title: Imipenem/Cilastatin - Neonatal Intensive Care Drug Manual
text: |
  Neonatal Intensive Care Drug Manual
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  bet | 294/654 | Sana | 03.01.2022 | Hajmi | 1,5 Mb. | | #14803 |
  Imipenem/Cilastatin
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  Revision Date : 23-12-2020
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  Approved: TC, KOH
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  Alert
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  High risk medicine.
  Antimicrobial Stewardship Team recommends this drug is listed as Restricted.
  Widespread use of carbapenems has been linked with increasing prevalence of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multi resistant Gram-negative organisms and Clostridium difficile.
  NOT the preferred carbapenem in neonates because of possible adverse effects. Should be avoided in preterm neonates because of cilastatin accumulation.
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  Indication
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  Non-CNS sepsis caused by susceptible organisms including enteric Gram-negative rods, extended-spectrum beta-lactamase [ESBL] organisms, Pseudomonas aeruginosa, anaerobic organisms (including Bacteroides fragilis) and many Gram-positive organisms.
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  Action
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  Inhibits cell wall synthesis. Cilastatin prevents renal metabolism of imipenem.
  Meropenem is a better choice for central nervous system infections as it attains a higher concentration in the cerebrospinal fluid and has a lower incidence of seizures than imipenem + cilastatin.
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  Drug type
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  Carbapenem antibiotic
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  Trade name
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  Primaxin
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  Presentation
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  500 mg vial.
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  Dose
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  Dose based on imipenem component
  Condition
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  Dose
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  Dosing Interval
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  Infusion Time
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  Non-Pseudomonas aeruginosa
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  25 mg/kg
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  12 hourly
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  30 minutes
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  Pseudomonas aeruginosa
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  25 mg/kg
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  8 hourly
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  90 minutes
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  Dose adjustment
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  Dose may need to be reduced in impaired renal function.
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  Maximum dose
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  75 mg/kg/day
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  Total cumulative dose
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  Route
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  IV Infusion
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  Preparation
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  Add 9.2 mL of sodium chloride 0.9% to the 500 mg vial to make a 50 mg/mL solution
  FURTHER DILUTE
  Draw up 2 mL (100 mg of Imipenem + cilastatin) of the above solution and add 8 mL sodium chloride 0.9% to make a final volume of 10 mL with a final concentration of 10 mg/mL.
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  Administration
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  Non-Pseudomonas aeruginosa − IV infusion over 30 minutes.
  Pseudomonas aeruginosa − IV infusion over 90 minutes.
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  Monitoring
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  Renal function. Dose may need to be reduced in impaired renal function.
  Blood count and liver function.
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  Contraindications
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  Hypersensitivity to penicillins, cephalosporins or carbapenems.
  CNS infections.
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  Precautions
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  Seizures can occur in infants with renal impairment or central nervous system infection.
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  Drug interactions
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  Ganciclovir − risk of seizures. Do not give concomitantly unless the potential benefits outweigh the risks.
  Valproate − results in decreased concentrations of valproate.
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  Adverse reactions
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  Seizures, impaired renal function, impaired liver function, tachycardia, local phlebitis, urticaria, diarrhoea, pseudomembranous colitis (Clostridium difficile) and vomiting.
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  Compatibility
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  Fluids: Glucose 5%, glucose 10%, sodium chloride 0.9%
  Y-site: Aciclovir, amifostine, anidulafungin, aztreonam, caspofungin, cisatracurium besilate, foscarnet, granisetron, linezolid, remifentanil, tigecycline, zidovudine.
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  Incompatibility
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  Fluids: Hartmann’s.
  Y-site: Amiodarone, amoxycillin, azathioprine, azithromycin, ceftriaxone, chlorpromazine, daptomycin, fluconazole, ganciclovir, haloperidol lactate, metaraminol, midazolam, milrinone, mycophenolate mofetil, palonosetron, pethidine, sodium bicarbonate, vecuronium.
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  Stability
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  Reconstituted or diluted solution stable for 4 hours below 25°C or for 24 hours at 2−8°C.
