Metronidazole (metronidazole in sodium chloride)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Metronidazole is a synthetic, nitroimidazole-derivative antibacterial and antiprotozoal agent.
Metronidazole is a nitroimidazole antimicrobial that exerts antibacterial effects in an anaerobic environment against most obligate anaerobes. Metronidazole enters anaerobic organisms via passive diffusion and is activated in the cytoplasm of susceptible bacteria via reduction. Upon reduction, a concentration gradient is formed, promoting the intracellular transport of metronidazole.
The reduced form of metronidazole and free radicals produced during reduction interact with bacterial DNA, which inhibit DNA synthesis and cause DNA degradation.
Pylera(R) is a combination of antibacterial medications (bismuth subcitrate potassium, metronidazole, and tetracycline). Tetracycline interacts with the 30S ribosomal subunit and inhibits bacterial protein synthesis. Reduction of metronidazole creates a concentration gradient which promotes the drug's intracellular transport into bacteria.
Free radicals are also formed during the reduction of metronidazole reduction, which cause bacterial death. The antibacterial activity of bismuth salts has not been fully elucidated.
Pharmacokinetics are similar for oral and IV formulations of metronidazole. Metronidazole capsules and conventional tablets are bioequivalent at a single dose of 750 mg. The rate of absorption and peak plasma concentrations of metronidazole are decreased when capsules are administered with food; however, the total amount absorbed is not affected.
Plasma concentrations of IV metronidazole are proportional to the administered dose.
Metronidazole is the major circulating component in plasma, with lesser quantities of metabolites present. Metronidazole is <20% bound to plasma proteins. Metronidazole crosses into CSF, saliva, and breast milk at concentrations similar to those in plasma.
Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.
Following single-dose administration of 500 mg of IV metronidazole, peak gastric juice concentrations of 5-6 mcg/mL were detected in healthy patients undergoing gastrointestinal endoscopy at 1-hour post-dose. In patients receiving IV metronidazole that are undergoing continuous nasogastric aspiration, sufficient metronidazole may be removed in gastric aspirate to reduce plasma levels.
Metabolites of metronidazole are primarily formed from side-chain oxidation and glucuronide conjugation. Both the parent compound and hydroxyl metabolite possess in vitro activity. Metronidazole and its metabolites are primarily eliminated in the urine (60-80% of the dose), with 6-15% of a dose excreted in the feces.
The mean elimination half-life of metronidazole is reported to be 8-9 hours in healthy adults. Newborns exhibit a reduced capacity to eliminate metronidazole. The elimination half-life in the first 3 days of life was inversely correlated with gestational age.
In infants with a gestational age of 28-40 weeks, the elimination half-life ranged from 22.5-109 hours. Reduced renal function does not alter single-dose pharmacokinetics of metronidazole. There were no significant changes in metronidazole pharmacokinetics in patients with end-stage renal disease (ESRD) receiving a single dose infusion of 500 mg of IV metronidazole; however, patients had 2-fold higher peak plasma concentrations of hydroxy-metronidazole and 5-fold higher peak plasma concentrations of metronidazole acetate.
Due to the potential accumulation of metronidazole metabolites in patients with ESRD, monitoring for metronidazole-associated adverse effects is recommended. Metronidazole is removed by hemodialysis but not by peritoneal dialysis.(r495) Hemodialysis sessions lasting 4-8 hours remove 40-65% of a metronidazole dose. If the administration of metronidazole cannot be separated from a dialysis session or administered after the dialysis session, consider supplementing a metronidazole dose following hemodialysis.
Following a single IV infusion of metronidazole, total exposure to metronidazole increased by 114% in patients with severe (Child Pugh class C) hepatic impairment, and by 54% and 53% in mild and moderate hepatic impairment (Child Pugh class A and B), respectively.
USES: Metronidazole is an antibiotic that is used to treat a wide variety of infections. It may also be used to prevent infection after bowel surgery. It works by stopping the growth of certain bacteria and parasites.
