Metronidazole - Metronidazole injection, Solution
(Metronidazole)Metronidazole - Metronidazole injection, Solution Prescribing Information
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, antibacterial drugs appropriate for the treatment of the aerobic infection should be used in addition to metronidazole injection.
Metronidazole injection is effective in
- Intra-Abdominal Infections, including peritonitis, intra-abdominal abscess and liver abscess, caused byBacteroidesspecies including theB. fragilisgroup (B. fragilis,B. distasonis,B. ovatus,B. thetaiotaomicron,B. vulgatus),Clostridiumspecies,Eubacteriumspecies,Peptococcusspecies andPeptostreptococcusspecies in adults and pediatric patients less than 4 months of age.
- Skin and Skin Structure Infectionscaused byBacteroidesspecies including theB. fragilisgroup,Clostridiumspecies,Peptococcusspecies,Peptostreptococcusspecies andFusobacteriumspecies in adults.
- Gynecologic Infections, including endometritis, endomyometritis, tubo-ovarian abscess and postsurgical vaginal cuff infection, caused byBacteroidesspecies including theB. fragilisgroup,Clostridiumspecies,Peptococcusspecies,Peptostreptococcusspecies andFusobacteriumspecies in adults.
- Bacterial Septicemiacaused byBacteroidesspecies including theB. fragilisgroup andClostridiumspecies in adults.
- Bone and Joint Infections, as adjunctive therapy, caused byBacteroidesspecies including theB. fragilisgroup in adults.
- Central Nervous System (CNS) Infections, including meningitis and brain abscess, caused byBacteroidesspecies including theB. fragilisgroup in adults.
- Lower Respiratory Tract Infections, including pneumonia, empyema and lung abscess, caused byBacteroidesspecies including theB. fragilisgroup in adults.
- Endocarditiscaused byBacteroidesspecies including theB. fragilisgroup in adults.
Dosage, rate of administration, and duration of treatment are to be individualized and depend upon the indication for use, the patient’s age, weight, clinical condition and concomitant treatment, and on the patient’s clinical and laboratory response to the treatment.
The recommended dosage schedule for adults for the treatment of anaerobic infections is presented in the Table 1 :
Loading Dose | 15 mg/kg infused intravenously over one hour (approximately 1 gram for a 70-kg adult). |
Maintenance Dosage | 7.5 mg/kg infused intravenously over one hour every six hours (approximately 500 mg for a 70-kg adult). The first maintenance dose should be instituted six hours following the initiation of the loading dose. |
Parenteral therapy may be changed to oral metronidazole therapy 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 (approximately 500 mg for a 70-kg adult).
A maximum of 4 grams should not be exceeded during a 24-hour period.
The usual duration of therapy is 7 days to 10 days; however, infections of the bone and joint, lower respiratory tract and endocardium may require longer treatment.
The recommended dosage schedule for
Post-menstrual age (Completed weeks) | Loading Dose (mg/kg) | Maintenance Dose* (mg/kg) | Dosing interval (hours) |
23 to <34 | 15 | 7.5 | 12 |
34 to 40 | 15 | 7.5 | 8 |
>40 to 48 | 15 | 7.5 | 6 |
*The first maintenance dose is given 24 hours after the start of the loading dose. | |||
For patients with severe hepatic impairment (Child-Pugh C), the metronidazole dose should be reduced by 50% (see
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
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.
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 minutes to 60 minutes and completed approximately one hour before surgery; followed by
b. 7.5 mg/kg infused over 30 minutes to 60 minutes at 6 hours 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.
Metronidazole injection is incompatible with (includes but is not limited to): Aztreonam, Cefamandole nafate, Cefoxitin, Penicillin G.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products (see
Metronidazole injection is a ready-to-use iso-osmotic solution.
Do not connect flexible plastic containers in series in order to avoid air embolism due to possible residual air contained in the primary container.
Pressurizing intravenous solutions contained in flexible plastic containers to increase flow rates can result in air embolism if the residual air in the container is not fully evacuated prior to administration.
