Imipenem + Cilastatin


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IV Lower respiratory tract infections; Skin and skin structure infections; Complicated intra-abdominal infections; Bone and joint infections; Bacterial septicaemia; Complicated urinary tract infections; Gynaecological infections; Bacterial endocarditis Each vial contains imipenem (mg)/cilastatin (mg): 250/250, 500/500: Doses are individualised based on the expected susceptible pathogen, severity and site of infection. Recommended dose: 500 mg/500 mg 6 hourly or 1,000 mg/1,000 mg 8 hourly. For infections due to less susceptible bacterial species and very severe infections: 1,000 mg/1,000 mg 6 hourly. All doses are to be given via infusion over 20-30 minutes for doses ≤500 mg/500 mg or over 40-60 minutes for doses >500 mg/500 mg. Max: 4,000 mg/4,000 mg/day.
Dosage Details
Intravenous
Bacterial endocarditis, Bacterial septicaemia, Bone and joint infections, Complicated intra-abdominal infections, Complicated urinary tract infections, Gynaecological infections, Lower respiratory tract infections, Skin and skin structure infections
Adult: Available preparations:
Imipenem 250 mg and cilastatin 250 mg powder for solution for infusion
Imipenem 500 mg and cilastatin 500 mg powder for solution for infusion

Doses are individualised based on the expected susceptible pathogen, severity and site of infection. Recommended dose: 500 mg/500 mg 6 hourly or 1,000 mg/1,000 mg 8 hourly. For infections due to less susceptible bacterial species and very severe infections: 1,000 mg/1,000 mg 6 hourly. All doses are to be given via infusion over 20-30 minutes for doses ≤500 mg/500 mg or over 40-60 minutes for doses >500 mg/500 mg. Max: 4,000 mg/4,000 mg daily.
Child: Available preparations:
Imipenem 250 mg and cilastatin 250 mg powder for solution for infusion
Imipenem 500 mg and cilastatin 500 mg powder for solution for infusion