Generic name: metronidazole in sodium chloride
Pronunciation: (MET-roe-NID-a-zole)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Metronidazole
Indications
The following indications are listed for Metronidazole:
- B. Fragilis Infection
- Bacterial Endocarditis
- Bacterial Sepsis
- Bacteroides Brain Abscess
- Bacteroides Empyema
- Bacteroides Endocarditis
- Bacteroides Endometritis
- Bacteroides Endomyometritis
- Bacteroides Joint Infection
- Bacteroides Liver Abscess
- Bacteroides Osteomyelitis
- Bacteroides Peritonitis
- Bacteroides Pneumonia
- Bacteroides Septicemia
- Bacteroides Tubo-Ovarian Abscess
- Bone Infection
- Brain Abscess
- Clostridium Endometritis
- Clostridium Endomyometritis
- Clostridium Liver Abscess
- Clostridium Peritonitis
- Clostridium Septicemia
- Clostridium Tubo-Ovarian Abscess
- Colorectal Perioperative Infection
- Endometritis
- Eubacterium Liver Abscess
- Eubacterium Peritonitis
- Female Genital Tract Infection
- Infectious Disease Of Abdomen
- Infectious Disorder Of Joint
- Inflammatory Disease Of Female Pelvic Organs
- Intra-Abdominal Abscess
- Intra-Abdominal Anaerobic Abscess
- Intra-Abdominal Bacteroides Abscess
- Intra-Abdominal Clostridium Abscess
- Intra-Abdominal Eubacterium Abscess
- Intra-Abdominal Peptococcus Abscess
- Intra-Abdominal Peptostreptococcus Abscess
- Liver Abscess
- Lower Respiratory Infection
- Meningitis Due To Bacteroides
- Peptococcus Endometritis
- Peptococcus Endomyometritis
- Peptococcus Liver Abscess
- Peptococcus Peritonitis
- Peptococcus Tubo-Ovarian Abscess
- Peptostreptococcus Endometritis
- Peptostreptococcus Endomyometritis
- Peptostreptococcus Liver Abscess
- Peptostreptococcus Peritonitis
- Peptostreptococcus Tubo-Ovarian Abscess
- Peritonitis
- Post-Operative Vaginal Cuff Peptostreptococcus Infection
- Prevention Of Perioperative Infection
- Skin And Skin Structure Bacteroides Fragilis Infection
- Skin And Skin Structure Clostridium Infection
- Skin And Skin Structure Fusobacterium Infection
- Skin And Skin Structure Infection
- Skin And Skin Structure Peptococcus Infection
- Skin And Skin Structure Peptostreptococcus Infection
- Tubo-Ovarian Abscess
- Vaginal Cuff Surgery Post-Op Bacteroides Infection
- Vaginal Cuff Surgery Post-Op Clostridium Infection
- Vaginal Cuff Surgery Post-Op Infection
- Vaginal Cuff Surgery Post-Op Peptococcus Infection
Also known as: Abdominal Abscess, Abdominal Abscess Due To Anaerobic Bacteria, Abdominal Abscess Due To Bacteroides, Abdominal Abscess Due To Clostridium, Abdominal Abscess Due To Eubacterium, Abdominal Abscess Due To Peptococcus, Abdominal Abscess Due To Peptostreptococcus, Bacillus Fragilis Infection, Bacteremia With Sepsis, Bacterial Septicemia, Bacteroides Fragilis Infection, Brain Abscess Due To Bacteroides Species, Brain Abscess Due To Bacteroides Spp., Colorectal Paraoperative Infection, Empyema Due To Bacteroides Species, Endocarditis Due To Bacteroides Species, Endometritis Due To Bacteroides Species, Endometritis Due To Clostridium Species, Endometritis Due To Peptococcus, Endometritis Due To Peptostreptococcus, Endomyometritis Due To Bacteroides Species, Endomyometritis Due To Clostridium Species, Endomyometritis Due To Peptococcus Species, Endomyometritis Due To Peptostreptococcus Species, Eubacterium Species Liver Abscess, Gynecologic Infection, Hepatic Abscess, Hepatic Abscess Due To Bacteroides Species, Hepatic Abscess Due To Clostridium Species, Hepatic Abscess Due To Eubacterium, Hepatic Abscess Due To Peptococcus Species, Hepatic Abscess Due To Peptostreptococcus, Infection Of Skin And/Or Subcutaneous