Cefepime

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:

• Aminoglycosides such as Garamycin (gentamicin)
• Diuretics (water pills)

Tell your doctor if you are breastfeeding or plan to breastfeed.

Cefepime has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from cefepime, a choice should be made whether to stop nursing or to stop use of cefepime. The importance of the drug to the mother should be considered.

This medication is available in an injectable form to be given directly into a vein (IV) or muscle (IM) by a healthcare professional.

• It is used to treat bacterial infections.

Hypersensitivity Reactions to Cefepime, Cephalosporins, Penicillins, or Other Drugs

Before therapy with Cefepime for Injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to Cefepime, cephalosporins, penicillins, or other drugs. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefepime for Injection occurs, discontinue the drug.

Use in Patients with Renal Impairment

In patients with creatinine clearance less than or equal to 60 mL/min, adjust the dose of Cefepime (Cefepime hydrochloride) to compensate for the slower rate of renal elimination [see DOSAGE AND ADMINISTRATION]. Because high and prolonged serum Cefepime concentrations can occur from usual dosages in patients with renal impairment, the Cefepime dosage should be reduced when it is administered to such patients. Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organisms.

Neurotoxicity

During postmarketing surveillance, serious adverse reactions have been reported including life-threatening or fatal occurrences of the following: encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and nonconvulsive status epilepticus (see ADVERSE REACTIONS: Postmarketing Experience). Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. However, some cases of neurotoxicity occurred in patients receiving a dosage adjustment appropriate for their degree of renal impairment. In the majority of cases, symptoms of neurotoxicity were reversible and resolved after discontinuation of Cefepime and/or after hemodialysis. If neurotoxicity associated with Cefepime therapy occurs, consider discontinuing Cefepime or making appropriate dosage adjustments in patients with renal impairment.

Clostridium difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefepime, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

General

Prescribing Cefepime for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

As with other antimicrobials, prolonged use of Cefepime may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.

Many cephalosporins, including Cefepime, have been associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk, and exogenous vitamin K administered as indicated.

Positive direct Coombs' tests have been reported during treatment with Cefepime. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs' test may be due to the drug.

Cefepime for injection should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Arginine has been shown to alter glucose metabolism and elevate serum potassium transiently when administered at 33 times the amount provided by the maximum recommended human dose of Cefepime. The effect of lower doses is not presently known.

Information for Patients

Before therapy with Cefepime for Injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to Cefepime, cephalosporins, penicillins, or other drugs. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefepime for Injection occurs, discontinue the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures including oxygen, corticosteroids, intravenous fluids, intravenous antihistamines, pressor amines, and airway management, as clinically indicated.

Patients should be counseled that antibacterial drugs including Cefepime for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefepime for injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Cefepime for injection or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Patients should be advised of neurological adverse events that could occur with Cefepime for injection use. Patients should be instructed to inform their healthcare provider at once of any neurological signs and symptoms, including encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and nonconvulsive status epilepticus for immediate treatment, dosage adjustment, or discontinuation of Cefepime for injection.

Drug Interactions

Renal function should be monitored carefully if high doses of aminoglycosides are to be administered with Cefepime because of the increased potential of nephrotoxicity and ototoxicity of aminoglycoside antibiotics. Nephrotoxicity has been reported following concomitant administration of other cephalosporins with potent diuretics such as furosemide.

Drug/Laboratory Test Interactions

The administration of Cefepime may result in a false-positive reaction for glucose in the urine when using ClinitestTM tablets. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as ClinistixTM) be used.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No animal carcinogenicity studies have been conducted with Cefepime. In chromosomal aberration studies, Cefepime was positive for clastogenicity in primary human lymphocytes, but negative in Chinese hamster ovary cells. In other in vitro assays (bacterial and mammalian cell mutation, DNA repair in primary rat hepatocytes, and sister chromatid exchange in human lymphocytes), Cefepime was negative for genotoxic effects. Moreover, in vivo assessments of Cefepime in mice (2 chromosomal aberration and 2 micronucleus studies) were negative for clastogenicity. No untoward effects on fertility were observed in rats when Cefepime was administered subcutaneously at doses up to 1000 mg/kg/day (1.6 times the recommended maximum human dose calculated on a mg/m2 basis).

Pregnancy

Teratogenic Effects: Pregnancy Category B

Cefepime was not teratogenic or embryocidal when administered during the period of organogenesis to rats at doses up to 1000 mg/kg/day (1.6 times the recommended maximum human dose calculated on a mg/m2 basis) or to mice at doses up to 1200 mg/kg (approximately equal to the recommended maximum human dose calculated on a mg/m2 basis) or to rabbits at a dose level of 100 mg/kg (0.3 times the recommended maximum human dose calculated on a mg/m2 basis).

There are, however, no adequate and well-controlled studies of Cefepime use in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Cefepime is excreted in human breast milk in very low concentrations (0.5 mcg/mL). Caution should be exercised when Cefepime is administered to a nursing woman.

Labor and Delivery

Cefepime has not been studied for use during labor and delivery. Treatment should only be given if clearly indicated.

Pediatric Use

The safety and effectiveness of Cefepime in the treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, pneumonia, and as empiric therapy for febrile neutropenic patients have been established in the age groups 2 months up to 16 years. Use of Cefepime in these age groups is supported by evidence from adequate and well-controlled studies of Cefepime in adults with additional pharmacokinetic and safety data from pediatric trials (see CLINICAL PHARMACOLOGY).

Safety and effectiveness in pediatric patients below the age of 2 months have not been established. There are insufficient clinical data to support the use of Cefepime for injection in pediatric patients under 2 months of age or for the treatment of serious infections in the pediatric population where the suspected or proven pathogen is Haemophilus influenzae type b.

