Imipenem + Cilastatin


Generic Medicine Info
Indications and Dosage
Intravenous
Bacterial endocarditis, Bacterial septicaemia, Bone and joint infections, Complicated urinary tract infections, Gynaecological infections, Intra-abdominal infections, Lower respiratory tract infections, Skin and soft tissue infections, Uncomplicated urinary tract infections
Adult: Imipenem 250 mg and cilastatin 250 mg powder for solution for infusion
Imipenem 500 mg and cilastatin 500 mg powder for solution for infusion
500 mg 6 hourly or 1,000 mg 6-8 hourly. Max: 4,000 mg daily. Dosage is expressed in terms of imipenem and individualised based on the type and severity of infection, and the degree of pathogen susceptibility (refer to detailed product guideline). All doses are given via infusion over 20-30 minutes for doses ≤500 mg; over 40-60 minutes for doses >500 mg. The rate of infusion may be reduced in patients who experience nausea during the infusion.
Child: Imipenem 250 mg and cilastatin 250 mg powder for solution for infusion
Imipenem 500 mg and cilastatin 500 mg powder for solution for infusion
Recommended doses for non-CNS infections: ≥3 months 15-25 mg/kg 6 hourly. Max: 4,000 mg daily. Dosage is expressed in terms of imipenem and individualised based on the type and severity of infection, and the degree of pathogen susceptibility (refer to detailed product guideline). All doses are given via infusion over 20-30 minutes for doses ≤500 mg; over 40-60 minutes for doses >500 mg. The rate of infusion may be reduced for patients who experience nausea during the infusion.
Renal Impairment
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 6 or 8 hourly.
≥60-<90 400 mg or 500 mg 6 hourly, or 750 mg 8 hourly.
Doses are given after haemodialysis session. Dosage is expressed in terms of imipenem and individualised based on the type and severity of infection, and the degree of pathogen susceptibility (refer to detailed product guideline).
Reconstitution
Reconstitute vial with approx 10 mL of compatible diluent (e.g. NaCl 0.9%, dextrose 5% in water, dextrose 5% in water with NaCl 0.9%, dextrose 5% in water with NaCl 0.225% or NaCl 0.45%). Further dilute with a compatible infusion solution to a final concentration of not exceeding 5 mg/mL. May repeat the process of reconstitution with another 10 mL of compatible diluent to ensure a complete transfer of contents to the infusion solution.
Incompatibility
Lactate, and other antibiotics.
Contraindications
Hypersensitivity to imipenem, cilastatin, or to any other carbapenems; severe hypersensitivity to other β-lactam antibiotics (e.g. penicillins or cephalosporins).
Special Precautions
Patient with CNS disorders (e.g. brain lesions or history of seizures), myasthenia gravis, history of colitis, or those who experienced diarrhoea after antibiotic use. Not recommended for children weighing <30 kg with renal impairment, or with CNS infections. Renal and hepatic impairment. Neonates, and children. Pregnancy and lactation.
Adverse Reactions
Significant: CNS effects (e.g. seizures, myoclonic activity, hallucinations, confusional states). Rarely, aggravation of myasthenia gravis.
Blood and lymphatic system disorders: Eosinophilia, pancytopenia, neutropenia including agranulocytosis, leucopenia, thrombocytopenia, thrombocytosis. Rarely, haemolytic anaemia, bone marrow depression.
Cardiac disorders: Hypotension. Rarely, tachycardia or palpitations.
Ear and labyrinth disorders: Hearing loss, tinnitus.
Eye disorders: Ocular myasthenia.
Gastrointestinal disorders: Diarrhoea, vomiting, nausea, staining of teeth and/or tongue, abdominal pain, heartburn, glossitis, tongue papilla hypertrophy, increased salivation, taste perversion.
General disorders and administration site conditions: Fever, injection site reaction (e.g. pain, induration, erythema).
Hepatobiliary disorders: Rarely, hepatic failure, hepatitis, fulminant hepatitis.
Investigations: Increased serum AST, serum ALT, serum LDH, serum alkaline phosphatase, serum bilirubin, serum creatinine, and BUN; decreased haemoglobin, prolonged prothrombin time.
Nervous system disorders: Dizziness, somnolence, headache, agitation, vertigo, dyskinesia, paresthesia, encephalopathy.
Renal and urinary disorders: Oliguria, anuria, polyuria.
Respiratory, thoracic, and mediastinal disorders: Dyspnoea, hyperventilation.
Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus, angioedema, erythema multiforme, pruritus vulvae, flushing, hyperhidrosis.
Vascular disorders: Thrombophlebitis.
Potentially Fatal: Serious hypersensitivity/anaphylactic reactions; Clostridioides difficile-associated diarrhoea (CDAD), pseudomembranous colitis.
Patient Counseling Information
This drug may cause dizziness or sleepiness, if affected, do not drive, or operate machinery.
Monitoring Parameters
Perform culture and susceptibility tests prior to treatment initiation; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor LFT, renal and haematologic function tests. Assess for signs and symptoms of anaphylaxis during 1st dose.
Drug Interactions
May induce generalised seizures with ganciclovir. Increased plasma levels and half-life with probenecid. May increase anticoagulant effect of warfarin.
Imipenem: May decrease the serum concentration of valproic acid which can lead to inadequate seizure control.
Lab Interference
May result to positive direct Coombs' test. Interferes with urinary glucose determinations using Clinitest®.
Action
Description:
Mechanism of Action: Imipenem is a broad-spectrum carbapenem β-lactam antibiotic and a semisynthetic derivative of thienamycin. It inhibits the 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 bacterial cell walls resulting in cell wall assembly arrest and eventually bacterial cell lysis. Imipenem is susceptible to degradation by dehydropeptidase I (DHP-I), an enzyme in the brush border of the proximal renal tubules.
Cilastatin is a competitive, reversible, and specific inhibitor of DHP-I. When given concomitantly, it prevents the renal metabolism of imipenem into its inactive and potentially nephrotoxic metabolites. It has no clinically significant antibacterial activity nor affects the antibacterial effect of imipenem.
Pharmacokinetics:
Distribution: Crosses the 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: Partially metabolised in the kidneys by DHP-I into inactive and nephrotoxic metabolites. Also metabolised to some extent via nonspecific hydrolysis of the β-lactam ring by a nonrenal mechanism unrelated to DHP-I.
Cilastatin: Partially metabolised in the kidneys to N-acetylcilastatin.
Excretion: Elimination half-life: Approx 60 minutes.
Imipenem: Mainly via urine (approx 70% as unchanged drug); faeces (<1%).
Cilastatin: Mainly via urine (approx 70% as unchanged drug, approx 12% 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 Oct. 26, 2023.


