FLAGYL I.V. RTU IN PLASTIC CONTAINER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLAGYL I.V. RTU IN PLASTIC CONTAINER (FLAGYL I.V. RTU IN PLASTIC CONTAINER).
Metronidazole, a nitroimidazole, exerts bactericidal and antiprotozoal activity via reduction of its nitro group by bacterial or protozoal nitroreductases, forming toxic intermediates that disrupt DNA helical structure and inhibit nucleic acid synthesis.
| Metabolism | Hepatic metabolism via oxidation and glucuronidation; major metabolites include hydroxy-metronidazole (active) and acid metabolites. Enzymes: CYP450 (primarily CYP2A6 and CYP3A4). |
| Excretion | Renal (60-80% as unchanged drug and metabolites), fecal (6-15%), biliary (minor). |
| Half-life | 8 hours (6-10 hours) in adults with normal renal function; prolonged to 12-24 hours in severe hepatic impairment. |
| Protein binding | <20%, primarily to albumin. |
| Volume of Distribution | 0.8-1.2 L/kg; indicates extensive tissue penetration including CNS, bone, and abscesses. |
| Bioavailability | Oral: 100% (nearly complete absorption). |
| Onset of Action | IV: Immediate (peak concentration at end of infusion); oral: 1-2 hours after dose. |
| Duration of Action | 12-24 hours; therapeutic concentration maintained for 8-12 hours after IV dose. |
Metronidazole: Initial loading dose of 15 mg/kg IV, followed by 7.5 mg/kg IV every 6 hours (max 4 g/day). For surgical prophylaxis: 15 mg/kg IV 1 hour before surgery.
| Dosage form | INJECTABLE |
| Renal impairment | No adjustment required for GFR >10 mL/min. For GFR <10 mL/min: administer every 12 hours. Hemodialysis: administer normal dose after dialysis; no supplemental dose needed. Peritoneal dialysis: administer normal dose every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% (e.g., 7.5 mg/kg every 12 hours). Child-Pugh C: use contraindicated or reduce dose to 7.5 mg/kg every 24 hours with close monitoring. |
| Pediatric use | Neonates (0-6 weeks): 15 mg/kg IV loading, then 7.5 mg/kg IV every 12 hours. Infants/children (>6 weeks): 15 mg/kg IV loading, then 7.5 mg/kg IV every 6 hours (max 4 g/day). For surgical prophylaxis: 15 mg/kg IV 1 hour before surgery. |
| Geriatric use | No specific dose adjustment based solely on age. Monitor renal function and adjust if GFR <10 mL/min. Consider reduced hepatic clearance; use lowest effective dose and monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FLAGYL I.V. RTU IN PLASTIC CONTAINER (FLAGYL I.V. RTU IN PLASTIC CONTAINER).
| Breastfeeding | Metronidazole is excreted into breast milk with an M/P ratio of approximately 0.9. Infant serum levels may be up to 20% of maternal levels. Due to potential carcinogenicity in animal studies and concerns for infant gastrointestinal effects, the manufacturer recommends discontinuing breastfeeding during therapy and for 24-48 hours after last dose. Alternative washing and pumping may be considered. |
| Teratogenic Risk | Metronidazole crosses the placenta. First trimester: Avoid use; data suggest possible teratogenic risk (cleft palate), though not conclusively. Second and third trimesters: Generally considered safe for short-term treatment of bacterial vaginosis or trichomoniasis; no evidence of increased major malformations. However, use only if clearly needed. |
■ FDA Black Box Warning
Carcinogenicity: Metronidazole has been shown to be carcinogenic in mice and rats. Its use should be reserved for conditions described in the indications. Unnecessary use should be avoided.
| Serious Effects |
["Hypersensitivity to metronidazole or other nitroimidazoles","First trimester of pregnancy (for trichomoniasis; relative contraindication)","Concurrent use of disulfiram (psychotic reactions possible)","Patients with Cockayne syndrome (risk of severe hepatic adverse reactions)"]
| Precautions | ["Carcinogenicity risk (animal data; avoid unnecessary use)","Seizures and peripheral neuropathy (discontinue if abnormal neurologic signs occur)","Hepatic impairment: dose adjustment may be required; caution in severe liver disease","Renal impairment: accumulation of metabolites; monitor for toxicity","Blood dyscrasias: history of or current; monitor CBC with prolonged therapy","Candidiasis: may cause overgrowth; treat appropriately","Disulfiram-like reaction with alcohol: avoid alcohol during and for 48 hours after therapy","Drug interactions: warfarin (increased INR), lithium (increased toxicity), CYP450 inducers/inhibitors","Pregnancy: reserve for serious infections; use in trichomoniasis only if no alternative","Lactation: discontinue breastfeeding or drug, considering importance to mother"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal liver function, renal function, and CBC especially with prolonged therapy. Infant monitoring for signs of metronidazole toxicity (e.g., diarrhea, candidiasis) if breastfeeding occurs. No specific fetal monitoring required but routine ultrasound may be considered if used in early gestation. |
| Fertility Effects | No significant adverse effects on fertility reported in animal studies or human data. Possible reversible decrease in sperm motility with high doses in males, but clinical significance is unclear. |