Apotex Corporation
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Apotex Corporation Drugs
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Ceftriaxone
Ceftriaxone for injection may be administered intravenously or intramuscularly.
Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone for injection and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see WARNINGS).
There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).
Neonates
Hyperbilirubinemic neonates, especially prematures, should not be treated with ceftriaxone for injection (see CONTRAINDICATIONS).
Ceftriaxone for injection is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone- calcium (see CONTRAINDICATIONS).
Pediatric Patients
For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams.
For the treatment of acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 gram) is recommended (see INDICATIONS AND USAGE).
For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams.
In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.
Adults
The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. For infections caused by Staphylococcus aureus (MSSA), the recommended daily dose is 2 to 4 grams, in order to achieve >90% target attainment. The total daily dose should not exceed 4 grams.
If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism.
For the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended.
For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended.
Generally, ceftriaxone for injection therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.
When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.
No dosage adjustment is necessary for patients with impairment of renal or hepatic function.
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Cefoxitin
The intent of this pharmacy bulk package is for the preparation of solution for intravenous infusion only.
TREATMENT
Adults
The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 1 for dosage guidelines).
If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.
Cefoxitin for injection may be used in patients with reduced renal function with the following dosage adjustments:
In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 2) may be used as a guide.
When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males: Weight (kg) x (140–age) 72 x serum creatinine (mg/100 mL) Females: 0.85 x above valueIn patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 2.
Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.
Pediatric Patients
The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.
At this time no recommendation is made for pediatric patients from birth to three months of age (see PRECAUTIONS).
In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 2).
PREVENTION
Effective prophylactic use depends on the time of administration. Cefoxitin for injection usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.
For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:
Adults:
2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.
Pediatric Patients (3 months and older):
30 to 40 mg/kg doses may be given at the times designated above.
Cesarean section patients:
For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3 dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended. (See CLINICAL STUDIES.)
Table 1 - Guidelines for Dosage of Cefoxitin for InjectionType of Infection
Daily Dosage
Frequency and Route
Uncomplicated forms+ of infections such as pneumonia, urinary tract infection, cutaneous infection
3-4 grams
1 gram every 6-8 hours IV
Moderately severe or severe infections
6-8 grams
1 gram every 4 hoursor2 grams every 6-8 hours IV
Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)
12 grams
2 grams every 4 hoursor3 grams every 6 hours IV
+ Including patients in whom bacteremia is absent or unlikely.
Table 2 - Maintenance Dosage of Cefoxitin for Injection in Adults with Reduced Renal FunctionRenal Function
Creatinine Clearance (mL/min)
Dose (grams)
Frequency
Mild impairment
Moderate impairment
Severe impairment
Essentially no function
50-30
29-10
9-5
<5
1-2
1-2
0.5-1
0.5-1
every 8-12 hours
every 12-24 hours
every 12-24 hours
every 24-48 hours
Table 3 - Preparation of Solution for Intravenous AdministrationStrength
Amount of Diluent to be Added (mL)++
Approximate Withdrawable Volume (mL)
Approximate Average Concentration (mg/mL)
1 gram Vial
2 gram Vial
10 gram Bulk
10
10 or 20
43 or 93
10.5
11.1 or 21
49 or 98.5
95
180 or 95
200 or 100
++ Shake to dissolve and let stand until clear.
PREPARATION OF SOLUTION
Table 3 is provided for convenience in constituting cefoxitin for injection for intravenous administration.
For Pharmacy Bulk Packages
The 10 gram bulk packages should be constituted with 43 or 93 mL of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection. CAUTION: THE 10 GRAM BULK STOCK SOLUTION IS NOT FOR DIRECT INFUSION. These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the Pharmacy Bulk Packages portion of the COMPATIBILITY AND STABILITY section.
Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, in whom use of cefoxitin for injection may be indicated, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluent containing benzyl alcohol should not be used when cefoxitin for injection is constituted for administration to pediatric patients in this age range.
ADMINISTRATION
Cefoxitin for injection may be administered intravenously after constitution.
The intent of this pharmacy bulk package is for the preparation of solution for intravenous infusion only.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.
During infusion of the solution containing cefoxitin, it is advisable to temporarily discontinue administration of any other solutions at the same site.
For the administration of higher doses by continuous intravenous infusion, a solution of cefoxitin may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection. BUTTERFLY®†† or scalp vein-type needles are preferred for this type of infusion.
_________________________________________________________________
†† Registered trademark of Abbott Laboratories, Inc.
Solutions of cefoxitin, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, cefoxitin and aminoglycosides may be administered separately to the same patient.
COMPATIBILITY AND STABILITY
Pharmacy Bulk Package
Cefoxitin for injection, as supplied in the bulk package and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see PREPARATION OF SOLUTION), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, maintains satisfactory potency for 4 hours at room temperature.
