MEFOXIN * (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:

images/15/24022101.jpg

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 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.

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 MEFOXIN with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria. While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the section is unknown.

Gram-positive

Staphylococcus aureus, including penicillinase and non-penicillinase producing strains.

Staphylococcus epidermidis

Beta-hemolytic and other streptococci (most strains of enterococci, e.g., Enterococcus faecalis [formerly Streptococcus faecalis ], are resistant)

Streptococcus pneumoniae

Gram-negative

Eikenella corrodens (beta-lactamase negative strains)

Escherichia coli

Klebsiella species (including K. pneumoniae  )

Haemophilus influenzae

Neisseria gonorrhoeae, including penicillinase and non-penicillinase producing strains

Proteus mirabilis

Morganella morganii

Proteus vulgaris

Providencia species, including Providencia rettgeri

Anaerobic organisms

Peptococcus niger

Peptostreptococcus species

Clostridium species

Bacteroides species, including the B. fragilis group (includes B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron )

MEFOXIN is inactive in vitro against most strains of Pseudomonas aeruginosa and enterococci and many strains of Enterobacter cloacae.

Methicillin-resistant staphylococci are almost uniformly resistant to MEFOXIN.

Susceptibility Tests

For fast-growing aerobic organisms, quantitative methods that require measurements of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure* has been recommended for use with discs to test susceptibility to cefoxitin. Interpretation involves correlation of the diameters obtained in the disc test with minimal inhibitory concentration (MIC) values for cefoxitin.

Reports from the laboratory giving results of the standardized single disc susceptibility test* using a 30 mcg cefoxitin disc should be interpreted according to the following criteria:

Organisms producing zones of 18 mm or greater are considered susceptible, indicating that the tested organism is likely to respond to therapy.

Organisms of intermediate susceptibility produce zones of 15 to 17 mm, indicating that the tested organism would be susceptible if high dosage is used or if the infection is confined to tissues and fluids (e.g., urine) in which high antibiotic levels are attained.

Resistant organisms produce zones of 14 mm or less, indicating that other therapy should be selected.

The cefoxitin disc should be used for testing cefoxitin susceptibility.

Cefoxitin has been shown by in vitro tests to have activity against certain strains of Enterobacteriaceae found resistant when tested with the cephalosporin class disc. For this reason, the cefoxitin disc should not be used for testing susceptibility to cephalosporins, and cephalosporin discs should not be used for testing susceptibility to cefoxitin.

Dilution methods, preferably the agar plate dilution procedure, are most accurate for susceptibility testing of obligate anaerobes.

A bacterial isolate may be considered susceptible if the MIC value for cefoxitin** is not more than 16 mcg/mL. Organisms are considered resistant if the MIC is greater than 32 mcg/mL.


*Bauer, A. W.; Kirby, W. M. M.; Sherris, J. C.; Turck, M.: Antibiotic susceptibility testing by a standardized single disc method, Amer. J. Clin. Path. 45  : 493-496, Apr. 1966. Standardized disc susceptibility test, Federal Register 37  : 20527-20529, 1972. National Committee for Clinical Laboratory Standards: Performance Standards for Antimicrobial Disc Susceptibility Tests-Fifth Edition; Approved Standard, NCCLS Document M2-A5, Vol 13, No. 24, NCCLS, Villanova, PA, December 1993.

**Determined by the ICS agar dilution method (Ericsson and Sherris, Acta Path. Microbiol. Scand. (B) Suppl. No. 217, 1971) or any other method that has been shown to give equivalent results.

