Cefepime

CEFEPIME- cefepime hydrochloride injection, powder, for solution
Qilu Pharmaceutical Co., Ltd.

1 INDICATIONS AND USAGE

1.1 Pneumonia

Cefepime for Injection is indicated in the treatment of pneumonia (moderate to severe) caused by susceptible strains of Streptococcus pneumoniae , including cases associated with concurrent bacteremia, Pseudomonas aeruginosa , Klebsiella pneumoniae , or Enterobacter species.

1.2 Empiric Therapy for Febrile Neutropenic Patients

Cefepime for Injection as monotherapy is indicated for empiric treatment of febrile neutropenic patients. In patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia), antimicrobial monotherapy may not be appropriate. Insufficient data exist to support the efficacy of cefepime monotherapy in such patients [see Clinical Studies (14.1) ].

1.3 Uncomplicated and Complicated Urinary Tract Infections (including pyelonephritis)

Cefepime for Injection is indicated in the treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by susceptible isolates of Escherichia coli or Klebsiella pneumoniae , when the infection is severe, or caused by Escherichia coli , Klebsiella pneumoniae , or Proteus mirabilis , when the infection is mild to moderate, including cases associated with concurrent bacteremia with these bacteria.

1.4 Uncomplicated Skin and Skin Structure Infections

Cefepime for Injection is indicated in the treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes.

1.5 Complicated Intra-abdominal Infections (used in combination with metronidazole)

Cefepime for Injection is indicated in the treatment of complicated intra-abdominal infections (used in combination with metronidazole) in adults caused by susceptible isolates of Escherichia coli , viridans group streptococci, Pseudomonas aeruginosa , Klebsiella pneumoniae , Enterobacter species, or Bacteroides fragilis [see Clinical Studies (14.2) ].

1.6 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefepime for Injection and other antibacterial drugs, Cefepime for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage for Adults

The recommended adult dosages and routes of administration are outlined in Table 1 below for patients with creatinine clearance greater than 60 mL/min. Administer Cefepime for Injection intravenously over approximately 30 minutes.

Table 1: Recommended Dosage Schedule for Cefepime for Injection in Adult Patients with Creatinine Clearance (CrCL) Greater Than 60 mL/min

*or until resolution of neutropenia. In patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be re-evaluated frequently.**Intramuscular route of administration is indicated only for mild to moderate, uncomplicated or complicated UTIs due to E. coli.§ For P. aeruginosa , use 2 g IV every 8 hours.
Site and Type of Infection	Dose	Frequency	Duration
			(days)
Adults	Intravenous (IV)/Intramuscular (IM)
Moderate to Severe Pneumonia§	1 to 2 g IV	Every 8 to12 hours	10
Empiric therapy for febrile neutropenic patients	2 g IV	Every 8 hours	7*
Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis	0.5 to 1 g IV/IM**	Every 12 hours	7 to 10
Severe Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis	2 g IV	Every 12 hours	10
Moderate to Severe Uncomplicated Skin and Skin Structure Infections	2 g IV	Every 12 hours	10
Complicated Intra-abdominal Infections§ (used in combination with metronidazole)	2 g IV	Every 8 to12 hours	7 to 10

2.2 Pediatric Patients (2 months up to 16 years)

The maximum dose for pediatric patients should not exceed the recommended adult dose.

The usual recommended dosage in pediatric patients up to 40 kg in weight for durations as given above for adults is:

•

50 mg per kg per dose, administered every 12 hours for uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, and pneumonia (see below).

•

For moderate to severe pneumonia due to P. aeruginosa give 50 mg per kg per dose, every 8 hours.

•

50 mg per kg per dose, every 8 hours for febrile neutropenic patients.

2.3 Dosage Adjustments in Patients with Renal Impairment

Adult Patients

Adjust the dose of Cefepime for Injection in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination. In these patients, the recommended initial dose of Cefepime for Injection should be the same as in patients with CrCL greater than 60 mL/min except in patients undergoing hemodialysis. The recommended doses of Cefepime for Injection in patients with renal impairment are presented in Table 2.

When only serum creatinine is available, the following formula (Cockcroft and Gault equation)¹ may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:

Males: Creatinine Clearance (mL/min) =	Weight (kg) x (140 – age)
	72 × serum creatinine (mg/dL)
Females: 0.85 × above value

Table 2: Recommended Dosing Schedule for Cefepime for Injection in Adult Patients With Creatinine Clearance Less Than or Equal to 60 mL/min

* On hemodialysis days, cefepime should be administered following hemodialysis. Whenever possible, cefepime should be administered at the same time each day.
Creatinine Clearance (mL/min)	Recommended Maintenance Schedule
Greater than 60	500 mg every12 hours	1 g every12 hours	2 g every12 hours	2 g every 8 hours
30 to 60	500 mg every 24 hours	1 g every 24 hours	2 g every 24 hours	2 g every 12 hours
11 to 29	500 mg every 24 hours	500 mg every 24 hours	1 g every 24 hours	2 g every 24 hours
Less than 11	250 mg every 24 hours	250 mg every 24 hours	500 mg every 24 hours	1 g every 24 hours
Continuous Ambulatory Peritoneal Dialysis (CAPD)	500 mg every 48 hours	1 g every 48 hours	2 g every 48 hours	2 g every 48 hours
Hemodialysis *	1 g on day 1, then 500 mg every 24 hours thereafter			1 g every 24 hours

In patients undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD), Cefepime for Injection may be administered at the recommended doses at a dosage interval of every 48 hours (see Table 2).

In patients undergoing hemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period. The dosage of Cefepime for Injection for hemodialysis patients is 1 g on Day 1 followed by 500 mg every 24 hours for the treatment of all infections except febrile neutropenia, which is 1 g every 24 hours.

Cefepime for Injection should be administered at the same time each day and following the completion of hemodialysis on hemodialysis days (see Table 2).

Pediatric Patients

Data in pediatric patients with impaired renal function are not available; however, since cefepime pharmacokinetics are similar in adults and pediatric patients [see Clinical Pharmacology (12.3) ], changes in the dosing regimen proportional to those in adults (see Tables 1 and 2) are recommended for pediatric patients.