Dosing and uses of Flagyl, Flagyl ER (metronidazole)
Adult dosage forms and strengths
capsule
- 375mg
tablet
- 250mg
- 500mg
tablet, extended-release
- 750mg
infusion solution
- 500mg/100mL
Anaerobic Bacterial Infections
Loading dose: 15 mg/kg IV; not to exceed 4 g/day
Maintenance dose: 7.5 mg/kg PO/IV (over 1 h) q6hr x 7-10 days (or 2-3 weeks if severe)
Sexually Transmitted Disease
Prevention following sexual assault
2 g PO as a single dose; 3-drug regimen that also includes ceftriaxone or cefixime, PLUS azithromycin or doxycycline (CDC STD guidelines, 2010)
Bacterial Vaginosis
Nonpregnant women
- 500 mg PO BID x 7 days, OR
- 2 g PO qDay single dose, OR
- Extended-release: 750 mg PO qDay x 7 days
Pregnant women
- 500 mg PO BID x 7 days, OR
- 250 mg PO TID x 7 days
Colorectal Surgical Infection
Prophylaxis; start after mechanical bowel preparation the afternoon and evening before surgery
1 g PO q6-8hr for 3 doses
15 mg/kg IV over 30-60 min; complete approximately 1 hr before surgery; may administer 7.5 mg/kg IV over 30-60 min at 6 and 12 hr after initial dose for maintenance; discontinue within 12 hr after surgery
Trichomoniasis
250 mg PO q8hr for 7 days; alternatively, 375 mg PO q12hr for 7 days
2 g PO qDay single dose; alternatively, 1g PO q12hr for 2 doses
Amebiasis
500-750 mg PO q8hr for 5-10 days
Giardiasis (Off-label)
500 mg PO q12hr for 5-7 days
Gardnerella Infection
Immediate release: 500 mg PO q12hr
Extended-release: 750 mg PO qDay for 7 days; take on empty stomach
Helicobacter Pylori Infection (Off-label)
250-500 mg PO QID in combination with tetracycline (500 mg) and bismuth subsalicylate (525 mg) x 14 days
Nongonococcal Urethritis (Off-label)
2 g PO qDay single dose with erythromycin (500 mg QID) or erythromycin ethylsuccinate (800 mg QID) x 7 days
Pelvic Inflammatory Disease (Off-label)
500 mg PO q12hr for 14 days in conjunction with ofloxacin or levofloxacin
Pouchitis (Orphan)
Orphan indication sponsor
- Formac Pharmaceuticals, NV; Gaston Geenslaan 1; Belgium
Crohn Disease (Orphan)
Topical treatment of active perianal Crohn disease
Orphan indication sponsor
- Braintree Laboratories, Inc; 60 Columbian Street West; PO Box 850929; Braintree, MA 02185-0929
Perioral Dermatitis (Orphan)
Orphan indication sponsor
- Galderma Laboratories, Inc; P.O. Box 331329; Fort Worth, TX 76163
Pediatric dosage forms and strengths
capsule
- 375mg
tablet
- 250mg
- 500mg
tablet, extended-release
- 750mg
infusion solution
- 500mg/100mL
Neonatal (<28 Days) Anaerobic Infection
<1.2 kg
- 7.5 mg/kg IV/PO q48hr
<7 days
- 1.2-2 kg: 7.5 mg/kg IV/PO qDay
- >2 kg: 15 mg/kg/day IV/PO divided q12hr
>7 days
- 1.2-2 kg: 15 mg/kg/day IV/PO divided q12hr
- >2 kg: 30 mg/kg/day IV/PO divided q12hr
Infants and Children
- 30 mg/kg/day PO/IV divided q6hr; not to exceed 4 g/day
Clostridium Difficile Colitis
30 mg/kg/day IV/PO divided q6hr IV/PO for 7-10 days (American Academy of Pediatrics)
Amebiasis
35-50 mg/kg PO divided q8hr for 10 days
Giardiasis
15 mg/kg/day IV/PO divided q8hr for 5 days
Trichomoniasis
< 45 kg body weight: 15 mg/kg/day IV/PO divided q8hr for 7 days; not to exceed 2 g/day
Helicobacter Pylori-Associated Peptic Ulcer Disease (Off-label)
With amoxicillin and bismuth subsalicylate: 15-20 mg/kg/day PO divided q12hr for 4 weeks
Flagyl, Flagyl ER (metronidazole) adverse (side) effects
Frequency not defined
Appetite loss
Candidiasis
Diarrhea
Dizziness
Headache
Nausea
Vomiting
Ataxia
Dark urine
Disulfiram-type reaction with ethanoL
Furry tongue
Hypersensitivity
Neutropenia
Metallic taste
Neuropathy
Pancreatitis
Seizures
Thrombophlebitis
Xerostomia
Encephalopathy
Aseptic meningitis
Optic neuropathy
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Decreased libido
Postmarketing Reports
Dyspareunia, proctitis, fleeting joint pains that may resemble serum sickness, Crohn’s disease, hiccup, psychosis
Warnings
Black box warnings
Animal data have shown possible carcinogenic effect
Contraindications