These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:
0.9 percent Sodium Chloride Injection 5 percent or 10 percent Dextrose Injection 5 percent Dextrose and 0.9 percent Sodium Chloride Injection 5 percent Dextrose Injection with 0.2 percent or 0.45 percent Sodium Chloride Injection. Lactated Ringer's Injection 5 percent Dextrose in Lactated Ringer's Injection 5 percent Sodium Bicarbonate Injection M/6 sodium lactate solution Mannitol 5% and 10%
After the periods mentioned above, any unused solutions should be discarded.
Directions for Dispensing: Pharmacy Bulk Package-Not for Direct Infusion
The Pharmacy Bulk Package is for use in a pharmacy admixture service only under a laminar flow hood. Entry into the vial must be made only one time with a sterile transfer set or other sterile dispensing device, and the contents dispensed in aliquots using aseptic technique. The use of syringe and needle is not recommended as it may cause leakage (see DOSAGE AND ADMINISTRATION). AFTER INITIAL ENTRY, USE ENTIRE CONTENTS OF VIAL PROMPTLY. ANY UNUSED PORTION MUST BE DISCARDED WITHIN 4 HOURS.
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Ceftriaxone
Ceftriaxone for injection may be administered intravenously or intramuscularly.
Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone¬calcium can also occur when ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone for injection and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see WARNINGS).
There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).
Neonates
Hyperbilirubinemic neonates, especially prematures, should not be treated with ceftriaxone for injection (see CONTRAINDICATIONS).
Ceftriaxone for injection is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone- calcium (see CONTRAINDICATIONS).
Pediatric Patients
For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams.
For the treatment of acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 gram) is recommended (see INDICATIONS AND USAGE).
For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams.
In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.
Adults
The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. For infections caused by Staphylococcus aureus (MSSA), the recommended daily dose is 2 to 4 grams, in order to achieve >90% target attainment. The total daily dose should not exceed 4 grams.
If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism.
For the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended.
For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended.
Generally, ceftriaxone for injection therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.
When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.
No dosage adjustment is necessary for patients with impairment of renal or hepatic function.
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Ceftriaxone
Ceftriaxone for injection may be administered intravenously.
Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone for injection and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see WARNINGS).
There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).
Neonates
Hyperbilirubinemic neonates, especially prematures, should not be treated with ceftriaxone for injection (see CONTRAINDICATIONS).
Ceftriaxone for injection is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone- calcium (see CONTRAINDICATIONS).
Pediatric Patients
For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams.
For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams.
In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.
Adults
The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. For infections caused by Staphylococcus aureus (MSSA), the recommended daily dose is 2 to 4 grams, in order to achieve >90% target attainment. The total daily dose should not exceed 4 grams.
If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism.
For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended.
Generally, ceftriaxone for injection therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.
When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.
No dosage adjustment is necessary for patients with impairment of renal or hepatic function.
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Cefepime
The recommended adult and pediatric dosages and routes of administration are outlined in the following table. Cefepime for injection should be administered intravenously over approximately 30 minutes.
Table 12: Recommended Dosage Schedule for Cefepime for injection in Patients with CrCL Greater Than 60 mL/minSite and Type of Infection
Dose
Frequency
Duration (days)
AdultsModerate to Severe Pneumonia due to S. pneumoniae*, P. aeruginosa, K. pneumoniae, or Enterobacter species
1 to 2 g IV
Every 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 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.
*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.
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 should be adjusted to compensate for the slower rate of renal elimination. The recommended initial dose of cefepime should be the same as in patients with normal renal function except in patients undergoing hemodialysis. The recommended doses of cefepime in patients with renal impairment are presented in Table 13.
When only serum creatinine is available, the following formula (Cockcroft and Gault equation)3 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 x serum creatinine (mg/dL) Females: 0.85 x above value Table 13: Recommended Dosing Schedule for Cefepime for injection in Adult Patients (Normal Renal Function, Renal Impairment, and Hemodialysis)CreatinineClearance(mL/min)
Recommended Maintenance ScheduleGreater 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
*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, cefepime for injection may be administered at normally recommended doses at a dosage interval of every 48 hours (see Table 13).
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 13).
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 12 and 13) 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.
Intramuscular Administration
For intramuscular administration, 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 14).
Preparation of cefepime for injection solutions is summarized in Table 14.
Table 14: Preparation of Solutions of Cefepime for injection Single-Dose Vials for Intravenous/Intramuscular AdministrationAmount of Diluentto be added (mL)
Approximate AvailableVolume (mL)
ApproximateCefepimeConcentration(mg/mL)
cefepime vial content
500 mg (IV)
5
5.6
100
500 mg (IM)
1.3
1.8
280
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, NormosolTM-R, and NormosolTM-M in 5% Dextrose Injection. These solutions may be stored up to 24 hours at controlled room temperature 20° to 25° C (68° to 77° F) or 7 days in a refrigerator 2° to 8° C (36° to 46° F).
