500 mg/ 100 mL (5 mg/mL)

Sterile

For Intravenous Infusion Only.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Metronidazole Injection USP and other antibacterial drugs, Metronidazole Injection USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Metronidazole Injection USP is a sterile, parenteral dosage form of metronidazole in water.

Each 100 mL of Metronidazole Injection USP contains a sterile, nonpyrogenic, isotonic, buffered solution of Metronidazole USP 500 mg, Sodium Chloride USP 740 mg, Dibasic Sodium Phosphate•7H2O USP 112 mg, and Citric Acid Anhydrous USP 40 mg in Water for Injection USP. Metronidazole Injection USP has a calculated osmolarity of 297 mOsmol/liter and a pH of 5.8 (4.5–7.0). Sodium content: 13.5 mEq/container.

Metronidazole is classified as a nitroimidazole antimicrobial and is administered by the intravenous route.

Metronidazole USP is chemically designated 2-methyl-5-nitroimidazole-1-ethanol (C6H9N3O3):

Not made with natural rubber latex, PVC, or DEHP.

The plastic container is a copolymer of ethylene and propylene formulated and developed for parenteral drugs. The copolymer contains no plasticizers. The safety of the plastic container has been confirmed by biological evaluation procedures.

The material passes Class VI testing as specified in the U.S. Pharmacopeia for Biological Tests – Plastic Containers. The container/solution unit is a closed system and is not dependent upon entry of external air during administration. No vapor barrier is necessary.

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 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/1.73 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 human 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 to 4,000 mg of metronidazole in normal subjects showed a linear relationship between dose and peak plasma concentration.

In patients treated with metronidazole injection 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.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Metronidazole Injection USP and other antibacterial drugs, Metronidazole Injection USP 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.

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

The following are the most serious adverse reactions reported in patients treated with metronidazole and are also described elsewhere in the labeling: convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy (characterized mainly by numbness or paresthesia of an extremity) (see WARNINGS).

The following adverse reactions associated with the use of metronidazole products were identified in clinical studies or postmarketing reports or published literature. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

GASTROINTESTINAL: Nausea, anorexia, vomiting, abdominal discomfort, diarrhea, an unpleasant metallic taste, epigastric distress, abdominal cramping, constipation and pancreatitis.

MOUTH:  A sharp metallic taste. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy with metronidazole.

HEMATOPOIETIC: Reversible neutropenia (leukopenia); thrombocytopenia, eosinophilia.

HEPATOBILIARY DISORDERS: Hepatotoxicity and liver failure especially in patients with Cockayne syndrome (see CONTRAINDICATIONS), jaundice.

CARDIOVASCULAR: QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. Flattening of the T-wave may be seen in electrocardiographic tracings.

SKIN AND SUBCUTANEOUS DISORDERS: Toxic epidermal necrolysis, Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), erythematous rash, bullae, pruritus, swelling face, urticaria, and hyperhidrosis.

CENTRAL NERVOUS SYSTEM: Encephalopathy, aseptic meningitis, convulsive seizures, optic neuropathy, peripheral neuropathy (mainly numbness or paresthesia of an extremity), dizziness, vertigo, incoordination, ataxia, confusion, psychosis, dysarthria, irritability, depression, weakness, headache, and insomnia.

LABORATORY INVESTIGATIONS: Hepatic enzymes increased.

HYPERSENSITIVITY: Anaphylaxis, angioedema, hypotension, flushing, nasal congestion, and dryness of mouth (or vagina or vulva).

RENAL: Dysuria, cystitis, polyuria, incontinence, a sense of pelvic pressure, and darkened urine.

HEPATIC: Cases of severe irreversible hepatotoxicity/acute liver failure, including cases with fatal outcomes with very rapid onset after initiation of systemic use of metronidazole, have been reported in patients with Cockayne Syndrome (latency from drug start to signs of liver failure as short as 2 days) (see CONTRAINDICATIONS).

LOCAL REACTIONS: Thrombophlebitis after intravenous infusion. This reaction can be minimized or avoided by avoiding prolonged use of indwelling intravenous catheters.

OTHER: Fever, hiccup, proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness”. If patients receiving metronidazole 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.

Patients with Crohn’s disease 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 Metronidazole Injection USP.

Darkened Urine:

Instances of darkened urine have also been reported, and this manifestation has been the subject of a special investigation. 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.

The use of dosages of metronidazole higher than those recommended has been reported. These include the use of 27 mg/kg three times a day for 20 days, and the use of 75 mg/kg as a single loading dose followed by 7.5 mg/kg maintenance doses. No adverse reactions were reported in either of the two cases.

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.

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

Metronidazole Injection USP, sterile, is supplied in 100 mL fill PAB® containers, each containing an isotonic, buffered solution of 500 mg metronidazole; packaged 24 per case. Metronidazole injection is sterile premixed solution intended for single use only.