Tissue, Intra-Abdominal Infection, Intracranial Abscess, Joint Infection, Joint Infection Due To Bacteroides Species, Liver Abscess Due To Bacteroides Species, Liver Abscess Due To Clostridium Species, Liver Abscess Due To Eubacterium, Liver Abscess Due To Peptococcus Species, Liver Abscess Due To Peptostreptococcus, Lower Respiratory Tract Infection, Meningitis Due To Bacteroides Species, Osteomyelitis Due To Bacteroides, Osteomyelitis Due To Bacteroides Species, Perioperative Colorectal Infection, Perioperative Infection Prophylaxis, Peritonitis Due To Bacteroides, Peritonitis Due To Clostridium Species, Peritonitis Due To Eubacterium, Peritonitis Due To Peptococcus, Peritonitis Due To Peptostreptococcus, Pneumonia Due To Bacteroides Species, Postsurgical Peptostreptococcus Vaginal Cuff Infection, Postsurgical Vaginal Cuff Infection, Postsurgical Vaginal Cuff Infection Due To Bacteroides, Postsurgical Vaginal Cuff Infection Due To Clostridium, Postsurgical Vaginal Cuff Infection Due To Peptococcus, Pyogenic Bone Infection Due To Bacteroides, Pyothorax Due To Bacteroides Species, Sepsis Due To Clostridium Species, Sepsis Of The Uterine Tissues Due To Peptococcus Species, Sepsis Of Uterine Tissue Due To Bacteroides Species, Sepsis Of Uterine Tissue Due To Clostridium, Sepsis Of Uterine Tissues Due To Peptostreptococcus, Septicemia Due To Bacteroides, Septicemia Due To Clostridium Species, Septicemia Due To Clostridium Spp., Skin And Skin Soft Tissue Bacteroides Fragilis Infection, Skin And Skin Soft Tissue Clostridium Infection, Skin And Skin Soft Tissue Fusiformis Infection, Skin And Skin Soft Tissue Fusobacterium Infection, Skin And Skin Soft Tissue Peptococcus Infection, Skin And Skin Soft Tissue Peptostreptococcus Infection, Skin And Soft Tissue Skin Infection, Tubo-Ovarian Abscess Due To Bacteroides Species, Tubo-Ovarian Abscess Due To Clostridium Species, Tubo-Ovarian Abscess Due To Peptococcus Species, Tubo-Ovarian Abscess Due To Peptostreptococcus Species.
Dosing
No dosing information is available for this tab.
Metronidazole is administered orally or by continuous or intermittent IV infusion.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Cytochrome P-450 (CYP) isoenzymes, including CYP3A, CYP2E1, and CYP2A6, are involved in the metabolism of metronidazole.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Metronidazole is contraindicated in individuals with a history of hypersensitivity to the medication or other nitroimidazole derivatives.
*Metronidazole is contraindicated in patients who have received disulfiram within the last 2 weeks.
*Because metronidazole has been thought to be associated with a disulfiram-like reaction to alcohol (e.g., cramps, nausea, vomiting, headache, flushing), the manufacturers state that consumption of alcohol or products containing propylene glycol are contraindicated during and for at least 3 days after stopping metronidazole therapy. However, the Centers for Disease Control and Prevention (CDC) states that patients taking metronidazole do not need to abstain from alcohol because the medication does not inhibit acetaldehyde dehydrogenase and therefore does not have a disulfiram-like interaction with alcohol.
*Metronidazole is contraindicated for the treatment of trichomoniasis in patients during the first trimester of pregnancy. Combination bismuth subcitrate, metronidazole, and tetracycline (Pylera(R)) capsules are contraindicated for use throughout pregnancy.
*Combination bismuth subcitrate, metronidazole, and tetracycline (Pylera(R)) capsules are contraindicated in severe renal impairment.
