Cefepime (cefepime HCl in iso-osmotic dextrose)

Cefepime is commercially available as cefepime hydrochloride, which is monohydrated; dosage is expressed in terms of cefepime, calculated on the anhydrous basis.

In patients with renal impairment (i.e., creatinine clearance of 60 mL/minute or less), doses and/or frequency of administration of cefepime should be modified in response to the degree of renal impairment, severity of the infection, and susceptibility of the causative organism.

The manufacturers recommend that adults with creatinine clearance of 60 mL/minute or less (not receiving hemodialysis) receive the same initial dose of cefepime recommended for patients with normal renal function followed by a maintenance dosage of cefepime based on the patient's measured or estimated creatinine clearance. (See Table 1 and Table 2.)

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

Creatinine Initial dose: 500 Initial dose: 1 g Initial dose: 2 g Clearance mg (mL/minute) 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 Impairment

Creatinine Clearance (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

The manufacturers recommend that adults undergoing hemodialysis receive an initial 1-g dose of cefepime on day 1, then 500 mg once daily thereafter for the treatment of infections or 1 g once daily for empiric therapy of presumed bacterial infections in febrile neutropenic patients. The manufacturers also recommend that the daily dose be given at the same time of day whenever possible; on hemodialysis days, the dose should be given after the procedure.

Adults undergoing continuous ambulatory peritoneal dialysis (CAPD) should receive the usual cefepime dose every 48 hours.

Data regarding use of cefepime in pediatric patients with impaired renal function are not available. Because the pharmacokinetics of cefepime are similar in pediatric and adult patients, the manufacturers recommend that dosage modifications proportional to those recommended for adults be used in pediatric patients with impaired renal function.

Since pharmacokinetics of cefepime appear not to be altered in patients with hepatic impairment, the manufacturers state that dosage adjustments are not necessary in such patients.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Selected Cephalosporins & Penicillins/Probenecid

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Probenecid impairs the clearance of some cephalosporins and penicillins via inhibition of renal anion transporters in the proximal tubule.(49) It has also been hypothesized that probenecid may affect tissue distribution of cephalosporins.(1-5)

CLINICAL EFFECTS: The concurrent administration of probenecid may result in increased maximum concentration (Cmax), area-under-curve (AUC), and half-life of the cephalosporin or penicillin.(49) While this may improve antibiotic efficacy,(46-48) increased levels may also increase the risk for antibiotic-associated nephrotoxicity.(4)

PREDISPOSING FACTORS: Underlying renal dysfunction may increase the risk for nephrotoxicity.

PATIENT MANAGEMENT: In patients receiving the combination to improve antibiotic efficacy, monitor for antibiotic adverse effects and consider monitoring renal function. In patients receiving probenecid therapy to prevent or treat hyperuricemia, exposure to the antibiotic will be increased. A decrease in antibiotic dose or frequency may be required. The US manufacturer of piperacillin-tazobactam states probenecid should not be coadministered with piperacillin-tazobactam unless the benefit outweighs the risk.(50)

DISCUSSION: Concurrent use of probenecid with a cephalosporin or penicillin may cause an increase in the Cmax, AUC, and an increased elimination half life of the antibiotic.(6-8,49) This may be beneficial or necessary in difficult to treat infections,(46-48) but an increased risk for adverse effects should be expected. Antibiotics not dose adjusted for concurrent use with probenecid may be associated with an increased risk for adverse effects, such as nephrotoxicity. Probenecid administered concurrently with piperacillin-tazobactam prolongs the half-life of piperacillin by 21% and tazobactam by 71%. In a study in 8 healthy males, concurrent administration of probenecid (1 g) with piperacillin (1 g IM) increased piperacillin's Cmax and AUC by 30% and 60%. Renal clearance was reduced by 40%.(51) The cephalosporins affected by probenecid include cefazolin,(9-11) cephacetrile,(12,13) cephaloglycin,(14,15) cephalexin,(16-21) cephradine, (22-23) cefoxitin,(24-28) cefadroxil(29), cefaclor,(23) cefamandole,(30) ceftizoxime,(31,32) cefuroxime,(33,34) cefprozil,(35) cefonicid,(36) cefmetazole,(37) cefmenoxime,(38) and cefditoren.(39) Probenecid has been shown not to affect moxalactam,(4,40,41) ceforanide, (4,42), cefoperazone, ceftazidime(4,34,43) or ceftriaxone.(4)

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There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Clostridioides difficile infection
• Seizure disorder

• Colitis
• Hypoprothrombinemia
• Increased risk of bleeding
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Myoclonus

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More Frequent

• Abnormal hepatic function tests
• Hypophosphatemia
• Increased alanine transaminase
• Increased aspartate transaminase
• Injection site sequelae
• Pruritus of skin
• Skin rash

Less Frequent

• Drug fever
• Hypersensitivity drug reaction

Rare or Very Rare

• Acute generalized exanthematous pustulosis
• Agranulocytosis
• Anaphylaxis
• Anemia
• Aphasia
• Aplastic anemia
• Cholestasis
• Clostridioides difficile infection
• Colitis
• Coma
• DRESS syndrome
• Encephalopathy
• Erythema multiforme
• Hemolytic anemia
• Hypoprothrombinemia
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Leukopenia
• Myoclonus
• Neutropenic disorder
• Nonconvulsive status epilepticus
• Pancytopenia
• Seizure disorder
• Stevens-johnson syndrome
• Stupor
• Thrombocytopenic disorder
• Toxic epidermal necrolysis

More Frequent

• Diarrhea
• Headache disorder
• Nausea
• Vomiting

Less Frequent

• Erythema
• Gastrointestinal irritation
• Oral candidiasis
• Phlebitis after infusion
• Vaginitis
• Vulvovaginal candidiasis

Rare or Very Rare

• Acute cognitive impairment
• Hallucinations
• Urticaria

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Reproduction studies in rats, rabbits, or mice using cefepime dosages approximately 1.6 times or 0.3 times, or equal to the recommended maximum human dosage (calculated on a mg/m2 basis), respectively, have not revealed evidence of teratogenicity or embryotoxicity. There are no adequate and controlled studies using cefepime in pregnant women or during labor and delivery, and the drug should be used during pregnancy only when clearly needed.

Cefepime is distributed into milk in low concentrations following parenteral administration, and the drug should be used with caution in nursing women.

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