1. Ralph ED, Kirby WMM: Bioassay of Metronidazole 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. Pharmacol. 6:430-432, 1978.

Revised: December 2021

PAB is a registered trademark of B. Braun Medical Inc.

ATCC is a registered trademark of the American Type Culture Collection.

CAUTION:  ADDING ADDITIVES INTO THE PAB CONTAINER IS PROHIBITED. DO NOT ADD SUPPLEMENTARY MEDICATIONS.

For intravenous infusion only.

Store the individual container in the storage carton until ready to use.

Aseptic technique is required.

Before use, perform the following checks:



Read the label. Ensure solution is the one ordered and is within the expiration date.



Inspect the solution in good light for cloudiness, haze or particulate matter; check the container for leakage or damage. Any container which is suspect should not be used.



Use only if solution is clear and container and seals are intact.



Single dose plastic container.

Discard unused portion.



Consult Package Insert for complete product information.

WARNING: DO NOT USE PLASTIC CONTAINER IN SERIES CONNECTION.

1. Identify Set Port (See Figure A).
   
   
   
   
   
   
   
   
2. Caution – Adding additives into the Metronidazole Injection USP solution bag is prohibited. If used with a primary intravenous fluid system, the primary solution should be discontinued during metronidazole infusion. Do not use equipment containing aluminum (e.g., needles, cannulae, etc.) that may contact the drug solution.
   
   
   
   
3. To Attach Administration Set
   
   To aseptically remove the set port closure: hold container below the set port and grasp the foil tab between the thumb and forefinger then pull the tab in two steps as shown in Figure B Steps 1 and 2.
   
   
   
   
   
   
   
   
4. Push spike through the diaphragm of the port (See Figure C). Hang container using hole on the lower flap. Prime set in accordance with the Directions for Use provided with the set in use.
   
   
   
   
   

PAB® containers can be safely transported in a standard 6-inch carrier through a pneumatic tube system that is well maintained and running properly.

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

Prepared in USA. API from Italy.

Y36-003-049   LD-438-10

Metronidazole Injection USP

METRONIDAZOLE

500 mg/ 100 mL (5 mg/mL)

NDC 0264-5535-32     



100 mL fill

PAB® Container

For Intravenous Infusion Only.

CAUTION:  ADDING ADDITIVES INTO THE PAB CONTAINER IS

PROHIBITED. DO NOT ADD SUPPLEMENTARY MEDICATIONS.

Single dose plastic container. Discard unused portion.

Protect from light until use.

Each 100 mL contains: Metronidazole USP 500 mg; Sodium

Chloride USP 740 mg; Dibasic Sodium Phosphate•7H2O USP

112 mg; Citric Acid Anhydrous USP 40 mg; Water for Injection USP, qs

pH: 5.8 (4.5-7.0) Calc. Osmolarity: 297 mOsmol/liter

Sodium content: 13.5 mEq/container

Sterile, nonpyrogenic. Use only if solution is clear and container and

seals are intact. For intravenous use only.

Recommended Storage: Room temperature (25°C). Avoid

excessive heat. Protect from freezing. See Package Insert.

Not made with natural rubber latex, PVC or DEHP. 

Rx only

PAB is a registered trademark of B. Braun Medical Inc.

REF D5353-5224       HK 41283





B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

Prepared in USA. API from Italy.

Y94-003-379   LD-491-4

LOT

EXP

Metronidazole Injection USP

METRONIDAZOLE

500 mg/ 100 mL (5 mg/mL)

Four 100 mL fill PAB® Containers

NDC 0264-5535-32

For Intravenous Infusion Only.

CAUTION:  ADDING ADDITIVES INTO THE PAB CONTAINER IS

PROHIBITED. DO NOT ADD SUPPLEMENTARY MEDICATIONS.

Single dose plastic container. Discard unused portion.

Protect from light until use.

Each 100 mL contains: Metronidazole USP 500 mg; Sodium Chloride

USP 740 mg; Dibasic Sodium Phosphate•7H2O USP 112 mg;

Citric Acid Anhydrous USP 40 mg; Water for Injection USP, qs

pH: 5.8 (4.5-7.0) Calc. Osmolarity: 297 mOsmol/liter

Sodium content: 13.5 mEq/container

Sterile, nonpyrogenic. Use only if solution is clear and container

and seals are intact. For intravenous use only.

Recommended Storage: Room temperature (25°C). Avoid

excessive heat. Protect from freezing. See Package Insert.

Not made with natural rubber latex, PVC or DEHP. 

Rx only

PAB is a registered trademark of B. Braun Medical Inc.

REF D5353-5224       HK 41283

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

Prepared in USA. API from Italy.

X12-002-495 LD-492-4

LOT

EXP