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 Oct. 26, 2023.

Storage
Intact vial: Store below 25°C. Reconstituted solutions: Store at 25°C for 4 hours or at 5°C for 24 hours. Do not freeze.
MIMS Class
Other Beta-Lactams
ATC Classification
J01DH51 - imipenem and cilastatin ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
References
Committee on Infectious Diseases, American Academy of Pediatrics, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH. "Tables of Antibacterial Drug Dosages", Red Book: 2021-2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics [online]. Accessed 27/09/2023.

Anon. Imipenem and Cilastatin Sodium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 17/07/2023.

Anon. Imipenem and Cilastatin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 17/07/2023.

Buckingham R (ed). Cilastatin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/07/2023.

Buckingham R (ed). Imipenem. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/07/2023.

Douglas Pharmaceuticals Ltd. Imipenem + Cilastatin RBX 500 mg/500 mg Powder for Solution for Infusion data Sheet 30 September 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 17/07/2023.

Imipenem and Cilastatin (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/09/2023.

Imipenem and Cilastatin Sodium, MSD IV Infusion (Merck Sharp & Dohme [Malaysia] Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 17/07/2023.

Imipenem/Cilastatin 500 mg/500 mg Powder for Solution for Infusion (Accord Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 17/07/2023.

Imipenem; Cilastatin. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 28/09/2023.

Joint Formulary Committee. Imipenem with Cilastatin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/07/2023.

Paediatric Formulary Committee. Imipenem with Cilastatin. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 27/09/2023.

Primaxin IV Injection, Powder, for Solution (Merck Sharp & Dohme LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 17/07/2023.

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 © 2024 MIMS. All rights reserved. Powered by MIMS.com
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