Metronidazole

Metronidazole has been shown to be carcinogenic in mice and rats (see

). Its use, therefore, should be reserved for the conditions described in the section below.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Metronidazole Injection and other antibacterial drugs, Metronidazole Injection 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 is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with Metronidazole Injection therapy. In a mixed aerobic and anaerobic infection, antibiotics appropriate for the treatment of the aerobic infection should be used in addition to Metronidazole Injection.

Metronidazole Injection is effective in infections resistant to clindamycin, chloramphenicol, and penicillin.

, including peritonitis, intra-abdominal abscess, and liver abscess, caused by species including the group (, species, species, species, and species.

caused by species including the group, species, species, species, and species.

, including endometritis, endomyometritis, tubo-ovarian abscess, and post-surgical vaginal cuff infection, caused by species including the group, species, species, and species.

caused by species including the group and species.

, as adjunctive therapy, caused by species including the group.

, including meningitis and brain abscess, caused by species including the group. 

, including pneumonia, empyema, and lung abscess, caused by species including the group. 

caused by species including the group.





The prophylactic administration of Metronidazole Injection 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 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 ).

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 antimicrobial 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 metronidazole may be altered and therefore monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

The recommended dosage schedule for Adults is:

Loading Dose	15 mg/kg infused over one hour (approximately 1 g for a 70-kg adult).
Maintenance Dose	7.5 mg/kg infused over one hour every six hours (approximately 500mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose.

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 levels and toxicity is recommended.1

In patients receiving metronidazole injection 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.

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

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.

For surgical prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery, the recommended dosage schedule for adults is:

a. 15 mg/kg infused over 30 to 60 minutes and completed approximately one hour before surgery, followed by:

b. 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 be administered, if necessary, at 6-hour intervals to maintain effective drug levels. Prophylactic use of Metronidazole Injection should be limited to the day of surgery only, following the above guidelines.



Parenteral therapy may be changed to oral metronidazole when conditions warrant, based upon the severity of the disease and the response of the patient to treatment with Metronidazole Injection. The usual adult oral dosage is 7.5 mg/kg every six hours.



A maximum of 4 g should not be exceeded during a 24-hour period.





Metronidazole Injection is a ready-to-use isotonic solution.Do not refrigerate. Each container of Metronidazole Injection contains 13.5 mEq of sodium.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if cloudy or precipitated or if the seals are not intact.

Use sterile equipment. It is recommended that the intravenous administration apparatus be replaced at least once every 24 hours.

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

.



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.

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

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.

Reversible neutropenia (leukopenia); thrombocytopenia, eosinophilia.

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

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.

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

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, tinnitus, hearing impairment, hearing loss, and insomnia.

Hepatic enzymes increased.

Toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) (see ), anaphylaxis, angioedema, hypotension, flushing, nasal congestion, and dryness of mouth (or vagina or vulva).

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

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 ).

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

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.

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.