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. Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and nonconvulsive status epilepticus.
Cefepime Northia is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibiotics, penicillins or other beta-lactam antibiotics.
The following adverse reactions are discussed in the Warnings and Precautions section and below:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials using multiple doses of cefepime, 4137 patients were treated with the recommended dosages of cefepime (500 mg to 2 g intravenous every 12 hours). There were no deaths or permanent disabilities thought related to drug toxicity. Sixty-four (1.5%) patients discontinued medication due to adverse reactions. Thirty-three (51%) of these 64 patients who discontinued therapy did so because of rash. The percentage of cefepime-treated patients who discontinued study drug because of drug-related adverse reactions was similar at daily doses of 500 mg, 1 g, and 2 g every 12 hours (0.8%, 1.1%, and 2%, respectively). However, the incidence of discontinuation due to rash increased with the higher recommended doses.
The following adverse reactions (Table 5) were identified in clinical trials conducted in North America (n=3125 cefepime-treated patients).
Table 5: Adverse Reactions in Cefepime Multiple-Dose Dosing Regimens Clinical Trials in North America
| Incidence equal to or greater than 1% | Local adverse reactions (3%), including phlebitis (1.3%), pain and/or inflammation (0.6%)*; rash (1.1%) |
| Incidence less than 1% but greater than 0.1% | Colitis (including pseudomembranous colitis), diarrhea, erythema, fever, headache, nausea, oral moniliasis, pruritus, urticaria, vaginitis, vomiting, anemia |
At the higher dose of 2 g every 8 hours, the incidence of adverse reactions was higher among the 795 patients who received this dose of cefepime. They consisted of rash (4%), diarrhea (3%), nausea (2%), vomiting (1%), pruritus (1%), fever (1%), and headache (1%).
The following (Table 6) adverse laboratory changes, with cefepime, were seen during clinical trials conducted in North America.
Table 6: Adverse Laboratory Changes in Cefepime Multiple-Dose Dosing Regimens Clinical Trials in North America
| Incidence equal to or greater than 1% | Positive Coombs’ test (without hemolysis) (16.2%); decreased phosphorus (2.8%); increased Alanine Transaminase (ALT) (2.8%), Aspartate Transaminase (AST) (2.4%), eosinophils (1.7%); abnormal PTT (1.6%), Prothrombin Time (PT) (1.4%) |
| Incidence less than 1% but greater than 0.1% | Increased alkaline phosphatase, Blood Urea Nitrogen (BUN), calcium, creatinine, phosphorus, potassium, total bilirubin; decreased calcium*, hematocrit, neutrophils, platelets, White Blood Cells (WBC) |
| * Hypocalcemia was more common among elderly patients. Clinical consequences from changes in either calcium or phosphorus were not reported. |
A similar safety profile was seen in clinical trials of pediatric patients
Postmarketing ExperienceThe following adverse reactions have been identified during post-approval use of Cefepime Northia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
In addition to the adverse reactions reported during the North American clinical trials with cefepime, the following adverse reactions have been reported during worldwide postmarketing experience. Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus have been reported.
Anaphylaxis including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia, have been reported.
Cephalosporin-Class Adverse ReactionsIn addition to the adverse reactions listed above that have been observed in patients treated with cefepime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterial drugs:
Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, hepatic dysfunction including cholestasis, and pancytopenia.
Cefepime Northia 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.
Empiric Therapy For Febrile Neutropenic PatientsCefepime Northia 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.
Uncomplicated And Complicated Urinary Tract Infections (Including Pyelonephritis)Cefepime Northia 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.
Uncomplicated Skin And Skin Structure InfectionsCefepime Northia is indicated in the treatment of 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)Cefepime Northia 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.
UsageTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefepime Northia and other antibacterial drugs, Cefepime Northia should be used only to treat 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.
Similar to other beta-lactam antimicrobial agents, the time that the unbound plasma concentration of cefepime exceeds the MIC of the infecting organism has been shown to best correlate with efficacy in animal models of infection. However, the pharmacokinetic/pharmacodynamics relationship for cefepime has not been evaluated in patients.
Pharmacokinetic parameters for cefepime in healthy adult male volunteers (n=9) following single 30-minute infusions (IV) of cefepime 500 mg, 1 g, and 2 g are summarized in Table 7. Elimination of cefepime is principally via renal excretion with an average (±SD) half-life of 2 (±0.3) hours and total body clearance of 120 (±8) mL/min in healthy volunteers. Cefepime pharmacokinetics are linear over the range 250 mg to 2 g. There is no evidence of accumulation in healthy adult male volunteers (n=7) receiving clinically relevant doses for a period of 9 days.
Table 7: Mean Pharmacokinetic Parameters for Cefepime (±SD), Intravenous Administration
| Cefepime Northia | |||
| Parameter | 500 mg IM | 1 g IM | 2 g IM |
| Cmax, mcg/mL | 39.1 (3.5) | 81.7 (5.1) | 163.9 (25.3) |
| AUC, h•mcg/mL | 70.8 (6.7) | 148.5 (15.1) | 284.8 (30.6) |
| Number of subjects (male) | 9 | 9 | 9 |
Pharmacokinetic parameters for cefepime following a single intramuscular injection are summarized in Table 8. The pharmacokinetics of cefepime are linear over the range of 500 mg to 2 g intramuscularly and do not vary with respect to treatment duration.
