cefepime 2 GM Injection

WARNINGS

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 for injection 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 non-convulsive 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 for injection, 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.

DRUG INTERACTIONS

Drug Interactions Renal function should be monitored carefully if high doses of aminoglycosides are to be administered with cefepime for injection 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.

OVERDOSAGE

Patients who receive an overdose should be carefully observed and given supportive treatment.

In the presence of renal insufficiency, hemodialysis, not peritoneal dialysis, is recommended to aid in the removal of cefepime from the body.

Accidental overdosing has occurred when large doses were given to patients with impaired renal function.

Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and non-convulsive status epilepticus.

(See WARNINGS , ADVERSE REACTIONS , and DOSAGE AND ADMINISTRATION .)

DESCRIPTION

Cefepime for injection, USP is a semi-synthetic, broad spectrum, cephalosporin antibiotic for parenteral administration.

The chemical name is 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)-glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo [4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium chloride, 7 2 -(Z)-(O-methyloxime), monohydrochloride, monohydrate, which corresponds to the following structural formula: Cefepime hydrochloride is a white to pale yellow powder.

Cefepime hydrochloride contains the equivalent of not less than 825 mcg and not more than 911 mcg of cefepime (C 19 H 24 N 6 O 5 S 2 ) per mg, calculated on an anhydrous basis.

It is highly soluble in water.

Cefepime for injection, USP is supplied for intramuscular or intravenous administration in strengths equivalent to 1 g, and 2 g of cefepime.

(See DOSAGE AND ADMINISTRATION .) Cefepime for injection, USP is a sterile, dry mixture of cefepime hydrochloride and L-arginine.

It contains the equivalent of not less than 90 percent and not more than 115 percent of the labeled amount of cefepime (C 19 H 24 N 6 O 5 S 2 ).

The L-arginine, at an approximate concentration of 707 mg/g of cefepime, is added to control the pH of the constituted solution at 4 to 6.

Freshly constituted solutions of cefepime for injection, USP will range in color from pale yellow to amber.

Cefepime Chemical Structure

CLINICAL STUDIES

Febrile Neutropenic Patients The safety and efficacy of empiric cefepime monotherapy of febrile neutropenic patients have been assessed in two multicenter, randomized trials comparing cefepime monotherapy (at a dose of 2 g intravenously every 8 hours) to ceftazidime monotherapy (at a dose of 2 g intravenously every 8 hours).

These studies comprised 317 evaluable patients.

Table 6 describes the characteristics of the evaluable patient population.

Table 6: Demographics of Evaluable Patients (First Episodes Only) Cefepime Ceftazidime Total 164 153 Median age (yr) 56 (range, 18 to 82) 55 (range, 16 to 84) Male 86 (52%) 85 (56%) Female 78 (48%) 68 (44%) Leukemia 65 (40%) 52 (34%) Other hematologic malignancies 43 (26%) 36 (24%) Solid tumor 54 (33%) 56 (37%) Median ANC nadir (cells/microliter) 20 (range, 0 to 500) 20 (range, 0 to 500) Median duration of neutropenia (days) 6 (range, 0 to 39) 6 (range, 0 to 32) Indwelling venous catheter 97 (59%) 86 (56%) Prophylactic antibiotics 62 (38%) 64 (42%) Bone marrow graft 9 (5%) 7 (5%) SBP less than 90 mm Hg at entry 7 (4%) 2 (1%) ANC = absolute neutrophil count; SBP = systolic blood pressure Table 7 describes the clinical response rates observed.

For all outcome measures, cefepime was therapeutically equivalent to ceftazidime.