Use of a vented intravenous administration set with the vent in the open position could result in air embolism. Vented intravenous administration sets with the vent in the open position should not be used with flexible plastic containers.
Discard any unused portion.
For single-dose only.
Tear overwrap at notch and remove solution container. Visually inspect the container. If the twist-off port is damaged, detached, or not present, discard container as solution path sterility may be impaired. 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.
1. Suspend container from eyelet support.
2. Remove twist-off port from bag.
3. Attach administration set. Refer to complete directions accompanying set.
Manufactured by:
Ahmedabad 382110, INDIA
Distributed by:
Bridgewater, NJ 08807
Rev. 07-2025-04
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless the solution is clear and the seal is intact.
- Hypersensitivity
Metronidazole injection is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
- Psychotic Reaction with Disulfiram
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
- Disulfiram
Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer metronidazole injection to patients who have taken disulfiram within the last two weeks (see
- Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with metronidazole injection (see
- Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When metronidazole injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.
- Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary.
- Busulfan
Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis and hepatic veno-occlusive disease. Metronidazole injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.
- Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.
- Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy.
- Cytochrome P450 3A4 (CYP3A4) substrates
Concomitant use of metronidazole injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
- 5-Fluorouracil
Metronidazole injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.
- Vecuronium
Metronidazole injection may potentiate the effects of vecuronium.
- Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
- Drug/Laboratory Test Interactions
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 glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.
- Disulfiram
Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer metronidazole injection to patients who have taken disulfiram within the last two weeks (see
- Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with metronidazole injection (see
- Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When metronidazole injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.
- Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary.
- Busulfan
Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis and hepatic veno-occlusive disease. Metronidazole injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.
- Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.
- Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy.
- Cytochrome P450 3A4 (CYP3A4) substrates
Concomitant use of metronidazole injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
- 5-Fluorouracil
Metronidazole injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.
- Vecuronium
Metronidazole injection may potentiate the effects of vecuronium.
- Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
- Drug/Laboratory Test Interactions
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 glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.
- Disulfiram
Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer metronidazole injection to patients who have taken disulfiram within the last two weeks (see
- Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with metronidazole injection (see
- Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When metronidazole injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.
- Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary.
- Busulfan
Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis and hepatic veno-occlusive disease. Metronidazole injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.
- Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.
- Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy.
- Cytochrome P450 3A4 (CYP3A4) substrates
Concomitant use of metronidazole injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
- 5-Fluorouracil
Metronidazole injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.
- Vecuronium
Metronidazole injection may potentiate the effects of vecuronium.
- Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
- Drug/Laboratory Test Interactions
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 glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.
- Interaction with Alcohol
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
- Disulfiram
Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer metronidazole injection to patients who have taken disulfiram within the last two weeks (see
- Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with metronidazole injection (see
- Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When metronidazole injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.
- Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary.
- Busulfan
Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis and hepatic veno-occlusive disease. Metronidazole injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.
- Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.
- Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy.
- Cytochrome P450 3A4 (CYP3A4) substrates
Concomitant use of metronidazole injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
- 5-Fluorouracil
Metronidazole injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.
- Vecuronium
Metronidazole injection may potentiate the effects of vecuronium.
- Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
- Drug/Laboratory Test Interactions
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 glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.
- Disulfiram
Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer metronidazole injection to patients who have taken disulfiram within the last two weeks (see
- Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with metronidazole injection (see
- Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When metronidazole injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.
- Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary.
- Busulfan
Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis and hepatic veno-occlusive disease. Metronidazole injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.
- Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.
- Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy.
- Cytochrome P450 3A4 (CYP3A4) substrates
Concomitant use of metronidazole injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
- 5-Fluorouracil
Metronidazole injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.
- Vecuronium
Metronidazole injection may potentiate the effects of vecuronium.
- Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
- Drug/Laboratory Test Interactions
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 glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.