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  Storage
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  Store vial below 25°C.
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  Excipients
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  Sodium bicarbonate
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  Special comments
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  Solutions of imipenem + cilastatin range from colourless to yellow. Variations of colour within this range do not affect the potency.
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  Evidence
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  Pharmacokinetics
  Imipenem + cilastatin is excreted via kidneys, mainly though glomerular filtration. Imipenem clearance is not influenced by postnatal or postmenstrual age. Infusions (0.5 hours) of 25 mg/kg every 12 hours (50 mg/kg/day) is sufficient against common bacterial isolates in neonates. However, 1.5 hour infusions of 25 mg/kg every 8 hours (75 mg/kg/day) in neonates are required to be effective against Pseudomonas aeruginosa.1
  Safety:
  Seizures can occur in neonates with meningitis, other CNS infections and in patients with renal impairment.1,4,6,9
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  Practice points
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  References
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  1. Yoshizawa K, Ikawa K, Ikeda K, Ohge H, Morikawa N. Population pharmacokinetic-pharmacodynamic target attainment analysis of imipenem plasma and urine data in neonates and children. Pediatr Infect Dis J [Internet]. 2013 [cited 2013 Nov];32(11):1208–16. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=medl&NEWS=N&AN=23676856
  2. Fujimura S, Nakano Y, Sato T, Shirahata K, Watanabe A. Relationship between the usage of carbapenem antibiotics and the incidence of imipenem-resistant Pseudomonas aeruginosa. J Infect Chemother [Internet]. 2007 [cited 2007 Jun];13(3):147–50. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med5&NEWS=N&AN=17593500
  3. Schlossberg D, Pietroski N. Carbapenems. Semin Pediatr Infect Dis [Internet]. 2002 [cited 2002 Jan];13(1):4. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med4&NEWS=N&AN=12118842
  4. Boswald M, Dobig C, Kandler C, Kruger C, Scharf J, Soergel F, Zink S, Guggenbichler JP. Pharmacokinetic and clinical evaluation of serious infections in premature and newborn infants under therapy with imipenem/cilastatin. Infection [Internet]. 1999 [cited 1999];27(4-5):299–304. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med4&NEWS=N&AN=10885853
  5. Blumer JL. Pharmacokinetic determinants of carbapenem therapy in neonates and children. Pediatr Infect Dis J [Internet]. 1996 [cited 1996 Aug];15(8):733–7. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med4&NEWS=N&AN=8858691
  6. Stuart RL, Turnidge J, Grayson ML. Safety of imipenem in neonates. Pediatr Infect Dis J [Internet]. 1995 [cited 1995 Sep];14(9):804–5. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med3&NEWS=N&AN=8559632
  7. Reed MD, Kliegman RM, Yamashita TS, Myers CM, Blumer JL. Clinical pharmacology of imipenem and cilastatin in premature infants during the first week of life. Antimicrob Agents Chemother [Internet]. 1990 [cited 1990 Jun];34(6):1172–7. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med3&NEWS=N&AN=2393278
  8. Ahonkhai VI, Cyhan GM, Wilson SE, Brown KR. Imipenem-cilastatin in pediatric patients: an overview of safety and efficacy in studies conducted in the United States. Pediatr Infect Dis J [Internet]. 1989 [cited 1989 Nov];8(11):740–4. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med3&NEWS=N&AN=2687787
  9. Nalin DR, Jacobsen CA. Imipenem/cilastatin therapy for serious infections in neonates and infants. Scand J Infect Dis Suppl [Internet]. 1987 [cited 1987];5246–55. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med2&NEWS=N&AN=3331042
  10. Micromedex 2.0 accessed via CIAP 4nd November 2015.
  11. Australian Injectable Drugs Handbook, 6th Edition, Society of Hospital Pharmacists of Australia 2015.
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  Original version Date: 5/12/2015
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  Author: NeoMed Consensus Group
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  Current Version number: 5
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  Current Version Date: 17/9/2020
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  Risk Rating: Medium
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  Due for Review: 17/9/2025
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  Approval by: DTC
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  Approval Date:TBA
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