No

Antibiotic, Cephalosporin (Fourth Generation)

Treatment of uncomplicated and complicated urinary tract infections, including pyelonephritis caused by typical urinary tract pathogens; monotherapy for febrile neutropenia; uncomplicated skin and skin structure infections caused by Streptococcus pyogenes; moderate to severe pneumonia caused by pneumococcus, Pseudomonas aeruginosa, and other gram-negative organisms; complicated intra-abdominal infections (in combination with metronidazole). Also active against methicillin-susceptible staphylococci, Enterobacter sp, and many other gram-negative bacilli.

B

Hypersensitivity to cefepime or its components, or other cephalosporins

Modify dosage in patients with severe renal impairment; prolonged use may result in superinfection; use with caution in patients with a history of penicillin or cephalosporin allergy, especially IgE-mediated reactions (eg, anaphylaxis, urticaria); may cause antibiotic-associated colitis or colitis secondary to C. difficile

>10%: Hematologic: Positive Coombs' test without hemolysis

1% to 10%:

Dermatologic: Rash, pruritus

Gastrointestinal: : Diarrhea, nausea, vomiting

Central nervous system: Fever (1%), headache (1%)

Local: Pain, erythema at injection site

<1%: Leukopenia, neutropenia, agranulocytosis, thrombocytopenia, myoclonus, seizures, encephalopathy, neuromuscular excitability

Other reactions with cephalosporins include toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, prolonged PT, pancytopenia, vaginitis, superinfection

Symptoms of overdose include neuromuscular hypersensitivity, convulsions; many beta-lactam antibiotics have the potential to cause neuromuscular hyperirritability or seizures

Hemodialysis may be helpful to aid in the removal of the drug from the blood; however, most often treatment is supportive and symptom directed

Increased effect: High-dose probenecid decreases clearance

Increased toxicity: Aminoglycosides increase nephrotoxic potential

Cefepime is compatible and stable with normal saline, D₅W, and a variety of other solutions for 24 hours at room temperature and 7 days refrigerated

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacterial eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysis and murein hydrolases) while cell wall assembly is arrested.

Absorption: I.M.: Rapid and complete; T_max: 0.5-1.5 hours

Distribution: V_d: Adults: 14-20 L; penetrates into inflammatory fluid at concentrations ~80% of serum levels and into bronchial mucosa at levels ~60% of those reached in the plasma, crosses blood-brain barrier

Protein binding, plasma: 16% to 19%

Metabolism: Very little

Half-life: 2 hours

Elimination: 85% eliminated as unchanged drug in urine

I.V.:

Febrile neutropenia: 50 mg/kg every 8 hours for 7-10 days

Uncomplicated skin/soft tissue infections, pneumonia, and complicated/uncomplicated UTI: 50 mg/kg twice daily

Adults:

Most infections: 1-2 g every 12 hours for 5-10 days; higher doses or more frequent administration may be required in pseudomonal infections

Urinary tract infections, uncomplicated: 500 mg every 12 hours

Monotherapy for febrile neutropenic patients: 2 g every 8 hours for 7 days or until the neutropenia resolves

Dosing adjustment in renal impairment: Recommended maintenance schedule based on creatinine clearance (mL/minute), compared to normal dosing schedule:

When normal (Cl_cr >60) dosing schedule is 500 mg every 12 hours

Adjust dose as follows:

Cl_cr 30-60: 500 mg every 24 hours

Cl_cr 11-29: 500 mg every 24 hours

Cl_cr <10: 250 mg every 24 hours

When normal (Cl_cr >60) dosing schedule is 1 g every 12 hours

Adjust dose as follows:

Cl_cr 30-60: 1 g every 24 hours

Cl_cr 11-29: 500 g every 24 hours

Cl_cr <10: 250 mg every 24 hours

When normal (Cl_cr >60) dosing schedule is 2 g every 12 hours

Adjust dose as follows:

Cl_cr 30-60: 1 g every 24 hours

Cl_cr 11-29: 1 mg every 24 hours

Cl_cr <10: 500 mg every 24 hours

Hemodialysis: Removed by dialysis; administer supplemental dose of 250 mg after each dialysis session

Peritoneal dialysis: Removed to a lesser extent than hemodialysis; administer 250 mg every 48 hours

Continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD): Dose as normal Cl_cr (eg, >30 mL/minute)

Obtain specimen for culture and sensitivity prior to the first dose; monitor for signs of anaphylaxis during first dose

Positive direct Coombs', false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest®, Fehling's solution), false-positive serum or urine creatinine with Jaffé reaction, false-positive urinary proteins and steroids

May cause nervousness; case reports of euphoria, delusion, illusions, and depersonalization with cephalosporins

May rarely cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug is administered I.V. or I.M. Drink 2-3 L fluid/day. If diarrhea occurs, yogurt or buttermilk may help. May cause false-positive test with Clinitest®; use another form of testing. May interfere with oral contraceptives; additional contraceptive measures are necessary. Report severe, unresolved diarrhea; vaginal itching or drainage; sores in mouth; blood, pus, or mucus in stool or urine; easy bleeding or bruising; unusual fever or chills; rash; or respiratory difficulty. Breast-feeding precautions: Consult prescriber if breast-feeding.

Do not admix with aminoglycosides in the same bottle/bag; observe for signs and symptoms of bacterial infection, including defervescence; observe for anaphylaxis during first dose

Infusion, piggy-back: 1 g (100 mL); 2 g (100 mL)

Infusion (ADD-Vantage®): 1 g

Injection: 500 mg, 1 g, 2 g

Allaouchiche B, Breilh D, Jaumain H, et al, "Pharmacokinetics of Cefepime During Continuous Veno-Venous Hemodiafiltration," Antimicrob Agents Chemother, 1997, 41(11):2424-7.

Arguedas AG, Stutman HR, Zaleska M, et al, "Cefepime. Pharmacokinetics and Clinical Response in Patients With Cystic Fibrosis," Am J Dis Child, 1992, 146(7):797-802.

Barbhaiya RH, Knupp CA, and Pittman KA, "Effects of Age and Gender on Pharmacokinetics of Cefepime," J Antimicrob Chemother, 1992, 36(6):1181-5.

Barradell LB and Bryson HM, "Cefepime. A Review of Its Antibacterial Activity, Pharmacokinetic Properties, and Therapeutic Use," Drugs, 1994, 47(3):471-505.

Blumer JL, Reed MD, Lemon E, et al, "Pharmacokinetics (PK) of Cefepime in Pediatric Patients Administered Single and Multiple 50 mg/kg Doses Every 8 Hours by the Intravenous (I.V.) or Intramuscular (I.M.) Route," 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, 1994, Orlando, Fl. Abs. A69.

Cunha BA and Gill MV, "Cefepime," Med Clin North Am, 1995, 79(4):721-32.

Marshall WF and Blair JE, "The Cephalosporins," Mayo Clin Proc, 1999, 74(2):187-95.

Okamoto MP, Nakahiro RK, Chin A, et al, "Cefepime: A New Fourth-Generation Cephalosporin," Am J Hosp Pharm, 1994, 51(4):463-77.

Saez-Llorens X, Castano E, Garcia R, et al, "Prospective Randomized Comparison of Cefepime and Cefotaxime for Treatment of Bacterial Meningitis in Infants and Children", Antimicrob Agents Chemother, 1995, 39(4):937-40.

Sanders CC, "Cefepime: The Next Generation?" Clin Infect Dis, 1993, 17(3):369-79.

Wynd MA and Paladino JA, "Cefepime: A Fourth-Generation Parenteral Cephalosporin," Ann Pharmacother, 1996, 30(12):1414-24.