- Disulfiram
Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer metronidazole injection to patients who have taken disulfiram within the last two weeks (see
- Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with metronidazole injection (see
- Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When metronidazole injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.
- Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary.
- Busulfan
Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis and hepatic veno-occlusive disease. Metronidazole injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.
- Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.
- Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy.
- Cytochrome P450 3A4 (CYP3A4) substrates
Concomitant use of metronidazole injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
- 5-Fluorouracil
Metronidazole injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.
- Vecuronium
Metronidazole injection may potentiate the effects of vecuronium.
- Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
- Drug/Laboratory Test Interactions
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 glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.
- Cockayne Syndrome
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
The following reactions have been reported during treatment with metronidazole formulations:
INFECTIONS AND INFESTATIONS: Vaginal candidiasis
BLOOD AND LYMPHATIC SYSTEM DISORDERS: Agranulocytosis, Leukopenia, Neutropenia, Thrombocytopenia, Eosinophilia
IMMUNE SYSTEM DISORDERS: Anaphylactic reaction, Hypersensitivity
METABOLISM AND NUTRITION DISORDERS: Decreased appetite
PSYCHIATRIC DISORDERS: Confusional state, Depression, Insomnia, Decreased libido
NERVOUS SYSTEM DISORDERS: Encephalopathy, Seizure, Neuropathy peripheral, Ataxia, Dizziness, Hypoesthesia, Paresthesia, Dysgeusia, Headache, Nystagmus, Aseptic meningitis, Somnolence, Dysarthria, Numbness, Syncope
EYE DISORDERS: Optic neuropathy, Saccadic eye movement
EAR AND LABYRINTH DISORDERS: Vertigo, tinnitus, hearing impairment, hearing loss
CARDIAC DISORDERS: 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, Tachycardia, Palpitation
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Dyspnea
GASTROINTESTINAL DISORDERS: Pancreatitis, Abdominal pain, Diarrhea, Nausea, Vomiting, Asthenia, Proctitis
HEPATOBILIARY DISORDERS: Hepatotoxicity/Liver Failure in patients with Cockayne syndrome (see
SKIN AND SUBCUTANEOUS DISORDERS: Toxic epidermal necrolysis, Swelling face, Pruritus, Urticaria, Hyperhidrosis, Erythema, Rash; Stevens-Johnson syndrome,
Fixed drug eruption, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) (see
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: Muscle spasms, Arthralgia, Myalgia
RENAL AND URINARY DISORDERS: Chromaturia, Dysuria
REPRODUCTIVE: Dyspareunia
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Injection site reaction, Malaise, Face edema, Edema peripheral, Chest pain, Chills.
INVESTIGATIONS: Hepatic enzyme increased.
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.
The following reactions have been reported during treatment with metronidazole formulations:
INFECTIONS AND INFESTATIONS: Vaginal candidiasis
BLOOD AND LYMPHATIC SYSTEM DISORDERS: Agranulocytosis, Leukopenia, Neutropenia, Thrombocytopenia, Eosinophilia
IMMUNE SYSTEM DISORDERS: Anaphylactic reaction, Hypersensitivity
METABOLISM AND NUTRITION DISORDERS: Decreased appetite
PSYCHIATRIC DISORDERS: Confusional state, Depression, Insomnia, Decreased libido
NERVOUS SYSTEM DISORDERS: Encephalopathy, Seizure, Neuropathy peripheral, Ataxia, Dizziness, Hypoesthesia, Paresthesia, Dysgeusia, Headache, Nystagmus, Aseptic meningitis, Somnolence, Dysarthria, Numbness, Syncope
EYE DISORDERS: Optic neuropathy, Saccadic eye movement
EAR AND LABYRINTH DISORDERS: Vertigo, tinnitus, hearing impairment, hearing loss
CARDIAC DISORDERS: 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, Tachycardia, Palpitation
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Dyspnea
GASTROINTESTINAL DISORDERS: Pancreatitis, Abdominal pain, Diarrhea, Nausea, Vomiting, Asthenia, Proctitis
HEPATOBILIARY DISORDERS: Hepatotoxicity/Liver Failure in patients with Cockayne syndrome (see
- Hypersensitivity
Metronidazole injection is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
- Psychotic Reaction with Disulfiram
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
- Interaction with Alcohol
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
- Cockayne Syndrome
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
SKIN AND SUBCUTANEOUS DISORDERS: Toxic epidermal necrolysis, Swelling face, Pruritus, Urticaria, Hyperhidrosis, Erythema, Rash; Stevens-Johnson syndrome,
Fixed drug eruption, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) (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.
