Imipenem with Cilastatin

Imipenem with Cilastatin

[1 vial $21.61]

ADMINISTRATION ROUTES:

  • IV

ALTERNATIVE NAMES:

  • Primaxin

ICU INDICATIONS:

  1. treatment of infections caused by susceptible organisms
  2. broad spectrum cover of hospital-acquired infections (particularly in the setting of intra-abdominal sepsis)

PRESENTATION AND ADMINISTRATION:

  • IV:
    Injection (vial) 500mg imipenem and 500mg cilastatin (powder)
    Add 10ml of compatible IV fluid to the powder in each 500mg vial and shake to form a suspension (which must be further diluted before IV infusion). Transfer this suspension to IV fluid container. Each 500mg of dose should be diluted with 100ml of compatible IV fluid, whilst for a 1g dose use a 250ml bag. Agitate the contained until the solution is clear
    Infuse doses of 500mg over 20 minutes.
    Infuse doses of 500mg to 1gm over 40 to 60 minutes.
    If patient develops nausea during infusion, the rate of infusion may be slowed.
    Compatible with the following IV fluids:
    Normal saline, 5% glucose and 0.15% KCL, 5% or 10% glucose, 5% and 10% Mannitol, Glucose and sodium chloride

DOSAGE:

  • IV:
    500mg – 1gm 6 hourly

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose in renal impairment [GFR (ml/min)]
    <20: 250mg (or 3.5mg/kg which ever is lower) every 12 hours
    21-30: 500mg-1g every 12 hours
    >31-70: 500mg-1g every 8 hours
  • Dose in renal replacement therapy
    CAPD: 500mg-1g every 8 hours
    HD: 500mg-1g every 12 hours
    CVVHDF: 500mg-1g every 12 hours

DOSAGE IN PAEDIATRICS:

  • IV:
    15-25mg/kg 6 hourly

CLINICAL PHARMACOLOGY:

  • Imipenem is a carbapenem antibiotic. The bactericidal activity of imipenem results from the inhibition of cell wall synthesis. Imipenem has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases produced by gram-negative and gram-positive bacteria. It is a potent inhibitor of betalactamases from certain gram-negative bacteria which are inherently resistant to most beta-lactam antibiotics, e.g., Pseudomonas aeruginosa, Serratia spp., and Enterobacter spp.
  • Imipenem has in vitro activity against a wide range of gram-positive and gram-negative organisms. In vitro tests show imipenem to act synergistically with aminoglycoside antibiotics against some isolates of Pseudomonas aeruginosa. Imipenem has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections.

    Gram-positive aerobes:
    Enterococcus faecalis
    (NOTE: Imipenem is inactive in vitro against Enterococcus faecium)
    Staphylococcus aureus including penicillinase-producing strains
    Staphylococcus epidermidis including penicillinase-producing strains
    (NOTE: Methicillin- resistant staphylococci should be reported as resistant to imipenem.) Streptococcus agalactiae (Group B streptococci)
    Streptococcus pneumoniae
    Streptococcus pyogenes

    Gram-negative aerobes:
    Acinetobacter spp.
    Citrobacter spp.
    Enterobacter spp.
    Escherichia coli
    Gardnerella vaginalis
    Haemophilus influenzae
    Haemophilus parainfluenzae
    Klebsiella spp.
    Morganella morganii
    Proteus vulgaris
    Providencia rettgeri
    Pseudomonas aeruginosa
    (NOTE: Imipenem is inactive in vitro against Xanthomonas (Pseudomonas) maltophilia and some strains of P. cepacia.)
    Serratia spp., including S. marcescens

    Gram-positive anaerobes:
    Bifidobacterium spp.
    Clostridium
    spp.
    Eubacterium
    spp.
    Peptococcus
    spp.
    Peptostreptococcus
    spp.
    Propionibacterium
    spp.

    Gram-negative anaerobes:
    Bacteroides spp., including B. fragilis
    Fusobacterium
    spp.

CONTRAINDICATIONS:

  1. hypersensitivity to carbapenems

WARNINGS

  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more apt to occur in persons with a history of sensitivity to multiple allergens.
  • There have been reports of patients with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam. Before initiating therapy with imipenem iv, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens.

PRECAUTIONS

  • General:
    Seizures and other CNS adverse experiences, such as confusional states and myoclonic activity, have been reported during treatment with imipenem
    Pseudomembranous colitis has been reported with nearly all antibacterial agents, including imipenem-cilastatin sodium, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.
  • Laboratory Tests:
    No tests in addition to routine ICU tests are required.
  • Drug/Laboratory Test Interactions:
    None noted.

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • Generalized seizures have been reported in patients who received ganciclovir and Imipenem. These drugs should not be used concomitantly unless the potential benefits outweigh the risks.

ADVERSE REACTIONS

  • Body as a whole:
    Polyarthralgia, asthenia/weakness, drug fever.
  • Gastrointestinal:
    Pseudomembranous colitis, diarrhoea, nausea, vomiting, hemorrhagic colitis, hepatitis (including fulminant hepatitis), jaundice, gastroenteritis, abdominal pain, glossitis, tongue papillar hypertrophy, staining of the teeth and/or tongue, heartburn, pharyngeal pain, increased salivation.
  • Hematologic:
    Pancytopenia, bone marrow depression, thrombocytopenia, neutropenia, leukopenia, hemolytic anemia.
  • CNS:
    Seizures, encephalopathy, tremor, confusion, myoclonus, paresthesia, vertigo, headache, psychic disturbances including hallucinations.
  • Respiratory:
    Chest discomfort, dyspnea, hyperventilation, thoracic spine pain.
  • Cardiovascular:
    Palpitations, tachycardia.
  • Skin:
    Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioneurotic edema, flushing, cyanosis, hyperhidrosis, skin texture changes, candidiasis, pruritus vulvae.
  • Renal:
    Acute renal failure, oliguria/anuria, polyuria, urine discoloration.

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