Cefepime Hydrochloride

Antibacterial; β-lactam antibiotic; fourth generation cephalosporin.1 6

Administration

Administer by IV infusion1 3 5 6 12 14 92 95 or deep IM injection.1 3 5 6 12 14

Use IM route only for treatment of mild to moderate, uncomplicated or complicated UTIs caused by E. coli when this route is considered more appropriate.1 5

IV Infusion

If Y-type administration set used, discontinue other solution flowing through the tubing during cefepime infusion.1 92 95

Manufacturers recommend that aminoglycosides, ampicillin (>40 mg/mL), metronidazole, vancomycin, or aminophylline be administered separately from cefepime.1 92 95 (See Drug Compatibility under Compatibility.)

Reconstitution and Dilution

Reconstitute vials containing 500 mg, 1 g, or 2 g of cefepime with 5, 10, or 10 mL, respectively, of compatible IV solution to provide solutions containing approximately 100, 100, or 160 mg/mL, respectively.1 Then further dilute the appropriate dose of reconstituted solution in a compatible IV solution.1 (See Solution Compatibility under Compatibility.)

Reconstitute ADD-Vantage vials containing 1 or 2 g of cefepime with 50 or 100 mL of 0.9% sodium chloride or 5% dextrose injection according to the manufacturer’s directions.1

Reconstitute (activate) commercially available Duplex drug delivery system that contains 1 or 2 g of cefepime and 50 mL of 5% dextrose injection in separate chambers according to the manufacturer's directions.95 If refrigerated after reconstitution (see Storage under Stability), allow solution to reach room temperature prior to administration.95

Thaw commercially available premixed injection (frozen) at room temperature (25°C) or under refrigeration (5°C); do not thaw by immersion in a water bath or by exposure to microwave radiation.92 A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.92 Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact or leaks are found.92 Do not use in series connections with other plastic containers; such use could result in air embolism from residual air being drawn from primary container before administration of fluid from secondary container is complete.92

Rate of Administration

Administer by IV infusion over approximately 30 minutes.1 92 95

IM Injection

Reconstitution

For IM injection, reconstitute vial containing 500 mg or 1 g of cefepime with 1.3 or 2.4 mL, respectively, of sterile water for injection, 0.9% sodium chloride, 5% dextrose, 0.5 or 1% lidocaine hydrochloride, or bacteriostatic water for injection (with parabens or benzyl alcohol) to provide a solution containing approximately 280 mg/mL.1

Dosage

Available as cefepime hydrochloride; dosage expressed in terms of cefepime, calculated on the anhydrous basis.1 92 95

Pediatric Patients

General Pediatric Dosage IV or IM

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours.1 92 95

Neonates ≤28 days of age†: AAP recommends 30 mg/kg every 12 hours; 50 mg/kg every 12 hours may be needed for Pseudomonas infections.64

Children beyond neonatal period: AAP recommends 100 mg/kg daily in 2 equally divided doses for treatment of mild to moderate infections and 100–150 mg/kg daily in 2 or 3 equally divided doses for treatment of severe infections.64

Do not use cefepime available in Duplex containers or the cefepime premixed injection (frozen) in pediatric patients who require less than the entire 1- or 2-g dose in the container.92 95

Intra-abdominal Infections Complicated Infections IV

50 mg/kg every 12 hours for 4–7 days (in conjunction with IV metronidazole) recommended by IDSA.70 Longer treatment duration not associated with improved outcome and not recommended unless adequate source control difficult to achieve.70

Respiratory Tract Infections Pneumonia IV

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 10 days.1 92 95

Skin and Skin Structure Infections Uncomplicated Infections IV

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 10 days.1 92 95

Urinary Tract Infections (UTIs) Uncomplicated or Complicated UTIs IV or IM

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 7–10 days.1 92 95

Endocarditis† Culture-negative Endocarditis† IV

150 mg/kg daily given in 3 equally divided doses in conjunction with vancomycin (40 mg/kg IV daily in 2 or 3 equally divided doses), gentamicin (3 mg/kg IV or IM daily in 3 equally divided doses), and rifampin (20 mg/kg orally or IV daily in 3 equally divided doses) recommended by AHA.94 Continue multiple-drug regimen for 6 weeks; discontinue gentamicin after first 2 weeks.94