Cefepime for injection admixture compatibility information is summarized in Table 15.
Table 15: Cefepime Admixture StabilityCefepimeConcentration
Admixture and Concentration IV Infusion Solutions Stability Time forRT/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
AminosynTM II 4.25% with electrolytes and calcium
8 hours
3 days
0.125 to 0.25 mg/mL
na
InpersolTM 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 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° to 25° C (68° to 77° F) or for 7 days in a refrigerator 2° to 8° C (36° 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 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.
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Cefepime
The recommended adult and pediatric dosages and routes of administration are outlined in the following table. Cefepime for injection should be administered intravenously over approximately 30 minutes.
Table 12: Recommended Dosage Schedule for Cefepime for injection in Patients with CrCL Greater Than 60 mL/minSite and Type of Infection
Dose
Frequency
Duration (days)
AdultsModerate to Severe Pneumonia due to S. pneumoniae*, P. aeruginosa, K. pneumoniae, or Enterobacter species
1 to 2 g IV
Every 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 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.
*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.
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 should be adjusted to compensate for the slower rate of renal elimination. The recommended initial dose of cefepime should be the same as in patients with normal renal function except in patients undergoing hemodialysis. The recommended doses of cefepime in patients with renal impairment are presented in Table 13.
When only serum creatinine is available, the following formula (Cockcroft and Gault equation)3 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 x serum creatinine (mg/dL) Females: 0.85 x above value Table 13: Recommended Dosing Schedule for Cefepime for injection in Adult Patients (Normal Renal Function, Renal Impairment, and Hemodialysis)CreatinineClearance(mL/min)
Recommended Maintenance ScheduleGreater 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
*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, cefepime for injection may be administered at normally recommended doses at a dosage interval of every 48 hours (see Table 13).
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 13).
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 12 and 13) 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 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 14).
Preparation of cefepime for injection solutions is summarized in Table 14.
Table 14: Preparation of Solutions of Cefepime for injection Single-Dose Vials for Intravenous/Intramuscular AdministrationAmount of Diluentto be added (mL)
Approximate AvailableVolume (mL)
ApproximateCefepimeConcentration (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, NormosolTM-R, and NormosolTM-M in 5% Dextrose Injection. These solutions may be stored up to 24 hours at controlled room temperature 20° to 25° C (68° to 77° F) or 7 days in a refrigerator 2° to 8° C (36° to 46° F).
Cefepime for injection admixture compatibility information is summarized in Table 15.
Table 15: Cefepime Admixture StabilityCefepimeConcentration
Admixture andConcentration
IV InfusionSolutions
Stability Time forRT/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
AminosynTM II 4.25% with electrolytes and calcium
8 hours
3 days
0.125 to 0.25 mg/mL
na
InpersolTM 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 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° to 25° C (68° to 77° F) or for 7 days in a refrigerator 2° to 8° C (36° 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 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.
-
Cefoxitin
TREATMENT
Adults
The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 3 for dosage guidelines).
If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.
Cefoxitin for injection may be used in patients with reduced renal function with the following dosage adjustments:
In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 4) may be used as a guide.
When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males: Weight (kg) x (140–age) 72 x serum creatinine (mg/100 mL)
Females: 0.85 x above value
In patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 4.
Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.
Pediatric Patients
The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.
At this time no recommendation is made for pediatric patients from birth to three months of age (see PRECAUTIONS).
In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 4).
PREVENTION
Effective prophylactic use depends on the time of administration. Cefoxitin for injection usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.
For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:
Adults:
2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.
Pediatric Patients (3 months and older):
30 to 40 mg/kg doses may be given at the times designated above.
Cesarean section patients:
For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3 dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended. (See CLINICAL STUDIES.)
Table 3 - Guidelines for Dosage of Cefoxitin for Injection
Type of Infection
Daily Dosage
Frequency and Route
Uncomplicated forms+ of infections such as pneumonia, urinary tract infection, cutaneous infection
3 to 4 grams
1 gram every 6 to 8 hours IV
Moderately severe or severe infections
6 to 8 grams
1 gram every 4 hoursor2 grams every 6 to 8 hours IV
Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)
12 grams
2 grams every 4 hoursor3 grams every 6 hours IV
+ Including patients in whom bacteremia is absent or unlikely.