Table 8: Mean Pharmacokinetic Parameters for Cefepime (±SD), Intramuscular Administration
| Cefepime Northia | |||
| Parameter | 500 mg IM | 1 g IM | 2 g IM |
| Cmax, mcg/mL | 13.9 (3.4) | 29.6 (4.4) | 57.5 (9.5) |
| Tmax, h | 1.4 (0.9) | 1.6 (0.4) | 1.5 (0.4) |
| AUC, h•mcg/mL | 60 (8) | 137 (11) | 262 (23) |
| Number of subjects (male) | 6 | 6 | 12 |
Following intramuscular (IM) administration, cefepime is completely absorbed.
DistributionThe average steady-state volume of distribution of cefepime is 18 (±2) L. The serum protein binding of cefepime is approximately 20% and is independent of its concentration in serum.
Cefepime is excreted in human milk at a concentration of 0.5 mcg/mL. A nursing infant consuming approximately 1000 mL of human milk per day would receive approximately 0.5 mg of cefepime per day.
Concentrations of cefepime achieved in specific tissues and body fluids are listed in Table 9.
Table 9: Mean Concentrations of Cefepime in Specific Body Fluids (mcg/mL) or Tissues (mcg/g) Mean Time of Sample Mean Tissue or Fluid Dose/Route # of Patients Post-Dose Concentration
| Tissue or Fluid | Dose/Route | # of Patients | Mean Time of Sample Post-Dose (h) | Mean Concentration |
| Blister Fluid | 2 g IV | 6 | 1.5 | 81.4 mcg/mL |
| Bronchial Mucosa | 2 g IV | 20 | 4.8 | 24.1 mcg/g |
| Sputum | 2 g IV | 5 | 4 | 7.4 mcg/mL |
| Urine | 500 mg IV | 8 | 0 to 4 | 292 mcg/mL |
| 1 g IV | 12 | 0 to 4 | 926 mcg/mL | |
| 2 g IV | 12 | 0 to 4 | 3120 mcg/mL | |
| Bile | 2 g IV | 26 | 9.4 | 17.8 mcg/mL |
| Peritoneal Fluid | 2 g IV | 19 | 4.4 | 18.3 mcg/mL |
| Appendix | 2 g IV | 31 | 5.7 | 5.2 mcg/g |
| Gallbladder | 2 g IV | 38 | 8.9 | 11.9 mcg/g |
| Prostate | 2 g IV | 5 | 1 | 31.5 mcg/g |
Data suggest that cefepime does cross the inflamed blood-brain barrier. The clinical relevance of these data is uncertain at this time.
Metabolism And ExcretionCefepime is metabolized to N-methylpyrrolidine (NMP) which is rapidly converted to the N-oxide (NMP-N-oxide). Urinary recovery of unchanged cefepime accounts for approximately 85% of the administered dose. Less than 1% of the administered dose is recovered from urine as NMP, 6.8% as NMP-N-oxide, and 2.5% as an epimer of cefepime. Because renal excretion is a significant pathway of elimination, patients with renal dysfunction and patients undergoing hemodialysis require dosage adjustment.
Included as part of the "PRECAUTIONS" Section
PRECAUTIONS Hypersensitivity ReactionsBefore therapy with Cefepime Northia 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 beta-lactams. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs 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 Northia occurs, discontinue the drug and institute appropriate supportive measures.
NeurotoxicitySerious adverse reactions have been reported including life-threatening or fatal occurrences of the following: encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus. 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, discontinue cefepime and institute appropriate supportive measures.
Clostridium Difficile Associated DiarrheaClostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefepime Northia, 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 antibacterial drug 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 antibacterial drug 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.
Development Of Drug-Resistant BacteriaPrescribing Cefepime Northia in the absence of a proven or strongly suspected bacterial infection 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 Northia 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.
Drug/Laboratory Test Interactions Urinary GlucoseThe administration of cefepime may result in a false-positive reaction for glucose in the urine when using some methods (e.g. Clinitest™ tablets).
Coombs’ TestsPositive direct Coombs’ tests have been reported during treatment with Cefepime Northia. In patients who develop hemolytic anemia, discontinue the drug and institute appropriate therapy. Positive Coombs’ test may be observed in newborns whose mothers have received cephalosporin antibiotics before parturition.
Prothrombin TimeMany 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.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of FertilityNo 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 body surface area basis).
Use In Specific Populations Pregnancy Pregnancy Category BThere are 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.
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 body surface area basis) or to mice at doses up to 1200 mg/kg (approximately equal to the recommended maximum human dose calculated on a body surface area basis) or to rabbits at a dose level of 100 mg/kg (0.3 times the recommended maximum human dose calculated on a body surface area basis).
Labor And DeliveryCefepime has not been studied for use during labor and delivery. Treatment should only be given if clearly indicated.
Nursing MothersCefepime is excreted in human breast milk. Caution should be exercised when cefepime is administered to a nursing woman.