Empiric Therapy in Febrile Neutropenic Patients IV

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 8 hours for 7 days or until neutropenia resolves.1 92 95

Frequently reevaluate need for continued anti-infective therapy if fever resolves but neutropenia remains for >7 days.1 92 95

Adults

Intra-abdominal Infections Complicated Infections IV

2 g every 12 hours for 7–10 days; use in conjunction with IV metronidazole.1 92 95

Some clinicians recommend 2 g every 8–12 hours for 4–7 days;70 longer treatment duration not associated with improved outcome and not recommended unless adequate source control difficult to achieve.70

Respiratory Tract Infections Moderate to Severe Pneumonia IV

1–2 g every 12 hours for 10 days.1 92 95

1–2 g every 8–12 hours recommended for initial therapy of hospital-acquired pneumonia, ventilator-associated pneumonia, or healthcare-associated pneumonia.67 92

Skin and Skin Structure Infections Moderate to Severe Uncomplicated Infections IV

2 g every 12 hours for 10 days.1 92 95

Urinary Tract Infections (UTIs) Mild to Moderate Uncomplicated or Complicated UTIs IV or IM

0.5–1 g every 12 hours for 7–10 days.1 92 95

Severe Uncomplicated or Complicated UTIs IV

2 g every 12 hours for 10 days.1 92 95

Endocarditis† Culture-negative Endocarditis† IV

6 g daily given in 3 equally divided doses in conjunction with vancomycin (30 mg/kg IV daily given in 2 equally divided doses), gentamicin (3 mg/kg IV or IM daily given in 3 equally divided doses), and rifampin (900 mg orally or IV daily in 3 equally divided doses) recommended by AHA.94 Continue multiple-drug regimen for 6 weeks; discontinue gentamicin after first 2 weeks.94

Empiric Therapy in Febrile Neutropenic Patients IV

2 g every 8 hours for 7 days or until neutropenia resolves.1 34 35 36 92 95

Frequently reevaluate need for continued anti-infective therapy if fever resolves but neutropenia remains for >7 days.1 92 95

Prescribing Limits

Pediatric Patients

Do not exceed recommended adult dosage.1 92 95

Special Populations

Hepatic Impairment

Dosage adjustments not required.1 92

Renal Impairment

Dosage adjustments necessary in patients with Clcr ≤60 mL/minute.1 92 95

Adults with Clcr ≤60 mL/minute (not undergoing hemodialysis): Give an initial dose using usually recommended adult dosage followed by maintenance dosage based on Clcr.1 92 95 (See Table 1 and Table 2.)

Table 1. Maintenance Dosage for Treatment of Infections in Adults with Renal Impairment19295

Clcr (mL/minute)	Initial dose: 500 mg	Initial dose: 1 g	Initial dose: 2 g
30–60	500 mg every 24 h	1 g every 24 h	2 g every 24 h
11–29	500 mg every 24 h	500 mg every 24 h	1 g every 24 h
<11	250 mg every 24 h	250 mg every 24 h	500 mg every 24 h

Table 2. Maintenance Dosage for Empiric Therapy in Febrile Neutropenic Adults with Renal Impairment19295

Clcr (mL/minute)	Initial Dose: 2 g
30–60	2 g every 12 h
11–29	2 g every 24 h
<11	1 g every 24 h

Adults undergoing hemodialysis: 1 g on the first day of treatment followed by 500 mg every 24 hours for treatment of infections or 1 g on the first day followed by 1 g every 24 hours for empiric therapy in febrile neutropenic patients.1 92 95 Administer the dose at the same time each day (given at completion of procedure on hemodialysis days).1 92 95

