title: Metronidazole - Neonatal Intensive Care Drug Manual
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  Neonatal Intensive Care Drug Manual
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  bet | 352/654 | Sana | 03.01.2022 | Hajmi | 1,5 Mb. | | #14803 |
  Metronidazole
  Revision Date : 11-12-2020
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  Approved: TC, KOH
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  Alert
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  High risk medicine. There are few data from prospective trials on the safety and efficacy of metronidazole in newborn infants.
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  Indication
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  Anaerobic bacterial and protozoal infections including meningitis.
  Necrotising enterocolitis.
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  Action
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  Bactericidal against anaerobic bacteria and an antiprotozoal agent.
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  Drug type
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  Antibacterial — nitromethylimidazole
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  Trade name
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  Metronidazole Sandoz IV Solution for infusion, DBL Metronidazole Intravenous Infusion, Metronidazole Intravenous Infusion (Baxter) Solution for infusion, Metronidazole-Claris Solution for infusion, Metronidazole Kabi solution fort Infusion.
  Flagyl S oral Suspension
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  Presentation
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  500 mg/100 mL IV solution
  200 mg/5 mL Oral Suspension
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  Dose
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  IV or Oral
  Postmenstrual age/Corrected age
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  Loading dose
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  Maintenance
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  < 27 weeks
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  15 mg/kg
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  7.5 mg/kg 24 hourly
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  27+0–33+6 weeks
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  15 mg/kg
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  7.5 mg/kg 12 hourly
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  34+0–40+6 weeks
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  15 mg/kg
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  7.5 mg/kg 8 hourly
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  ≥ 41+0 weeks
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  15 mg/kg
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  7.5 mg/kg 6 hourly
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  Dose adjustment
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  Maximum dose
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  Total cumulative dose
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  Route
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  IV, oral
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  Preparation
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  Use undiluted.
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  Administration
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  IV Infusion over 30 minutes.
  Oral: Give 1 hour before feeds.
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  Monitoring
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  Full blood count if patient is on therapy > 1 week.
  Liver and renal function tests.
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  Contraindications
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  Hypersensitivity to metronidazole or other nitroimidazoles.
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  Precautions
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  Patients with seizures or peripheral neuropathy, blood dyscrasias, renal or hepatic impairment – dose reduction may be required.
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  Drug interactions
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  Co-administration with phenobarbital (phenobarbitone) and phenytoin may reduce metronidazole concentrations and increase phenytoin concentrations. Monitor anticonvulsant concentrations.
  Concurrent use with QT-prolonging drugs may result in increase of QT interval resulting in arrhythmias (torsades de pointes).
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  Adverse reactions
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  More common: GI upset, stomatitis and candida overgrowth. Drug metabolite may cause brownish discolouration of urine.
  Rare: Convulsive seizures and peripheral neuropathy characterised mainly by numbness or paraesthesia of an extremity have been reported in adults. May cause reversible leucopenia and/or thrombocytopenia.
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  Compatibility
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  Fluids: Glucose 5%, glucose 10% (not recommended due to high osmolarity of the resulting solution), sodium chloride 0.9%, glucose/sodium chloride fluids.
  Y-site: Amino acid solution, aciclovir, dopamine, esmolol, fluconazole, labetalol, lipid emulsion, magnesium sulfate, methylprednisolone sodium succinate, midazolam, morphine sulfate, piperacillin-tazobactam (EDTA-free), remifentanil.
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  Incompatibility
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  Amphotericin, aztreonam, cefepime, ganciclovir
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  Stability
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  Once removed from original container, use as soon as practicable.
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  Storage
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  IV: Store below 25°C. Do NOT refrigerate.
  Oral suspension: Store below 25°C. Protect from light.
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  Excipients
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  Injection: Citric acid, dibasic sodium phosphate, sodium chloride.
  Suspension: Aluminium magnesium silicate, ethanol, methyl hydroxybenzoate, monobasic sodium phosphate, natural soluble lemon flavour, orange oil terpeneless, propyl hydroxybenzoate, sucrose.
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  Special comments
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  Metronidazole oral suspension is best absorbed on an empty stomach.
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  Evidence
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  Efficacy and Safety
  There is a lack of data from prospective trials on the safety and efficacy of metronidazole in newborn infants. A retrospective study reported broad-spectrum antibiotics plus metronidazole may not prevent the deterioration of NEC in full-term and near-term infants. (1) (LOE III-3 GOR D)
  Pharmacokinetics
  Metronidazole principally undergoes hepatic metabolism with clearance increasing with weight and post-menstrual age (PMA). Cohen-Wolkowiez et al evaluated the pharmacokinetics of metronidazole in 32 infants born at ≤ 32 weeks’ gestation and less than 120 days old. The study correlated metronidazole clearance with PMA and developed a PK model using nonlinear mixed-effect modeling (NONMEM). Monte Carlo simulations were performed and the study gives dosing recommendations based on PMA separated into < 34 weeks, 34 weeks to 40 weeks, and > 40 weeks. (2,3) Suyagh et al evaluated the pharmacokinetics of 32 infants born at ≤ 37 weeks gestation and less than 55 days old. A 1-compartment model was developed using NONMEM. Monte Carlo simulations were performed and dose recommendations are given based on PMA separated into < 26 weeks, 26–27 weeks, 28–33 weeks, and ≥ 34 weeks. (4) (LOE IV GOR C)
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  Practice points
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  References
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  Luo LJ, Li X, Yang KD, Lu JY, Li LQ. Broad-spectrum antibiotic plus metronidazole may not prevent the deterioration of necrotizing enterocolitis from stage II to III in full-term and near-term infants: A propensity score-matched cohort study. Medicine. 2015;94(42).
  Cohen-Wolkowiez M, Ouellet D, Smith PB, et al. Population pharmacokinetics of metronidazole evaluated using scavenged samples from preterm infants. Antimicrob Agents Chemother 2012;56:1828–37.
  Cohen-Wolkowiez M, Sampson M, Bloom BT, et al. Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants. Pediatr Infect Dis J 2013;32:956–61.
  Suyagh M, Collier PS, Millership JS, Iheagwaram G, Millar M, Halliday HL, McElnay JC. Metronidazole population pharmacokinetics in preterm neonates using dried blood-spot sampling. Pediatrics. 2011 Feb 1;127(2):e367-74.1.
  MIMS Product Information (2014) DBL Metronidazole Intravenous Infusion, Hospira
  Australian Injectable Drugs Handbook, 6th Edition 2016.
  Micromedex. Metronidazole monograph, accessed on 10/10/2016
  MIMS Product Information (2016) Flagyl S Suspension, Sanofi-Aventis
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  Original version Date: 29/12/2016
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  Author: NMF Consensus Group
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  Current Version number: 2
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  Current Version Date: 11-12-2020
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  Risk Rating: Low
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  Due for Review: 11-12-2025
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  Approval by: DTC
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  Approval Date: TBA
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