DRUGS INDEX | MANUFACTURERS INDEX | ANATOMY | GEOGRAPHY | USA STATISTICS | CHINA STATISTICS | RELIGION | JOBS |
![]() |
||
Mefoxin for Injection (Merck) | ||
- Drugs index - Manufacturers - Feedback ![]() |
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 bacteria. DESCRIPTIONMEFOXIN * (Cefoxitin for Injection) is a semi-synthetic, broad-spectrum cepha antibiotic sealed under nitrogen for intravenous administration. It is derived from cephamycin C, which is produced by Streptomyces lactamdurans. Its chemical name is sodium (6 R , 7 S )-3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate carbamate (ester). The empirical formula is C 16 H 16 N 3 NaO 7 S 2 , and the structural formula is:
MEFOXIN contains approximately 53.8 mg (2.3 milliequivalents) of sodium per gram of cefoxitin activity. Solutions of MEFOXIN range from colorless to light amber in color. The pH of freshly constituted solutions usually ranges from 4.2 to 7.0. *Registered trademark of Merck & CO., Inc.
CLINICAL PHARMACOLOGYClinical Pharmacology Following an intravenous dose of 1 gram, serum concentrations were 110 mcg/mL at 5 minutes, declining to less than 1 mcg/mL at 4 hours. The half-life after an intravenous dose is 41 to 59 minutes. Approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6-hour period, resulting in high urinary concentrations. Probenecid slows tubular excretion and produces higher serum levels and increases the duration of measurable serum concentrations. Cefoxitin passes into pleural and joint fluids and is detectable in antibacterial concentrations in bile. In a published study of geriatric patients ranging in age from 64 to 88 years with normal renal function for their age (creatinine clearance ranging from 31.5 to 174.0 mL/min), the half-life for cefoxitin ranged from 51 to 90 minutes, resulting in higher plasma concentrations than in younger adults. These changes were attributed to decreased renal function associated with the aging process. Microbiology The bactericidal action of cefoxitin results from inhibition of cell wall synthesis. Cefoxitin has in vitro activity against a wide range of gram-positive and gram-negative organisms. The methoxy group in the 7(alpha) position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria. Cefoxitin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Aerobic gram-positive microorganisms Staphylococcus aureus a (including penicillinase-producing strains) Staphylococcus epidermidis a Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes a Staphylococci resistant to methicillin/oxacillin should be considered resistant to cefoxitin. Most strains of enterococci, e.g., Enterococcus faecalis , are resistant. Aerobic gram-negative microorganisms Escherichia coli Haemophilus influenzae Klebsiella spp. (including K. pneumoniae ) Morganella morganii Neisseria gonorrhoeae (including penicillinase-producing strains) Proteus mirabilis Proteus vulgaris Providencia spp. (including Providencia rettgeri ) Anaerobic gram-positive microorganisms Clostridium spp. Peptococcus niger Peptostreptococcus spp. Anaerobic gram-negative microorganisms Bacteroides distasonis Bacteroides fragilis Bacteroides ovatus Bacteroides thetaiotaomicron Bacteroides spp. The following in vitro data are available, but their clinical significance is unknown . Cefoxitin exhibits in vitro minimum inhibitory concentrations (MIC's) of 8 µg/mL or less for aerobic microorganisms and 16 µg/mL or less for anaerobic microorganisms against most (>/=90%) strains of the following microorganisms; however, the safety and effectiveness of cefoxitin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials. Aerobic gram-negative microorganisms Eikenella corrodens [non-(beta)-lactamase producers] Klebsiella oxytoca Anaerobic gram-positive microorganisms Clostridium perfringens Anaerobic gram-negative microorganisms Prevotella bivia (formerly Bacteroides bivius ) Cefoxitin is inactive in vitro against most strains of Pseudomonas aeruginosa and enterococci and many strains of Enterobacter cloacae. Susceptibility Tests Dilution Techniques : Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on a dilution method 1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of cefoxitin powder. The MIC values should be interpreted according to the following criteria: For testing aerobic microorganisms a, b, c other than Neisseria gonorrhoeae :
For testing Neisseria gonorrhoeae d :
d Interpretative criteria applicable only to tests performed by agar dilution method using GC agar base with 1% defined growth supplement and incubated in 5% CO 2 1 . A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected. Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard cefoxitin powder should provide the following MIC values:
Diffusion Techniques : Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure 2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30-µg cefoxitin to test the susceptibility of microorganisms to cefoxitin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-µg cefoxitin disk should be interpreted according to the following criteria: For testing aerobic microorganisms a, b, c other than Neisseria gonorrhoeae :
For testing Neisseria gonorrhoeae d :
d Interpretative criteria applicable only to tests performed by disk diffusion method using GC agar base with 1% defined growth supplement and incubated in 5% CO 2 2 . Interpretation should be as stated above for results using dilution techniques.Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cefoxitin.As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-µg cefoxitin disk should provide the following zone diameters in these laboratory test quality control strains:
Anaerobic Techniques : For anaerobic bacteria, the susceptibility to cefoxitin as MIC's can be determined by standardized test methods 3 . The MIC values obtained should be interpreted according to the following criteria:
Interpretation is identical to that stated above for results using dilution techniques. As with other susceptibility techniques, the use of laboratory control microorganisms is required to control the technical aspects of the laboratory standardized procedures. Standard cefoxitin powder should provide the following MIC values: Using either an Agar Dilution Method a or Using a Broth b Microdilution Method :
INDICATIONS AND USAGETreatment MEFOXIN is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms in the diseases listed below.
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.
CONTRAINDICATIONS
|
|
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.
|
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).
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 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.
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.
|
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.
**/* Registered trademark of Abbott Laboratories.
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.
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.
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 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%) |
7882342 Issued June 2004
COPYRIGHT © Merck & CO., Inc., 1985, 1996, 2000
All rights reserved