Table 7: Pooled Response Rates for Empiric Therapy of Febrile Neutropenic Patients % Response Cefepime Ceftazidime Outcome Measures (n=164) (n=153) Primary episode resolved with no treatment modification, no new febrile episodes or infection, and oral antibiotics allowed for completion of treatment 51 55 Primary episode resolved with no treatment modification, no new febrile episodes or infection and no post-treatment oral antibiotics 34 39 Survival, any treatment modification allowed 93 97 Primary episode resolved with no treatment modification and oral antibiotics allowed for completion of treatment 62 67 Primary episode resolved with no treatment modification and no post-treatment oral antibiotics 46 51 Insufficient data exist to support the efficacy of cefepime monotherapy 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).

No data are available in patients with septic shock.

Complicated Intra-Abdominal Infections Patients hospitalized with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter trial comparing the combination of cefepime (2 g every 12 hours) plus intravenous metronidazole (500 mg every 6 hours) versus imipenem/cilastatin (500 mg every 6 hours) for a maximum duration of 14 days of therapy.

The study was designed to demonstrate equivalence of the two therapies.

The primary analyses were conducted on the protocol-valid population, which consisted of those with a surgically confirmed complicated infection, at least one pathogen isolated pretreatment, at least 5 days of treatment, and a 4 to 6 week follow-up assessment for cured patients.

Subjects in the imipenem/cilastatin arm had higher APACHE II scores at baseline.

The treatment groups were otherwise generally comparable with regard to their pretreatment characteristics.

The overall clinical cure rate among the protocol-valid patients was 81% (51 cured/63 evaluable patients) in the cefepime plus metronidazole group and 66% (62/94) in the imipenem/cilastatin group.

The observed differences in efficacy may have been due to a greater proportion of patients with high APACHE II scores in the imipenem/cilastatin group.

HOW SUPPLIED

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.

1 g Based on cefepime activity vial (tray of 10) NDC 0781-3222-95 2 g vial (tray of 10) NDC 0781-3223-95 Storage IN THE DRY STATE STORE AT 20° TO 25°C (68° TO 77°F) [SEE USP CONTROLLED ROOM TEMPERATURE].

PROTECT FROM LIGHT.

RETAIN IN CARTON UNTIL TIME OF USE.

GERIATRIC USE

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 .)

INDICATIONS AND USAGE

Cefepime for injection, USP is indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms (see also PRECAUTIONS: Pediatric Use and DOSAGE AND ADMINISTRATION ): Pneumonia (moderate to severe) caused by Streptococcus pneumoniae , including cases associated with concurrent bacteremia, Pseudomonas aeruginosa , Klebsiella pneumoniae , or Enterobacter species.

Empiric Therapy for Febrile Neutropenic Patients.

Cefepime 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 .) Uncomplicated and Complicated Urinary Tract Infections (including pyelonephritis) caused by 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 microorganisms.

Uncomplicated Skin and Skin Structure Infections caused by Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes .

Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by Escherichia coli , viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae , Enterobacter species, or Bacteroides fragilis .

(See CLINICAL STUDIES .) To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefepime for injection, USP and other antibacterial drugs, cefepime for injection, USP 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.

PEDIATRIC USE

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 for injection 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.

PREGNANCY

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/m 2 basis) or to mice at doses up to 1200 mg/kg (approximately equal to the recommended maximum human dose calculated on a mg/m 2 basis) or to rabbits at a dose level of 100 mg/kg (0.3 times the recommended maximum human dose calculated on a mg/m 2 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.

NUSRING MOTHERS

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.

INFORMATION FOR PATIENTS

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 non-convulsive status epilepticus for immediate treatment, dosage adjustment, or discontinuation of cefepime for injection.

DOSAGE AND ADMINISTRATION

The recommended adult and pediatric dosages and routes of administration are outlined in the following table 10.

Cefepime for injection should be administered intravenously over approximately 30 minutes.

Table 10: Recommended Dosage Schedule for Cefepime for Injection in Patients with CrCL Greater Than 60 mL/min Adjust dose in patients with CrCL less than or equal to 60 mL/min Site and Type of Infection Dose Frequency Duration (days) Adults Moderate to Severe Pneumonia due to S.

pneumoniae including cases associated with concurrent bacteremia.