Pediatric UseThe 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 Northia 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.
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 Northia in pediatric patients for the treatment of serious infections in the pediatric population where the suspected or proven pathogen is H. 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 UseOf the more than 6400 adults treated with Cefepime Northia 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.
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.
Renal ImpairmentAdjust the dose of Cefepime Northia in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination.
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 Northia intravenously over approximately 30 minutes.
Table 1: Recommended Dosage Schedule for Cefepime Northia in Adult Patients with Creatinine Clearance (CrCL) Greater Than 60 mL/min Duration
| 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 to 12 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 to 12 hours | 7 to 10 |
| *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. |
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:
Adjust the dose of Cefepime Northia 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 Northia should be the same as in patients with CrCL greater than 60 mL/min except in patients undergoing hemodialysis. The recommended doses of Cefepime Northia in patients with renal impairment are presented in Table 2.
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: | (weight in kg) x (140 – age) |
| (72) x serum creatinine (mg/100 mL) | |
| Females: | (0.85) x (above value) |
Table 2: Recommended Dosing Schedule for Cefepime Northia in Adult Patients With Creatinine Clearance Less Than or Equal to 60 mL/min Creatinine Recommended Maintenance Schedule Clearance (mL/min)
| Creatinine Clearance (mL/min) | Recommended Maintenance Schedule | |||
| Greater than 60 | 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 |
| 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 | ||
| *On hemodialysis days, cefepime should be administered following hemodialysis. Whenever possible, cefepime should be administered at the same time each day. |
In patients undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD), Cefepime Northia 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 Northia 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 Northia should be administered at the same time each day and following the completion of hemodialysis on hemodialysis days (see Table 2).
Pediatric PatientsData in pediatric patients with impaired renal function are not available; however, since cefepime pharmacokinetics are similar in adults and pediatric patients , changes in the dosing regimen proportional to those in adults (see Tables 1 and 2) are recommended for pediatric patients.
Preparation Of Cefepime Northia For Intravenous Infusion VialsVials Constitute only with 50 mL or 100 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection in ADD-Vantage flexible diluent containers as described in the instructions for reconstitution.
Preparation For Intramuscular AdministrationConstitute Cefepime Northia vials 0.5 gram, 1 gram and 2 grams 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 3 below for the amount of diluent to be added to each vial and the amount of reconstituted volume to be withdrawn.
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.
Table 3: Preparation of Reconstituted Solutions of Cefepime Northia for Injection
| Single-Dose Vials for Intravenous (IV)/Intramuscular (IM)Administration | Amount of Diluent to be added (mL) | Approximate Cefepime Concentration (mg/mL) | Amount of Reconstituted Volume to be Withdrawn (mL) |
| Cefepime vial content | |||
| 500 mg (IV) | 5 | 100 | 5 |
| 500 mg (IM) | 1.3 | 280 | 1.8 |
| 1 g (IV) | 10 | 100 | 10.5 |
| 1 g (IM) | 2.4 | 280 | 3.6 |
| 2 g (IV) | 10 | 160 | 12.5 |
| ADD-Vantage Vials for Intravenous (IV) Administration | Amount of Diluent to be added (mL) | Approximate Cefepime Concentration (mg/mL) | Approximate Available Volume for Withdrawal (mL) |
| ADD-Vantage | |||
| 1 g vial | 50 | 20 | 50 |
| 1 g vial | 100 | 10 | 100 |
| 2 g vial | 50 | 40 | 50 |
| 2 g vial | 100 | 20 | 100 |
Intravenous Infusion Compatibility
Cefepime Northia vials are 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 Northia in ADD-Vantage vials are stable at concentrations of 10 to 40 mg per mL in 5% Dextrose Injection or 0.9% Sodium Chloride Injection for 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).
Admixture Compatibility
Cefepime Northia admixture compatibility information is summarized in Table 4.
Table 4: Cefepime Admixture Stability
| Stability Time for | ||||
| Cefepime Northia Concentration | Admixture and Concentration | Intravenous (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 |
| 4 mg/mL | Ampicillin1 mg/mL | D5W | 8 hours | 8 hours |
| 4 mg/mL | Ampicillin 10 mg/mL | D5W | 2 hours | 8 hours |
| 4 mg/mL | Ampicillin 1 mg/mL | NS | 24 hours | 48 hours |
| 4 mg/mL | Ampicillin 10 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. |
Cefepime Northia Admixture Incompatibility
Do not add solutions of Cefepime Northia, to solutions of ampicillin at a concentration greater than 40 mg per mL, or to metronidazole, vancomycin, gentamicin, tobramycin, netilmicin sulfate, or aminophylline because of potential interaction. However, if concurrent therapy with Cefepime Northia is indicated, each of these antibiotics can be administered separately.
Intramuscular Cefepime Northia
Cefepime Northia 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.
Intramuscular and Intravenous
Cefepime Northia As with other cephalosporins, the color of Cefepime Northia 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.
ADD-Vantage Instructions For Reconstitution And Intravenous Administration To OpenPeel overwrap at corner and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.
Assembly Of Vial And Flexible Diluent Container
