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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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