Table 4 - Maintenance Dosage of Cefoxitin for Injection in Adults with Reduced Renal Function
Renal Function
CreatinineClearance(mL/min)
Dose(grams)
Frequency
Mild impairment Moderate impairment Severe impairment Essentially no function
50 to 30 29 to 10 9 to 5<5
1 to 21 to 20.5 to 10.5 to 1
every 8 to 12 hoursevery 12 to 24 hoursevery 12 to 24 hoursevery 24 to 48 hours
Table 5 - Preparation of Solution for Intravenous Administration
Strength
Amount of Diluent to beAdded (mL)++
ApproximateWithdrawableVolume (mL)
ApproximateAverageConcentration(mg/mL)
1 gram Vial 2 gram Vial 10 gram Bulk
1010 or 20 43 or 93
10.511.1 or 21 49 or 98.5
95180 or 95200 or 100
++ Shake to dissolve and let stand until clear.
PREPARATION OF SOLUTION
Table 5 is provided for convenience in constituting cefoxitin for injection for intravenous administration.
For Vials
One gram should be constituted with at least 10 mL, and 2 grams with 10 or 20 mL, of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection. These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the Vials and Bulk Packages portion of the COMPATIBILITY AND STABILITY section.
Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, in whom use of cefoxitin for injection may be indicated, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluent containing benzyl alcohol should not be used when cefoxitin for injection is constituted for administration to pediatric patients in this age range.
ADMINISTRATION
Cefoxitin for injection may be administered intravenously after constitution.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.
For intermittent intravenous administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Using an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. However, during infusion of the solution containing cefoxitin, it is advisable to temporarily discontinue administration of any other solutions at the same site.
For the administration of higher doses by continuous intravenous infusion, a solution of cefoxitin may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection. BUTTERFLY®†† or scalp vein-type needles are preferred for this type of infusion.
Solutions of cefoxitin, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, cefoxitin and aminoglycosides may be administered separately to the same patient.
COMPATIBILITY AND STABILITY
Vials
Cefoxitin for injection, as supplied in vials and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see PREPARATION OF SOLUTION), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, maintains satisfactory potency for 6 hours at room temperature or for one week under refrigeration (below 5°C).
These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:
0.9 percent Sodium Chloride Injection5 percent or 10 percent Dextrose Injection5 percent Dextrose and 0.9 percent Sodium Chloride Injection5 percent Dextrose Injection with 0.2 percent or 0.45 percent Sodium Chloride Injection.
________________________________________________________†† Registered trademark of Abbott Laboratories, Inc.
Lactated Ringer's Injection5 percent Dextrose in Lactated Ringer's Injection5 percent Sodium Bicarbonate InjectionM/6 sodium lactate solutionMannitol 5% and 10%
After the periods mentioned above, any unused solutions should be discarded.
TREATMENT
Adults
The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 3 for dosage guidelines).
If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.
Cefoxitin for injection may be used in patients with reduced renal function with the following dosage adjustments:
In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 4) may be used as a guide.
When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males: Weight (kg) x (140–age) 72 x serum creatinine (mg/100 mL)
Females: 0.85 x above value
In patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 4.
Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.
Pediatric Patients
The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.
At this time no recommendation is made for pediatric patients from birth to three months of age (see PRECAUTIONS).
In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 4).
PREVENTION
Effective prophylactic use depends on the time of administration. Cefoxitin for injection usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.
For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:
Adults:
2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.
Pediatric Patients (3 months and older):
30 to 40 mg/kg doses may be given at the times designated above.
Cesarean section patients:
For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3 dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended. (See CLINICAL STUDIES.)
Table 3 - Guidelines for Dosage of Cefoxitin for Injection
Type of Infection
Daily Dosage
Frequency and Route
Uncomplicated forms+ of infections such as pneumonia, urinary tract infection, cutaneous infection
3 to 4 grams
1 gram every 6 to 8 hours IV
Moderately severe or severe infections
6 to 8 grams
1 gram every 4 hoursor2 grams every 6 to 8 hours IV
Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)
12 grams
2 grams every 4 hoursor3 grams every 6 hours IV
+ Including patients in whom bacteremia is absent or unlikely.
Table 4 - Maintenance Dosage of Cefoxitin for Injection in Adults with Reduced Renal Function
Renal Function
CreatinineClearance(mL/min)
Dose(grams)
Frequency
Mild impairment Moderate impairment Severe impairment Essentially no function
50 to 30 29 to 10 9 to 5<5
1 to 21 to 20.5 to 10.5 to 1
every 8 to 12 hoursevery 12 to 24 hoursevery 12 to 24 hoursevery 24 to 48 hours
Table 5 - Preparation of Solution for Intravenous Administration
Strength
Amount of Diluent to beAdded (mL)++
ApproximateWithdrawableVolume (mL)
ApproximateAverageConcentration(mg/mL)
1 gram Vial 2 gram Vial 10 gram Bulk
1010 or 20 43 or 93
10.511.1 or 21 49 or 98.5
95180 or 95200 or 100
++ Shake to dissolve and let stand until clear.
