A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Mefoxin Indications, Dosage, Storage, Stability - Cefoxitin
Mefoxin Indications, Dosage, Storage, Stability - Cefoxitin
INDICATIONS AND USAGE
Treatment
MEFOXIN is indicated for the treatment of serious infections
caused by susceptible strains of the designated microorganisms in the diseases
listed below.
(1) Lower respiratory tract infections, including pneumonia
and lung abscess, caused by Streptococcus pneumoniae, other streptococci
(excluding enterococci, e.g., Enterococcus faecalis [formerly Streptococcus
faecalis]), Staphylococcus aureus (including penicillinase-producing
strains), Escherichia coli, Klebsiella species, Haemophilus influenzae,
and Bacteroides species.
(2) Urinary tract infections caused by Escherichia
coli, Klebsiella species, Proteus mirabilis, Morganella morganii, Proteus
vulgaris and Providencia species (including P. rettgeri).
(3) Intra-abdominal infections, including peritonitis
and intra-abdominal abscess, caused by Escherichia coli, Klebsiella species,
Bacteroides species including Bacteroides fragilis, and Clostridium
species.
(4) Gynecological infections, including endometritis,
pelvic cellulitis, and pelvic inflammatory disease caused by Escherichia
coli, Neisseria gonorrhoeae (including penicillinase-producing strains),
Bacteroides species including B. fragilis, Clostridium
species, Peptococcus niger, Peptostreptococcus species,
and Streptococcus agalactiae. MEFOXIN, like cephalosporins, has no activity
against Chlamydia trachomatis. Therefore, when MEFOXIN is used in the
treatment of patients with pelvic inflammatory disease and C. trachomatis
is one of the suspected pathogens, appropriate anti-chlamydial coverage should
be added.
(5) Septicemia caused by Streptococcus pneumoniae,
Staphylococcus aureus (including penicillinase-producing strains), Escherichia
coli, Klebsiella species, and Bacteroides species including B.
fragilis.
(6) Bone and joint infections caused by Staphylococcus
aureus (including penicillinase-producing strains).
(7) Skin and skin structure infections caused by Staphylococcus
aureus (including penicillinase-producing strains), Staphylococcus epidermidis,
Streptococcus pyogenes and other streptococci (excluding enterococci
e.g., Enterococcus faecalis [formerly Streptococcus faecalis]),
Escherichia coli, Proteus mirabilis, Klebsiella species, Bacteroides
species including B. fragilis, Clostridium species, Peptococcus
niger, and Peptostreptococcus species.
Appropriate culture and susceptibility studies should be performed
to determine the susceptibility of the causative organisms to MEFOXIN. Therapy
may be started while awaiting the results of these studies.
In randomized comparative studies, MEFOXIN and cephalothin
were comparably safe and effective in the management of infections caused by
gram-positive cocci and gram-negative rods susceptible to the cephalosporins.
MEFOXIN has a high degree of stability in the presence of bacterial beta-lactamases,
both penicillinases and cephalosporinases.
Many infections caused by aerobic and anaerobic gram-negative
bacteria resistant to some cephalosporins respond to MEFOXIN. Similarly, many
infections caused by aerobic and anaerobic bacteria resistant to some penicillin
antibiotics (ampicillin, carbenicillin, penicillin G) respond to treatment with
MEFOXIN. Many infections caused by mixtures of susceptible aerobic and anaerobic
bacteria respond to treatment with MEFOXIN.
Prevention
MEFOXIN is indicated for the prophylaxis of infection in patients
undergoing uncontaminated gastrointestinal surgery, vaginal hysterectomy, abdominal
hysterectomy, or cesarean section.
If there are signs of infection, specimens for culture should
be obtained for identification of the causative organism so that appropriate
treatment may be instituted.
To reduce the development of drug-resistant bacteria and maintain
the effectiveness of MEFOXIN and other antibacterial drugs, MEFOXIN should be
used only to treat or prevent infections that are proven or strongly suspected
to be caused by susceptible bacteria. When culture and susceptibility information
are available, they should be considered in selecting or modifying antibacterial
therapy. In the absence of such data, local epidemiology and susceptibility
patterns may contribute to the empiric selection of therapy.
DOSAGE AND ADMINISTRATION
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.
MEFOXIN 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 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 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.
