains are:

Metronidazole Injection, USP RTU is a ready-to-use iso-osmotic solution. No dilution or buffering is required. Do not refrigerate. Each container of Metronidazole Injection, USP RTU contains 14 mEq of sodium.

Warning: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.

To open

Tear overwrap down side at slit and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for leaks. Do not add supplementary medication.

Preparation for Administration

1. Suspend container from eyelet support.
2. Remove protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.

Container Label

LOT
EXP

2B3421
NDC 0338-1055-48

500mg

Metronidazole
metronidazole injection USP
RTU (5 mg/mL)

100 mL 
ISO-OSMOTIC
EACH 100 mL CONTAINS 500 mg
METRONIDAZOLE USP 790 mg SODIUM
CHLORIDE USP 47.6 mg DIBASIC SODIUM
PHOSPHATE DRIED USP 22.9 mg CITRIC
ACID ANHYDROUS USP pH 5.5 (4.5 TO
7.0) OSMOLARITY 310 mOsmol/L (CALC)
STERILE NONPYROGENIC SINGLE DOSE
CONTAINER DOSAGE INTRAVENOUSLY AS
DIRECTED BY A PHYSICIAN SEE DIRECTIONS
CAUTIONS DO NOT ADD SUPPLEMENTARY
MEDICATION MUST NOT BE USED IN SERIES
CONNECTIONS CHECK FOR MINUTE LEAKS
AND SOLUTION CLARITY RX ONLY
MFD UNDER SUBLICENSE FROM
SCS PHARMACEUTICALS
CHICAGO IL 60680 USA

RTU IS A TRADEMARK OF
SEARLE PHARMACEUTICALS INC
BAXTER VIAFLEX AND PL 146
ARE TRADEMARKS OF
BAXTER INTERNATIONAL INC

PL 146 PLASTIC
VIAFLEX PLUS CONTAINER
Baxter logo
BAXTER HEALTHCARE CORPORATION
DEERFIELD IL 60015 USA
MADE IN USA

Carton Label

Lot: xxxxx 
QTY: 24-100 mL 

Exp: xxx xx
Code: 2B3421

NDC: 0338-1055-48

METRONIDAZOLE 500MG / 100 mL RTU INJ

(17)xx00(10)xxxxx

(01)50303381055481