Yes

Amebicide; Antibiotic, Topical; Antibiotic, Miscellaneous; Antiprotozoal

Dental: Treatment of oral soft tissue infections due to anaerobic bacteria including all anaerobic cocci, anaerobic gram-negative bacilli ( Bacteroides), and gram-positive spore-forming bacilli ( Clostridium). Useful as single agent or in combination with amoxicillin, Augmentin®, or ciprofloxacin in the treatment of periodontitis associated with the presence of Actinobacillus actinomycetemcomitans, (AA).

Medical: Treatment of susceptible anaerobic bacterial and protozoal infections in the following conditions: amebiasis, symptomatic and asymptomatic trichomoniasis; skin and skin structure infections; CNS infections; intra-abdominal infections; systemic anaerobic infections; topically for the treatment of acne rosacea; treatment of antibiotic-associated pseudomembranous colitis (AAPC), bacterial vaginosis; used in combination with other agents (eg, tetracycline, bismuth subsalicylate, and an H₂-antagonist) to treat duodenal ulcer disease due to Helicobacter pylori; also used in Crohn's disease and hepatic encephalopathy

B (may be contraindicated in 1st trimester)

Hypersensitivity to metronidazole or any component, 1st trimester of pregnancy since found to be carcinogenic in rats

Use with caution in patients with liver impairment due to potential accumulation, blood dyscrasias; history of seizures, congestive heart failure, or other sodium retaining states; reduce dosage in patients with severe liver impairment, CNS disease, and severe renal failure (Cl_cr <10 mL/minute); if H. pylori is not eradicated in patients being treated with metronidazole in a regimen, it should be assumed that metronidazole-resistance has occurred and it should not again be used; seizures and neuropathies have been reported especially with increased doses and chronic treatment; if this occurs, discontinue therapy

>10%:

Central nervous system: Dizziness, headache

Gastrointestinal (12%): Nausea, diarrhea, loss of appetite, vomiting

<1%: Ataxia, seizures, disulfiram-type reaction with alcohol, pancreatitis, xerostomia, metallic taste, furry tongue, vaginal candidiasis, leukopenia, thrombophlebitis, neuropathy, hypersensitivity, change in taste sensation, dark urine

Symptoms of overdose include nausea, vomiting, ataxia, seizures, peripheral neuropathy

Treatment is symptomatic and supportive

CYP2C9 enzyme substrate; CYP2C9, 3A3/4, and 3A5-7 enzyme inhibitor

Increased toxicity: Alcohol results in disulfiram-like reactions; metronidazole increases P-T prolongation with warfarin and increases lithium levels/toxicity; cimetidine may increase metronidazole levels

Metronidazole injection should be stored at 15°C to 30°C and protected from light

Product may be refrigerated but crystals may form; crystals redissolve on warming to room temperature

Prolonged exposure to light will cause a darkening of the product. However, short-term exposure to normal room light does not adversely affect metronidazole stability. Direct sunlight should be avoided.

Stability of parenteral admixture at room temperature (25°C): Out of overwrap stability: 30 days

Standard diluent: 500 mg/100 mL NS

Reduced to a product which interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death in susceptible organisms

Absorption:

Oral: Well absorbed

Topical: Concentrations achieved systemically after application of 1 g topically are 10 times less than those obtained after a 250 mg oral dose

Distribution: To saliva, bile, seminal fluid, breast milk, bone, liver, and liver abscesses, lung and vaginal secretions; crosses placenta and blood-brain barrier; appears in breast milk

Ratio of CSF to blood level (%): Normal meninges: 16-43; Inflamed meninges: 100

Protein binding: <20%

Metabolism: 30% to 60% in the liver

Half-life:

Neonates: 25-75 hours

Others: 6-8 hours, increases with hepatic impairment

End-stage renal disease: 21 hours

Time to peak serum concentration: Within 1-2 hours

Elimination: Final excretion via the urine (20% to 40% as unchanged drug) and feces (6% to 15%)

Neonates: Anaerobic infections: Oral, I.V.:

0-4 weeks: <1200 g: 7.5 mg/kg/dose every 48 hours

Postnatal age <7 days:

1200-2000 g: 7.5 mg/kg/day every 24 hours

>2000 g: 15 mg/kg/day in divided doses every 12 hours

Postnatal age >7 days:

