FLAGYL ER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLAGYL ER (FLAGYL ER).
Metronidazole, a nitroimidazole antibiotic, undergoes intracellular reduction by bacterial nitroreductases, forming cytotoxic compounds that damage DNA and inhibit nucleic acid synthesis, selectively targeting anaerobic bacteria and protozoa.
| Metabolism | Hepatic metabolism via side-chain oxidation and glucuronidation; metabolites are 5-nitroimidazoles and hydroxy metabolites; CYP450 enzymes (CYP2A6, CYP3A4, CYP2B6) partially involved. |
| Excretion | Renal: 60-80% (metabolites and unchanged drug). Fecal: 6-15%. Minimal biliary. |
| Half-life | Terminal elimination half-life: 6-8 hours (increased to 10-12 hours with hepatic impairment; unchanged in renal impairment). |
| Protein binding | <20% (albumin). |
| Volume of Distribution | 0.5-0.8 L/kg; indicates extensive tissue distribution including CNS. |
| Bioavailability | Oral: 80-95% (extended-release formulation). |
| Onset of Action | Oral: 1-2 hours for systemic effects; peak plasma concentrations at 2-4 hours. |
| Duration of Action | Approximately 12-24 hours; clinical antibacterial effect persists beyond serum levels due to tissue penetration. |
| Molecular Weight | 171.15 |
| Action Class | 5-Nitroimidazole (Antiprotozoal & Antibacterial) |
| Brand Substitutes | Metrogyl ER Tablet, Meetgyl ER 600 Tablet |
750 mg orally once daily for 10 days for bacterial vaginosis.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No adjustment necessary for GFR >10 mL/min; for GFR <10 mL/min, consider using immediate-release metronidazole instead of FLAGYL ER due to lack of data in severe renal impairment. |
| Liver impairment | Child-Pugh Class A/B: no adjustment necessary. Child-Pugh Class C: reduce dose to 375 mg orally once daily (50% of usual dose). |
| Pediatric use | Safety and efficacy not established for FLAGYL ER in pediatric patients. Use immediate-release metronidazole for pediatric dosing. |
| Geriatric use | No specific dose adjustment recommended based on age alone; use caution due to potential for decreased renal function and monitor for adverse effects. |
| 1st trimester | Contraindicated in first trimester due to risk of teratogenicity based on animal studies and limited human data; avoid use unless no safer alternative. |
| 2nd trimester | Use with caution if clearly needed; no well-controlled studies but animal data suggest potential risk. |
| 3rd trimester | Use with caution if clearly needed; may increase risk of premature labor and neonatal liver toxicity. |
Clinical note
Comprehensive clinical and safety monograph for FLAGYL ER (FLAGYL ER).
| Placental transfer | Metronidazole readily crosses the placenta, achieving fetal plasma concentrations comparable to maternal levels. Significant placental transfer confirmed. |
| Breastfeeding | Metronidazole is excreted into breast milk in concentrations similar to maternal plasma, potentially causing infant exposure. Avoid breastfeeding during therapy and for 12-24 hours after last dose to minimize risk. |
■ FDA Black Box Warning
Carcinogenicity: Metronidazole has been shown to be carcinogenic in mice and rats. Avoid chronic use. Reserved for anaerobic and protozoal infections.
| Serious Effects |
Hypersensitivity to metronidazole or other nitroimidazole derivativesFirst trimester of pregnancy (unless no safer alternative)Active organic neurological disorderBlood dyscrasiasConcurrent use with disulfiram (within 2 weeks) or alcohol-containing products
| Precautions | Peripheral neuropathy (risk with prolonged use), CNS effects (seizures, encephalopathy), disulfiram-like reaction with alcohol, sodium overload (each tablet contains 84 mg sodium), hepatic impairment may increase risk of toxicity, renal impairment (dose adjustment not typically required but monitor), superinfection including C. difficile diarrhea. |
| Food/Dietary | Avoid alcohol and any products containing alcohol (e.g., mouthwash, cough syrups, cooking wine) during therapy and for 48 hours after last dose. No specific food restrictions otherwise. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Trimester 1: Crosses placenta; contraindicated in first trimester due to risk of carcinogenicity in animal studies and potential teratogenicity; use only for life-threatening infections. Trimester 2 and 3: Use with caution; associated with increased risk of cleft lip/palate in some studies; avoid if possible. |
| Fetal Monitoring | Monitor maternal CBC with differential due to risk of neutropenia; monitor for signs of peripheral neuropathy or CNS toxicity; fetal ultrasound if used in pregnancy. |
| Fertility Effects | No significant effects on fertility reported in animal studies; human data limited; use not known to impair fertility. |
| Clinical Pearls | FLAGYL ER (metronidazole extended-release) is indicated for bacterial vaginosis. Avoid alcohol during therapy and for 48 hours after completion due to disulfiram-like reaction. Monitor for peripheral neuropathy; discontinue if signs occur. Use with caution in hepatic impairment; dose adjustment may be needed. May cause metallic taste. |
| Patient Advice | Take this medication exactly as prescribed; do not crush or chew the extended-release tablets. · Avoid all alcohol and alcohol-containing products during treatment and for 48 hours after the last dose to prevent severe nausea, vomiting, and flushing. · Complete the full course even if symptoms improve to ensure infection is fully treated. · Report any numbness, tingling, or pain in hands or feet to your doctor immediately. · Inform your healthcare provider if you have liver disease, a history of blood disorders, or are pregnant or breastfeeding. |