METRO I.V.
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METRO I.V. (METRO I.V.).
Metronidazole is a nitroimidazole antibiotic that exerts its bactericidal effect by entering bacterial cells and undergoing reduction by bacterial nitroreductases to form reactive intermediates that damage DNA, leading to cell death. It is selectively toxic to anaerobic bacteria and protozoa.
| Metabolism | Metronidazole is extensively metabolized in the liver via oxidation and glucuronidation. The major metabolic pathways involve hydroxylation and side-chain oxidation, mediated by CYP450 enzymes (CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4). The primary metabolites are 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-acetic acid, which have minimal antimicrobial activity. |
| Excretion | Renal: 60-80% unchanged; fecal: 6-15% (includes metabolites); biliary: minor contribution. |
| Half-life | 8 hours (range 6-10 hours) in adults; prolonged to 12-24 hours in hepatic impairment. |
| Protein binding | <20%, primarily to albumin. |
| Volume of Distribution | 0.6-0.7 L/kg; indicates extensive distribution into tissues including CSF and abscess cavities. |
| Bioavailability | Oral: 80-90%; IV: 100%. |
| Onset of Action | IV: rapid, within minutes; oral: 1-2 hours. |
| Duration of Action | IV: 12-24 hours; oral: 8-12 hours; clinical effect persists for dosing interval. |
15-30 mg/kg IV loading dose, then 7.5-15 mg/kg IV every 6 hours. Typical adult dose: 500 mg IV every 6-8 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl > 50 mL/min: no adjustment; CrCl 10-50 mL/min: increase dosing interval to every 12 hours; CrCl < 10 mL/min: increase interval to every 24 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: reduce dose by 75%. |
| Pediatric use | Loading dose: 15-30 mg/kg IV; maintenance: 7.5 mg/kg IV every 6 hours. For neonates < 7 days: 15 mg/kg IV every 24 hours; 7-28 days: 15 mg/kg IV every 12 hours. |
| Geriatric use | Use with caution; adjust dose based on renal function (CrCl) and monitor for neurotoxicity. Start at lower end of dosing range. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METRO I.V. (METRO I.V.).
| Breastfeeding | Excreted in breast milk in low concentrations; M/P ratio approximately 1.0. Considered compatible with breastfeeding; monitor infant for diarrhea or candidiasis. |
| Teratogenic Risk | Pregnancy category B. No evidence of teratogenicity in human studies; crosses placenta. Avoid during first trimester unless benefit outweighs risk; use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
Carcinogenicity: Metronidazole has been shown to be carcinogenic in mice and rats. It should be used only for approved indications and for the shortest duration necessary.
| Serious Effects |
["Hypersensitivity to metronidazole or other nitroimidazole derivatives","First trimester of pregnancy (unless alternative treatments not available)","Breastfeeding (withhold nursing for 12-24 hours after dose)","Concurrent use of disulfiram (psychotic reactions may occur)","Severe hepatic impairment (metronidazole is hepatically cleared)"]
| Precautions | ["Carcinogenicity: Avoid unnecessary use","Peripheral neuropathy: Risk with high doses or prolonged treatment; discontinue if signs occur","Central nervous system effects: Encephalopathy, convulsions, aseptic meningitis; discontinue if symptoms develop","Hepatotoxicity: Risk of severe hepatic injury, including acute liver failure; monitor liver function","Blood dyscrasias: Leukopenia, neutropenia; caution in patients with history of blood disorders","Interaction with alcohol: Disulfiram-like reaction (nausea, vomiting, flushing); avoid alcohol during therapy and for at least 3 days after","Cochrane interaction: Increased INR with warfarin; monitor INR","Renal impairment: Accumulation of metabolites; dosage adjustment may be needed","Prolonged therapy: Monitor for superinfection and neurological symptoms"] |
Loading safety data…
| Monitor maternal renal function, hepatic function, and complete blood count. In prolonged therapy, monitor for signs of superinfection. Fetal assessment if used in late pregnancy. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility at therapeutic doses. |