, P.

aeruginosa For Pseudomonas aeruginosa, use 2 g IV every 8 hours (50 mg per kg per dose in pediatric patients 2 months up to 16 years) , K.

pneumoniae , or Enterobacter species 1 to 2 g IV Every 8 to 12 hours 10 Empiric therapy for febrile neutropenic patients (See INDICATIONS AND USAGE and CLINICAL STUDIES .) 2 g IV Every 8 hours 7 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.

Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E.

coli, K.

pneumoniae , or P.

mirabilis 0.5 to 1 g IV/IM Intramuscular route of administration is indicated only for mild to moderate, uncomplicated or complicated UTIs due to E.

coli when the intramuscular route is considered to be a more appropriate route of drug administration.

Every 12 hours 7 to 10 Severe Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E.

coli or K.

pneumoniae 2 g IV Every 12 hours 10 Moderate to Severe Uncomplicated Skin and Skin Structure Infections due to S.

aureus or S.

pyogenes 2 g IV Every 12 hours 10 Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by E.

coli , viridans group streptococci, P.

aeruginosa , K.

pneumoniae , Enterobacter species, or B.

fragilis .

(See CLINICAL STUDIES .) 2 g IV Every 8 to 12 hours 7 to 10 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 uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, and pneumonia is 50 mg per kg per dose, administered every 12 hours (50 mg per kg per dose, every 8 hours for febrile neutropenic patients), for durations as given above.

Patients with Hepatic Impairment No adjustment is necessary for patients with hepatic impairment.

Patients with Renal Impairment In patients with creatinine clearance less than or equal to 60 mL/min, the dose of cefepime for injection should be adjusted to compensate for the slower rate of renal elimination.

The recommended initial dose of cefepime for injection should be the same as in patients with normal renal function except in patients undergoing hemodialysis.

The recommended doses of cefepime for injection in patients with renal impairment are presented in Table 11.

When only serum creatinine is available, the following formula (Cockcroft and Gault equation) 4 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) × (140-age) 72 × serum creatinine (mg/dL) Females: 0.85 × above value Table 11: Recommended Dosing Schedule for Cefepime for Injection in Adult Patients (Normal Renal Function, Renal Impairment, and Hemodialysis) Creatinine Clearance (mL/min) Recommended Maintenance Schedule Greater than 60 Normal recommended dosing schedule 500 mg every 12 hours 1 g every 12 hours 2 g every 12 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 CAPD 500 mg every 48 hours 1 g every 48 hours 2 g every 48 hours 2 g every 48 hours Hemodialysis On hemodialysis days, cefepime should be administered following hemodialysis.

Whenever possible, cefepime should be administered at the same time each day.

1 g on day 1, then 500 mg every 24 hours thereafter 1 g every 24 hours In patients undergoing continuous ambulatory peritoneal dialysis, cefepime for injection may be administered at normally recommended doses at a dosage interval of every 48 hours (see Table 11).

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 11).

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 ), changes in the dosing regimen proportional to those in adults (see Tables 10 and 11) are recommended for pediatric patients.

Administration For Intravenous Infusion Dilute with a suitable parenteral vehicle prior to intravenous infusion.

Constitute the 1 g, or 2 g vial, and add an appropriate quantity of the resulting solution to an intravenous container with one of the compatible intravenous fluids listed in the Compatibility and Stability subsection.

THE RESULTING SOLUTION SHOULD BE ADMINISTERED OVER APPROXIMATELY 30 MINUTES.

Intermittent intravenous infusion with a Y-type administration set can be accomplished with compatible solutions.

However, during infusion of a solution containing cefepime, it is desirable to discontinue the other solution.

Intramuscular Administration For intramuscular administration, cefepime for injection should be constituted with one of the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride, 5% Dextrose Injection, 0.5% or 1% Lidocaine Hydrochloride, or Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol (refer to Table 12).

