Imipenem-Cilastatin Sodium (imipenem/cilastatin sodium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Imipenem and cilastatin sodium is a fixed combination of imipenem monohydrate (a carbapenem beta-lactam antibiotic) and cilastatin sodium (a renal dehydropeptidase inhibitor that prevents renal metabolism of imipenem).
Imipenem usually is bactericidal in action. The antibacterial activity of imipenem results from inhibition of synthesis in the bacterial cell wall. Imipenem has an affinity for and binds to most penicillin-binding proteins (PBPs) of susceptible organisms, including PBPs 1a, 1b, 2, 4, 5, and 6 of Escherichia coli and PBPs 1a, 1b, 2, 4, and 5 of Pseudomonas aeruginosa.
The bactericidal effect of imipenem is related to its binding to PBP2 and PBP1B.
Cilastatin, an inhibitor of dehydropeptidase I in the kidneys, prevents the renal metabolism of imipenem, so when given concomitantly, adequate antibacterial levels of imipenem are attained in the urine.
Cilastatin prevents metabolism of imipenem by dehydropeptidase I (DHP I) in the kidneys and, when administered concomitantly, results in urinary concentrations of active imipenem that are higher than could be obtained following administration of the antibiotic alone.
Imipenem is administered as the monohydrate, but dosages and concentrations of the drug are expressed in terms of anhydrous imipenem. Dosage of imipenem and cilastatin is expressed in terms of the imipenem content of the drug.
Following IV infusion over 20 minutes of a single 500-mg or 1-g dose of imipenem/cilastatin, peak plasma levels of imipenem antimicrobial activity range from 21-58 and 41-83 mcg/mL, respectively. Plasma levels of antimicrobial activity declined to 1 mcg/mL or less within 4-6 hours. In a dose-ranging study in premature, low-birthweight neonates (0.7-1.9 kg) 1 week of age or younger who received imipenem/cilastatin in a dosage of 20 mg/kg every 12 hours given by IV infusion over 15-30 minutes, peak and trough plasma concentrations averaged 43 and 1.7 mcg/mL, respectively.
While the clinical importance is unclear, multiple IV doses of imipenem/cilastatin in neonates may result in moderate accumulation of cilastatin. No accumulation of imipenem or cilastatin occurs following multiple doses in patients with normal renal function. Following IV administration, imipenem distributes into tissues, including vitreous humor, aqueous humor, lung, peritoneal fluid, CSF, bone, interstitial fluid, skin, and fascia.
Imipenem is approximately 20% and cilastatin is approximately 40% bound to serum proteins. The elimination half-life of imipenem and cilastatin is approximately 1 hour. In healthy geriatric individuals 65-75 years of age (with normal renal function for their age) who received a single dose of 500 mg of imipenem and 500 mg of cilastatin given IV over 20 minutes, the mean plasma half-lives of imipenem and cilastatin were approximately 1.5 and 1.1 hours, respectively, and were similar to half-lives expected in individuals with slight renal impairment.
Multiple doses in healthy geriatric individuals have no effect on the pharmacokinetics of either imipenem or cilastatin and accumulation of imipenem/cilastatin has not been observed. Approximately 70% of the imipenem/cilastatin dose is excreted in urine within 10 hours. Urine concentrations of imipenem in excess of 10 mcg/mL can be maintained for up to 8 hours with a 500-mg dose of imipenem and cilastatin.
USES: This medication is used to treat a wide variety of bacterial infections. This medication is known as a carbapenem-type antibiotic. It works by stopping the growth of bacteria.
Generic name: imipenem/cilastatin sodium
Pronunciation: (IM-i-PEN-em/SYE-la-STAT-in)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Imipenem-Cilastatin Sodium
Indications
The following indications are listed for Imipenem-Cilastatin Sodium:
- Bacterial Endocarditis
- Bacterial Pneumonia
- Bacterial Sepsis
- Bacterial Urinary Tract Infection
- Bone Infection
- Diabetic Foot Infection
- Enterobacter Pneumonia
- Escherichia Coli Pneumonia
- Female Genital Tract Infection
- Gram-Negative Aerobic Bacillary Pneumonia
- Haemophilus Influenzae Pneumonia
- Infectious Disease Of Abdomen
- Infectious Disorder Of Joint
- Inflammatory Disease Of Female Pelvic Organs
- Intra-Abdominal Abscess
- Klebsiella Pneumonia
- Lower Respiratory Infection
- Peritonitis
- Skin And Skin Structure Infection
Also known as: Abdominal Abscess, Bacteremia With Sepsis, Bacterial Septicemia, E. Coli Pneumonia, Gynecologic Infection, H. Flu Pneumonia, H. Influenzae Pneumonia, Hemophilus Influenzae Pneumonia, Infection Of Skin And/Or Subcutaneous Tissue, Infection Of The Lungs Due To Enterobacter, Influenza Bacillus Pneumonia, Intra-Abdominal Infection, Joint Infection, Lower Respiratory Tract Infection, Pfeiffer's Bacillus Pneumonia, Pneumonia Due To E. Coli, Pneumonia Due To Escherichia Coli, Pneumonia Due To Gram-Negative Organism, Pneumonia Due To Haemophilus Influenzae, Pneumonia Due To Klebsiella Species, Pneumonia Due To Klebsiella Spp., Skin And Soft Tissue Skin Infection.
