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. |
| Molecular Weight | 171.15 |
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 | Contraindicated in first trimester. Metronidazole crosses placenta; association with cleft palate in some animal studies, although human data do not show consistent teratogenic risk. Use only if clearly needed. |
| 2nd trimester | Use with caution if benefit outweighs risk. Avoid high-dose or prolonged therapy. |
| 3rd trimester | Use with caution. Theoretical risk of neurodevelopmental effects; avoid near term if possible. |
Clinical note
Comprehensive clinical and safety monograph for METRO I.V. (METRO I.V.).
| Placental transfer | Metronidazole readily crosses the placenta, achieving fetal plasma concentrations similar to maternal levels. Extensive placental transfer documented. |
| Breastfeeding | Metronidazole is excreted into breast milk, achieving concentrations similar to maternal plasma. Because of potential for adverse effects in the nursing infant (e.g., diarrhea, candidiasis), the manufacturer recommends discontinuing breastfeeding or the drug. However, a single 2 g dose may be acceptable if breastfeeding is withheld for 12-24 hours. For longer courses, consider alternate therapy. |
■ 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 derivativesFirst trimester pregnancy (relative contraindication, but absolute in labeling)Concomitant use with disulfiram (psychotic reactions possible)
| 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…
| Lactation Rating | L3 - Moderately Safe |
| 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 | 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. |
| Food/Dietary |
| No significant food interactions. However, alcohol is strictly contraindicated. Use alcohol-free formulations of medications and avoid alcoholic beverages. |
| Clinical Pearls | METRO I.V. (metronidazole) is a nitroimidazole antibiotic effective against anaerobic bacteria and protozoa. It has excellent bioavailability following intravenous administration. Monitor for peripheral neuropathy with prolonged use. Avoid alcohol during therapy and for 48 hours after last dose due to disulfiram-like reaction. Dose adjustment required in severe hepatic impairment (Child-Pugh C). May cause metallic taste, which is benign. Use with caution in patients with CNS disorders due to risk of seizures. |
| Patient Advice | Do not drink any alcohol or take products containing alcohol (e.g., mouthwash, cough syrup) while using this medication and for 48 hours after stopping, as it can cause severe nausea, vomiting, headache, and abdominal cramps. · May cause a metallic or bitter taste in the mouth; this is harmless and temporary. · Report any numbness, tingling, or weakness in your arms or legs to your healthcare provider immediately, as this could be a sign of nerve damage. · Take the full course of therapy exactly as prescribed, even if you feel better. · If you have severe liver disease, your dose may need to be adjusted. |