PREPARATION OF SOLUTION
Table 5 is provided for convenience in constituting cefoxitin for injection for intravenous administration.
For Vials
One gram should be constituted with at least 10 mL, and 2 grams with 10 or 20 mL, of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection. These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the Vials and Bulk Packages portion of the COMPATIBILITY AND STABILITY section.
Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, in whom use of cefoxitin for injection may be indicated, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluent containing benzyl alcohol should not be used when cefoxitin for injection is constituted for administration to pediatric patients in this age range.
ADMINISTRATION
Cefoxitin for injection may be administered intravenously after constitution.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.
For intermittent intravenous administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Using an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. However, during infusion of the solution containing cefoxitin, it is advisable to temporarily discontinue administration of any other solutions at the same site.
For the administration of higher doses by continuous intravenous infusion, a solution of cefoxitin may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection. BUTTERFLY®†† or scalp vein-type needles are preferred for this type of infusion.
Solutions of cefoxitin, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, cefoxitin and aminoglycosides may be administered separately to the same patient.
COMPATIBILITY AND STABILITY
Vials
Cefoxitin for injection, as supplied in vials and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see PREPARATION OF SOLUTION), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, maintains satisfactory potency for 6 hours at room temperature or for one week under refrigeration (below 5°C).
These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:
0.9 percent Sodium Chloride Injection5 percent or 10 percent Dextrose Injection5 percent Dextrose and 0.9 percent Sodium Chloride Injection5 percent Dextrose Injection with 0.2 percent or 0.45 percent Sodium Chloride Injection.
________________________________________________________†† Registered trademark of Abbott Laboratories, Inc.
Lactated Ringer's Injection5 percent Dextrose in Lactated Ringer's Injection5 percent Sodium Bicarbonate InjectionM/6 sodium lactate solutionMannitol 5% and 10%
After the periods mentioned above, any unused solutions should be discarded.
-
Cefoxitin
TREATMENT
Adults
The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 3 for dosage guidelines).
If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.
Cefoxitin for injection may be used in patients with reduced renal function with the following dosage adjustments:
In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 4) may be used as a guide.
When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males: Weight (kg) x (140–age) 72 x serum creatinine (mg/100 mL)
Females: 0.85 x above value
In patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 4.
Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.
Pediatric Patients
The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.
At this time no recommendation is made for pediatric patients from birth to three months of age (see PRECAUTIONS).
In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 4).
PREVENTION
Effective prophylactic use depends on the time of administration. Cefoxitin for injection usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.
For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:
Adults:
2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.
Pediatric Patients (3 months and older):
30 to 40 mg/kg doses may be given at the times designated above.
Cesarean section patients:
For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3 dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended. (See CLINICAL STUDIES.)
Table 3 - Guidelines for Dosage of Cefoxitin for Injection
Type of Infection
Daily Dosage
Frequency and Route
Uncomplicated forms+ of infections such as pneumonia, urinary tract infection, cutaneous infection
3 to 4 grams
1 gram every 6 to 8 hours IV
Moderately severe or severe infections
6 to 8 grams
1 gram every 4 hoursor2 grams every 6 to 8 hours IV
Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)
12 grams
2 grams every 4 hoursor3 grams every 6 hours IV
+ Including patients in whom bacteremia is absent or unlikely.
Table 4 - Maintenance Dosage of Cefoxitin for Injection in Adults with Reduced Renal Function
Renal Function
CreatinineClearance(mL/min)
Dose(grams)
Frequency
Mild impairment Moderate impairment Severe impairment Essentially no function
50 to 30 29 to 10 9 to 5<5
1 to 21 to 20.5 to 10.5 to 1
every 8 to 12 hoursevery 12 to 24 hoursevery 12 to 24 hoursevery 24 to 48 hours
Table 5 - Preparation of Solution for Intravenous Administration
Strength
Amount of Diluent to beAdded (mL)++
ApproximateWithdrawableVolume (mL)
ApproximateAverageConcentration(mg/mL)
1 gram Vial 2 gram Vial 10 gram Bulk
1010 or 20 43 or 93
10.511.1 or 21 49 or 98.5
95180 or 95200 or 100
++ Shake to dissolve and let stand until clear.
PREPARATION OF SOLUTION
Table 5 is provided for convenience in constituting cefoxitin for injection for intravenous administration.
For Vials
One gram should be constituted with at least 10 mL, and 2 grams with 10 or 20 mL, of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection. These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the Vials and Bulk Packages portion of the COMPATIBILITY AND STABILITY section.
Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, in whom use of cefoxitin for injection may be indicated, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluent containing benzyl alcohol should not be used when cefoxitin for injection is constituted for administration to pediatric patients in this age range.
ADMINISTRATION
Cefoxitin for injection may be administered intravenously after constitution.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.
For intermittent intravenous administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Using an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. However, during infusion of the solution containing cefoxitin, it is advisable to temporarily discontinue administration of any other solutions at the same site.
For the administration of higher doses by continuous intravenous infusion, a solution of cefoxitin may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection. BUTTERFLY®†† or scalp vein-type needles are preferred for this type of infusion.
Solutions of cefoxitin, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, cefoxitin and aminoglycosides may be administered separately to the same patient.
COMPATIBILITY AND STABILITY
Vials
Cefoxitin for injection, as supplied in vials and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see PREPARATION OF SOLUTION), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, maintains satisfactory potency for 6 hours at room temperature or for one week under refrigeration (below 5°C).
These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:
0.9 percent Sodium Chloride Injection5 percent or 10 percent Dextrose Injection5 percent Dextrose and 0.9 percent Sodium Chloride Injection5 percent Dextrose Injection with 0.2 percent or 0.45 percent Sodium Chloride Injection.
________________________________________________________†† Registered trademark of Abbott Laboratories, Inc.
Lactated Ringer's Injection5 percent Dextrose in Lactated Ringer's Injection5 percent Sodium Bicarbonate InjectionM/6 sodium lactate solutionMannitol 5% and 10%
After the periods mentioned above, any unused solutions should be discarded.
TREATMENT
Adults
The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 3 for dosage guidelines).
If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.
Cefoxitin for injection may be used in patients with reduced renal function with the following dosage adjustments:
In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 4) may be used as a guide.
When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males: Weight (kg) x (140–age) 72 x serum creatinine (mg/100 mL)
Females: 0.85 x above value
In patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 4.
Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.
Pediatric Patients
The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.
At this time no recommendation is made for pediatric patients from birth to three months of age (see PRECAUTIONS).
In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 4).
PREVENTION
Effective prophylactic use depends on the time of administration. Cefoxitin for injection usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.
For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:
Adults:
2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.
Pediatric Patients (3 months and older):
30 to 40 mg/kg doses may be given at the times designated above.
Cesarean section patients:
For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3 dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended. (See CLINICAL STUDIES.)
Table 3 - Guidelines for Dosage of Cefoxitin for Injection
Type of Infection
Daily Dosage
Frequency and Route
Uncomplicated forms+ of infections such as pneumonia, urinary tract infection, cutaneous infection
3 to 4 grams
1 gram every 6 to 8 hours IV
Moderately severe or severe infections
6 to 8 grams
1 gram every 4 hoursor2 grams every 6 to 8 hours IV
Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)
12 grams
2 grams every 4 hoursor3 grams every 6 hours IV
+ Including patients in whom bacteremia is absent or unlikely.
Table 4 - Maintenance Dosage of Cefoxitin for Injection in Adults with Reduced Renal Function
Renal Function
CreatinineClearance(mL/min)
Dose(grams)
Frequency
Mild impairment Moderate impairment Severe impairment Essentially no function
50 to 30 29 to 10 9 to 5<5
1 to 21 to 20.5 to 10.5 to 1
every 8 to 12 hoursevery 12 to 24 hoursevery 12 to 24 hoursevery 24 to 48 hours
Table 5 - Preparation of Solution for Intravenous Administration
Strength
Amount of Diluent to beAdded (mL)++
ApproximateWithdrawableVolume (mL)
ApproximateAverageConcentration(mg/mL)
1 gram Vial 2 gram Vial 10 gram Bulk
1010 or 20 43 or 93
10.511.1 or 21 49 or 98.5
95180 or 95200 or 100
++ Shake to dissolve and let stand until clear.
PREPARATION OF SOLUTION
Table 5 is provided for convenience in constituting cefoxitin for injection for intravenous administration.
For Vials
One gram should be constituted with at least 10 mL, and 2 grams with 10 or 20 mL, of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection. These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the Vials and Bulk Packages portion of the COMPATIBILITY AND STABILITY section.
Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, in whom use of cefoxitin for injection may be indicated, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluent containing benzyl alcohol should not be used when cefoxitin for injection is constituted for administration to pediatric patients in this age range.
ADMINISTRATION
Cefoxitin for injection may be administered intravenously after constitution.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.
For intermittent intravenous administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Using an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. However, during infusion of the solution containing cefoxitin, it is advisable to temporarily discontinue administration of any other solutions at the same site.
For the administration of higher doses by continuous intravenous infusion, a solution of cefoxitin may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection. BUTTERFLY®†† or scalp vein-type needles are preferred for this type of infusion.
