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Imipenem, Cilastatin, and Relebactam

Medically reviewed by Drugs.com. Last updated on Feb 21, 2019.

Pronunciation

(IM i PEN em, SYE la STAT in, & REL e BAK tam )

Index Terms

  • Cilastatin Sodium, Imipenem Monohydrate, and Relebactam Monohydrate
  • Cilastatin, Imipenem, and Relebactam
  • Cilastatin, Relebactam, and Imipenem
  • Imipenem Monohydrate, Cilastatin Sodium, and Relebactam Monohydrate
  • Imipenem, Relebactam, and Cilastatin
  • Recarbrio
  • Relebactam Monohydrate, Cilastatin Sodium, and Imipenem Monohydrate
  • Relebactam, Cilastatin, and Imipenem
  • Relebactam, Imipenem, and Cilastatin

Pharmacologic Category

  • Antibiotic, Carbapenem
  • Beta-Lactamase Inhibitor

Pharmacology

Imipenem: Binds to PBP 2 and PBP 1B in Enterobacteriaceae and P. aeruginosa and subsequently inhibits penicillin-binding proteins, leading to the disruption of bacterial cell wall synthesis.

Cilastatin: Renal dehydropeptidase inhibitor that limits renal metabolism of imipenem.

Relebactam: Beta-lactamase inhibitor that protects imipenem from degradation by certain serine beta-lactamases (eg, Sulhydryl Variable, Temoneira, Cefotaximase-Munich, E. cloacae P99, Pseudomonas-derived cephalosporinase, and Klebsiella-pneumoniae carbapenemase).

Distribution

Vdss: Imipenem: 24.3 L; cilastatin: 13.8 L; relebactam: 19 L.

Metabolism

Imipenem is metabolized in the kidney by dehydropeptidase I; cilastatin prevents imipenem metabolism by this enzyme. Relebactam is minimally metabolized.

Excretion

Urine (as unchanged drug: imipenem: ~63%; cilastatin: ~77%; relebactam: >90%).

Half-Life Elimination

Imipenem: 1 hour; relebactam: 1.2 hours.

Protein Binding

Imipenem: ~20%; cilastatin: ~40%; relebactam: ~22%.

Special Populations: Renal Function Impairment

AUC is increased in patients with CrCl 15 to 89 mL/minute (imipenem: 1.1 to 2.6-fold; cilastatin: 1.2 to 5.5-fold; relebactam: 1.2 to 4.7-fold)

Use: Labeled Indications

Intra-abdominal infection, complicated: Treatment of complicated intra-abdominal infections in patients ≥18 years of age with limited or no alternative options caused by the following susceptible gram-negative microorganisms: Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium stercoris, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis, and Pseudomonas aeruginosa.

Urinary tract infection, complicated (including pyelonephritis): Treatment of complicated urinary tract infections, including pyelonephritis, in patients ≥18 years of age with limited or no alternative options caused by the following susceptible gram-negative microorganisms: E. cloacae, E. coli, K. aerogenes, K. pneumoniae, and P. aeruginosa.

Contraindications

Severe hypersensitivity (eg, anaphylaxis) to cilastatin, imipenem, relebactam, or any component of the formulation.

Documentation of allergenic cross-reactivity for carbapenems, penicillins, and cephalosporins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Adult doses are expressed as the combined amount of imipenem, cilastatin, and relebactam.

Intra-abdominal infection, complicated: IV: 1.25 g every 6 hours. Total duration of therapy is 4 to 7 days following adequate source control (SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2019; Pemberton 2019).

Urinary tract infection, complicated (including pyelonephritis): IV: 1.25 g every 6 hours. Duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days (Hooton 2019).

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Withdraw two 10 mL aliquots of diluent from a 100 mL infusion bag containing an appropriate diluent (NS, D5W, D5NS, D51/2NS, or D51/4NS). Constitute vial with one 10 mL aliquot of diluent; shake well and transfer to the remaining 80 mL of the infusion bag. Add the second 10 mL aliquot of diluent to the vial; shake well and repeat transfer to the infusion solution. Agitate the resulting mixture until clear; constituted solution ranges from colorless to yellow.

For patients with renal impairment, prepare a reduced dose by preparing 100 mL of solution containing 1.25 g (imipenem 500 mg, cilastatin 500 mg, relebactam 250 mg) as directed above, then withdraw and discard excess solution as follows:

1 g (imipenem 400 mg, cilastatin 400 mg, relebactam 200 mg) dose: Withdraw and discard 20 mL (resulting volume to administer: 80 mL).

750 mg (imipenem 300 mg, cilastatin 300 mg, relebactam 150 mg) dose: Withdraw and discard 40 mL (resulting volume to administer: 60 mL).

500 mg (imipenem 200 mg, cilastatin 200 mg, relebactam 100 mg) dose: Withdraw and discard 60 mL (resulting volume to administer: 40 mL).

Administration

IV: Infuse over 30 minutes.

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F). Reconstituted and further diluted solution in infusion bags may be stored for ≤2 hours at room temperature (up to 30°C [86°F]) or ≤24 hours under refrigeration (2°C to 8°C [36°F to 46°F]); do not freeze.

Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

CycloSPORINE (Systemic): May enhance the neurotoxic effect of Imipenem. Imipenem may decrease the serum concentration of CycloSPORINE (Systemic). Imipenem may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Imipenem. Specifically, the risk of seizures may be increased. Management: Avoid concomitant use of these agents unless the prospective benefits of therapy outweigh the risks. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Probenecid: May increase the serum concentration of Imipenem. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Valproate Products: Carbapenems may decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Consider therapy modification

Test Interactions

Positive Coombs.

Adverse Reactions

1% to 10%:

Cardiovascular: Phlebitis (≤2%)

Central nervous system: Headache (4%)

Gastrointestinal: Diarrhea (6%), vomiting (3%)

Hepatic: Increased serum alanine aminotransferase (3%), increased serum aspartate aminotransferase (3%)

Local: Erythema at injection site (≤2%), infusion site pain (≤2%)

Miscellaneous: Fever (2%)

Frequency not defined:

Gastrointestinal: Clostridioides difficile associated diarrhea

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: Carbapenems have been associated with CNS adverse effects, including confusional states and seizures (myoclonic); use caution with CNS disorders (eg, brain lesions, history of seizures) and adjust dose in renal impairment to avoid drug accumulation. Drug accumulation may increase seizure risk.

• Hypersensitivity reactions: Serious hypersensitivity/anaphylactic reactions, some fatal, have been reported with beta-lactams. Carefully inquire about previous hypersensitivity reactions to penicillins, carbapenems, cephalosporins, other beta-lactams, and other allergens. Discontinue treatment and institute supportive care if a hypersensitivity reaction occurs.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD); CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required. Increased seizure risk has been reported in patients with significant renal dysfunction. Do not use in patients with CrCl ≤15 mL/minute unless hemodialysis is instituted within 48 hours.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Periodic renal function tests; signs of hypersensitivity/anaphylaxis.

Pregnancy Considerations

Imipenem and cilastatin cross the placenta (Cho 1988; Heikkilä 1992). Information specific to relebactam has not been located.

Also refer to the imipenem/cilastatin monograph for additional information.

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Nausea

• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Seizures

• Confusion

• Abnormal movements

Clostridioides (formerly Clostridium) difficile (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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