CEFOXITIN: 750 Adverse Event Reports & Safety Profile

Cefoxitin for Injection and Dextrose Injection is a sterile, nonpyrogenic, single-dose packaged combination of cefoxitin sodium USP and Dextrose Injection (diluent) in the DUPLEX ® sterile container. The DUPLEX ® Container is a flexible dual chamber container. The drug chamber is filled with cefoxitin sodium USP, a semi-synthetic, broad-spectrum cephalosporin antibacterial sealed under nitrogen for intravenous administration. Cefoxitin sodium USP 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 molecular weight is 449.44. The structural formula is: Cefoxitin sodium contains approximately 53.8 mg (2.3 mEq) of sodium per gram of cefoxitin activity. The diluent chamber contains Dextrose Injection. The concentration of Dextrose Hydrous USP in Water for Injection USP has been adjusted to render the reconstituted drug product iso-osmotic.

Dextrose

Hydrous USP has been added to adjust the osmolality to approximately 290 mOsmol/kg (approximately 2 g (4% w/v) and 1.1 g (2.2% w/v) to the 1 g and 2 g doses, respectively).

Dextrose

Injection is sterile, nonpyrogenic, and contains no bacteriostatic and antimicrobial agents.

Dextrose

Hydrous USP has the following structural (molecular) formula: The molecular weight of Dextrose Hydrous USP is 198.17. After removing the peelable foil strip, activating the seals, and thoroughly mixing, the reconstituted drug product is intended for single intravenous use. When reconstituted according to instructions in the product labeling, the approximate osmolality of the reconstituted solution of Cefoxitin for Injection and Dextrose Injection is approximately 290 mOsmol/kg. After reconstitution, each 50 mL contains 1 gram of cefoxitin (equivalent to 1.05 gram of cefoxitin sodium) or 2 grams of cefoxitin (equivalent to 2.10 grams of cefoxitin sodium), with a pH of approximately 6.5. Solutions of Cefoxitin for Injection and Dextrose Injection range from colorless to light amber. The DUPLEX® dual chamber container is made from a specially formulated material. The product (diluent and drug) contact layer is a mixture of thermoplastic rubber and a polypropylene ethylene copolymer that contains no plasticizers. The safety of the container system is supported by USP biological evaluation procedures.

Structural

Formula illustration Molecular Formula illustration

AND USAGE Cefoxitin for Injection and Dextrose Injection is a cephalosporin antibacterial indicated for the treatment of the following infections caused by susceptible isolates of the designated bacteria ( 1 ): Lower respiratory tract infections ( 1.1 ); Urinary tract infections ( 1.2 ); Intra-abdominal infections ( 1.3 ); Gynecological infections ( 1.4 ); Septicemia ( 1.5 ); Bone and joint infections ( 1.6 ); Skin and skin structure infections ( 1.7 ); Prophylaxis ( 1.8 ). To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefoxitin for Injection and Dextrose Injection and other antibacterial drugs, Cefoxitin for Injection and Dextrose Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria ( 1.9 ).

1.1 Lower Respiratory Tract Infections Cefoxitin for Injection and Dextrose Injection is indicated for the treatment of 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.

1.2 Urinary Tract Infections Cefoxitin for Injection and Dextrose Injection is indicated for the treatment of urinary tract infections caused by Escherichia coli , Klebsiella species, Proteus mirabilis , Morganella morganii , Proteus vulgaris and Providencia species (including P. rettgeri ).

1.3 Intra-abdominal Infections Cefoxitin for Injection and Dextrose Injection is indicated for the treatment of intra-abdominal infections , including peritonitis and intra-abdominal abscess, caused by Escherichia coli, Klebsiella species, Bacteroides species including Bacteroides fragilis , and Clostridium species.

1.4 Gynecological Infections Cefoxitin for Injection and Dextrose Injection is indicated for the treatment of 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 . Cefoxitin has no activity against Chlamydia trachomatis . Therefore, when cefoxitin 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.

1.5 Septicemia Cefoxitin for Injection and Dextrose Injection is indicated for the treatment of Septicemia caused by Streptococcus pneumoniae , Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli , Klebsiella species, and Bacteroides species including B. fragilis .