Solutions of cefoxitin, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, cefoxitin and aminoglycosides may be administered separately to the same patient.
COMPATIBILITY AND STABILITY
Vials
Cefoxitin for injection, as supplied in vials and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see PREPARATION OF SOLUTION), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, maintains satisfactory potency for 6 hours at room temperature or for one week under refrigeration (below 5°C).
These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:
0.9 percent Sodium Chloride Injection5 percent or 10 percent Dextrose Injection5 percent Dextrose and 0.9 percent Sodium Chloride Injection5 percent Dextrose Injection with 0.2 percent or 0.45 percent Sodium Chloride Injection.
________________________________________________________†† Registered trademark of Abbott Laboratories, Inc.
Lactated Ringer's Injection5 percent Dextrose in Lactated Ringer's Injection5 percent Sodium Bicarbonate InjectionM/6 sodium lactate solutionMannitol 5% and 10%
After the periods mentioned above, any unused solutions should be discarded.
-
Piperacillin And Tazobactam
Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.
2.1 Adult Patients
The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.
Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.
2.2 Nosocomial Pneumonia
Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18 g (16 g piperacillin/2 g tazobactam). The recommended duration of piperacillin and tazobactam for injection treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.
2.3 Renal Impairment
In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:
Table 1: Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam) * Creatinine clearance for patients not receiving hemodialysis ** 0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis daysRenal Function(creatinine clearance,
All Indications (except nosocomial
Nosocomial
mL/min)
pneumonia)
Pneumonia
>40 mL/min
3.375 q 6 h
4.5 q 6 h
20 to 40 mL/min*
2.25 q 6 h
3.375 q 6 h
<20 mL/min*
2.25 q 8 h
2.25 q 6 h
Hemodialysis**
2.25 q 12 h
2.25 q 8 h
CAPD
2.25 q 12 h
2.25 q 8 h
For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.
2.4 Pediatric Patients
For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.
2.5 Reconstitution and Dilution of Powder Formulations
Pharmacy bulk vials
Reconstituted stock solution must be transferred and further diluted for intravenous infusion.
The pharmacy bulk vial is for use in a hospital pharmacy admixture service only under a laminar flow hood. After reconstitution, entry into the vial must be made with a sterile transfer set or other sterile dispensing device, and contents should be dispensed as aliquots into intravenous solution using aseptic technique. Use entire contents of pharmacy bulk vial promptly. Discard unused portion after 4 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]).
Reconstitute the pharmacy bulk vial with exactly 152 mL of a compatible reconstitution diluent, listed below, to a concentration of 200 mg/mL of piperacillin and 25 mg/mL of tazobactam. Shake well until dissolved. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.
Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.
Compatible Reconstitution Diluents for Pharmacy Vials
0.9% sodium chloride for injectionSterile water for injectionDextrose 5%Bacteriostatic saline/parabensBacteriostatic water/parabensBacteriostatic saline/benzyl alcoholBacteriostatic water/benzyl alcohol
Reconstituted piperacillin and tazobactam for injection solution for bulk vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.
Compatible Intravenous Solutions for Pharmacy Vials
0.9% sodium chloride for injectionsterile water for injection‡ Dextran 6% in saline Dextrose 5%Lactated Ringer’s Solution is not compatible with piperacillin and tazobactam for injection
‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.
Piperacillin and Tazobactam for Injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.
Piperacillin and Tazobactam for Injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.
Piperacillin and Tazobactam for Injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.
Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution
Piperacillin and Tazobactam for Injection reconstituted from bulk vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents. The pharmacy bulk vial should NOT be frozen after reconstitution. Discard unused portions after storage for 4 hours at room temperature.
Pharmacy vials should be used immediately after reconstitution. Discard any unused portion after 4 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]). Vials should not be frozen after reconstitution.
Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and Tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.
Piperacillin and Tazobactam for Injection reconstituted from bulk vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer’s instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.
2.7 Compatibility with Aminoglycosides
Due to the in vitro inactivation of aminoglycosides by piperacillin, piperacillin and tazobactam for injection and aminoglycosides are recommended for separate administration. Piperacillin and Tazobactam for injection and aminoglycosides should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated [see Drug Interactions (7.1)].
In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam for injection is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:
Table 2: Compatibility with Aminoglycosides a Diluent volumes apply only to bulk pharmacy containersb The concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10 to15 mg/kg/day in two daily doses for amikacin and 3 to 5 mg/kg/day in three daily doses for gentamicin). Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam for injection has not been evaluated. See package insert for each aminoglycoside for complete Dosage and Administration instructions.Aminoglycoside
Piperacillin and Tazobactam for Injection Dose (grams)
Piperacillin and Tazobactam for Injection Diluent Volumea(mL)
Aminoglycoside Concentration Rangeb (mg/mL)
AcceptableDiluents
Amikacin
2.25, 3.375, 4.5
50, 100, 150
1.75 to 7.5
0.9% sodium chloride or 5% dextrose
Gentamicin
2.253.3754.5
100 150
0.7 to 3.32
0.9% sodium chloride
Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.