Preparation of cefepime for injection solutions is summarized in Table 12.

Table 12: Preparation of Solutions of Cefepime for Injection Single-Dose Vials for Intravenous/Intramuscular Administration Amount of Diluent to be added (mL) Approximate Available Volume (mL) Approximate Cefepime Concentration (mg/mL) cefepime vial content 1 g (IV) 10 11.3 100 1 g (IM) 2.4 3.6 280 2 g (IV) 10 12.5 160 Compatibility and Stability Intravenous Cefepime for injection is compatible at concentrations between 1 mg per mL and 40 mg per mL with the following intravenous infusion fluids: 0.9% Sodium Chloride Injection, 5% and 10% Dextrose Injection, M/6 Sodium Lactate Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringers and 5% Dextrose Injection, Normosol™-R, and Normosol™-M in 5% Dextrose Injection.

These solutions may be stored up to 24 hours at controlled room temperature 20° C to 25° C (68° F to 77° F) or 7 days in a refrigerator 2° C to 8° C (36° F to 46° F).

Cefepime for injection admixture compatibility information is summarized in Table 13.

Table 13: Cefepime Admixture Stability Stability Time for Cefepime for Injection Concentration Admixture and Concentration IV Infusion Solutions RT/L (20° to 25° C) Refrigeration (2° to 8° C) 40 mg/mL Amikacin 6 mg/mL NS or D5W 24 hours 7 days 40 mg/mL Ampicillin 1 mg/mL D5W 8 hours 8 hours 40 mg/mL Ampicillin 10 mg/mL D5W 2 hours 8 hours 40 mg/mL Ampicillin 1 mg/mL NS 24 hours 48 hours 40 mg/mL Ampicillin 10 mg/mL NS 8 hours 48 hours 4 mg/mL Ampicillin 40 mg/mL NS 8 hours 8 hours 4 to 40 mg/mL Clindamycin Phosphate 0.25 to 6 mg/mL NS or D5W 24 hours 7 days 4 mg/mL Heparin 10 to 50 units/mL NS or D5W 24 hours 7 days 4 mg/mL Potassium Chloride 10 to 40 mEq/L NS or D5W 24 hours 7 days 4 mg/mL Theophylline 0.8 mg/mL D5W 24 hours 7 days 1 to 4 mg/mL na Aminosyn™ II 4.25% with electrolytes and calcium 8 hours 3 days 0.125 to 0.25 mg/mL na Inpersol™ with 4.25% dextrose 24 hours 7 days NS = 0.9% Sodium Chloride Injection D5W = 5% Dextrose Injection na = not applicable RT/L = Ambient room temperature and light Solutions of cefepime for injection, like those of most beta-lactam antibiotics, should not be added to solutions of ampicillin at a concentration greater than 40 mg per mL, and should not be added to metronidazole, vancomycin, gentamicin, tobramycin, netilmicin sulfate, or aminophylline because of potential interaction.

However, if concurrent therapy with cefepime for injection is indicated, each of these antibiotics can be administered separately.

Intramuscular Cefepime for injection constituted as directed is stable for 24 hours at controlled room temperature 20° C to 25° C (68° F to 77° F) or for 7 days in a refrigerator 2° C to 8° C (36° F to 46° F) with the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol, or 0.5% or 1% Lidocaine Hydrochloride.

NOTE: PARENTERAL DRUGS SHOULD BE INSPECTED VISUALLY FOR PARTICULATE MATTER BEFORE ADMINISTRATION.

IF PARTICULATE MATTER IS EVIDENT IN RECONSTITUTED FLUIDS, THE DRUG SOLUTION SHOULD BE DISCARDED.

As with other cephalosporins, the color of cefepime for injection powder, as well as its solutions, tend to darken depending on storage conditions; however, when stored as recommended, the product potency is not adversely affected.