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 (penicillinase and non-penicillinase producing), 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 the Bacteroides fragilis group***, and Clostridium species
  4. Gynecological infections, including endometritis, pelvic cellulitis, and pelvic inflammatory disease caused by Escherichia coli, Neisseria gonorrhoeae (penicillinase and non-penicillinase producing), Bacteroides species including B. fragilis , Clostridium species Peptococcus niger , Peptostreptococcus species, and Group B streptococci. 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 (penicillinase and non-penicillinase producing), Escherichia coli, Klebsiella species, and Bacteroides species including B. fragilis.
  6. Bone and joint infections caused by Staphylococcus aureus (penicillinase and non-penicillinase producing).
  7. Skin and skin structure infections caused by Staphylococcus aureus (penicillinase and non-penicillinase producing), Staphylococcus epidermidis, 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.


*** B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron.

CONTRAINDICATIONS
 

MEFOXIN is contraindicated in patients who have shown hypersensitivity to cefoxitin and the cephalosporin group of antibiotics.

BEFORE THERAPY WITH `MEFOXIN' IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFOXITIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN WITH CAUTION TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. IF AN ALLERGIC REACTION TO `MEFOXIN' OCCURS, DISCONTINUE THE DRUG. SERIOUS HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefoxitin, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and my permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."

After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis

PRECAUTIONS

General

The total daily dose should be reduced when MEFOXIN is administered to patients with transient or persistent reduction of urinary output due to renal insufficiency (see DOSAGE AND ADMINISTRATION ), because high and prolonged serum antibiotic concentrations can occur in such individuals from usual doses.

Antibiotics (including cephalosporins) should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

As with other antibiotics, prolonged use of MEFOXIN may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient' condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Laboratory Tests

As with any potent antibacterial agent, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy.

Drug Interactions

Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics.

Drug/Laboratory Test Interactions

As with cephalothin, high concentrations of cefoxitin (>100 micrograms/mL) may interfere with measurement of serum and urine creatinine levels by the Jaffé reaction, and produce false increases of modest degree in the levels of creatinine reported. Serum samples from patients treated with cefoxitin should not be analyzed for creatinine if withdrawn within 2 hours of drug administration.

High concentrations of cefoxitin in the urine may interfere with measurement of urinary 17-hydroxy-corticosteroids by the Porter-Silber reaction, and produce false increases of modest degree in the levels reported.

A false-positive reaction for glucose in the urine may occur. This has been observed with CLINITEST **** reagent tablets.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed with cefoxitin to evaluate carcinogenic or mutagenic potential. Studies in rats treated intravenously with 400 mg/kg of cefoxitin (approximately three times the maximum recommended human dose) revealed no effects on fertility or mating ability.

Pregnancy

Pregnancy Category B. Reproduction studies performed in rats and mice at parenteral doses of approximately one to seven and one-half times the maximum recommended human dose did not reveal teratogenic or fetal toxic effects, although a slight decrease in fetal weight was observed.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

In the rabbit, cefoxitin was associated with a high incidence of abortion and maternal death. This was not considered to be a teratogenic effect but an expected consequence of the rabbit's unusual sensitivity to antibiotic-induced changes in the population of the microflora of the intestine.

Nursing Mothers

MEFOXIN is excreted in human milk in low concentrations. Caution should be exercised when MEFOXIN is administered to a nursing woman.

Pediatric Use

Safety and efficacy in pediatric patients from birth to three months of age have not yet been established. In pediatric patients three months of age and older, higher doses of MEFOXIN have been associated with an increased incidence of eosinophilia and elevated SGOT.


**** Registered trademark of Ames Company, Division of Miles Laboratories, Inc.

ADVERSE REACTIONS

MEFOXIN is generally well tolerated. The most common adverse reactions have been local reactions following intravenous injection. Other adverse reactions have been encountered infrequently.

Local Reactions

Thrombophlebitis has occurred with intravenous administration.

Allergic Reactions

Rash (including exfoliative dermatitis and toxic epidermal necrolysis), pruritus, eosinophilia, fever, dyspnea, and other allergic reactions including anaphylaxis, interstitial nephritis and angioedema have been noted.

Cardiovascular

Hypotension

Gastrointestinal

Diarrhea, including documented pseudomembranous colitis which can appear during or after antibiotic treatment. Nausea and vomiting have been reported rarely.