Adults undergoing CAPD: Give usually recommended dose once every 48 hours.1 6 10 12 92 95

Pediatric patients with renal impairment: Dosage adjustments required proportional to those recommended for adults.1 92

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides	Possible increased risk of nephrotoxicity and ototoxicity1 92 95	Closely monitor renal function if used concomitantly1 92 95
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution1 92 95 a	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)1 92 95 a

Absorption

Bioavailability

Not appreciably absorbed from GI tract; must be administered parenterally.1

Almost completely absorbed following IM administration;1 44 peak serum concentrations attained within 1.4–1.6 hours.1

Distribution

Extent

Widely distributed into tissues and fluids, including blister fluid,1 39 48 bronchial mucosa,1 sputum,1 bile,1 27 peritoneal fluid,1 27 appendix,1 gallbladder,1 27 and prostate.1

Distributed into CSF following IV administration in adults or pediatric patients.1 5 46 78 81 82 84 92

Distributed into milk.1 6

Plasma Protein Binding

20%.1

Elimination

Metabolism

Partially metabolized in vivo to N-methylpyrrolidine (NMP), which is rapidly converted to the N-oxide (NMP-N-oxide).1

Elimination Route

Eliminated principally unchanged in urine by glomerular filtration.1 47 49

In adults with normal renal function, 80–82% of a single dose excreted unchanged in urine;1 42 47 49 < 1% of the dose eliminated as NMP, 6.8% as NMP-N-oxide, and 2.5% as an epimer of the drug.1

Half-life

Adults with normal renal function: 2–2.3 hours.1 3 39 49

Children 2 months to 16 years of age: 1.5-1.9 hours.44

Neonates <2 months of age: 4.9 hours.80

Special Populations

Pharmacokinetics not affected by hepatic impairment.1

Patients with renal impairment: Clearance decreased and plasma half-life prolonged.1 42 Half-life averages 4.9, 10.5, 13.5 hours in those with Clcr 31–60, 11–30, or <10 mL/minute, respectively.42

• Based on spectrum of activity, classified as a fourth generation cephalosporin.1 3 4 6 11 20 21 22 a

• Expanded spectrum of activity compared with first and second generation cephalosporins and more active than third generation cephalosporins against Enterobacteriaceae that produce inducible β-lactamases.3 4 11 20 21 22 More resistant to inactivation by chromosomally and plasmid-mediated β-lactamases than most other cephalosporins;a hydrolyzed by β-lactamases at a slower rate than third generation cephalosporins.a

• Usually bactericidal.1 a

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1 64

• Spectrum of activity includes many gram-positive bacteria3 4 and many gram-negative bacteria (including Pseudomonas aeruginosa and certain Enterobacteriaceae).3 4 23 Inactive against fungi and viruses.a

• Gram-positive aerobes: Active in vitro and in clinical infections against S. aureus, S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci), and viridans streptococci.1 a Also active in vitro against S. epidermidis (methicillin-susceptible [oxacillin-susceptible] strains only), S. saprophyticus, and S. agalactiae (group B streptococci).1 a Enterococci (e.g., Enterococcus faecalis), oxacillin-resistant (methicillin-resistant) staphylococci, and Listeria monocytogenes are resistant.1 a

• Gram-negative aerobes: Active in vitro and in clinical infections against Enterobacter, E. coli, K. pneumoniae, P. mirabilis, and Ps. aeruginosa.1 a Also active in vitro against Acinetobacter calcoaceticus, Citrobacter diversus, C. freundii, E. agglomerans, H. influenzae (including β-lactamase-producing strains), Havnia alvei, K. oxytoca, Moraxella catarrhalis (including β-lactamase-producing strains), Morganella morganii, P. vulgaris, Providencia rettgeri, P. stuartii, and Serratia marcescens.1 a Inactive against Stenotrophomonas.1

• Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) should be considered resistant to cefepime, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.55