Metronidazole

Mechanism of action:

Description:Metronidazole is converted to reduction products that interact w/ DNA to cause

destruction of helical DNA structure and strand leading to a protein synthesis inhibition and cell death
in susceptible organisms. It is active against most anaerobic protozoa, some gm+ve, gm-ve and
facultative anaerobes.
Pharmacokinetics:
Absorption:Readily and almost completely absorbed from the GI tract. Absorption may be delayed by
food. Time to peak plasma concentration: W/in 1-2 hr (oral); 5-12 hr (rectal); 8 hr (intravaginal).
Bioavailability: 60-80% (rectal); approx 20-25% (vag pessaries); 56% (intravaginal gel).
Distribution:Widely distributed into most body tissues and fluids. similar pattern for PO and IV.
Crosses the placenta and enters breast milk.
Metabolism:Undergoes hepatic metabolism by side-chain oxidation and glucuronide formation.
Principal oxidative metabolites are 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole (hydroxy
metabolite) and 2-methyl-5-nitroimidazole-1-acetic acid (acid metabolite).
Excretion:Via urine(77%) (mainly as metabolites) and faeces(14%) (small amounts). Elimination half-
life: 8 hr. 25-75 hr (neonates); prolonged in patients with hepatic impairment

Dosage

Intravenous
Anaerobic bacterial infections
Adult:500 mg infused as 100 mL of a 5 mg/mL soln at 5 mL/min 8 hrly. Alternatively, 15 mg/kg
infused over 1 hr, followed by 7.5 mg/kg infused over 1 hr 6 hrly. Max: 4 g/day. Substitute oral therapy
as soon as possible.
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)

Contraindication:
• hypersensitivity to metronidazole and other nitromidazoles
 special precautions:
• Patient w/ CNS disease, history of blood dyscrasias, ESRD. Re-administer immediately after
haemodialysis. Severe hepatic impairment esp hepatic encephalopathy. Pregnancy and
lactation.

Drug interaction overview

• Metronidazole reported to potentiate anticoagulant effect of warfarin and other oral coumarin
anticoagulants, resulting in a prolongation of prothrombin time and increased risk of
hemorrhages; prothrombin time and international normalized ratio (INR) should be carefully
monitored and anticoagulant dose adjusted accordingly; monitor patients for signs and symptoms
of bleeding
• Metronidazole reported to increase plasma concentrations of busulfan, which can result in an
increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome,
gastrointestinal mucositis, and hepatic veno-occlusive disease; metronidazole should not be
administered concomitantly with busulfan unless benefit outweighs risk
• Simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as
cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may
result in metronidazole toxicity
• Simultaneous administration of drugs that induce microsomal liver enzyme activity, such as
phenytoin or phenobarbital, may accelerate elimination of metronidazole and therefore decrease
its efficacy
• Concomitant use of metronidazole and CYP3A4 substrates (e.g., amiodarone, tacrolimus,
cyclosporine, carbamazepine, phenytoin, and quinidine) may increase respective CYP3A4-
substrate plasma levels; monitoring of plasma concentrations of CYP3A4 substrates may be
necessary
• Metronidazole decreases clearance of 5-fluorouracil and may therefore cause 5-fluorouracil
toxicity
• Metronidazole may potentiate effects of vecuronium

Drug reactions

GI disturbances (e.g. nausea, anorexia, unpleasant metallic taste, vomiting, diarrhoea, abdominal
discomfort, constipation); furred tongue, glossitis, stomatitis; weakness, dizziness, ataxia, headache,
drowsiness, insomnia, hallucinations, changes in mood or mental state (e.g. depression or confusion);
urethral discomfort, darkening of the urine; rashes, urticaria, pruritus; raised liver enzyme values,
cholestatic hepatitis, jaundice, pancreatitis, thrombophlebitis (IV). Rarely, agranulocytosis, leucopenia,
pancytopenia, thrombocytopenia, erythema multiforme, angioedema, anaphylaxis, antibiotic-associated
colitis.
Potentially Fatal: Encephalopathy, peripheral neuropathy including optic neuropathy, convulsive
seizures, aseptic meningitis, Stevens-Johnson syndrome.

Overdosage:
Symptoms: Vomiting, ataxia and slight disorientation.
Management: Symptomatic and supportive treatment.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your
doctor if you have any other medical problems, especially:
•Blood or bone marrow problems, or history of or
•Brain disease (eg, aseptic meningitis, encephalopathy) or
•Edema (too much fluid in the body) or
•Leukopenia (low white blood cells), history of or
•Optic neuropathy (eye disease with vision changes), history of or
•Oral thrush (Candida infection) or
•Peripheral neuropathy (nerve problem), history of or
•Seizures, history of or
•Vaginal yeast infection (Candida infection)—Use with caution. May make these conditions worse.
•Cockayne syndrome (genetic disorder)—Use with caution. May increase the risk of liver
problems, which may be life-threatening.
•Kidney disease, end-stage or
•Liver disease, severe—Use with caution. The effects may be increased because of slower removal
of the medicine from the body.

What do the results of a BUN test mean?

Results of a BUN test are measured in milligrams per deciliter (mg/dL). Normal BUN values tend to
vary depending on gender and age. It’s also important to note that each laboratory has different ranges
for what’s normal.
In general, normal BUN levels fall in the following ranges:
• adult men: 8 to 24 mg/dL
• adult women: 6 to 21 mg/dL
• children 1 to 17 years old: 7 to 20 mg/dL

ALANINE AMINOTRANSFERASE (ALT) 1,2 *

(Major sources: Liver, skeletal muscle, and myocardium)
Infant aged <12 mo 13–45 U/L 13–45 U/L
1–3 yr 5–45 U/L 5–45 U/L
4–6 yr 10–25 U/L 10–25 U/L
7–9 yr 10–35 U/L 10–35 U/L
10–11 yr
Female 10–30 U/L 10–30 U/L
Male 10–35 U/L 10–35 U/L
12–13 yr
Female 10–30 U/L 10–30 U/L
Male 10–55 U/L 10–55 U/L
14–15 yr
Female 5–30 U/L 5–30 U/L
Male 10–45 U/L 10–45 U/L
>16 yr
Female 5–35 U/L 5–35 U/L
Male 10–40 U/L 10–40 U/L

CREATININE (SERUM) 2 (Enzymatic)

Cord 0.6–1.2 mg/dL 53–106 µmol/L
Newborn 0.3–1.0 mg/dL 27–88 µmol/L
Infant 0.2–0.4 mg/dL 18–35 µmol/L
Child 0.3–0.7 mg/dL 27–62 µmol/L
Adolescent 0.5–1.0 mg/dL 44–88 µmol/L
Adult male 0.9–1.3 mg/dL 80–115 µmol/L
Adult female 0.6–1.1 mg/dL 53–97 µmol/L