Neuromuscular

Possible exacerbation of myasthenia gravis

Blood

Eosinophilia, leukopenia, including granulocytopenia, neutropenia, anemia, including hemolytic anemia, thrombocytopenia, and bone marrow depression. A positive direct Coombs test may develop in some individuals, especially those with azotemia.

Liver Function

Transient elevations in SGOT, SGPT, serum LDH, serum alkaline phosphatase; and jaundice have been reported.

Renal Function

Elevations in serum creatinine and/or blood urea nitrogen levels have been observed. As with the cephalosporins, acute renal failure has been reported rarely. The role of MEFOXIN in changes in renal function tests is difficult to assess, since factors predisposing to prerenal azotemia or to impaired renal function usually have been present.

In addition to the adverse reactions listed above which have been observed in patients treated with MEFOXIN, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics:

Urticaria, erythema multiforme, Stevens-Johnson syndrome, serum sickness-like reactions, abdominal pain, colitis, renal dysfunction, toxic nephropathy, false-positive test for urinary glucose, hepatic dysfunction including cholestasis, elevated bilirubin, aplastic anemia, hemorrhage, prolonged prothrombin time, pancytopenia, agranulocytosis, superinfection, vaginitis including vaginal candidiasis.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. (See DOSAGE AND ADMINISTRATION.) If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

OVERDOSAGE

The acute intravenous LD 50 in the adult female mouse and rabbit was about 8.0 g/kg and greater than 1.0 g/kg respectively. The acute intraperitoneal LD 50 in the adult rat was greater than 10.0 g/kg.

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.

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 infections
6-8 grams
1 gram every 4 hours
or
2 grams every 6-8 hours IV
Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)
12 grams
2 grams every 4 hours
or
3 grams every 6 hours IV
+ Including patients in whom bacteremia is absent or unlikely

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.

Table 2--Maintenance Dosage of MEFOXIN in Adults with Reduced 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

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) × (140 - age)    
72 × serum creatinine (mg/100 mL)
Females:
  0.85 × 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 .)

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.

Table 3--Preparation of Solution
MEFOXIN
Amount of
Diluent to
be Added (mL) ++
Approximate
Withdrawable
Volume (mL)
Approximate Average
Concentration (mg/mL)
10 10.5 95
10 or 20 11.1 or 21.0 180 or 95
50 or 100 50 or 100 20 or 10
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.

  *** Registered trademark of Abbott Laboratories.

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.


**** Registered trademark of Abbott Laboratories.

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' Injection

  5 percent Dextrose in Lactated Ringer' Injection

  10 percent invert sugar in water

  10 percent invert sugar in saline solution

  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

(6505-01-119-6005, 1 g 25's).

No. 3368--1 gram cefoxitin equivalent

NDC 0006-3368-71 in trays of 10 infusion bottles

(6505-01-195-0649, 1 g infusion bottle 10's).

No. 3357--2 gram cefoxitin equivalent

NDC 0006-3357-53 in trays of 25 vials

(6505-01-104-6393, 2 g 25's).

No. 3369--2 gram cefoxitin equivalent

NDC 0006-3369-73 in trays of 10 infusion bottles

(6505-01-185-2624, 2 g infusion bottle 10's).

No. 3388--10 gram cefoxitin equivalent

NDC 0006-3388-67 in trays of 6 bulk bottles

(6505-01-263-0730, 10 g 6's).

No. 3548--1 gram cefoxitin equivalent

NDC 0006-3548-45 in trays of 25 ADD-Vantage® vials.

(6505-01-262-9509, 1 g ADD-Vantage® 25's).

No. 3549--2 gram cefoxitin equivalent

NDC 0006-3549-53 in trays of 25 ADD-Vantage® vials.

(6505-01-263-4531, 2 g ADD-Vantage® 25's).

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 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%)

7882337   Issued October 1996

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