*Metronidazole is contraindicated in patients with Cockayne syndrome because of severe, potentially fatal irreversible hepatotoxicity and/or acute liver failure that has occurred.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects reported with oral metronidazole include GI reactions such as nausea (sometimes accompanied by headache, anorexia, and vomiting), diarrhea, epigastric distress, abdominal cramping, and constipation.
Adverse effects reported in at least 5% of patients receiving the fixed combination bismuth subcitrate, metronidazole, and tetracycline capsules (Pylera(R)) include abnormal feces, diarrhea, nausea, and headache.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of metronidazole injection for the treatment of intra-abdominal infections have been established in pediatric patients from birth up to 4 months of age. Safety and efficacy for the treatment of intra-abdominal infections in pediatric patients >=4 months of age have not been established.
Safety and efficacy of metronidazole injection in pediatric patients <4 months of age have not been established for the treatment of anaerobic infections (other than intra-abdominal infections), or for postoperative infection.
Safety and efficacy of oral metronidazole have been established for the treatment of amebiasis in pediatric patients, but not for the treatment of trichomoniasis or anaerobic bacterial infections.
Safety and efficacy of combination bismuth subcitrate, metronidazole, and tetracycline (Pylera(R)) have not been established for the treatment of Helicobacter pylori infection in pediatric patients. Pylera(R) should not be used in children <8 years of age because of the risk of tooth discoloration and enamel hypoplasia from tetracycline.
There are no adequate or well-controlled studies to date using metronidazole in pregnant females. Published data include case-control studies, cohort studies, and 2 meta-analyses of over 5000 pregnant females who received metronidazole during pregnancy, many during the first trimester. Although these findings have not been confirmed, 1 study found an increased risk of cleft lip, with or without cleft palate in infants exposed to metronidazole in utero. Most other data, which include more than 10 randomized, placebo-controlled trials that assessed the effect of antibiotic treatment (including metronidazole) for bacterial vaginosis on preterm delivery, did not show an increased risk for congenital anomalies or other adverse fetal outcomes. Three studies assessed the risk of infant cancer following in utero exposure; however these studies were limited in their ability to assess risk. Metronidazole does cross the placental barrier, and its effects on human fetal organogenesis are not known.
Combination bismuth subcitrate, metronidazole, and tetracycline (Pylera(R)) capsules are contraindicated in women who are pregnant. Use of tetracyclines (a component of Pylera(R)) during the second and third trimester can cause permanent discoloration of the teeth in infants. All tetracyclines form a stable calcium complex in any bone forming tissue and can potentially inhibit bone development; however, a long-term follow-up study in children exposed to tetracycline in utero showed no adverse effects on bone growth and development.
Healthcare providers should weigh the potential risks and benefits of therapy prior to initiating metronidazole.
Metronidazole is distributed into human milk at concentrations similar to human plasma levels. Because of the tumorigenic potential of metronidazole in mice and rats, a decision should be made whether to discontinue nursing or the medication, taking into account the risk/benefit of treatment. Alternately, choosing to pump and discard milk throughout metronidazole therapy and for 24 hours after discontinuing metronidazole may be an option.
Patients receiving combination bismuth subcitrate, metronidazole, and tetracycline (Pylera(R)) should pump and discard milk throughout therapy and for 2 days after the last dose.
Although there are not specific dosage adjustments in geriatric patients, dosage of metronidazole should generally be undertaken with caution, reflecting the greater frequency of reduced hepatic, renal, cardiac function, concomitant disease or other medication therapies in geriatric individuals.
The manufacturers recommend monitoring for metronidazole-associated adverse effects in geriatric patients.
Following administration of a single 500 mg oral or IV dose of metronidazole, geriatric individuals >70 years of age with no apparent renal or hepatic dysfunction experienced 40-80% higher mean exposures of the active metabolite, hydroxy-metronidazole, compared to healthy patients <40 years of age. Therefore, monitoring for metronidazole-associated adverse events is recommended in geriatric patients.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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