Doses are individualised based on the expected susceptible pathogen, severity and site of infection. Recommended doses: Neonates and infants weighing ≥1.5 kg: <1 week 25 mg/25 mg/kg 12 hourly; 1-4 weeks 25 mg/25 mg/kg 8 hourly; 4 weeks to 3 months 25 mg/25 mg/kg 6 hourly. ≥3 months 15 mg/15 mg/kg to 25 mg/25 mg/kg 6 hourly. All doses are to be given via infusion over 20-30 minutes for doses ≤500 mg/500 mg and over 40-60 minutes for doses >500 mg/500 mg. Max: 2,000 mg/2,000 mg daily (fully susceptible bacteria) or 4,000 mg/4,000 mg daily (moderately susceptible bacteria). Dosage requirements may vary in some countries, refer to specific product or local treatment guideline.
Renal Impairment
Doses are expressed in terms of imipenem. In patients with CrCl <15 mL/min who are undergoing haemodialysis (only if dialysis is initiated within 48 hours): 200 mg 6 hourly or 500 mg 12 hourly.
CrCl (mL/min) Dosage
≥15-<30 200 mg 6 hourly or 500 mg 12 hourly.
≥30-<60
300 mg 6 hourly or 500 mg 8 hourly or 6 hourly.
≥60-<90
400 mg or 500 mg 6 hourly, or 750 mg 8 hourly.
Dosage requirements and frequency depends on the total daily dose that would be applicable to patients with normal renal function or the severity of infection (refer to detailed product guideline).
Reconstitution
Contents of the vial must be suspended to 100 mL of the appropriate diluent (e.g. 0.9% NaCl, dextrose 5% in water). Initially, withdraw 20 mL (2 separate 10 mL withdrawals) from the infusion bag of diluent. Add the first 10 mL to the vial and transfer the resulting suspension to the infusion bag. To ensure complete transfer of contents, repeat the process with the other 10 mL of infusion solution.
Contraindications
Hypersensitivity to imipenem, cilastatin, or to any other carbapenems; severe hypersensitivity to other β-lactam antibiotics (e.g. penicillins or cephalosporins).
Special Precautions
CNS disorders (e.g. history of seizures, brain lesions). Renal impairment. Children. Pregnancy and lactation. Not recommended in children <30 kg with renal impairment or children with CNS infections.
Adverse Reactions
Significant: CNS adverse reactions (e.g. myoclonic activity, seizures, confusional states).
Blood and lymphatic system disorders: Eosinophilia, neutropenia.
Gastrointestinal disorders: Diarrhoea, nausea, vomiting, staining of the teeth and/or tongue, taste perversion.
General disorders and administration site conditions: Phlebitis/thrombophlebitis, pain, erythema, or induration at the injection site; fever.
Investigations: Increased serum transaminases, serum alkaline phosphatase, serum bilirubin; decreased platelet count.
Nervous system disorders: Dizziness, somnolence.
Renal and urinary disorders: Proteinuria, oliguria/anuria.
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria.
Vascular disorders: Hypotension.
Potentially Fatal: Anaphylactic or hypersensitivity reactions; Clostridium difficile-associated diarrhoea (CDAD), pseudomembranous colitis (prolonged use). Rarely, Stevens-Johnson syndrome, toxic epidermal necrolysis.
MonitoringParameters
Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor haematologic, renal, and hepatic function tests (periodically during prolonged therapy). Assess for signs of anaphylaxis during 1st dose.
Drug Interactions
May induce generalised seizures with ganciclovir. Increased plasma concentration and half-life with probenecid. May increase anticoagulant effect of warfarin.
Imipenem: May decrease serum concentrations and therapeutic efficacy of valproic acid.
Lab Interference
May result to positive direct or indirect Coombs test. Interferes with urinary glucose determinations using cupric sulfate (e.g. Clinitest®, Benedict’s solution).
Action
Description: Imipenem, a semisynthetic carbapenem antibiotic, inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs), thereby blocking the final transpeptidation step of peptidoglycan synthesis in the bacterial cell walls. It is susceptible to degradation by the enzyme dehydropetidase-I (DHP I) which is present on the brush border of proximal renal tubular cells.
Cilastatin is a competitive, reversible and specific inhibitor of DHP I, it prevents the metabolism of imipenem to inactive metabolite in the kidneys. It does not exert any clinically significant antibacterial effect.
Pharmacokinetics:
Distribution: Crosses placenta, enters breast milk (small amounts).
Imipenem: Widely distributed in body tissues and fluids. Plasma protein binding: Approx 20%.
Cilastatin: Plasma protein binding: Approx 40%.
Metabolism: Cilastatin: Metabolised partially in the kidneys to N-acetylcilastatin.
Excretion: Elimination half-life: Approx 60 minutes.
Imipenem: Via urine (approx 70% as unchanged drug); faeces (<1%).
Cilastatin: Via urine (approx 70-80% as unchanged drug, approx 10% as N-acetyl metabolite); faeces (<2%).
Chemical Structure

Chemical Structure Image
Imipenem

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 104838, Imipenem. https://pubchem.ncbi.nlm.nih.gov/compound/Imipenem. Accessed Sept. 25, 2020.


Chemical Structure Image
Cilastatin

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6435415, Cilastatin. https://pubchem.ncbi.nlm.nih.gov/compound/Cilastatin. Accessed Sept. 25, 2020.

Storage
Store intact vials below 25°C. Reconstituted solutions may be stored at room temperature for 4 hours or at 5°C for 24 hours. Do not freeze.
MIMS Class
ATC Classification
J01DH51 - imipenem and cilastatin ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
References
Anon. Imipenem and Cilastatin Sodium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 20/07/2020.

Anon. Imipenem and Cilastatin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/07/2020.

Buckingham R (ed). Cilastatin Sodium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/07/2020.

Buckingham R (ed). Imipenem. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/07/2020.

Imipenem/Cilastatin 250 mg/250 mg Powder for Solution for Infusion (Accord Healthcare Limited). MHRA. https://products.mhra.gov.uk/. Accessed 09/09/2020.

Joint Formulary Committee. Imipenem with Cilastatin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/07/2020.

Primaxin IV (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 20/07/2020.

Primaxin IV 500 mg/500 mg Powder for Solution for Infusion (Merck Sharp & Dohme Limited). MHRA. https://products.mhra.gov.uk/. Accessed 20/07/2020.

Tienam (Merck Sharp & Dohme Corp.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 20/07/2020.

Disclaimer: This information is independently developed by MIMS based on Imipenem + Cilastatin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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