cus species, peptostreptococcus species and fusobacterium species. gynecologic infections , including endometritis, endomyometritis, tubo-ovarian abscess, and post-surgical 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. fragilis group 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, and lung abscess, caused by bacteroides species including the b. fragilis group. endocarditis caused by bacteroides species including the b. fragilis group. prophylaxis the prophylactic administration of metronidazole injection, usp preoperatively, intraoperatively, and postoperatively may reduce the incidence of postoperative infection in patients undergoing elective colorectal surgery which is classified as contaminated or potentially contaminated. prophylactic use of metronidazole injection, usp should be discontinued within 12 hours after surgery. if there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism(s) so that appropriate therapy may be given (see dosage and administration ). to reduce the development of drug-resistant bacteria and maintain the effectiveness of metronidazole and other antibacterial drugs, metronidazole 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.

has been reported and is characterized by numbness 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 ).

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 metronidazole dose 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 a hemodialysis session, supplementation of metronidazole dosage following a hemodialysis session should be considered, depending on the patient's clinical situation (see clinical pharmacology ). prophylaxis for surgical prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery, the recommended dosage schedule for adults is: • 15 mg/kg infused over 30 to 60 minutes and completed approximately one hour before surgery; followed by • 7.5 mg/kg infused over 30 to 60 minutes at 6 and 12 hours after the initial dose. it is important that (1) administration of the initial preoperative dose be completed approximately one hour before surgery so that adequate drug levels are present in the serum and tissues at the time of initial incision, and (2) metronidazole injection, usp be administered, if necessary, at 6-hour intervals to maintain effective drug levels. prophylactic use of metronidazole injection, usp should be limited to the day of surgery only, following the above guidelines. caution: metronidazole injection, usp is to be administered by slow intravenous drip infusion only, either as a continuous or intermittent infusion. i.v. admixtures containing metronidazole and other drugs should be avoided. additives should not be introduced into this solution. 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) that would come in contact with the drug solution. metronidazole injection, usp is a ready-to-use isotonic solution. no dilution or buffering is required. do not refrigerate. each container of metronidazole injection contains 14 meq of sodium. do not use if cloudy or precipitated or if the seal is not intact. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. use sterile equipment. it is recommended that the intravenous administration apparatus be replaced at least once every 24 hours.

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; abdominal cramping; and constipation. mouth a sharp, unpleasant metallic taste is not unusual. furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of candida which may occur during effective therapy. dermatologic dermatitis bullous, fixed drug eruption, erythematous rash and pruritus. hematopoietic reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia. local reactions thrombophlebitis after intravenous infusion. this reaction can be minimized or avoided by avoiding prolonged use of indwelling intravenous catheters. 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. hypersensitivity toxic epidermal necrolysis (ten), stevens-johnson syndrome (sjs), drug reaction with eosinophilia and systemic symptoms (dress), acute generalized exanthematous pustulosis (agep), 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. 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 ). other proliferation of candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling "serum sickness." rare cases of pancreatitis, which abated on withdrawal of the drug, have 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.

e have also been detected in pus from hepatic abscesses. following a single intravenous dose of metronidazole 500 mg, 4 healthy subjects who underwent gastrointestinal endoscopy had peak gastric juice metronidazole concentrations of 5 to 6 mcg/ml at one hour post-dose. in patients receiving intravenous metronidazole in whom gastric secretions are continuously removed by nasogastric aspiration, sufficient metronidazole may be removed in the aspirate to cause a reduction in serum levels. metabolism the metabolites of metronidazole result primarily from side-chain oxidation [1-(βhydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-ylacetic acid] and glucuronide conjugation. both the parent compound and the hydroxyl metabolite possess in vitro antimicrobial activity. excretion the major route of elimination of metronidazole and its metabolites is via the urine (60 to 80% of the dose), with approximately 20% of the amount excreted appearing as unchanged metronidazole. renal clearance of metronidazole is approximately 10 ml/min/1.73 m 2 . fecal excretion accounts for 6 to 15% of the dose. renal impairment decreased renal function does not alter the single-dose pharmacokinetics of metronidazole. 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 in metronidazole pharmacokinetics but had 2-fold higher c max of hydroxy-metronidazole and 5-fold higher c max of metronidazole acetate, compared to healthy subjects with normal 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, the clearance 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 the dialyzer membrane used and the duration of the dialysis session. if the administration of metronidazole cannot be separated from the dialysis session, supplementation of metronidazole dose following hemodialysis should be considered (see dosage 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. 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 a 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 hydroxy-metronidazole in these hepatically 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 to moderate hepatic impairment. patients with mild to moderate hepatic impairment should be monitored for metronidazole associated adverse events (see precautions and dosage 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 of hydroxy-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 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 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 intra-cellular 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, a concentration gradient is created and maintained which promotes the drug's intracellular transport. 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 bacteria. the precise mechanism of action of metronidazole is unclear. 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 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/ml or less against most (≥ 90%) isolates of the following bacteria; however, the safety and effectiveness of metronidazole in treating clinical infections due to these bacteria have not 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 ) susceptibility testing for specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by fda for this drug, please see: https://www.fda.gov/stic.