Dosing
Dosage of imipenem/cilastatin is usually expressed in terms of the imipenem content of the fixed combination; dosage of imipenem monohydrate is expressed in terms of anhydrous imipenem.
Imipenem/cilastatin is administered by IV infusion. The fixed-combination preparation is commercially available as a powder that must be reconstituted and further diluted prior to IV infusion.
Imipenem/cilastatin should not be admixed with other antibacterials.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Hypersensitivity to any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects reported in >=0.2% of adults include phlebitis, nausea, diarrhea, vomiting, rash, pain and erythema at the injection site, fever, hypotension, seizures, dizziness, pruritus, vein induration, urticaria, and somnolence.
The most common adverse effects reported in >1% of pediatric patients >=3 months of age include diarrhea, rash, phlebitis, gastroenteritis, vomiting, IV site irritation, and urine discoloration.
The most common adverse effects reported in >1% of neonates and infants <3 months of age include convulsions, diarrhea, oliguria/anuria, oral candidiasis, rash, and tachycardia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of imipenem/cilastatin in pediatric patients is supported by evidence from adequate and well-controlled studies in adults and clinical studies in pediatric patients.
Adverse effects reported with the drug in neonates and children are similar to those reported in adults and include GI effects (e.g., diarrhea, vomiting, gastroenteritis), rash, urogenital effects (e.g., urine discoloration, oliguria, anuria), and reactions at the site of IV infusion (e.g., phlebitis, IV site irritation). Such adverse effects generally have been reported in 1-4% of pediatric patients receiving imipenem and cilastatin. However, seizures have been reported in neonates and children <=3 months of age receiving the drug. Therefore, because of the risk of seizures, the manufacturer recommends that IV imipenem/cilastatin should not be used in pediatric patients with CNS infections. The manufacturer also recommends that because there are insufficient data to date evaluating IV imipenem/cilastatin in pediatric patients with impaired renal function who weigh <30 kg, the drug should not be used in these patients.
Diluents containing benzyl alcohol should not be used to prepare imipenem/cilastatin for IV administration to neonates. Administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity has not been demonstrated in pediatric patients older than 3 months of age, although small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity.
Data available from small numbers of postmarketing cases of imipenem/cilastatin use during pregnancy are insufficient to identify any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Developmental toxicity studies in animals (mice, rats, rabbits, monkeys) using imipenem and cilastatin (alone or in combination) administered at doses 0.4-2.9 times the recommended human dose (based on body surface area) showed no evidence of drug-induced fetal malformations. Embryofetal development studies using imipenem and cilastatin in cynomolgus monkeys at doses similar to the recommended human dose (based on body surface area) showed an increase in embryonic loss.
Data are insufficient regarding the presence of imipenem and cilastatin in human milk, and data are not available on possible effects on the breast-fed child or effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for imipenem/cilastatin and any potential adverse effects on the breast-fed child from the drugs or from the underlying maternal condition.
The manufacturer states that age-based dosage adjustment of imipenem/cilastatin is not necessary. However, because geriatric patients are more likely to have decreased renal function, dosage should be selected with caution in these patients and monitoring of renal function may be useful. Dosage should be modified in response to the degree of renal impairment.
In clinical studies of imipenem/cilastatin involving approximately 2800 adults 18 years of age or older, approximately 800 were >=65 years of age and 300 were >=75 years of age. There were no apparent differences in safety or effectiveness between these individuals and younger adults and other clinical experience has not revealed evidence of differences in response between these age groups. However, the possibility that some geriatric patients may exhibit increased sensitivity to the drug cannot be ruled out.
Imipenem is substantially excreted by the kidney, and the risk of severe adverse reactions may be increased in patients with impaired renal function. Limited data indicate that the mean serum half-life of imipenem in healthy geriatric adults 65-75 years of age (with renal function normal for their age) is similar to that expected in individuals with slight renal impairment. The manufacturer states that age-based dosage adjustment is not necessary. However, because geriatric patients are more likely to have decreased renal function, dosage should be selected with caution in these patients and monitoring of renal function may be useful. Dosage should be adjusted in geriatric patients with renal impairment.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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