Metronidazole:
Class: Amebicide; Antibiotic,Antiprotozoal.
Indications:
Treatment of susceptible anaerobic bacterial and protozoal infections in the following
conditions: Amebiasis, symptomatic and asymptomatic trichomoniasis; skin and skin
structure infections, bone and joint infections, CNS infections, endocarditis, gynecologic
infections, intra-abdominal infections (as part of combination regimen), respiratory tract
infections (lower), systemic anaerobic infections; treatment of antibiotic-associated
pseudomembranous colitis (AAPC); as part of a multidrug regimen for H. pylori eradication
to reduce the risk of duodenal ulcer recurrence; surgical prophylaxis (colorectal); useful as
single agent or in combination with amoxicillin, amoxicillin/clavulanic acid, or ciprofloxacin
in the treatment of periodontitis associated with the presence of Actinobacillus
actinomycetemcomitans (AA).
Available dosage form in the hospital: 500MG/100 I.V. INFUSION VIAL, 125MG/5ML
SUSP, 250MG TAB, 500MG TAB.
Trade Names:
Dosage:
-Anaerobic infections (diverticulitis, intra-abdominal, peritonitis, cholangitis, or
abscess): Oral, I.V.: 500 mg every 6-8 hours, not to exceed 4 g/day; Note: Initial: 1 g
I.V. loading dose may be administered
-Amebiasis: Oral: 500-750 mg every 8 hours for 5-10 days
-Antibiotic-associated pseudomembranous colitis: IDSA Guidelines (Cohen, 2010):
-Mild-to-moderate infection: Oral: 500 mg 3 times/day for 10-14 days
-Severe complicated infection: I.V.: 500 mg 3 times/day with oral vancomycin
(recommended agent) for 10-14 days
-Note: Due to the emergence of a new strain of C. difficile, some clinicians recommend
converting to oral vancomycin therapy if the patient does not show a clear clinical
response after 2 days of metronidazole therapy.
-Crohns disease (unlabeled use): I.V.: 10-20 mg/kg/day; long-term (eg, several months)
safety has not been established (Lichtenstein, 2009). Note: Reserved for mild-to-
moderate disease in patients not responsive to sulfasalazine and/or who have colonic
involvement (eg ileocolitis and colitis) (Lichtenstein, 2009; Sutherland, 1991).
-Giardiasis: 500 mg twice daily for 5-7 days
-Intra-abdominal infection, complicated, community-acquired, mild-to-moderate (in
combination with cephalosporin or fluoroquinolone): I.V.: 500 mg every 8-12
hours or 1.5 g every 24 hours for for 4-7 days (provided source controlled)
-Peptic ulcer disease: Helicobacter pylori eradication: Oral: 250-500 mg with meals and at
bedtime for 14 days; requires combination therapy with at least one other antibiotic and
an acid-suppressing agent (proton pump inhibitor or H2 blocker)
-Bacterial vaginosis or vaginitis due to Gardnerella, Mobiluncus: Oral: 500 mg twice daily
(regular release) or 750 mg once daily (extended release tablet) for 7 days
-Pelvic inflammatory disease (unlabeled use): Oral: 500 mg twice daily for 14 days (in
combination with a cephalosporin and doxycycline) (CDC, 2010)
-Periodontitis treatment (monotherapy or combination) associated with presence
of Actinobacillus actinomycetemcomitans (AA): Oral: 250-500 mg every 8 hours for 8-
10 days used in addition to scaling and root planing (Varela, 2011)
-Surgical prophylaxis (colorectal): I.V. 15 mg/kg 1 hour prior to surgery; followed by 7.5
mg/kg 6 and 12 hours after initial dose
-Trichomoniasis: Oral: 250 mg every 8 hours for 7 days or 375 mg twice daily for 7
days or 2 g as a single dose or 1 g twice daily for 2 doses (on same day)
-Urethritis (unlabeled use): Oral: 2 g as a single dose with azithromycin (CDC, 2010)
- Renal Impairment :
-Clcr <10 mL/minute (not on dialysis): Recommendations vary: To reduce possible
accumulation in patients receiving multiple doses, consider reduction to 50% of dose or
administer normal dose every 12 hours; Note: Dosage reduction is unnecessary in short
courses of therapy. Some references do not recommend reduction at any level of renal
impairment (Lamp, 1999).
-Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days):
Dialyzable (50% to 100%): 500 mg every 8-12 hours. Note: Dosing regimen highly
dependent on clinical indication (trichomoniasis vs C. difficile colitis) (Heintz,
2009). Note: Dosing dependent on the assumption of thrice weekly, complete IHD
sessions.
-Peritoneal dialysis (PD): Dose as for Clcr <10 mL/minute
-Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug
clearance is highly dependent on the method of renal replacement, filter type, and flow
rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of
adverse reactions due to drug accumulation, as well as drug concentrations in relation to
target trough (if appropriate). The following are general recommendations only (based
on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function)
and should not supersede clinical judgment:
-CVVH/CVVHD/CVVHDF: 500 mg every 6-12 hours (or per clinical indication;
dosage reduction generally not necessary)
Hepatic adjustement :
Manufacturers recommendations:
Mild or moderate impairment (Child-Pugh A or B): No dosage adjustment is
necessary; use with caution.
Severe impairment (Child-Pugh C):
Extended-release tablets: Use is not recommended.
Immediate-release capsules:
Amebiasis: 375 mg 3 times daily for 5-10 days
Trichomoniasis: 375 mg once daily for 7 days
Immediate-release tablets, injection: Reduce dose by 50%.
Alternative recommendations: The pharmacokinetics of a single oral 500 mg dose
were not altered in patients with cirrhosis; initial dose reduction is therefore not
necessary (Daneshmend, 1982). In one study of I.V. metronidazole, patients with
alcoholic liver disease (with or without cirrhosis), demonstrated a prolonged
elimination half-life (eg, ~18 hours). The authors recommended the dose be
reduced accordingly (clearance was reduced by ~62%) and the frequency may be
prolonged (eg, every 12 hours instead of every 6 hours) (Lau, 1987). In another
single I.V. dose study using metronidazole metabolism to predict hepatic
function, patients classified as Child-Pugh class C demonstrated a half-life of
~21.5 hours (Muscara, 1995).
Common side effect:
Cardiovascular: Flattening of the T-wave, flushing, syncope
Central nervous system: Aseptic meningitis, ataxia, confusion, coordination impaired,
depression, dizziness, , fever, headache, insomnia, irritability, seizure, vertigo
Dermatologic: Erythematous rash, pruritus, Stevens-Johnson syndrome, urticaria
Endocrine & metabolic: Disulfiram-like reaction, dysmenorrhea
Gastrointestinal: Nausea, anorexia, abdominal cramping, constipation, diarrhea, epigastric
distress, furry tongue, unusual/metallic taste, vomiting.
Genitourinary: darkened urine.
Pregnancy Risk Factor: B