MEFOXIN 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 MEFOXIN
|
|
Type 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
|
6-8 grams
|
1 gram every 4 hours
|
|
infections
|
|
or
|
| |
|
2 grams every 6-8 hours IV
|
|
Infections commonly needing
|
12 grams
|
2 grams every 4 hours
|
|
antibiotics in higher dosage
|
|
or
|
|
(e.g., gas gangrene)
|
|
3 grams every 6 hours IV
|
|
+ Including patients in whom bacteremia is absent or
unlikely.
|
|
Table 2 - Maintenance Dosage of MEFOXIN in Adults with
Reduced Renal Function
|
|
Renal Function
|
Creatinine Clearance (mL/min)
|
Dose (grams)
|
Frequency
|
|
Mild impairment
|
50-30
|
1-2
|
every 8-12 hours
|
|
Moderate impairment
|
29-10
|
1-2
|
every 12-24 hours
|
|
Severe impairment
|
9-5
|
0.5-1
|
every 12-24 hours
|
|
Essentially no function
|
<5
|
0.5-1
|
every 24-48 hours
|
|
Table 3 - Preparation of Solution for Intravenous Administration
|
|
|
Amount of Diluent to be Added (mL)++
|
Approximate Withdrawable
|
Approximate Average Concentration
|
|
Strength
|
|
Volume (mL)
|
(mg/mL)
|
|
1 gram Vial
|
10
|
10.5
|
95
|
|
2 gram Vial
|
10 or 20
|
11.1 or 21.0
|
180 or 95
|
|
1 gram Infusion Bottle
|
50 or 100
|
50 or 100
|
20 or 10
|
|
2 gram Infusion Bottle
|
50 or 100
|
50 or 100
|
40 or 20
|
|
10 gram Bulk
|
43 or 93
|
49 or 98.5
|
200 or 100
|
|
++ Shake to dissolve and let stand until clear.
|
PREPARATION OF SOLUTION
Table 3 is provided for convenience in constituting MEFOXIN
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.
For 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 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 MEFOXIN 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
MEFOXIN is constituted for administration to pediatric patients in this age
range.
For Infusion Bottles
One or 2 grams of MEFOXIN for infusion may be constituted with
50 or 100 mL of 0.9 percent Sodium Chloride Injection, or 5 percent or 10 percent
Dextrose Injection.
For ADD-Vantage®†† Vials
See separate INSTRUCTIONS FOR USE OF MEFOXIN IN ADD-Vantage®
VIALS. MEFOXIN in ADD-Vantage® vials should be constituted with
ADD-Vantage® diluent containers containing 50 mL or 100 mL of
either 0.9 percent Sodium Chloride Injection or 5 percent Dextrose Injection.
MEFOXIN in ADD-Vantage® vials is for IV use only.
ADMINISTRATION
MEFOXIN 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 MEFOXIN, 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 MEFOXIN 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 MEFOXIN, 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, MEFOXIN
and aminoglycosides may be administered separately to the same patient.
COMPATIBILITY AND STABILITY
Vials and Bulk Packages
MEFOXIN, as supplied in vials or 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 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 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
saline solution
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%
Infusion Bottles
MEFOXIN, as supplied in infusion bottles and constituted with
50 to 100 mL of 0.9 percent Sodium Chloride Injection, or 5 percent or 10 percent
Dextrose Injection, maintains satisfactory potency for 24 hours at room temperature
or for 1 week under refrigeration (below 5°C).
ADD-Vantage® Vials
MEFOXIN is supplied in single dose ADD-Vantage®
vials and should be prepared as directed in the accompanying INSTRUCTIONS FOR
USE OF MEFOXIN IN ADD-Vantage® VIALS using ADD-Vantage®
diluent containers containing 50 mL or 100 mL of either 0.9 percent Sodium Chloride
Injection or 5 percent Dextrose Injection. When prepared with either of these
diluents, MEFOXIN maintains satisfactory potency for 24 hours at room temperature.
After the periods mentioned above, any unused solutions should
be discarded.
HOW SUPPLIED
Sterile MEFOXIN is a dry white to off-white powder supplied
in vials and infusion bottles containing cefoxitin sodium as follows: No. 3356
— 1 gram cefoxitin equivalent NDC 0006-3356-45 in trays of 25 vials.