1200-2000 g: 15 mg/kg/day in divided doses every 12 hours

>2000 g: 30 mg/kg/day in divided doses every 12 hours

Infants and Children:

Amebiasis: Oral: 35-50 mg/kg/day in divided doses every 8 hours for 10 days

Trichomoniasis: Oral: 15-30 mg/kg/day in divided doses every 8 hours for 7 days

Anaerobic infections:

Oral: 15-35 mg/kg/day in divided doses every 8 hours

I.V.: 30 mg/kg/day in divided doses every 6 hours

Clostridium difficile (antibiotic-associated colitis): Oral: 20 mg/kg/day divided every 6 hours

Maximum dose: 2 g/day

Adults:

Amebiasis: Oral: 500-750 mg every 8 hours for 5-10 days

Trichomoniasis: Oral: 250 mg every 8 hours for 7 days or 2 g as a single dose

Anaerobic infections: Oral, I.V.: 500 mg every 6-8 hours, not to exceed 4 g/day

Antibiotic-associated pseudomembranous colitis: Oral: 250-500 mg 3-4 times/day for 10-14 days

H. pylori: 1 capsule with meals and at bedtime for 14 days in combination with other agents (eg, tetracycline, bismuth subsalicylate, and H₂-antagonist)

Vaginosis: 1 applicatorful (~37.5 mg metronidazole) intravaginally once or twice daily for 5 days; apply once in morning and evening if using twice daily, if daily, use at bedtime

Elderly: Use lower end of dosing recommendations for adults, do not administer as a single dose

Topical (acne rosacea therapy): Apply and rub a thin film twice daily, morning and evening, to entire affected areas after washing. Significant therapeutic results should be noticed within 3 weeks. Clinical studies have demonstrated continuing improvement through 9 weeks of therapy.

Dosing adjustment in renal impairment: Cl_cr <10 mL/minute: Administer every 12 hours

Hemodialysis: Extensively removed by hemodialysis and peritoneal dialysis (50% to 100%); administer dose posthemodialysis

Peritoneal dialysis: Dose as for Cl_cr <10 mL/minute

Continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD): Administer usual dose

Dosing adjustment/comments in hepatic disease: Unchanged in mild liver disease; reduce dosage in severe liver disease

Alcohol: A disulfiram-like reaction characterized by flushing, headache, nausea, vomiting, sweating or tachycardia; patients should be warned to avoid alcohol during and 72 hours after therapy

Food: Peak antibiotic serum concentration lowered and delayed, but total drug absorbed not affected. Take on an empty stomach. Drug may cause GI upset; if GI upset occurs, take with food.

May interfere with AST, ALT, triglycerides, glucose, and LDH testing

Dizziness is common; case reports of depression, insomnia, confusion, panic, delusions, hallucinations, exacerbation of schizophrenia

May rarely cause leukopenia; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

No information available to require special precautions

<1% of patients may experience dry mouth and metallic taste

Take exactly as directed, with meals. Avoid alcohol during and for 24 hours after last dose. With alcohol your may experience severe flushing, headache, nausea, vomiting, or chest and abdominal pain. May discolor urine (brown/black/dark) (normal). You may experience "metallic" taste disturbance or nausea or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Refrain from intercourse or use a barrier contraceptive if being treated for trichomoniasis. Report unresolved or severe fatigue; weakness; fever or chills; mouth or vaginal sores; numbness, tingling, or swelling of extremities; difficulty breathing; or lack of improvement or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Breast-feeding is not recommended.

No Antabuse®-like reactions have been reported after topical application, although metronidazole can be detected in the blood; avoid contact between the drug and aluminum in the infusion set

Capsule: 375 mg

Gel, topical: 0.75% [7.5 mg/mL] (30 g)

Gel, vaginal: 0.75% (5 g applicator delivering 37.5 mg; 70 g tube)

Injection, ready to use: 5 mg/mL (100 mL)

Powder for injection, as hydrochloride: 500 mg

Tablet: 250 mg, 500 mg

Tablet, extended release: 750 mg

To prepare metronidazole suspension 50 mg/mL, pulverize ten 250 mg tablets; levigate with a small amount of distilled water; add 10 mL Cologel® and levigate; add sufficient quantity of cherry syrup to total 50 mL and levigate until a uniform mixture is obtained; stable for 30 days if refrigerated

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