cefepime dihydrochloride monohydrate + enmetazobactam: clinical use

Prescribing considerations

• Obtain infection-site specimens and review microbiology and susceptibility findings when available.
• Consider the limited activity against most Gram-positive organisms and anaerobes; additional cover may be needed.
• Review renal function before and during therapy, especially in older adults, unstable renal function or concurrent nephrotoxic treatment.
• Remain alert to cefepime-associated neurotoxicity, including after renal adjustment.
• Review therapy if non-susceptible organisms, superinfection or Clostridioides difficile-associated diarrhoea is suspected.
• Hospital-acquired and ventilator-associated pneumonia use is supported by cefepime experience and pharmacokinetic–pharmacodynamic analyses for the combination.

Contraindications and cautions

• Hypersensitivity to cefepime, enmetazobactam or an excipient.
• Hypersensitivity to any cephalosporin.
• Previous severe hypersensitivity to another beta-lactam, including anaphylaxis or a severe skin reaction.

Monitoring

• Renal function and changes in renal clearance.
• Neurological state, especially with renal impairment.
• Infusion site and signs of immediate hypersensitivity.
• Diarrhoea during or after treatment.
• Blood counts, coagulation indices and hepatic laboratory results when clinically appropriate.
• Microbiology, clinical response and evidence of superinfection.

Clinical pharmacology

Cefepime is a bactericidal fourth-generation cephalosporin. Enmetazobactam protects cefepime against class A extended-spectrum beta-lactamases but does not reliably inhibit KPC and does not inhibit class B, C or D beta-lactamases. Both components undergo little metabolism and are predominantly excreted unchanged in urine.

Formulation and product differences

• The product is a single-use powder for concentrate requiring aseptic reconstitution and further dilution before intravenous infusion.
• The excipient is L-arginine.
• Compatible diluents include sodium chloride, glucose and the specified combined glucose–sodium chloride solution.
• The solution may become yellow to amber without reduced effectiveness, but it should be used only when clear and free of particles.