1.6 Bone and Joint Infections Cefoxitin for Injection and Dextrose Injection is indicated for the treatment of bone and joint infections caused by Staphylococcus aureus (including penicillinase-producing strains).

1.7 Skin and Skin Structure Infections Cefoxitin for Injection and Dextrose Injection is indicated for the treatment of 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.

1.8 Prophylaxis Cefoxitin for Injection and Dextrose Injection 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.

1.9 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefoxitin for Injection and Dextrose Injection and other antibacterial drugs, Cefoxitin for Injection and Dextrose Injection 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 Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should not be used in patients who require less than the 1 gram dose of cefoxitin. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR THE PREPARATION OF SOLUTIONS FOR INTRAVENOUS INFUSION ONLY. BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION TO A CONCENTRATION OF 100 MG/ML AND FURTHER DILUTION IN 50 mL OF A COMPATIBLE SOLUTION. THIS IS A PHARMACY BULK PACKAGE – NOT FOR DIRECT INJECTION USE THIS FORMULATION OF CEFOXITIN ONLY IN PATIENTS WHO REQUIRE A 1 GRAM DOSE.

Treatment Adults

Cefoxitin for Injection, USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of cefoxitin. 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. This formulation of Cefoxitin for Injection USP, Pharmacy Bulk Package SmartPak® should not be used in patients who require less than the 1 gram dose of cefoxitin. Cefoxitin for Injection may be used in patients with reduced renal function with the following dosage adjustments: In adults with renal insufficiency , Cefoxitin for Injection, USP, Pharmacy Bulk Package bag SmartPak ® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should not be used in patients with renal impairment who require less than the 1 gram dose of cefoxitin. 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

Cefoxitin for Injection, USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in pediatric patients who require less than the 1 gram dose of cefoxitin. 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

Cefoxitin for Injection, USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of cefoxitin. 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: Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of cefoxitin. 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 Injection * Including patients in whom bacteremia is absent or unlikely. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should not be used in patients who require less than the 1 gram dose of cefoxitin. 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 I.V. Moderately severe or severe infections 6 to 8 grams 1 gram every 4 hours or 2 grams every 6 to 8 hours I.V. Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene) 12 grams 2 grams every 4 hours or 3 grams every 6 hours I.V.

Renal Impairment

Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should not be used in patients with renal impairment who require less than the 1 gram dose of cefoxitin.

Table

2.

Maintenance

Dosage of Cefoxitin for Injection in Adults with Reduced Renal Function Renal Function Creatinine Clearance (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 2 1 to 2 0.5 to 1 0.5 to 1 Every 8 to 12 hours Every 12 to 24 hours Every 12 to 24 hours Every 24 to 48 hours Cefoxitin for Injection, USP, Pharmacy Bulk Package bag SmartPak ® should be used only in patients who require a 1 gram dose and not any fraction thereof. Cefoxitin for Injection USP, Pharmacy Bulk Package bag SmartPak ® should not be used in patients who require less than the 1 gram dose of cefoxitin. Directions for Proper Use of a Pharmacy Bulk Package NOT FOR DIRECT INFUSION.

The Pharmacy Bulk

Package is for use in the hospital pharmacy admixture service only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container closure may be penetrated only one time after reconstitution using a suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial reconstitution port closure entry is permitted to complete fluid transfer operations. This time limit should begin with the introduction of the solvent or diluent into the Pharmacy Bulk Package. Discard any unused portion after 4 HOURS . This pharmacy bulk package is not intended to be dispensed as a unit. PRIOR TO RECONSTITUTION : DO NOT USE THE INNER BAG IF PARTICULATE OR FOREIGN MATTER IS PRESENT, IF THE DRY POWDER IS DARK YELLOW OR BROWN, IF THE SEALS ARE NOT INTACT, OR IF THERE IS ANY OTHER DAMAGE TO THE BAG. IN SUCH CASES, DISCARD THE BAG IMMEDIATELY. After initial reconstitution port entry, use entire contents of the Pharmacy Bulk Package promptly. Any unused portion must be discarded after 4 HOURS . Gather the following items prior to the reconstitution of the product: Appropriate number of bags of Sterile Water for Injection and, depending upon the method of filling, appropriate sterile tubing and adapters.

