Metronidazole Prescribing Information
Metronidazole has been shown to be carcinogenic in mice and rats (see
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.
Administration of solutions containing sodium ions may result in sodium retention. Care should be taken when administering Metronidazole Injection to patients receiving corticosteroids or to patients predisposed to edema.
Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with Metronidazole Injection and requires treatment with a candicidal agent.
Prescribing Metronidazole Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Patients should be counseled that antibacterial drugs including Metronidazole Injection should only be used to treat bacterial infections. They do not treat viral infections (
Advise patients that Metronidazole Injection may increase the risk of serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS). Instruct the patient to be alert for skin rash, blisters, fever or other signs and symptoms of these hypersensitivity reactions. Advise patients to stop Metronidazole Injection immediately if they develop any type of rash and seek medical attention.
Metronidazole is a nitroimidazole, and Metronidazole Injection should be used with caution in patients with evidence of or history of blood dyscrasia. A mild leukopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to metronidazole have been observed in clinical studies. Total and differential leukocyte counts are recommended before and after therapy.
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. This possible drug interaction should be considered when Metronidazole Injection is prescribed for patients on this type of anticoagulant therapy.
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.
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole.
Alcoholic beverages should not be consumed during metronidazole therapy because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.
Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD+⇄NADH). Interference is due to the similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.
Metronidazole has shown evidence of carcinogenic activity in studies involving chronic, oral administration in mice and rats, but similar studies in the hamster gave negative results. Also, metronidazole has shown mutagenic activity in a number of
Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Reproduction studies have been performed in rats at doses up to five times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to metronidazole. Metronidazole administered intraperitoneally to pregnant mice at approximately the human dose caused fetotoxicity; administered orally to pregnant mice, no fetotoxicity was observed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed (see
Metronidazole is secreted in human milk in concentrations similar to those found in plasma. Because of the potential for tumorigenicity shown for metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in children have not been established.
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
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.
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.
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 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
Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of metronidazole. Symptoms can be serious and potentially life threatening. If symptoms or signs of SCARs develop, discontinue Metronidazole Injection immediately and institute appropriate therapy.
Convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with metronidazole products. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged oral administration of metronidazole, patients should be observed carefully. The appearance of abnormal neurologic signs demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy.
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.
Metronidazole Injection is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within the last two weeks (see
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
Metronidazole Injection is 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
Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of metronidazole. Symptoms can be serious and potentially life threatening. If symptoms or signs of SCARs develop, discontinue Metronidazole Injection immediately and institute appropriate therapy.
Convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with metronidazole products. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged oral administration of metronidazole, patients should be observed carefully. The appearance of abnormal neurologic signs demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy.
Metronidazole Injection is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within the last two weeks (see
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
Metronidazole Injection is 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
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.
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. This possible drug interaction should be considered when Metronidazole Injection is prescribed for patients on this type of anticoagulant therapy.
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.
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole.
Alcoholic beverages should not be consumed during metronidazole therapy because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.
Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.