Piperacillin and Tazobactam for Injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
-
Piperacillin And Tazobactam
Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.
2.1 Adult Patients
The usual total daily dose of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/1.5 g tazobactam). The usual duration of piperacillin and tazobactam for injection treatment is from 7 to 10 days.
Piperacillin and Tazobactam for Injection should be administered by intravenous infusion over 30 minutes.
2.2 Nosocomial Pneumonia
Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18 g (16 g piperacillin/2 g tazobactam). The recommended duration of piperacillin and tazobactam for injection treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.
2.3 Renal Impairment
In patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced to the degree of actual renal function impairment. The recommended daily doses of piperacillin and tazobactam for injection for patients with renal impairment are as follows:
Table 1: Recommended Dosing of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam) * Creatinine clearance for patients not receiving hemodialysis ** 0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis daysRenal Function(creatinine clearance,mL/min)
All Indications (except nosocomialpneumonia)
NosocomialPneumonia
>40 mL/min
3.375 q 6 h
4.5 q 6 h
20 to 40 mL/min*
2.25 q 6 h
3.375 q 6 h
<20 mL/min*
2.25 q 8 h
2.25 q 6 h
Hemodialysis**
2.25 q 12 h
2.25 q 8 h
CAPD
2.25 q 12 h
2.25 q 8 h
For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam for injection is necessary for CAPD patients.
2.4 Pediatric Patients
For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam for injection dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended piperacillin and tazobactam for injection dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)]. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. It has not been determined how to adjust piperacillin and tazobactam for injection dosage in pediatric patients with renal impairment.
2.5 Reconstitution and Dilution of Powder Formulations
Single dose vials
Reconstitute piperacillin and tazobactam for injection vials with a compatible reconstitution diluent from the list provided below.
2.25 g, 3.375 g, and 4.5 g piperacillin and tazobactam for injection should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.
Compatible Reconstitution Diluents for Single Dose Vials
0.9% sodium chloride for injectionSterile water for injectionDextrose 5%Bacteriostatic saline/parabensBacteriostatic water/parabensBacteriostatic saline/benzyl alcoholBacteriostatic water/benzyl alcohol
Reconstituted piperacillin and tazobactam for injection solution for single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.
Compatible Intravenous Solutions for Single Dose Vials
0.9% sodium chloride for injectionsterile water for injection‡ Dextran 6% in saline Dextrose 5%Lactated Ringer’s Solution is not compatible with piperacillin and tazobactam for injection
‡ Maximum recommended volume per dose of sterile water for injection is 50 mL.
Piperacillin and Tazobactam for Injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.
Piperacillin and Tazobactam for Injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.
Piperacillin and Tazobactam for Injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.
Stability of Piperacillin and Tazobactam for Injection Powder Formulations Following Reconstitution
Piperacillin and Tazobactam for Injection reconstituted from single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents. Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).
Single dose vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.
Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and Tazobactam for injection contains no preservatives. Appropriate consideration of aseptic technique should be used.
Piperacillin and Tazobactam for Injection reconstituted from single vials can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer’s instructions. Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump.
2.7 Compatibility with Aminoglycosides
Due to the in vitro inactivation of aminoglycosides by piperacillin, piperacillin and tazobactam for injection and aminoglycosides are recommended for separate administration. Piperacillin and Tazobactam for injection and aminoglycosides should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated [see Drug Interactions (7.1)].
In circumstances where co-administration via Y-site is necessary, piperacillin and tazobactam for injection is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:
Table 2: Compatibility with Aminoglycosides a Diluent volumes apply only to single vialsb The concentration ranges in Table 2 are based on administration of the aminoglycoside in divided doses (10 to15 mg/kg/day in two daily doses for amikacin and 3 to 5 mg/kg/day in three daily doses for gentamicin). Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam for injection has not been evaluated. See package insert for each aminoglycoside for complete Dosage and Administration instructions.Aminoglycoside
Piperacillin and Tazobactam for Injection Dose (grams)
Piperacillin and Tazobactam for Injection Diluent Volumea(mL)
Aminoglycoside Concentration Rangeb (mg/mL)
Acceptable Diluents
Amikacin
2.25, 3.375, 4.5
50, 100, 150
1.75 to 7.5
0.9% sodium chloride or 5% dextrose
Gentamicin
2.253.3754.5
100 150
0.7 to 3.32
0.9% sodium chloride
Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.
Piperacillin and Tazobactam for Injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
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