Hypersensitivity to metronidazole or other nitroimidazoles (although cautious desensitization has been applied)
Pregnancy, 1st trimester (controversial)
Use of disulfiram within past 2 weeks; use of alcohol during therapy or within 3 days of discontinuing therapy
Cautions
Encephalopathcy, seizures, aseptic meningitis, and neuropathies reported with increase in dose and chronic therapy
Superinfection may occur with prolonged use
Severe hepatic impairment; administer lower doses with caution
Use with caution; potential accumulation in end stage renal disease; supplemental doses may be needed in patients receiving hemodialysis
Use with caution in history of blood dyscrasias, heart failure, hepatic failure, H. pylori infection, renal impairment
Avoid alcohol while taking medication and for at least 1 day after discontinuation
Antiandrogen: May cause gynecomastia
Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with Metronidazole Injection and requires treatment with a candicidal agent
Pregnancy and lactation
Pregnancy category: B
Lactation
Excreted in human milk; not recommended
Following PO administration, concentrations in human milk are similar to concentrations in plasma
Potential for tumorigenicity shown in animal studies; a decision should be made whether to discontinue nursing or to discontinue metronidazole; breastfeeding women may choose to pump and discard milk for the duration of therapy and for 24 hours after therapy ends and to feed her infant stored human milk or formula
Study Data
There are published data from case-control studies, cohort studies, and 2 meta-analyses that included more than 5000 pregnant women who used metronidazole systemically during pregnancy
Many studies included first trimester exposures
One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in utero; however, these findings were not confirmed
In addition, more than 10 randomized, placebo-controlled clinical trials that together enrolled over 5000 pregnant women assessed the possible effect of systemic antibiotic treatment (including with metronidazole) for bacterial vaginosis on the incidence of preterm delivery; most studies did not show an increased risk of congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy
Three studies conducted to assess the risk of infant cancer following systemic metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Flagyl, Flagyl ER (metronidazole)
Mechanism of action
Inhibits nucleic acid synthesis by disrupting DNA and causing strand breakage; amebicidal, bactericidal, trichomonacidaL
Absorption
Bioavailability: 80% absorption from GI tract (PO)
Protein binding (<20%)
Peak serum time: 1-2 hr
Distribution
Widely distributed; similar pattern for PO and IV
Metabolism
Liver
Enzymes inhibited: Hepatic CYP2C9
Elimination
Half-life: 25-75 hr (neonates); 8 hr (others); prolonged in patients with hepatic impairment
Excretion: Urine (77%); feces (14%)
Administration
IV Incompatibilities
Some drugs may be incompatible with reconstituted solution from powder (which contains metronidazole HCl) but compatible with RTU IV solution (which contains metronidazole), and vice versa
Additive: Aztreonam, cefepime(?), ciprofloxacin (may be compatible with RTU solution), dopamine, meropenem
Y-site: Amphotericin B cholesteryl sulfate, aztreonam, filgrastim, meropenem, warfarin
IV Preparation
Reconstitute powder with 4.4 mL sterile water for injection, bacteriostatic water for injection, NS, or bacteriostatic NS to a final concentration of 100 mg/mL (pH 0.5-2)
Further dilute in glass or plastic container to no more than 8 mg/mL with NS, D5W, or Lr
Neutralize with approximately 5 mEq NaHCO3 per 500 mg metronidazole; final pH 6-7
No dilution or buffering necessary for ready-to-use IV solution
IV Administration
Infusion only
Avoid contact between drug and aluminum in infusion set (less critical for RTU infusion solution containing metronidazole rather than metronidazole HCl)
Storage
Store at 15-30°C
Protect from light
