The recommended adult and pediatric dosages and routes of administration are outlined in the following table 10. MAXIPIME should be administered intravenously over approximately 30 minutes.
Table 10: Recommended Dosage Schedule for MAXIPIME in Patients with CrCL Greater Than 60 mL/min†
†Adjust dose in patients with CrCL less than or equal to 60 mL/min
*including cases associated with concurrent bacteremia
**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 when the intramuscular route is considered to be a more appropriate route of drug administration.
§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)
Site and Type of Infection
Dose
Frequency
Duration
(days)
Adults
Moderate to Severe Pneumonia due to S. pneumoniae*,
P. aeruginosa§, 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**
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***
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 MAXIPIME should be adjusted to compensate for the slower rate of renal elimination. The recommended initial dose of MAXIPIME should be the same as in patients with normal renal function except in patients undergoing hemodialysis. The recommended doses of MAXIPIME 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) x (140–age)
72 × serum creatinine (mg/dL)
Females: 0.85 × above value
Table 11: Recommended Dosing Schedule for MAXIPIME in Adult Patients (Normal Renal Function, Renal Impairment, and Hemodialysis)
*
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
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*
1 g on day 1, then 500 mg every 24 hours thereafter
1 g
every 24 hours
In patients undergoing continuous ambulatory peritoneal dialysis, MAXIPIME 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 MAXIPIME 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.
MAXIPIME 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 500 mg, 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.
ADD-Vantage™ vials are to be constituted only with 50 mL or 100 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection in ADD-Vantage flexible diluent containers. (See ADD-Vantage Vial Instructions for Use.)
Intramuscular Administration: For intramuscular administration, MAXIPIME (cefepime hydrochloride) 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 MAXIPIME solutions is summarized in Table 12.
Table 12: Preparation of Solutions of MAXIPIME
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
500 mg (IV)
500 mg (IM)
1 g (IV)
1 g (IM)
2 g (IV)
5
1.3
10
2.4
10
5.6
1.8
11.3
3.6
12.5
100
280
100
280
160
ADD-Vantage
1 g vial
1 g vial
2 g vial
2 g vial
50
100
50
100
50
100
50
100
20
10
40
20
Compatibility and Stability
Intravenous: MAXIPIME 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). MAXIPIME in ADD-Vantage vials is 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 or 7 days in a refrigerator 2°C to 8°C.
MAXIPIME admixture compatibility information is summarized in Table 13.
Table 13: Cefepime Admixture Stability
NS = 0.9% Sodium Chloride Injection
D5W = 5% Dextrose Injection
na = not applicable
RT/L = Ambient room temperature and light
Stability Time for
MAXIPIME
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
Solutions of MAXIPIME, 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 MAXIPIME is indicated, each of these antibiotics can be administered separately.
Intramuscular: MAXIPIME (cefepime hydrochloride) 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 MAXIPIME 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.
INSTRUCTIONS FOR USE
These instructions for use should be made available to the individuals who perform the reconstitution steps.
To Open:
Peel 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.
To Assemble Vial and Flexible Diluent Container:
(Use Aseptic Technique)
1. Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
a. To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (SEE FIGURE 1.), then pull straight up to remove the cap. (SEE FIGURE 2.)
NOTE: Once the breakaway cap has been removed, do not access vial with syringe.
b. To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (SEE FIGURE 3.)
2. Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (SEE FIGURE 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go.
NOTE: Once vial is seated, do not attempt to remove. (SEE FIGURE 4.)
3. Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.
4. Label appropriately.
To Reconstitute the Drug:
1. Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.
2. With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (SEE FIGURE 5.)
3. Pull the inner cap from the drug vial. (SEE FIGURE 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.
4. Mix container contents thoroughly and use within the specified time.
5. Look through the bottom of the vial to verify that the stopper has been removed and complete mixing has occurred. (SEE FIGURE 7.)
If the rubber stopper is not removed from the vial and medication is not released on the first attempt, the inner cap may be manipulated back into the rubber stopper without removing the drug vial from the diluent container. Repeat steps 3 through 5.
Preparation for Administration:
(Use Aseptic Technique)
1. Confirm the activation and admixture of vial contents.
2. Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.
3. Close flow control clamp of administration set.
4. Remove cover from outlet port at bottom of container.
5. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton.
6. Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.
7. Squeeze and release drip chamber to establish proper fluid level in chamber.
8. Open flow control clamp and clear air from set. Close clamp.
9. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
10. Regulate rate of administration with flow control clamp.
WARNING: Do not use flexible container in series connections.