Instruction For Reconstitution Of The Pharmacy Bulk Package Bag

SmartPak ® The entire contents of the bag and the preparation process (reconstitution and dilution) should be completed within 4 hours of initial entry. Document the date and time reconstitution starts in the designated place on the container label. The entire contents of the bag must be used within 4 hours from the time of initial entry. Remove the translucent unthreaded cap from the reconstitution (smaller) port and discard it. Reconstitute the powder through the reconstitution (smaller) port, using Sterile Water for Injection according to the table below.

Table

3.

Reconstitution Table

SmartPak ® Bag Size Amount of Sterile Water Approximate Concentration 100 grams 930 mL 100 mg/mL (1 gram/10 mL) After reconstitution is complete, remove the transfer needle from the reconstitution port. Place the bag on a flat surface of a laminar flow hood and mix for at least 15 minutes by rocking gently from side to side. CAUTION: To avoid possible leakage caused by the heavy weight of the added water, do not shake vigorously or pull strongly on the bag. When foam dissipates, visually inspect the bag to verify the solution is clear, colorless to pale yellow and free of particulate matter. DO NOT USE THE INNER BAG IF PARTICULATE OR FOREIGN MATTER IS PRESENT. Unscrew the clear threaded cap from the transfer (larger) port and discard it. Attach sterile tubing and filling adapter unit to the transfer port. Reconstituted solution can now be transferred using the transfer port and the filling adapter. It should be noted that the spike placed into the transfer port of the Pharmacy Bulk Package SmartPak ® is NEVER removed during this procedure and that the reconstitution port is self-sealing.

Dilution

Hang the bag from two eyelets. Following reconstitution, transfer 10 mL of the reconstituted solution into transfusion bags, each containing 50 mL of one of the compatible solutions below. Compatible solutions for dilution are the following: Sodium Chloride Injection, USP 5% Dextrose Injection, USP Dilution should be completed within the 4 hour preparation process. When diluted according to the instructions above, cefoxitin is stable for 18 hours at room temperature or for 48 hours if stored under refrigeration (5°C or 41°F). After the periods mentioned above, any unused solutions should be discarded.

Administration

This formulation of Cefoxitin for Injection USP, Pharmacy Bulk Package SmartPak ® is for intravenous infusion only after reconstitution. Parenteral products should be inspected visually for particulates 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: Using an infusion system, a solution containing 1 gram or 2 grams may be given over a 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. Solutions of Cefoxitin for Injection, 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. image description

Hypersensitivity to cefoxitin or other beta-lactam antibacterial drugs. ( 4.1 ) Hypersensitivity to corn products. ( 4.2 )

4.1 Hypersensitivity to Cefoxitin or other Beta-lactam Antibacterial Drugs Cefoxitin for Injection and Dextrose Injection is contraindicated in patients who have shown hypersensitivity to cefoxitin or to other β-lactam antibacterial drugs (e.g., penicillins and cephalosporins).

4.2 Hypersensitivity to Corn Products Solutions containing dextrose may be contraindicated in patients with hypersensitivity to corn products.

REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of labeling:

• Hypersensitivity Reactions to Cefoxitin or other Beta-lactam Antibacterial Drugs [see Warnings and Precautions (5.1)]
• Use in Patients with Renal Impairment [see Dosage and Administration (2.3) , Use in Specific Populations (8.6)]
• Clostridium difficile -associated Diarrhea [see Warnings and Precautions (5.2)]
• Risk of Development of Drug-resistant Bacteria [see Warnings and Precautions (5.3)]
• Drug/Laboratory Test Interactions [see Warnings and Precautions (5.4)]
• Patients with a History of Gastrointestinal Disease [see Warnings and Precautions (5.5) ]
• Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance [see Warnings and Precautions (5.6) ] The most common adverse reactions have been local reactions following intravenous injection.

Local Reactions

Thrombophlebitis has occurred with intravenous administration. Skin and Subcutaneous Tissue Disorders Rash (including exfoliative dermatitis and toxic epidermal necrolysis), urticaria, flushing, pruritus, eosinophilia, fever, dyspnea, and other allergic reactions including anaphylaxis, interstitial nephritis and angioedema have been noted.