Severe neurological disturbances, including encephalopathy, cerebellar symptoms, convulsive seizures, peripheral neuropathy, optic neuropathy, and aseptic meningitis, have been reported in patients treated with metronidazole.
Encephalopathy associated with metronidazole may manifest as confusion or decreased level of consciousness, and is associated with widespread lesions on magnetic resonance imaging (MRI) of the brain. Cerebellar toxicity associated with metronidazole may manifest as ataxia, dizziness, dysarthria, nystagmus and saccadic pursuit and is accompanied by T2 flair lesions within the dentate nuclei seen on MRI. Cerebellar toxicity may concurrently occur with encephalopathy, peripheral neuropathy or seizures. CNS symptoms and CNS lesions are generally reversible within days to weeks upon discontinuation of metronidazole injection. Peripheral neuropathy, usually symmetric and mainly of sensory type is characterized by numbness or paresthesia of an extremity. Symptoms may be prolonged after drug discontinuation. Aseptic meningitis may occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued (see
Advise patients to report neurologic symptoms that occur during metronidazole administration. Discontinue metronidazole treatment if any abnormal neurologic symptoms occur such as ataxia, dizziness, confusion or any other CNS adverse reaction (see
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: Muscle spasms, Arthralgia, Myalgia
RENAL AND URINARY DISORDERS: Chromaturia, Dysuria
REPRODUCTIVE: Dyspareunia
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Injection site reaction, Malaise, Face edema, Edema peripheral, Chest pain, Chills.
INVESTIGATIONS: Hepatic enzyme increased.
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.
- Disulfiram
Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer metronidazole injection to patients who have taken disulfiram within the last two weeks (see
- Hypersensitivity
Metronidazole injection is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
- Psychotic Reaction with Disulfiram
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
- Interaction with Alcohol
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
- Cockayne Syndrome
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
- Alcoholic Beverages
Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with metronidazole injection (see
- Hypersensitivity
Metronidazole injection is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
- Psychotic Reaction with Disulfiram
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
- Interaction with Alcohol
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
- Cockayne Syndrome
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
- Warfarin and other Oral Anticoagulants
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When metronidazole injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.
- Lithium
In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary.
- Busulfan
Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis and hepatic veno-occlusive disease. Metronidazole injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.
- Drugs that Inhibit CYP450 Enzymes
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.
- Drugs that Induce CYP450 Enzymes
The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy.
- Cytochrome P450 3A4 (CYP3A4) substrates
Concomitant use of metronidazole injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
- 5-Fluorouracil
Metronidazole injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.
- Vecuronium
Metronidazole injection may potentiate the effects of vecuronium.
- Drugs that Prolong the QT interval
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
- Drug/Laboratory Test Interactions
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 glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.
Metronidazole injection, USP, is a parenteral formulation of the synthetic nitroimidazole antibacterial agent 2-methyl-5-nitro-1
Metronidazole injection USP, 500 mg/100 mL (5 mg/mL) is a sterile, clear, colorless to pale yellow color, nonpyrogenic, iso-osmotic, buffered solution supplied in 100 mL single-dose non-PVC plastic container. Each 100 mL contains 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 has an osmolarity of 308.66 mOsmol/L (calc) and a pH of 5.5 (4.5 to 7.0). Each container contains 14 mEq of sodium.