No. 3357 — 2 gram cefoxitin equivalent
NDC 0006-3357-53 in trays of 25 vials.
No. 3388 — 10 gram cefoxitin equivalent
NDC 0006-3388-67 in trays of 6 bulk bottles.
No. 3548 — 1 gram cefoxitin equivalent
NDC 0006-3548-45 in trays of 25 ADD-Vantage®
vials.
No. 3549 — 2 gram cefoxitin equivalent
NDC 0006-3549-53 in trays of 25 ADD-Vantage®
vials.
Special storage instructions
MEFOXIN in the dry state should be stored between 2-25°C (36-77°F).
Avoid exposure to temperatures above 50°C. The dry material as well as solutions
tend to darken, depending on storage conditions; product potency, however, is
not adversely affected.
CLINICAL STUDIES
A prospective, randomized, double-blind, placebo-controlled
clinical trial was conducted to determine the efficacy of short-term prophylaxis
with MEFOXIN in patients undergoing cesarean section who were at high risk for
subsequent endometritis because of ruptured membranes. Patients were randomized
to receive either three doses of placebo (n=58), a single dose of MEFOXIN (2
g) followed by two doses of placebo (n=64), or a three-dose regimen of MEFOXIN
(each dose consisting of 2 g) (n=60), given intravenously, usually beginning
at the time of clamping of the umbilical cord, with the second and third doses
given 4 and 8 hours post-operatively. Endometritis occurred in 16/58 (27.6%)
patients given placebo, 5/63 (7.9%) patients given a single dose of MEFOXIN,
and 3/58 (5.2%) patients given three doses of MEFOXIN. The differences between
the two groups treated with MEFOXIN and placebo with respect to endometritis
were statistically significant (p<0.01) in favor of MEFOXIN. The differences
between the one-dose and three-dose regimens of MEFOXIN were not statistically
significant.
Two double-blind, randomized studies compared the efficacy
of a single 2 gram intravenous dose of MEFOXIN to a single 2 gram intravenous
dose of cefotetan in the prevention of surgical site-related infection (major
morbidity) and non-site-related infections (minor morbidity) in patients following
cesarean section. In the first study, 82/98 (83.7%) patients treated with MEFOXIN
and 71/95 (74.7%) patients treated with cefotetan experienced no major or minor
morbidity. The difference in the outcomes in this study (95% CI: –0.03, +0.21)
was not statistically significant. In the second study, 65/75 (86.7%) patients
treated with MEFOXIN and 62/76 (81.6%) patients treated with cefotetan experienced
no major or minor morbidity. The difference in the outcomes in this study (95%
CI: –0.08, +0.18) was not statistically significant.
In clinical trials of patients with intra-abdominal infections
due to Bacteroides fragilis group microorganisms, eradication rates at
1 to 2 weeks posttreatment for isolates were in the range of 70% to 80%. Eradication
rates for individual species are listed below:
|
Bacteroides distasonis
|
7/10
|
(70%)
|
|
Bacteroides fragilis
|
26/33
|
(79%)
|
|
Bacteroides ovatus
|
10/13
|
(77%)
|
|
B. thetaiotaomicron
|
13/18
|
(72%)
|
REFERENCES
1. National Committee for Clinical Laboratory Standards.
Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow
Aerobically - Fourth Edition. Approved Standard NCCLS Document M7-A4, Vol. 17,
No. 2, NCCLS, Wayne, PA, January 1997.
2. National Committee for Clinical Laboratory Standards.
Performance Standards for Antimicrobial Disk Susceptibility Tests - Sixth Edition.
Approved Standard NCCLS Document M2-A6, Vol. 17, No. 1, NCCLS, Wayne, PA, January
1997.
3. National Committee for Clinical Laboratory Standards.
Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria - Fourth
Edition. Approved Standard NCCLS Document M11-A4, Vol. 17, No. 22, NCCLS, Villanova,
PA, December 1997.
_____________________________________
† Registered trademark of Ames Company,
Division of Miles Laboratories, Inc.
†† Registered trademark of Abbott Laboratories,
Inc.
* Registered trademark of MERCK & CO., Inc., COPYRIGHT
© MERCK & CO., Inc., 1985, 1996, 2000 All rights reserved
Issued August 2003 Printed in USA
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