Cardiovascular Disorders

Hypotension.

Gastrointestinal Disorders

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

Nervous System Disorders

Possible exacerbation of myasthenia gravis. Blood and Lymphatic System Disorders 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.

Hepatobiliary Disorders

Reversible elevation in SGOT, SGPT, serum LDH, and serum alkaline phosphatase; and jaundice have been reported. Renal and Urinary Disorders Elevations in serum creatinine and/or blood urea nitrogen levels have been observed. Acute renal failure has been reported. Most common adverse reactions: Local reactions. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact B.

Braun Medical

Inc. at 1-800-854-6851 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Cephalosporin-class Adverse Reactions In addition to the adverse reactions listed above which have been observed in patients treated with cefoxitin, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibacterials: pruritus, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, vomiting, abdominal pain, colitis, superinfection, vaginitis including vaginal candidiasis, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, elevated bilirubin, pancytopenia, and neutropenia. Several cephalosporins, including Cefoxitin for Injection and Dextrose Injection, have been implicated in triggering seizures, particularly in patients with renal impairment, when the dosage was not reduced [ see Dosage and Administration (2.3) and Overdosage (10 ) ] . If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

AND PRECAUTIONS Hypersensitivity reactions including anaphylaxis and serious skin reactions. If an allergic reaction occurs, discontinue the drug. ( 5.1 ) Use in patients with renal impairment: Dosage adjustment required for patients with impaired renal function. ( 2.3 ) Clostridium difficile -associated diarrhea: May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. ( 5.2 )

5.1 Hypersensitivity Reactions to Cefoxitin or other Beta-lactam Antibacterial Drugs Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) have been reported in patients on β-lactam antibacterials, including cefoxitin <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . These reactions are more likely to occur in individuals with a history of β-lactam hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Cefoxitin for Injection and Dextrose Injection is contraindicated in patients with a known hypersensitivity to Cefoxitin for Injection and Dextrose Injection or other β-lactam antibacterial drugs <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . Before initiating therapy with Cefoxitin for Injection and Dextrose Injection, inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue Cefoxitin for Injection and Dextrose Injection and institute appropriate therapy.

5.2 Clostridium difficile -associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefoxitin for Injection and Dextrose Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

5.3 Risk of Development of Drug-resistant Bacteria Prescribing Cefoxitin for Injection and Dextrose Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Prolonged use of Cefoxitin for Injection and Dextrose Injection may result in overgrowth of non-susceptible microorganisms. Repeated evaluation of the patient&apos;s condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.

5.4 Drug/Laboratory Test Interactions As with cephalothin, high concentrations of cefoxitin (&gt;100 mcg/mL) may interfere with measurement of serum and urine creatinine levels by 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.

5.5 Patients with a History of Gastrointestinal Disease Cefoxitin for Injection and Dextrose Injection is not recommended in individuals with a history of gastrointestinal disease, particularly colitis.

5.6 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance As with other dextrose-containing solutions, Cefoxitin for Injection and Dextrose Injection should be monitored if Cefoxitin for Injection and Dextrose Injection is prescribed in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

PRECAUTIONS: General This formulation of Cefoxitin for Injection USP – Pharmacy Bulk Package bags SmartPak® should not be used in renally impaired patients who require less than the 1 gram dose of cefoxitin. The total daily dose should be reduced when cefoxitin 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 cefoxitin may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Prescribing

Cefoxitin for Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Information for Patients Patients should be counseled that antibacterial drugs including Cefoxitin for Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefoxitin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefoxitin or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

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 mcg/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

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

Pediatric Use

Cefoxitin for Injection USP, Pharmacy Bulk Package bag, SmartPak® should not be used in pediatric patients who require less than the 1 gram adult dose of cefoxitin. 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 cefoxitin have been associated with an increased incidence of eosinophilia and elevated SGOT.

Geriatric

Use Of the 1,775 subjects who received cefoxitin in clinical studies, 424 (24%) were 65 and over, while 124 (7%) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out (see CLINICAL PHARMACOLOGY ). This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION and PRECAUTIONS ).

INTERACTIONS Aminoglycosides: Increased potential of nephrotoxicity. ( 7.1 )

7.1 Aminoglycosides Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibacterials.