Antipro

Approved Indications:

A. Anaerobic and Protozoal Infections

• Anaerobic bacterial infections, including:
• Intra-abdominal infections (e.g., peritonitis, abscess)
• Bacterial vaginosis
• Bone and joint infections
• CNS infections (e.g., brain abscess)
• Endocarditis (anaerobic)
• Lower respiratory tract infections (e.g., aspiration pneumonia, lung abscess)
• Pelvic inflammatory disease
• Skin and soft tissue infections caused by anaerobes
• Clostridioides difficile-associated diarrhea (CDAD)
• Trichomoniasis (urogenital infections caused by Trichomonas vaginalis)
• Giardiasis (Giardia lamblia)
• Amebiasis, including:
• Intestinal amebiasis
• Hepatic amebiasis (amebic liver abscess)
• Bacterial vaginosis
• Surgical prophylaxis for colorectal and gynecological surgeries (in combination with other agents)

Off-Label / Clinically Accepted Uses:

• Helicobacter pylori eradication (as part of combination regimens)
• Rosacea (topical metronidazole)
• Crohn’s disease (perianal fistulas)
• Hidradenitis suppurativa
• Radiation-induced proctitis or cystitis
• Foul-smelling wounds (topical use)

Routes: Oral, Intravenous (IV), Topical, Intravaginal

Adults:

• Anaerobic Infections (Oral/IV):
  500 mg every 8 hours for 7–10 days (duration may vary by site and severity)
• Trichomoniasis:
  Single 2 g oral dose or 500 mg orally twice daily for 7 days
• Bacterial Vaginosis:
  500 mg orally twice daily for 7 days or 0.75% gel intravaginally once or twice daily × 5 days
• Amebiasis:
• Intestinal: 750 mg orally three times daily × 5–10 days
• Hepatic abscess: 500–750 mg orally three times daily × 5–10 days
• Giardiasis:
  250 mg orally three times daily for 5–7 days
• C. difficile Infection (initial episodes):
  500 mg orally every 8 hours × 10 days (now replaced by vancomycin/fidaxomicin as first-line per updated guidelines; metronidazole reserved for non-severe cases when others unavailable)
• H. pylori (triple/quad therapy):
  500 mg orally twice daily as part of multi-drug regimen × 10–14 days
• Surgical Prophylaxis (IV):
  15 mg/kg IV over 30–60 minutes 1 hour prior to incision, followed by 7.5 mg/kg every 6 hours if prolonged procedure

Pediatrics:

• Anaerobic Infections: 30–50 mg/kg/day in 3 divided doses (Max: 4 g/day)
• Giardiasis: 15 mg/kg/day in 3 divided doses × 5–7 days
• Amebiasis: 35–50 mg/kg/day in 3 divided doses × 10 days

Elderly:

• No routine dose adjustment, but monitor hepatic function and neurologic status

Renal Impairment:

• No adjustment in mild/moderate impairment
• In end-stage renal disease: Hemodialysis removes drug; dose after dialysis

Hepatic Impairment:

• Reduce dose in severe hepatic dysfunction; monitor for accumulation and CNS toxicity

Metronidazole is a prodrug that becomes activated in anaerobic microorganisms and protozoa through reduction of its nitro group by electron transport proteins. The active nitroso free radical formed interacts with microbial DNA, causing strand breakage, inhibition of nucleic acid synthesis, and ultimately cell death. Its selectivity for anaerobes stems from the intracellular environment needed for activation, which is absent in aerobic organisms.

• Absorption: Nearly 100% bioavailable after oral administration
• Onset: 1–2 hours after oral dose
• Peak Plasma Levels: ~1–2 hours post-dose (oral)
• Distribution: Widely distributed; penetrates CSF, saliva, bone, abscesses, and vaginal secretions
• Protein Binding: <20%
• Metabolism: Primarily hepatic via oxidation and glucuronidation
• Active Metabolites: Yes (retain antimicrobial activity)
• Half-life: ~8 hours (may increase in hepatic impairment)
• Excretion: 60–80% in urine (20% unchanged), 6–15% in feces

• Pregnancy:
  Formerly FDA Category B. Not teratogenic in animals. Use during first trimester only if clearly needed (e.g., trichomoniasis with no alternative). Safe in second and third trimesters when clinically indicated.
• Lactation:
  Excreted into breast milk. May cause diarrhea, candidiasis, or metallic taste in infant. For single high-dose (2 g) therapy, avoid breastfeeding for 12–24 hours post-dose. Compatible with breastfeeding for lower divided doses.

• Primary Class: Nitroimidazole Antibacterial and Antiprotozoal
• Subclass: Anaerobic agent with protozoal activity

• Hypersensitivity to metronidazole or other nitroimidazoles
• First trimester of pregnancy for trichomoniasis (unless no alternatives)
• Use with disulfiram within the past 2 weeks (risk of psychosis)
• Concomitant alcohol consumption or within 3 days of alcohol use (disulfiram-like reaction)

• CNS Toxicity: Rare cases of seizures, peripheral neuropathy, and encephalopathy—monitor neurologic function with prolonged use
• Carcinogenicity (Boxed Warning): Shown to be carcinogenic in rodents; use only when clinically necessary
• Hepatic Impairment: Use cautiously in severe disease; adjust dosage
• Blood Dyscrasias: Rare reports of leukopenia; monitor CBC with prolonged therapy
• Alcohol Interaction: Disulfiram-like reaction (flushing, tachycardia, vomiting)
• Prolonged Use: May require periodic neurologic exam and hematologic monitoring

Common:

• Gastrointestinal: Nausea, metallic taste, anorexia, vomiting, diarrhea, abdominal discomfort
• Neurologic: Headache, dizziness
• Genitourinary: Vaginal candidiasis, urine discoloration (reddish-brown)
• Dermatologic: Skin rash

Serious/Rare:

• Peripheral neuropathy (dose or duration related)
• Encephalopathy, seizures (prolonged high-dose therapy)
• Aseptic meningitis (rare)
• Stevens-Johnson syndrome (rare)
• Leukopenia, neutropenia
• Hepatotoxicity (especially in patients with Cockayne syndrome)

Timing/Severity: Most side effects are mild and reversible. Neurologic effects are dose- and duration-dependent, typically after prolonged therapy (>10–14 days).

• Alcohol: Contraindicated during and 3 days post-treatment (disulfiram-like reaction)
• Disulfiram: May cause psychosis; avoid co-administration
• Warfarin and other coumarins: Enhanced anticoagulant effect—monitor INR closely
• CYP3A4/CYP2C9 Inhibitors: May affect metabolism (less clinically significant)
• Phenytoin, Phenobarbital: May decrease metronidazole levels
• Lithium: May increase lithium toxicity; monitor serum lithium levels
• 5-FU: Metronidazole may increase toxicity of fluorouracil

• 2021 IDSA C. difficile Guidelines: Metronidazole no longer first-line; reserved for non-severe CDI only when vancomycin or fidaxomicin are unavailable
• 2023 CDC STI Guidelines: Metronidazole remains first-line for trichomoniasis and bacterial vaginosis
• Safety Notices: CNS side effects (peripheral neuropathy, encephalopathy) reinforced for prolonged use; avoid chronic administration unless clearly necessary

• Tablets and Capsules:
  Store at 20°C to 25°C (68°F to 77°F); excursions allowed to 15°C–30°C
  Protect from light and moisture
• IV Solution:
  Store at 20°C to 25°C
  Do not refrigerate or freeze
  Use within recommended time after opening
  Protect from excessive heat
• Topical Gel/Cream:
  Store at room temperature (up to 25°C)
  Avoid freezing
• Vaginal Gel:
  Store at 20°C to 25°C
  Do not freeze; protect from heat