IN THOSE PATIENTS IN WHOM MENINGEAL SEEDING FROM A DISTANT INFECTION SITE OR IN WHOM MENINGITIS IS SUSPECTED OR DOCUMENTED, AN ALTERNATE AGENT WITH DEMONSTRATED CLINICAL EFFICACY IN THIS SETTING SHOULD BE USED.

Geriatric Use

Of the more than 6400 adults treated with Cefepime for injection in clinical studies, 35% were 65 years or older while 16% were 75 years or older. When geriatric patients received the usual recommended adult dose, clinical efficacy and safety were comparable to clinical efficacy and safety in non-geriatric adult patients.

Serious adverse events have occurred in geriatric patients with renal insufficiency given unadjusted doses of Cefepime, including life-threatening or fatal occurrences of the following: encephalopathy, myoclonus, and seizures. (See WARNINGS and ADVERSE REACTIONS.)

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored. (See CLINICAL PHARMACOLOGY: Specific Populations, WARNINGS, and DOSAGE AND ADMINISTRATION.)

Cefepime for Injection, USP is supplied as follows:

Cefepime for Injection, USP in the dry state, is a white to pale yellow powder. Constituted solution of Cefepime for Injection, USP can range in color from pale yellow to amber.

Storage

Cefepime FOR INJECTION IN THE DRY STATE SHOULD BE STORED BETWEEN 2° to 25° C (36° to 77° F) AND PROTECTED FROM LIGHT.

NOVAPLUS is registered trademark of Novation, LLC.

Mfg. by:                                                                                          Mfg. for:
Hospira Healthcare India Pvt. Ltd.                                                 Apotex Corp.
Irungattukottai - 602 105, India                                                                  Weston, FL 33326

 
REVISED: 4/2015

 
948026375

Single-Dose Vial
NDC 60505-6031-1

Cefepime
for Injection, USP

For IV Use
after constitution.

2 grams*

RxOnly

NOVAPLUS®

N+ and NOVAPLUS are registered
trademarks of Novation, LLC.

1 Box - 10 vials
NDC 60505-6031-4

Cefepime
for Injection, USP

For IV Use after constitution.

2 grams*

SINGLE DOSE VIALS

RETAIN IN CARTON UNTIL TIME OF USE

NOVAPLUS®

RxOnly

(SEF e pim)

• Antibiotic, Cephalosporin (Fourth Generation)

Bacterial meningitis

Based on the Infectious Diseases Society of America (IDSA) guidelines for the management of bacterial meningitis, cefepime is effective and recommended for the treatment of bacterial meningitis caused by P. aeruginosa; as an alternate agent for the treatment of meningitis caused by H. influenzae or S. pneumoniae (with a penicillin MIC 0.1 to 1 mcg/mL); and as empiric therapy (in combination with vancomycin) for purulent meningitis in patients who have a CSF shunt, are postneurosurgery, or those with penetrating head trauma.

Osteomyelitis, native vertebral

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, cefepime is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to Pseudomonas aeruginosa or Enterobacteriaceae.

Prosthetic joint infection

Based on the Infectious Diseases Society of America (IDSA) guidelines for the management of prosthetic joint infection, cefepime is an effective and recommended agent for the treatment of prosthetic joint infection with Pseudomonas aeruginosa or Enterobacter spp.

Hypersensitivity to cefepime, other cephalosporins, penicillins, other beta-lactam antibiotics, or any component of the formulation

General dosing, susceptible infection (Red Book [AAP 2015]): Infants, Children, and Adolescents: IM, IV:

Mild to moderate infection: 50 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose

Severe infection: 50 mg/kg/dose every 8 to 12 hours; maximum dose: 2,000 mg/dose

Febrile neutropenia: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours (maximum dose: 2,000 mg/dose) (Red Book [AAP 2015])

Pneumonia: Infants ≥2 months, Children, and Adolescents: IV:

Due to P. aeruginosa: 50 mg/kg/dose every 8 hours for 10 days (maximum dose: 2,000 mg/dose)

Not due to P. aeruginosa: 50 mg/kg/dose every 12 hours for 10 days (maximum dose: 2,000 mg/dose)

Skin and skin structure infections (uncomplicated): Infants ≥ 2 months, Children, and Adolescents: IV: 50 mg/kg/dose every 12 hours for 10 days (maximum dose: 2,000 mg/dose)

Urinary tract infections, complicated and uncomplicated: Infants ≥ 2 months, Children, and Adolescents: IV, IM: Note: IM may be considered for mild to moderate infection only.

Mild to moderate infection: IV, IM: 50 mg/kg/dose every 12 hours for 7 to 10 days (maximum dose: 1,000 mg/dose)

Severe infection: IV: 50 mg/kg/dose every 12 hours for 10 days (maximum dose: 2,000 mg/dose)

Intra-abdominal infection, complicated (off-label): Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 12 hours in combination with metronidazole (maximum dose: 2,000 mg/dose). Note: IDSA 2010 guidelines recommend duration of 4 to 7 days (provided source controlled) (Solomkin [IDSA] 2010).

IV: Reconstitute 500 mg vial with 5 mL and 1 or 2 g vial with 10 mL of a compatible diluent (resulting concentration of 100 mg/mL for 500 mg and 1 g vial and 160 mg/mL for 2 g vial) and further dilute in a compatible IV infusion fluid.

IM: Reconstitute 500 mg or 1 g vial with 1.3 mL or 2.4 mL, respectively, of SWFI, NS, D5W, lidocaine 0.5% or 1%, or bacteriostatic water for injection; resulting concentration is 280 mg/mL.